Motivating Change in Physicians’ Prescribing Behavior

Posted by James Yeh, M.D. M.P.H. • March 16th, 2016

2016-03-11_10-19-25High-risk prescribing

Drug prescribing is one of the armamentarium in a physician’s tool box to help manage disease and alleviate suffering. However, the risks of certain drugs in particular clinical contexts outweigh the benefits and may lead to preventable drug-related morbidity and mortality. Such high-risk prescribing is a common concern.

What is the safer prescribing trial about?

In this week’s issue of NEJM, Dreischulte and colleagues asked whether a 48-week intervention consisting of clinician education outreach, financial incentive, and clinician reviewing patient information can reduce high-risk prescribing of NSAIDs and anti-platelet therapy. The intervention is part of a data-drive program in which the primary care physicians are: 1) educated about the risks of NSAIDs and anti-platelet medications; 2) given access to a web-based tool that identifies patients at highest risk for adverse drug events associated with NSAIDs and anti-platelet medications; and 3) given financial incentives to review information about these high-risk patients ($600 fixed participation fee per practice and $25 per patient information reviewed).

The investigators randomized 34 primary care practices in Scotland with over 202,000 patients to different start dates of the intervention. The primary outcome was the percentage of patients at high risk for one of the three adverse drug events (gastrointestinal bleeding, renal failure, and heart failure) associated with use of NSAIDs and anti-platelet therapy who were currently prescribed such medication. Secondary outcomes included ongoing (prescribed within the past year) and new (not prescribed within the past year) high-risk prescription rates and emergency hospital admissions associated with one of the three adverse drug events of gastrointestinal bleeding, renal failure, and heart failure.

What did the study show?

The analysis included over 33,000 patients with risk factors for adverse drug events using NSAIDs and anti-platelet therapy. For the primary outcome, there was a reduction in the percentage of patients prescribed high-risk NSAIDs and anti-platelet therapies during the intervention compared with prior to the intervention (2.2% versus 3.7%; adjusted OR 0.63, 95%CI 0.57-0.68, p<0.001).

There were significant reductions in the rates of ongoing and new high-risk prescribing (adjusted ORs 0.60 and 0.77, respectively). Emergent hospitalization rates related to gastrointestinal bleeding and acute kidney injury associated with recent high-risk prescriptions were also significantly reduced (RR 0.09 and RR 0.32, respectively). However, the reduction in admission rates for heart failure associated with recent NSAIDs prescription was not significant (RR 0.54, 95%CI 0.20-1.51).

Post-hoc analysis determined the reduction of high-risk prescribing was sustained in the 48-week period after the end of the intervention when financial incentive stopped (adjusted OR 1.14, 95%CI 0.85-1.53, p=0.38).

So what are the caveats?

From this study we learned that a complex intervention consisting of clinician education, informatics to identify high-risk patients, and a financial incentive in the primary care setting can modify physicians’ prescribing behavior and reduce high-risk prescribing. The study, however, does not provide us with information about which component of this complex intervention matters the most and whether it can be effective by itself. Additionally, it is unclear whether a different type of approach is required for modifying prescribing behavior in other disease condition and drug treatments.

———————————————————————————————————————————–

What factors do you think affect a physician’s prescribing behavior?

Which drug classes are responsible for the majority of emergent hospitalizations in the elderly?  Read about the study here.

Learn the details of the initial study on educational outreach visit intervention, also known as academic detailing.

Carotid artery stenting versus carotid endarterectomy: Results of two randomized trials

Posted by Andrea Merrill • March 14th, 2016

2016-03-11_9-28-20As a 4th year medical student I rotated on the vascular surgery service at a local hospital. One of the vascular surgeons loved music (all music!) and would quiz me on the musicians as each song came on. I usually got them wrong and longed for him to just ask me an anatomy question instead so I could finally get something right. When it came to performing a carotid endarterectomy, however, he only played classical music, his “carotid playlist”. He wanted full concentration and focus for this delicate operation, one that carried a very real risk of myocardial infarction (MI) and/or stroke.

As we evolve in medicine, we are constantly looking for new ways to improve care and minimize risk to patients. This is especially evident in the field of surgery. Over the past 40 years, the practice of surgery has changed significantly, shifting away from big, open operations to minimally invasive operations with lower morbidity. Current surgical residents may never even see an open appendectomy  — I have only seen one!

In an effort to minimize the risk associated with carotid endarterectomy, carotid artery stenting was developed as a minimally invasive technique for higher risk patients (due to anatomical difficulties such as prior irradiation or significant medical comorbidities). The first major trial comparing carotid endarterectomy to stenting was the CREST trial by Brott et al. published in 2010 in NEJM.  In this week’s issue of NEJM, Brott et al. now report the results after 10 years follow-up.

This trial enrolled 2502 symptomatic and asymptomatic patients with carotid stenosis and randomly assigned them to endarterectomy or stenting with embolic protection (a device that captures and removes emboli). All patients undergoing stenting received dual-antiplatelet therapy while those undergoing endarterectomy received aspirin. Both groups of patents also received the standard of care medical therapy at the time. The primary composite endpoint was stroke, myocardial infarction, or death from any cause during the periprocedural period or any ipsilateral stroke at the designated follow-up period.

The 2010 publication had 4 years of follow-up and found that while there was a higher periprocedural risk of stroke in the stenting group (4.1% vs. 2.3%, P=0.01) and MI in the endarterectomy group (1.1% vs. 2.3%, P=0.03), there was no significant difference in the primary composite outcome between the two groups at 4 years (7.2% for stenting and 6.8%, for endarterectomy). Now, after 6 more years of follow-up (10 total), there remains no significant difference in the rate of primary composite end point between stenting and endarterectomy (11.8% vs. 9.9%). This remained true when stratified by symptomatic status. There was a significant different in rate of death or ipsilateral stroke at 10 years (11% for vs 7.9% for endarterectomy, p=0.04), however, this was attributed to the higher rate of periprocedural stroke with stenting.

ACT-I, a similar trial comparing endarterectomy to stenting by Rosenfield et al. was also published in this week’s NEJM.  This trial, however, only enrolled patients who were asymptomatic. As in CREST, patients received dual anti-platelet therapy in the stenting group, aspirin in the endarterectomy group, and current standard medical therapy.  This study was designed as a non-inferiority study and used a primary composite end point of death, stroke, or myocardial infarction within 30 days after the procedure or ipsilateral stroke within 1 year.  There was no difference in primary composite end point at 1 year (event rate, 3.8% and 3.4%, respectively; P=0.01 for noninferiority).  While there was numerically a higher rate of stroke in the stenting group within 30 days of procedure, it did not reach statistical significance (2.9 vs 1.7%  p=0.33), in contrast to CREST.  At 5-year follow-up, rate of freedom from ipsilateral stroke and overall survival rates did not differ.

What do the results of these two studies tell us?  Should all asymptomatic carotid stenosis patients undergo carotid stenting?  How do we put this into practice?  The accompanying editorial by Spence and Naylor sheds some light on these questions, remarking that the results of these two studies “should dispel any lingering concerns about the durability of stenting. That issue has now surely been resolved.”  What has not been resolved, though, is the generalizability of these two studies and how to manage an asymptomatic carotid stenosis patient.  To this end they comment, “No one should harbor any illusions that ACT I and CREST have resolved the latter [asymptomatic management] issue.”

Two major limitations vex both of these studies.  First, they were both conducted at centers of excellence with the best surgeons and interventionalists performing the procedures.  In places where this is not available, periprocedural stroke rates may be higher and thus the risk of intervening may outweigh the benefits.  Second, neither study compared stenting and endarterectomy to optimal medical treatment only.  Medical treatment for prevention of stroke has greatly improved over the past 20 years and this needs to be taken into account when interpreting these studies.  Spence and Naylor conclude, “Outside clinical trials, endarterectomy and stenting should be reserved for patients with symptomatic severe stenosis or for asymptomatic patients who are shown to be at higher risk for stroke with medical therapy than with intervention.”

 

A Man with an Ileocecal Mass

Posted by Carla Rothaus • March 11th, 2016

2016-03-10_9-25-35Misdiagnosis of Crohn’s disease in a patient with intestinal tuberculosis would generally result in treatment with glucocorticoids and biologic agents, which then has the potential to cause disease progression that leads to increased morbidity and mortality. A new Case Record summarizes.

An 80-year-old man presented with anorexia, weight loss, abdominal pain, diarrhea, and an ileocecal mass. 18F-fluorodeoxyglucose uptake was present in several pulmonary nodules, the stomach, and the terminal ileum. A diagnosis was made.

Clinical Pearl

• What diseases are included in the differential diagnosis of an ileocecal mass in an elderly patient?

Cancers of the colon and small bowel are relatively common in elderly patients. A carcinoid tumor can involve the ileocecal valve and appendix and may cause the carcinoid syndrome if the disease metastasizes to the liver. Primary gastrointestinal lymphoma may also occur in the region of the ileocecal valve and the appendix. Although Crohn’s disease can occur anywhere throughout the gastrointestinal tract, it commonly affects the ileocecal valve and terminal ileum. Crohn’s disease can be manifested at any age, including in an 80-year-old patient. Bacterial, fungal, and mycobacterial infection can occur at the ileocecal valve, cecum, and terminal ileum.

Clinical Pearl

• Are tissue samples positive for acid-fast bacilli in most cases of intestinal tuberculosis?

Tissue samples are positive for acid-fast bacilli in only 25 to 30% of cases of intestinal tuberculosis. The use of molecular techniques, such as polymerase-chain-reaction (PCR) assays of fresh biopsy specimens, can improve the diagnostic yield.

Figure 4. Biopsy Specimens Obtained during Colonoscopy.

Morning Report Questions

Q: Describe some of the endoscopic and histologic features of Crohn’s disease and intestinal tuberculosis.

A: On endoscopy, the lesion associated with Crohn’s disease is predominantly ulcerative, but polypoid lesions are seen with expansion of lamina propria and lymphoid structures; a mass that appears to be fungating is rare. On histologic examination, granulomas are seen in 20 to 25% of cases. The endoscopic appearance of intestinal tuberculosis is relatively indistinguishable from that of Crohn’s disease. Ulcerative, polypoid, and fungating lesions can be present. Granulomas are seen in 20 to 25% of cases. In patients with Crohn’s disease, mucosal injury has a cobblestone appearance with aphthous and longitudinal rake ulcers, whereas in patients with intestinal tuberculosis, the ulcers are transverse in orientation.

Q: Are Crohn’s disease and intestinal tuberculosis easy to differentiate?

A: Distinguishing between Crohn’s disease and intestinal tuberculosis is a challenge, because there is marked overlap in the clinical presentation and the radiographic, laboratory, and endoscopic findings, as well as in the presence of granulomas on histologic examination. Both diseases have an insidious onset. Diarrhea, hematochezia, and extraintestinal manifestations are more common in patients with Crohn’s disease. Intestinal tuberculosis can target extrapulmonary sites in a manner that resembles the classic extraintestinal manifestations of Crohn’s disease, such as reactive arthritis, erythema nodosum, and uveitis. Ascites and fever are more commonly seen in patients with intestinal tuberculosis. Both diseases involve the ileum and colonic segments of the bowel. Isolated involvement of the terminal ileum is commonly seen in patients with Crohn’s disease, whereas involvement of the ileocecal area and a patulous ileocecal valve is seen in patients with intestinal tuberculosis. The granulomas associated with intestinal tuberculosis are more frequent and confluent and larger than those associated with Crohn’s disease.

Mesenteric Ischemia

Posted by Carla Rothaus • March 11th, 2016

2016-03-10_9-18-19Although mesenteric ischemia is an uncommon cause of abdominal pain, accounting for less than 1 of every 1000 hospital admissions, an inaccurate or delayed diagnosis can result in catastrophic complications; mortality among patients in whom this condition is acute is 60 to 80%.

Although mesenteric ischemia is uncommon, it can be life-threatening, and its recognition is therefore crucial. This review article explains the pathophysiology, diagnosis, and treatment of intestinal ischemic syndromes.

Clinical Pearl

• What is the clinical presentation of mesenteric ischemia?

Patients with acute mesenteric ischemia may initially present with classic “pain out of proportion to examination,” with an epigastric bruit; many, however, do not. Other patients may have tenderness with palpation on examination owing to peritoneal irritation caused by full-thickness bowel injury. This finding may lead the physician to consider diagnoses other than acute mesenteric ischemia. Differentiation between arterial and venous obstruction is not always simple; however, patients with mesenteric venous thrombosis, as compared with those with acute arterial occlusion, tend to present with a less abrupt onset of abdominal pain. Patients with chronic mesenteric ischemia can present with a variety of symptoms, including abdominal pain, postprandial pain, nausea or vomiting (or both), early satiety, diarrhea or constipation (or both), and weight loss. Abdominal pain 30 to 60 minutes after eating is common and is often self-treated with food restriction, resulting in weight loss and, in extreme situations, fear of eating, or “food fear.”

Clinical Pearl

• What are the imaging modalities used in the diagnosis and management of mesenteric ischemia?

Given its 95 to 100% accuracy, computed tomographic angiography (CTA) has become the recommended method of imaging for the diagnosis of visceral ischemic syndromes. Magnetic resonance angiography (MRA) is an attractive option that may provide information about flow and avoid the risks of radiation and use of contrast material that are associated with CTA. However, this test takes longer to perform than CTA, lacks the necessary resolution, and can overestimate the degree of stenosis. Although MRA techniques are evolving, currently CTA imaging is almost always the preferred choice, and the advantages of CTA outweigh any risks associated with the use of this form of imaging among patients with acute mesenteric ischemia. Catheter angiography, which was previously considered to be the standard method of diagnosis of mesenteric ischemia, has become a component of initial therapy. Angiography can also be used to confirm the diagnosis before open abdominal exploration is undertaken. The value of ultrasonographic testing is extremely dependent on the skill of the technologist. In addition, adequate ultrasonographic imaging can be difficult to obtain in patients with obesity, bowel gas, and heavy calcification in the vessels. Adequate ultrasonographic assessment is often impossible in patients with acute mesenteric ischemia because of the length of the study and the abdominal pressure required; it is therefore best reserved for the evaluation of patients with chronic mesenteric ischemia and for monitoring after intervention.

Figure 1. Computed Tomographic Angiography (CTA) in a Patient with Acute Mesenteric Ischemia Caused by an Embolism in the Superior Mesenteric Artery.

Morning Report Questions

Q: What are current trends regarding open repair versus endovascular revascularization for the treatment of mesenteric ischemia?

A: Endovascular strategies can theoretically restore perfusion more rapidly than can open repair and may thus prevent progression of mesenteric ischemia to bowel necrosis. Although the use of endovascular techniques is becoming more common, the comparative data on the results with the two approaches in patients with acute mesenteric ischemia are insufficient to show a clear advantage of one approach over the other. Available data suggest that the use of endovascular procedures for acute mesenteric ischemia is becoming more common; the use of these procedures increased from 12% of cases in 2005 to 30% of cases in 2009. These data also show that this strategy may be most appropriate for patients with ischemia that is not severe and those who have severe coexisting conditions that place them at high risk for complications and death associated with open surgery. Revascularization is indicated for all patients with symptoms of chronic mesenteric ischemia in whom symptoms of this disease develop. Open repair, which was formerly considered to be the standard in such cases, has been surpassed in recent years by endovascular repair, which is now used in 70 to 80% of initial procedures. Open repair for chronic mesenteric ischemia is associated with slower recovery and longer hospital stays. Data on mortality are inconsistent; however, patients treated with open repair have improved rates of symptom relief at 5 years and of primary patency (both rates as high as 92%), and lower rates of reintervention.

Q: What are some of the components of long-term care in patients diagnosed with mesenteric ischemia?

A: The long-term care of patients with mesenteric ischemia is focused on managing coexisting conditions and risk factors. Therefore, aggressive smoking-cessation measures, blood-pressure control, and statin therapy are recommended. Lifelong preventive treatment with aspirin is recommended in all patients who undergo endovascular or open repair. Patients who undergo endovascular repair should also receive clopidogrel for 1 to 3 months after the procedure. Because the recurrence of symptoms is common in patients with a history of mesenteric ischemia, lifelong repeated assessment of vascular patency is indicated. Duplex ultrasonography should be performed every 6 months for the first year after repair, then yearly thereafter. All patients should be informed about the risks and warning signs of stenosis, occlusion, and repeated episodes of ischemia.

New Clinical Decisions article: Skin Abscess

Posted by Avery Fang • March 8th, 2016

4-23-clindec1A 22-year-old woman presents to the emergency department with a 3-day history of increasing redness, swelling, and pain in her left thigh. She tells you that she otherwise feels well. She reports no recent trauma and no fevers, chills, nausea, or vomiting. She has no relevant medical history. She is not currently taking any medications and has no known drug allergies. On physical examination, her body-mass index (the weight in kilograms divided by the square of the height in meters) is 26, she is afebrile, and her vital signs are within normal limits. Clinically, she appears well. Her examination is notable only for an area of fluctuance, approximately 2 cm in diameter, with associated tenderness, on the left anterior thigh approximately 12 cm above the patella and not involving the knee. Erythema extends approximately 2 cm beyond the edges of the fluctuance. There is no spontaneous drainage and no associated lymphadenopathy.

Experts disagree about which treatment the woman needs. In a new Clinical Decisions article, read advice from two clinical experts and find out about the numbers behind the statistics. What advice would you give?

We invite you to choose a treatment option and share your comments. Voting and discussion are open through March 16.

Another LEAP Forward: Testing the Stability of Peanut Tolerance after Early Peanut Exposure

Posted by Rachel Wolfson • March 7th, 2016

leaponOver the past few decades, allergies have been on the rise worldwide, particularly in the United States. Immunotherapy (or allergy shots), in which incremental exposure to allergens sensitizes the immune system to the allergen, have been effective for some allergies, such as dust mites. For food allergies, the effectiveness of oral exposure in infancy to sensitize patients to the allergen was under debate for many years.1 Last year, the LEAP study performed a much-needed randomized controlled trial for the effect of peanut exposure in early childhood on formation of peanut allergy. Their results were striking and conclusive – the prevalence of peanut allergy in the avoidance group was 17.2%, whereas the prevalence in the consumption group was 3.2%.

At the end of 60 months of exposure or avoidance of peanuts, the LEAP-study ended. However, the long-term effects of this early exposure on peanut tolerance remained unclear. To address this, the LEAP-On study group instructed all LEAP study members (those in both the avoidance and consumption groups) to avoid peanut exposure for 12 months after the end of the LEAP trial. The primary endpoint, peanut allergy at 72 months, was significantly more frequent in the patients that had avoided peanuts in the LEAP trial (18.6%) compared to the consumption group (4.8%, p<0.001). These results indicate that four years of consumption of peanuts in early childhood is sufficient to produce tolerance to peanuts that is maintained over the subsequent year, even with peanut avoidance for that year.

In addition, the authors report that there were three cases of new peanut allergy in both groups during the 12 months after the LEAP study. However, there was no statistical difference in peanut allergy over the year of avoidance in the LEAP consumption group (3.7% at 60 months, 4.8% at 72 months, p=0.250), indicating that avoidance after consumption did not increase de novo peanut allergy formation.

While it is clear that peanut tolerance is stable for 12 months after oral exposure, a variety of questions remain. First, how long will this tolerance be stable? Is it necessary to have exposure this early in life in order to acquire such tolerance? And importantly, do these results apply to other food allergens, beyond peanuts? Hopefully, with follow up studies and more randomized controlled trials, we can begin to tackle the ever-rising rates of allergies.

 

Portal Hypertension

Posted by Carla Rothaus • March 4th, 2016

37Portal hypertension, which is most often caused by cirrhosis, is seen frequently in medical practice. Noncirrhotic portal hypertension is much rarer, particularly in the developed world.

A 54-year-old man presented to the emergency department with a 1-month history of edema in the lower legs and a 1-week history of upper abdominal pain. He also reported intermittent nausea, early satiety, and diarrhea but did not have fevers, chills, or vomiting. A new Clinical Problem-Solving article summarizes.

Clinical Pearl

• What serum–ascites albumin gradient (SAAG) is consistent with portal hypertension?

A SAAG of 1.1 g per deciliter or higher is consistent with portal hypertension. Other causes of high SAAG include heart failure (although heart failure is usually associated with higher levels of ascitic fluid protein), hepatic vein obstruction (Budd–Chiari syndrome), and myxedema. Myxedema ascites is also characterized by a high level of ascitic fluid protein (>2.5 g deciliter).

Clinical Pearl

• What are some of the causes of noncirrhotic portal hypertension?

Numerous conditions may cause portal hypertension in the absence of cirrhosis by distorting hepatic architecture or increasing intrahepatic vascular resistance at the prehepatic, intrahepatic, or posthepatic level. Conditions that cause noncirrhotic portal hypertension at the prehepatic level include portal vein or splenic vein thrombosis and splanchnic arteriovenous malformation. Conditions that cause changes at the intrahepatic level include hepatic vasculitis, HIV infection, and infiltrative disease (medications may also cause changes at the intrahepatic level). The Budd–Chiari syndrome, inferior vena cava obstruction, and restrictive cardiac disease may cause changes at the posthepatic level. Vitamin A toxicity may also cause portal hypertension. Worldwide, schistosomiasis is the most common cause of noncirrhotic portal hypertension and is mediated by local inflammation and the microvascular obstruction caused by schistosoma larvae. Vinyl chloride, copper, and arsenic have also been reported to cause noncirrhotic portal hypertension.

Figure 2. Selected Causes of Portal Hypertension in the Absence of Cirrhosis.

Morning Report Questions

Q: What doses of vitamin A are associated with hepatic toxicity?

A: Liver injury, including noncirrhotic portal hypertension and cirrhosis, is a recognized complication of excessive consumption of vitamin A and may occur at doses as low as 25,000 IU daily. (The U.S. recommended daily allowance is 3000 IU per day.) In one case series of 41 patients with vitamin A–related liver toxicity, daily intakes ranged from 20,000 to 400,000 IU for an average of 7.1 years, although single ingestions of more than 500,000 IU have been reported to provoke noncirrhotic portal hypertension.

Q: How does excess vitamin A ingestion cause liver damage?

A: Vitamin A is stored primarily as retinol in hepatic stellate cells and may cause portal hypertension when the cells become engorged, obstructing blood flow through the liver sinusoids. Excess vitamin A also causes hepatocyte injury and necrosis in hepatocytes. Hepatic stellate cells participate in the deposition of extracellular matrix; their continued activation may lead to cirrhosis. Vitamin A overuse is best identified by obtaining a detailed history rather than by measuring retinol levels, since serum levels poorly reflect total body stores. In many reported cases, vitamin A–induced portal hypertension resolves within months to years after vitamin A has been withdrawn, although in several instances there has been progression to liver failure.

Figure 1. Liver-Biopsy Specimen.

Uncomplicated Skin Abscess

Posted by Carla Rothaus • March 4th, 2016

2016-03-03_14-22-56Between 1993 and 2005, annual emergency department visits for skin and soft-tissue infections in the United States increased from 1.2 million to 3.4 million, primarily because of an increased incidence of abscesses. The primary treatment of a cutaneous abscess is drainage. Whether adjunctive antibiotics lead to improved outcomes in patients with uncomplicated abscesses or just more cost and side effects is unclear. Talan et al. conducted a randomized trial at five U.S. emergency departments to determine whether trimethoprim–sulfamethoxazole would be superior to placebo in outpatients older than 12 years of age who had an uncomplicated abscess that was being treated with drainage. The primary outcome was clinical cure of the abscess, assessed 7 to 14 days after the end of the treatment period.

In this randomized clinical trial in patients presenting to U.S. emergency departments with an acute uncomplicated cutaneous abscess, drainage plus trimethoprim–sulfamethoxazole therapy for a week was associated with modest clinical benefits as compared with drainage alone. A new Original Article summarizes.

Clinical Pearl

• Have previous investigations shown a benefit of adjunctive antibiotics for uncomplicated skin abscess?

Previous investigations, which had small numbers of participants, did not show a benefit of antibiotic treatment. Larger studies are required to show relatively small differences in cure rates, because drainage alone may result in resolution in more than 80% of cases.

Clinical Pearl

• What are current practice guidelines regarding the adjunctive use of antibiotics for uncomplicated skin abscesses?

Practice guidelines for abscess treatment state that drainage is sufficient for many patients and, primarily on the basis of expert opinion, recommend adjunctive antibiotics for patients who have certain clinical or demographic characteristics, including the systemic inflammatory response syndrome, diabetes, very young or very old age, an infected site with a diameter of more than 5 cm, and surrounding cellulitis.

Morning Report Questions

Q: Do adjunctive antibiotics lead to an improved cure rate in patients with uncomplicated skin abscess?

A: In the study by Talan et al. involving 1265 patients with a drained cutaneous abscess, the authors found that patients who received trimethoprim–sulfamethoxazole (at doses of 320 mg and 1600 mg, respectively, twice daily, for 7 days) had a higher cure rate than those who received placebo. The abscess cure rate was 80.5% in the trimethoprim–sulfamethoxazole group and 73.6% in the placebo group in the modified intention-to-treat 1 population (difference, 6.9 percentage points; 95% confidence interval [CI], 2.1 to 11.7; P=0.005). The authors also found that many secondary outcomes were better in the trimethoprim–sulfamethoxazole group than in the placebo group, including fewer subsequent surgical drainage procedures, new skin infections, and infections among household members through 6 to 8 weeks after the end of the treatment period. Participants who received trimethoprim–sulfamethoxazole had only slightly more gastrointestinal side effects (mostly mild) than those who received placebo and had no serious or life-threatening drug-related adverse reactions.

Table 2. Baseline Characteristics in the Modified Intention-to-Treat 1 Population.

Table 3. Cure Rates among Patients with a Drained Cutaneous Abscess in Three Trial Populations.

Table 4. Secondary Outcomes in the Per-Protocol Population.

Q: How would you interpret the results of the study by Talan et al.?

A: Talan et al. found that the cure rate with respect to the primary lesion was approximately 7 percentage points higher with trimethoprim–sulfamethoxazole than with placebo. Thus, adjunctive oral treatment with trimethoprim–sulfamethoxazole — which is inexpensive, appears to be safe, and is associated with a higher cure rate of the primary lesion than that with placebo — offers the possibility of lower rates of costly subsequent medical visits, surgeries, and hospitalizations and of new infections among patients and their household contacts. On the other hand, drainage alone was associated with a similar rate of early response at 48 to 72 hours and a high overall cure rate. Trimethoprim–sulfamethoxazole can cause uncommon but serious complications such as Clostridium difficile colitis, renal and electrolyte problems, drug interactions, and rare life-threatening reactions (e.g., Stevens–Johnson syndrome, at an estimated rate of 3 cases per 100,000 exposed persons). Increased antibiotic use may promote bacterial resistance. A similar National Institutes of Health–funded trial (ClinicalTrials.gov number, NCT00730028) may also shed light on the efficacy of adjunctive antibiotics.

To Learn more about skin abscess, please read a new Clinical Decisions.

Take the Case Challenge: A Man with Weight Loss, Abdominal Pain, and an Ileocecal Mass

Posted by Avery Fang • March 2nd, 2016

2-23-2016 11-08-19 AMAn 80-year-old man presented with several years of intermittent abdominal pain, diarrhea, bleeding, weight loss, and an ileocecal mass. What is the most likely diagnosis?

Read the case description. Then vote and comment about what the diagnosis may be and what diagnostic tests will prove useful. Find the answers in the full text of the case to be published on March 9.  Follow the conversation on Facebook and Twitter with #NEJMCases.

Aspirin before Coronary Artery Surgery

Posted by Carla Rothaus • February 26th, 2016

2-25-2016 9-32-55 AMMost patients with coronary artery disease receive aspirin for primary or secondary prevention of myocardial infarction, stroke, and death. Aspirin poses a risk of bleeding in patients undergoing surgery, but it is unclear whether aspirin should be stopped before coronary artery surgery. Myles et al. used a 2-by-2 factorial trial design to randomly assign patients who were scheduled to undergo coronary artery surgery and were at risk for perioperative complications to receive aspirin or placebo and tranexamic acid or placebo. One aim of their ongoing trial was to determine whether aspirin would reduce the occurrence of death and thrombotic complications in at-risk patients who were undergoing coronary artery surgery. The results of the aspirin trial are reported in the February 25, 2016, issue of the New England Journal of Medicine.

In a randomized trial involving 2100 patients undergoing coronary-artery surgery, the risk of bleeding within 30 days after surgery was not higher with aspirin than with placebo, nor was the risk of death or thrombosis within 30 days after surgery lower with aspirin than with placebo. A new Review Article summarizes.

Clinical Pearl

• What has been the traditional practice with respect to stopping or continuing aspirin prior to coronary artery surgery?

Until recently, it has been traditional practice in most cardiac surgical centers to have patients stop taking aspirin 5 to 7 days before surgery to reduce the risk of bleeding. Aspirin is routinely recommenced within 24 hours after coronary artery bypass grafting (CABG) surgery, but this practice does not allow for the use of aspirin to help prevent thrombosis in the crucial early postoperative phase. Several observational studies have shown reductions in mortality, the rate of serious complications, or both when aspirin is administered preoperatively or soon after CABG surgery. Conflicting guidelines from expert professional organizations highlight the dearth of data from large clinical trials and the lack of reliable recommendations.

Clinical Pearl

• Are there any studies suggesting that the withdrawal of aspirin in patients scheduled for coronary artery surgery could be harmful?

The withdrawal of aspirin to reduce the risk of bleeding in patients scheduled for surgery could be harmful. The most recent meta-analysis that evaluated the use of aspirin in patients undergoing CABG surgery included 13 randomized trials with a total of 2399 participants. The authors found that the continuation of aspirin reduced the risk of perioperative myocardial infarction by nearly half. However, there was evidence of increased bleeding, increased need for red-cell transfusions, and a need for surgical reexploration.

Morning Report Questions

Q: Does the preoperative use of aspirin reduce the incidence of death or thrombotic complications, or surgical bleeding, in at-risk patients undergoing coronary artery surgery? 

A: In the trial by Myles et al., the use of preoperative aspirin before coronary artery surgery resulted in neither a lower risk of death or thrombotic complications than that with placebo nor a higher risk of surgical bleeding, need for transfusion, or need for reoperation. The authors concluded that there is therefore no reason to discontinue aspirin before coronary artery surgery. Death or thrombotic complications occurred within the first 30 days after surgery in 202 patients (19.3%) in the aspirin group and in 215 patients (20.4%) in the placebo group (relative risk with aspirin, 0.94; 95% CI, 0.80 to 1.12; P=0.55). Myocardial infarction was detected within the first 30 days after surgery in 144 patients (13.8%) in the aspirin group and in 166 patients (15.8%) in the placebo group (relative risk, 0.87; 95% CI, 0.71 to 1.07; P=0.20). The rates of death, stroke, pulmonary embolism, renal failure, and bowel infarction were similar in the two groups. Major hemorrhage leading to reoperation occurred in 1.8% of patients in the aspirin group and in 2.1% of patients in the placebo group (P=0.75), and cardiac tamponade occurred in 1.1% and 0.4%, respectively (P=0.08).

Table 2. Outcomes.

Figure 2. Subgroup Analysis of the Relative Risk of the Primary End Point with and without Preoperative Aspirin.

Table 3. Hemostasis, Blood Loss, and Adverse Events.

Q: In the Myles study, was there a significant interaction between aspirin and tranexamic acid?

A: There was no significant interaction between the effects of aspirin and tranexamic acid with regard to the primary end point or major hemorrhage (P>0.05 for each interaction).