Dabigatran risks may be greater than people realize, researchers report
The potential risks of dabigatran are not appreciated, particularly where the elderly are concerned, according to a letter written by researchers who tracked bleeding events in patients who took the drug.
New Zealand researchers collaborated with the Haematology Society of Australia and New Zealand to conduct an audit of bleeding events during the first two months that dabigatran was available in that country (July and August 2011). About 7,000 patients started treatment with dabigatran during that time, and there were 44 bleeding events, including 12 episodes of major bleeding, the researchers wrote in a letter to the New England Journal of Medicine published March 1.
After reviewing the 44 cases, the researchers found four major factors contributed to bleeding episodes: prescriber error, impaired renal function, older age, and complications arising from the lack of a reversal agent. In about 25% of the patients, prescriber errors contributed to the bleeding. Those errors included not allowing the international normalized ratio to go below 2.0 before starting dabigatran and using the drug in patients with severe renal impairment. Prolonged bleeding “possibly contributed to the death of one patient,” the researchers wrote, adding that bleeding risk isn't entirely mitigated by dose reduction, as 22 patients had a bleeding episode while getting a reduced dose. Bleeding is “potentially compounded by poor renal function and low body weight,” they wrote.
The audit shows that it's difficult to translate trial data into clinical practice, and it's important to conduct postmarketing surveillance and adverse-event reporting, the researchers noted. Dabigatran prescribers also need to be better educated to reduce the possibility of errors, they said. All patients need to have the risks and benefits of dabigatran weighed before treatment, but especially those who are age 80 years and older with impaired renal function or low body weight, the researchers concluded.
Most C. diff infections tied to health care exposure
Nearly all Clostridium difficile infections (CDIs) are associated with health care exposure, though actual CDI onset most often occurs in non-hospital settings, according to a recent report.
Researchers analyzed three data sources to identify health care exposures for CDI, to determine the proportion of CDIs that occurred outside of hospital settings, and to assess whether prevention programs effectively reduce CDIs. The data came from the Centers for Disease Control and Prevention's (CDC) Emerging Infections Program, the National Healthcare Safety Network (NHSN), and early results from three state-led programs for preventing CDI infections. Rates of hospital-onset CDIs were compared between two eight-month periods near the beginning and end of the CDI prevention programs, which focused mostly on measures to prevent intrahospital transmission of C. difficile. The report was released March 6 by the CDC's Morbidity and Mortality Weekly.
Ninety-four percent of CDIs in 2010 that were identified in the Emerging Infections Program data were associated with precedent and concurrent health care exposures, the report said. Of those CDIs, 75% had their onset outside the hospital in people who were outpatients, nursing home residents and/or recently discharged from hospitals. Fifty-two percent of CDIs reported to NHSN in 2010 were already present on hospital admission, though they were mostly related to other health care exposure, it said. The pooled CDI rate declined 20% in the 71 hospitals that participated in CDI prevention programs in Illinois, Massachusetts and New York, the report found.
The research results illustrate how CDI risks travel with patients across many health care settings, suggesting collaborative regional efforts are needed to lower CDI rates, the report said. Antibiotic stewardship and infection control have been successful in lowering CDI rates in hospitals, and efforts should be expanded to nursing homes and ambulatory settings when they don't already exist in those settings, it said.
ACP issues guideline on colorectal cancer screening
A recent guidance statement developed by ACP offers recommendations on when to screen patients for colorectal cancer.
The College's clinical guidelines committee based the statement on a review of existing U.S. guidelines for colorectal cancer screening. Existing guidelines (from organizations such as the American Cancer Society, American College of Radiology, American College of Gastroenterology and U.S. Preventive Services Task Force) recommend initiating screening in average-risk adults between 40 and 50 years of age depending on ethnicity, but they differed on the method of screening, the committee found. Based on the review, the ACP experts issued four guidance statements:
- Guidance Statement 1: ACP recommends that clinicians perform individualized assessment of risk for colorectal cancer in all adults.
- Guidance Statement 2: ACP recommends that clinicians screen for colorectal cancer in average-risk adults starting at the age of 50 years and in high-risk adults starting at the age of 40 years or 10 years younger than the age at which the youngest affected relative was diagnosed with colorectal cancer.
- Guidance Statement 3: ACP recommends using a stool-based test, flexible sigmoidoscopy, or optical colonoscopy as a screening test in patients who are at average risk. ACP recommends using optical colonoscopy as a screening test in patients who are at high risk. Clinicians should select the test based on the benefits and harms of the screening test, availability of the screening test, and patient preferences.
- Guidance Statement 4: ACP recommends that clinicians stop screening for colorectal cancer in adults over the age of 75 years or in adults with a life expectancy of less than 10 years.
The statement also notes that the screening interval for average-risk patients is 10 years for colonoscopy, five years for other endoscopic and radiologic tests, annually for fecal occult blood tests, and uncertain for stool DNA panels. Computed tomography colonography is another option supported by some guidelines, but the U.S. Preventive Services Task Force found insufficient evidence on its benefits and harms.
The recommendations are intended to highlight “how clinicians can contribute to delivering high-value, cost-conscious health care,” the statement said. Evidence shows that screening more frequently than recommended does not improve outcomes and contributes to avoidable health care costs, the authors noted. The guidance statement was published in the March 6 Annals of Internal Medicine.
AIDS care panel issues new HIV guidelines
The International Association of Physicians in AIDS Care (IAPAC) has issued new guidelines on improving adherence to antiretroviral therapy (ART).
To help clinicians monitor and support adherence to ART in HIV-infected patients, IAPAC convened a panel of experts who conducted a systematic review of 325 randomized, controlled trials and observational studies. Members of the panel drafted recommendations and then graded the overall quality of evidence for and strength of each.
The panel made a total of 37 recommendations in the following categories:
- entry into and retention in HIV medical care,
- monitoring ART adherence,
- interventions to improve ART adherence,
- adherence tools for patients,
- education and counseling interventions,
- health system and service delivery interventions, and
- special populations (including pregnant women, patients with substance use or mental health disorders, incarcerated or homeless patients, and children and adolescents).
The panel also called for further cost-effectiveness research on ART as well as research in areas where evidence was insufficient to make recommendations, such as in patients with HIV infection and one or more comorbid conditions.
The full recommendations were published early online March 5 by Annals of Internal Medicine.
Antibiotic use confers up to tenfold risk of C. diff infection
A patient's risk of developing Clostridium difficile infection (CDI) is 7 to 10 times higher during antibiotic therapy and in the month after stopping, and an elevated risk still exists three months after stopping antibiotics, a study found.
Dutch researchers performed a case-control study in nine hospitals between March 1, 2006 and May 1, 2009. They compared 337 hospitalized patients with diarrhea and a positive toxin test to 337 patients without diarrhea. A control group of 227 patients with diarrhea from a cause other than C. diff was also included. Results were reported in the March Journal of Antimicrobial Chemotherapy.
In the month prior to the reference date, 77% of CDI patients used an antibiotic compared with 48.9% of non-diarrheal patients (P<0.01). Of these, 35% of CDI patients and 25% of non-diarrheal patients were using an antibiotic at the time of diagnosis (P=0.01). On multivariate analysis, there was a more than sixfold increased risk for CDI during antibiotic use and in the first month after stopping antibiotics (odds ratio [OR], 6.67 to 10.37). The risk declined in the period between one and three months after the antibiotic was stopped (OR, 2.7 at three months). The control group comparison yielded similar results. All antibiotic classes were associated with CDI except first-generation cephalosporins and macrolides. The antibiotics with the strongest associated risks were second- and third- generation cephalosporins (OR, 3.3 and 5.3, respectively) and carbapenems (OR, 4.7). Compared with non-diarrheal patients, those with CDI used more antibiotic classes (P<0.01) and more defined daily doses.
One study limitation was the use of various enzyme immunoassays to diagnose CDI. Given their reported sensitivities of between 60% and 85%, some patients could have been missed as having CDI, which in turn might have led to overestimation of the duration of increased risk of non-CDI diarrhea after antibiotic use. Even so, clinicians should be made aware that antibiotic use can greatly increase the risk for CDI, even if the use preceded the symptoms by a month, the researchers wrote.