In the News

Alzheimer's guidelines, opioid education, and more.

Alzheimer's guidelines redefine stages

Updated guidelines on Alzheimer's disease describe new stages for diagnosis, including a pre-clinical stage, and suggest new biomarkers for research purposes.

The National Institute on Aging and the Alzheimer's Association issued three papers that update the last set of guidelines from 1984. The new guidelines appeared in the May issue of Alzheimer's and Dementia: The Journal of the Alzheimer's Association. The papers are:

Three stages identified by the new criteria are preclinical Alzheimer's disease, mild cognitive impairment due to Alzheimer's disease, and dementia due to Alzheimer's disease. Preclinical Alzheimer's disease is marked by measurable changes in biomarkers that indicate the earliest signs of disease, before symptoms such as memory loss and confusion about time or place are noticeable. While the criteria and guidelines identify this as a stage of Alzheimer's disease, they do not establish diagnostic criteria. Rather, they propose additional research into the kinds of tests that might confirm a person is in this or another stage of the disease, such as brain imaging strategies and spinal fluid proteins.

The definition of mild cognitive impairment due to Alzheimer's disease includes mild changes in memory and thinking that are noticeable to the person and to family members and friends and that can be measured, but that do not affect daily function. The guidelines define four levels of certainty for ruling out other causes and arriving at a diagnosis of mild cognitive impairment due to Alzheimer's disease. Markers of this stage include beta-amyloid accumulation in the brain and biomarkers showing that nerve cells in the brain are injured or actually degenerating.

Dementia due to Alzheimer's disease includes memory, thinking and behavioral symptoms that impair a person's ability to function in daily life, the workgroup concluded.

Opioid manufacturers told to develop physician, patient education

As part of a new federal effort to reduce prescription drug abuse in the U.S., the FDA will begin requiring a Risk Evaluation and Mitigation Strategy (REMS) for all extended-release and long-acting opioid medications.

The new REMS plan focuses primarily on educating doctors about proper pain management, patient selection and other requirements, and improving patient awareness about how to use the drugs safely. “The prescriber education component of this Opioid REMS balances the need for continued access to these medications with stronger measures to reduce their risks,” said FDA Commissioner Margaret A. Hamburg, MD, in an April 19 press release.

Although doctor training is not mandatory under the REMS plan, other federal agencies are working to get Congress to link mandatory physician training to the already required Drug Enforcement Administration registration number for prescribing controlled substances, according to the press release.

Doctor training, patient counseling, and other risk reduction measures developed by opioid makers as part of the REMS are expected to become effective by early 2012. They will be required for drugs including hydromorphone, oxycodone, morphine, oxymorphone, methadone, transdermal fentanyl and transdermal buprenorphine.

Elements of the overall federal plan, which is called “Epidemic: Responding to America's Prescription Drug Abuse Crisis”, include expansion of state-based prescription drug monitoring programs, supporting education for patients and clinicians, and reducing the number of “pill mills” and doctor-shopping through law enforcement.

CABG rates decline, PCI rates stay steady from 2001 to 2008

The annual rate of coronary artery bypass graft surgery (CABG) in the U.S. declined by more than 30% between 2001 and 2008, while rates of percutaneous coronary intervention (PCI) were steady, a study in the May 4 Journal of the American Medical Association found.

The authors sought to find how trends in coronary revascularization had changed in a time period when there were many advances in technology, techniques, guidelines and evidence. They examined data from the Nationwide Inpatient Sample (NIS), which contains patient-level hospital discharge data from about 1,000 hospitals. Coronary revascularizations were identified by procedure codes on NIS claims. Researchers compared age, sex, and geographic distributions between CABG surgery recipients in 2001 versus 2008, as well as PCI recipients in 2001 versus 2008. Since race is unreported for many hospitals in NIS data, they separately calculated the 2001-2008 difference in race among CABG surgery and PCI recipients using Medicare claims.

There was a 15% decrease in the annual rate of both procedures combined from 2001-2002 to 2007-2008. There were about one-third fewer CABG surgeries performed in 2008 compared to 2001, with the annual rate declining from 1,742 CABG surgeries per million adults per year in 2001-2002 to 1,081 CABG surgeries per million adults per year in 2007-2008 (P<0.001). This decline was observed across sex, age, racial and regional subgroups. PCI rates did not significantly change, with 3,827 PCIs per million adults per year in 2001-2002 versus 3,667 PCIs per million adults per year in 2007-2008 (P=0.74). The number of hospitals in the NIS that provided CABG surgery increased by 12% (212 vs. 241, P=0.03), and the number that provided PCI increased by 26% (246 vs. 331, P<0.001). The median CABG surgery caseload per hospital decreased by 28% (P<0.001). The use of drug-eluting stents, which were approved by the Food and Drug Administration in April 2003, peaked in 2005 at nearly 90%, and fell to 68% by the end of 2008.

The decrease in CABG surgery occurred as a roughly linear trend throughout the period measured, which suggests the decline was not triggered by a single event like a technological advance or new guidelines. The results also suggest several thousand patients who underwent PCI in 2008 would have undergone CABG surgery if patterns of care had not changed dramatically since 2001, the authors noted. While it is possible PCI truly was the best care option for those patients, “our observations combined with those of prior investigators suggest that a sizeable fraction of patients who did not undergo CABG surgery in 2007-2008 might have been appropriate CABG surgery recipients,” the authors wrote.

Beta-blocker use after hospital discharge appears beneficial in severe acute heart failure

Patients with severe acute heart failure appear to benefit from beta-blocker therapy after hospital discharge, a recent study reported.

Researchers performed a post hoc analysis of data from the SURVIVE trial to determine whether maintaining or starting beta-blocker therapy during hospitalization for severe acute heart failure would affect long- or short-term survival after discharge. Patients in the SURVIVE trial all had severe heart failure, defined as inadequate response to intravenous diuretic or vasodilators and at least one of the following characteristics: oliguria not related to hypovolemia, dyspnea at rest or need for mechanical ventilation, or hemodynamic impairment with Swan catheter use requiring intravenous inotropic support. Outcome measures were all-cause mortality 31 and 180 days after discharge with or without beta-blocker use at study entry and/or at discharge. The study results were published in the May Critical Care Medicine.

A total of 1,104 patients survived to hospital discharge and had data available on beta-blocker use. The 549 patients who were taking beta-blockers at study entry and at discharge had statistically significantly lower mortality rates at 31 days and 180 days (P<0.001 for both) than the 259 patients who were not taking beta-blockers at either time point. When the association was adjusted for age and comorbid conditions, the P values were 0.006 at 30 days and 0.003 at 180 days. In unadjusted analyses but not in adjusted analyses, the 40 patients who were taking beta-blockers at study entry but not at discharge had a higher mortality risk than those taking beta-blockers at both time points. The 259 patients who were not taking beta-blockers at either time point and patients taking beta-blockers only at study entry had a similar mortality risk.

The authors noted the study was retrospective and that data on beta-blocker use did not include information on aspects such as dose, among other limitations. Prospective trials are needed, they said, to determine whether and how the discharge dose of beta-blockers affects outcomes and whether any beta-blocker is superior to others. However, they concluded that beta-blocker therapy at hospital admission and discharge improves both long- and short-term outcomes in patients with severe acute heart failure, and that withdrawing such therapy at hospital admission has a detrimental effect. The author of an accompanying editorial agreed, writing, “There is solid support for prescribing beta-blockers, titrating to maximal tolerated doses, and continuing therapy even during acute exacerbations in patients with heart failure.”

Measles outbreak report describes potentially avoidable consequences

The course of the largest health care-associated measles outbreak in the post-elimination era offers lessons in outbreak preparedness for other hospitals, according to a new report.

The report, published in the June 1 Journal of Infectious Diseases, describes 14 confirmed cases of measles seen in Arizona in 2008. The outbreak began with an infected person who came from Switzerland and was treated at a Tucson hospital. Of the infected patients, seven acquired measles in a health care setting. All infected patients were unvaccinated or had unknown vaccination status, and all but two cases (in young children who were pre-vaccination age) could have been prevented by adherence to U.S. immunization policy.

Two hospitals spent almost $800,000 on their response. Four patients were hospitalized and two were treated in intensive care, but much of the cost resulted from the need to establish measles immunity among the hospitals' clinicians. Evidence of immunity was lacking for 25% of clinicians at the two hospitals (9% were eventually found to be seronegative), and about 4,500 clinicians ended up receiving emergency vaccination. Outbreak response was also hindered by delayed diagnosis of the index patient, who was hospitalized for multiple days before diagnosis, and failure to closely adhere to infection control practices, which include isolation and masking of patients.

Because the confirmed cases did not all appear to be linked, it's likely that the outbreak was actually larger than reported with additional community cases, the study authors said, adding that their cost analysis also did not include costs to insurers, health departments and patients. Potentially some of the actions taken and certainly some of the costs could have been prevented by some commonsense measures, concluded an accompanying editorial. The editorialist called for electronification of clinician records, immediate reporting of potential measles cases and wider vaccination of health care workers.