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Friday, November 21, 2014



Terminal cancer patients who enroll in hospice have lower rates of hospitalization, intensive care unit (ICU) admission, and invasive procedures at the end of life, as well as significantly lower total costs compared with patients who do not enroll in hospice, according to a new analysis published in the Nov. 17 issue of the Journal of the American Medical Association (JAMA).


Although the study focused on outcomes for terminal cancer patients specifically, the findings have ramifications for neurologists who advise their patients on end-of-life care and treatment options as well.  Moreover, as policymakers in the United States consider the evidence for reforming and streamlining end-of-life care, the research could be brought to bear on that debate, experts told Neurology Today.


“Because these [end-of-life] conversations are really hard to have, a lot of people don’t think ahead to what kind of care they want to receive,” Ziad Obermeyer, MD, an emergency medicine physician at Brigham and Women’s Hospital in Boston and one of the authors of the JAMA study, told Neurology Today. “So they end up getting sucked into this very aggressive mode of care as a kind of default option.”


The study provides more evidence that policymakers should reduce the systemic barriers that prevent some terminal patients from accessing hospice, Dr. Obermeyer said.



Currently, Medicare regulations limit the number of patients who are eligible for, or even informed about, hospice programs, Dr. Obermeyer said. For example, Medicare penalizes hospices with inappropriately long patient stays, and does not reimburse physicians for having advance care planning discussions with patients — a shortcoming that was also highlighted in an Institute of Medicine (IOM) report on end-of-life care released earlier this year.


“There is this sense in the policy establishment that we need to restrict the demand for hospice, largely because people are worried that [more hospice utilization] is going to drive up costs,” he said. With the current study, Dr. Obermeyer and colleagues hoped to dispute these claims.


The study looked at Medicare fee-for-service beneficiaries diagnosed with poor-prognosis cancers such as brain, lung, and pancreatic cancers, as well as metastatic, ill-defined, or hematologic malignancies. Using Medicare claims data, they identified a group of 86,851 patients who died in 2011 after a full year of Medicare coverage and were eligible for the Medicare Hospice Benefit, which requires a diagnosis of terminal illness and expected survival of less than six months.


Dr. Obermeyer and colleagues then created two matched patient groups that differed in their utilization of hospice care. They matched 18,165 terminal cancer patients who had enrolled in hospice with 18,165 patients who did not; the patients were matched on age, sex, geographic region, time from poor-prognosis diagnosis to death, baseline care utilization, and exposure period the amount of time spent in hospice, in the case of hospice beneficiaries, versus the equivalent amount of time not spent in hospice, in the case of nonhospice beneficiaries.


“The people who chose hospice lived just as long as the ones who didn’t. But the hospice patients did so with many fewer hospitalizations, ICU stays, invasive procedures, and, ultimately, the people who chose hospice were about five times less likely to die in a hospital or nursing home,” Dr. Obermeyer said.


Among patients who did not enroll in hospice, 65 percent were hospitalized at some point during the last year of life, 36 percent were admitted to an ICU, and 51 percent underwent invasive procedures. These aggressive modes of care were largely tied to acute conditions such as infections and organ failure, as well as exacerbations of medical comorbidities, the researchers noted.


“Such care is unlikely to fit with the preferences of most patients,” they wrote.


Among hospice beneficiaries, 42 percent were hospitalized in the last year of life, 15 percent were admitted to an ICU, and 27 percent underwent invasive procedures. And while 74 percent of nonhospice patients died in hospitals or in skilled nursing facilities, only 14 percent of hospice patients did the same.


            Overall costs during the last year of life were also found to be lower for patients enrolled in hospice: $62,819 for hospice beneficiaries compared with $71,517 for nonhospice beneficiaries. The difference in cost for shorter hospice stays of between one and two weeks was smaller, but still statistically significant, the authors noted. However, the 2 percent of hospice beneficiaries who remained in hospice for more than one year had higher total costs.


Looking at the cost-effectiveness of hospice was necessary, Dr. Obermeyer said, because “it’s intrinsically important to people who do the numbers at the policy level.” But an emphasis on cost should not be the driving force behind health care, he added. “The first priority is getting people the care that they want, and then if it happens to cost less, that’s great.”


Look for the full story in the Dec. 4 issue of Neurology Today. For more coverage of end-of-life care, browse our archives here.

Thursday, November 20, 2014



A specialized ambulance was found to increase the proportion of stroke patients who received thrombolytic therapy during the “golden hour” the 60-minute window after symptoms start in which doctors believe the treatment is most effective.


            The study, published in the Nov. 17 online issue of JAMA Neurology, builds on past research showing that a special “stroke ambulance” equipped with a computed tomographic (CT) scanner and staffed by a neurologist, a parademic, and a radiology technician could treat stroke patients more quickly and efficiently than could hospital care. The latest study found that treatment during the golden hour carried no higher risk for seven- or 90-day mortality, and that patients receiving swift treatment were less likely to have prolonged hospital or nursing home stays.


In ischemic stroke, thrombolysis with tissue plasminogen activator (tPA) can break down the blood clots that halt blood and oxygen flow to part of the brain, and the sooner treatment begins, the better, doctors believe. However, treating stroke patients within the golden hour is extremely difficult, the authors from Charité-Universitätsmedizin Berlin in Germany wrote. In fact, past studies have suggested that only around 10 percent of stroke patients receive treatment within the first 90 minutes after symptoms appear, and only 1.4 percent are treated within the first hour.


Image via Till Krech on Flickr.


            For the current study, the researchers looked at the treatment of 6,182 patients with suspected stroke in Berlin, both at times when the stroke ambulance (called the stroke emergency mobile unit, or STEMO) was available and at times when it was not. They determined how many patients during that period received thrombolytic treatment, either during the golden hour or later than 60 minutes after symptom onset.


They found that 200 of 614 patients with ischemic stroke (32.6 percent) received thrombolytic therapy when STEMO was in use, compared with 330 of 1,497 patients (22 percent) who were treated when STEMO was not available (p<0.01), deemed “conventional care.” In all cases of ischemic stroke, the rate of thrombolysis occurring during the golden hour increased from 16 out of 1,497 patients (1.1 percent) during conventional care to 62 of 614 (10.1 percent) when STEMO was in use.


In addition, among all patients who received thrombolysis, the proportion of people who were treated during the golden hour increased six-fold when STEMO was in use 62 of 200 patients (31 percent) in the STEMO group compared with 16 of 330 patients (4.9 percent) in the conventional care group (p<0.01). For thrombolysis occurring during the golden hour, the average time from symptom onset to treatment was 50 minutes, compared with 105 minutes for thrombolysis occurring after the first 60 minutes (p<0.001).


The researchers also found that patients who received treatment during the golden hour were no more likely to die after seven or 90 days than patients who received later care, and they were more likely to be discharged home from the hospital.


In an editorial published in the same issue of JAMA Neurology, Steven Warach, MD, PhD, a professor of neurology and neurotherapeutics at the University of Texas Southwestern Medical Center in Austin, who was not involved in the study, praised the findings. “Although evidence addressing the long-term benefits of STEMO is not yet available, [the researchers] present indirect early indicators of a benefit for the patients who receive golden hour thrombolysis,” he wrote. “They were more likely to be discharged to their homes and less likely to go to nursing homes, while not at increased risk of hemorrhagic complications or death.”


However, Dr. Warach warned, “many questions need to be answered in order to determine the appropriate niche where the benefit justifies the intensive use of resources that this approach requires.”


For example, since the mobile stroke unit is more expensive than traditional ambulances, further studies will need to weigh the financial costs against the benefits the stroke ambulance can provide. In addition, since it is likely that there will be a limited number of mobile stroke units in any ambulance fleet, future analyses should look at which regions, perhaps those with a high incidence of stroke, would be best served by a stroke ambulance. Lastly, there may be other conditions that could be treated in the specialized ambulance: “If blood products are stocked in this specialized ambulance, then prehospital treatment of anticoagulation-associated intracranial hemorrhage is an obvious example,” he wrote.


“It is the duty of the early adopters to resist the temptation to uncritically embrace this approach…and to address these issues through rigorous clinical investigations,” he concluded.


Look for the full article and discussion in an upcoming issue of Neurology Today. For more coverage of ambulatory stroke care, browse our archives here.

Tuesday, November 18, 2014



Neurologists and other physicians are well aware that patients with atrial fibrillation (afib), the most common form of arrhythmia in the elderly, are at an increased risk for stroke. Accordingly, doctors often recommend that patients with afib take the anticoagulant drug warfarin as a preventive measure. However, warfarin is also associated with an increased risk of intracerebral hemorrhage, and treatment with the drug requires lifelong monitoring by a physician.


Rhythm strip showing atrial fibrillation.


            Now, a new study suggests that a device partially implanted under the skin to close off the left atrial appendage (LAA) — a pouch-like structure in the upper left chamber of the heart, believed to be the main source of blood clots that cause strokes in patients with afib — is at least as effective as warfarin in preventing stroke, and carries a comparable risk of adverse side effects.


            The study, published in the Nov. 19 issue of JAMA, included 707 patients who had nonvalvular atrial fibrillation (NVAF) and an additional risk factor for stroke such as hypertension, diabetes, heart failure, or prior transient ischemic attack or stroke. Of those, 463 patients were assigned to receive an implanted LAA closure device, made by medical device manufacturer Atritech, who also funded the study. The remaining 244 patients were assigned to anticoagulant treatment with warfarin.

The patients were followed for an average of 3.8 years. At follow-up, 39 cases of stroke, systemic embolism, or cardiovascular death had occurred among the 463 patients using the LAA closure device, compared with 34 events among the 244 patients in the warfarin group. The authors reported 57 deaths from any cause in the device group (12.3 percent), compared with 44 deaths in the warfarin group (18 percent).


This diagram of the adult heart illustrates the structures that are affected by congenital heart diseases, with the estimated incidence of each disease per 1,000 live births indicated in parentheses.

Patients assigned to the LAA closure device also had lower rates of hemorrhagic stroke and cardiovascular death than those taking warfarin. Although rates of all stroke and ischemic stroke were the same in both groups, there were fewer fatal or disabling strokes in the device group, the authors noted.

The safety profiles of both preventive therapies were found to be similar, the authors reported. Patients assigned to the LAA closure device were more likely to experience serious pericardial effusions (a collection of fluid around the heart), while those taking warfarin were more likely to experience major bleeding. While patients using the device experienced more early adverse side effects related to the implantation surgery, patients taking warfarin were more likely to develop adverse side effects over the long term.

            “After 3.8 years of follow-up in patients with nonvalvular AF at elevated risk for stroke, percutaneous LAA closure met criteria for both noninferiority and superiority, compared with warfarin therapy, for preventing the combined outcome of stroke, systemic embolism, and cardiovascular death, as well as superiority for cardiovascular mortality and all-cause mortality,” the authors concluded.

However, they warned that the device should not be considered as an alternative preventive treatment for afib patients who are unable to take warfarin, as patients must still take an initial 45-day course of warfarin and aspirin after the surgery to implant the device.


            Look for the full article in an upcoming issue of Neurology Today. To read about the latest research in atrial fibrillation and stroke, browse our archives here.

Monday, November 17, 2014



The U.S. Food and Drug Administration (FDA) has awarded marketing approval to alemtuzumab (Lemtrada) for treating relapsing-remitting multiple sclerosis (RRMS), drug manufacturer Genzyme announced Friday. The drug has already been approved for use in MS in Canada, Europe, and Australia.


The announcement marks a tempered reversal of the FDA’s position on the drug. In December 2013, the agency stated that Lemtrada was not ready for approval, arguing that “Genzyme has not submitted evidence from adequate and well-controlled studies that demonstrate the benefits of Lemtrada outweigh its serious adverse effects."


At press time, the FDA had not yet issued a statement of its own regarding the drug’s approval.


The drug should still be considered a third-line treatment for RRMS, Genzyme’s parent company, Sanofi, noted in its announcement. “Because of its safety profile, the use of Lemtrada should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS,” the company said.


In MS, alemtuzumab, which is also sold under the brand name Campath as a leukemia treatment, is administered by intravenous infusion in two treatment courses of five consecutive days and three consecutive days 12 months later. The drug works to temporarily disable T and B cells, which leads to prolonged changes in the immune system. When these cells repopulate, the body’s autoimmune attack on myelin is halted or at least slowed considerably. Inflammation caused by the body’s attack on myelin is believed to cause the debilitating symptoms of MS.


Initiating IV fluid infusion.


In clinical trials of alemtuzumab, most RRMS patients showed significant declines in annual relapse rates that persisted beyond the final annual infusion. The drug was found to be more effective than interferon beta-1a at reducing relapse rates.


However, the FDA raised questions about the safety profile of the drug. Since alemtuzumab targets the immune system, it can increase a patient’s risk of developing other diseases and infections. A small but significant minority of patients in the clinical trials developed new, sometimes fatal autoimmune conditions such as thyroid disease, as well as malignancies such as thyroid cancer and melanoma. In addition, the FDA took issue with the open label design of the trials.


The FDA approval of alemtuzumab comes with a requirement for a black box warning about the potential for a host of severe side effects, most notably autoimmune disorders, infusion reactions, and malignant cancers, but also rash, headache, nausea, vomiting urinary tract infection, upper respiratory tract infection, fatigue, insomnia, fungal infection, back pain, diarrhea, dizziness, abdominal pain, and more.


In addition, the drug can only be prescribed, administered, and used by physicians, pharmacies, and patients who have obtained the proper certification. This is done in order to “educate healthcare providers and patients on the serious risks associated with Lemtrada and the appropriate periodic monitoring required to support the detection of these risks for 48 months after the last infusion,” Genzyme said.


The drug’s long-lasting effects “may profoundly influence the course of relapsing MS, but will require careful and sustained monitoring for side effects,” Bruce A. Cohen, MD, a professor of neurology and clinical neurosciences at Northwestern University and chair of the National MS Society’s National Medical Advisory Committee, said in a news release. “Individuals with MS who are considering treatment with this medicine should thoroughly educate themselves on its potential benefits and risks.”


For more information about alemtuzumab, see our past coverage here.

Friday, November 14, 2014



A new study has offered more insight into the complex processes that occur in the brain when an elderly person progresses from normal cognition to dementia or Alzheimer’s disease (AD).


The study, published in the Nov. 11 issue of Neurology, lends support to past research showing that a combination of low hippocampal volume, white matter lesions, and beta-amyloid (Aβ) deposition in the brain can serve as biomarkers of short-term progression from normal cognition or mild cognitive impairment (MCI) to dementia or AD in the very elderly.


It is currently thought that the accumulation of the Aβ protein is one of the earliest signs of Alzheimer’s disease, occurring in the brain before memory problems and other clinical symptoms set in, the study authors noted. Amyloid deposition on magnetic resonance imaging (MRI) and positron emission tomography (PET) scans has been associated with progression from normal cognition to MCI or AD, and from MCI to AD, in past research. In addition, low hippocampal volume, which is indicative of neurodegeneration, and lesions in the brain’s white matter, indicative of small vessel disease, have also been independently linked to progression from normal cognition to MCI and AD in elderly adults.


A 60-year-old man with progressive cortical dementia. Cortical atrophy is shown by MRI (A). FDG-PET (B) shows the typical bilateral temporoparietal hypometabolism seen in Alzheimer dementia.


            The study looked at these three biomarkers in 183 patients with a mean age of 85.5 years who were enrolled in the Ginkgo Evaluation of Memory (GEM) study, a randomized clinical trial that evaluated whether Ginkgo biloba supplementation could slow or halt the progression to dementia and AD. The study participants were evaluated for clinical signs of MCI or dementia and had brain structural MRI and PET scans in 2009 and again in 2011.


At baseline, 46 participants were classified as cognitively normal and 37 as having MCI. Nearly all of the participants had some measurable Aβ deposition, low hippocampal volume, or high white matter lesion volume on imaging.


Two years later, 111 participants, or 61 percent, remained cognitively normal, while 51 (28 percent) were classified as having MCI and 21 (11 percent) were diagnosed with dementia.


Of the 21 participants who progressed to dementia, 20 (95 percent), had evidence of one or more brain abnormality on imaging, the researchers found. Sixteen participants had more than one of the three biomarkers, and only one had none of the biomarkers, suggesting that “the risk of dementia was a function of a combination of the variables,” they wrote.


            Overall, they found that more amyloid deposition, greater volume of white matter lesions, and lower hippocampi volumes increased risk of incident dementia approximately threefold.


However, some study participants who had a high burden of Aβ, low hippocampal volume, or high volume of white matter lesions at baseline remained cognitively normal at follow-up. In contrast, some elderly patients with low levels of Aβ or with relatively normal hippocampal volume still progressed to AD during the two years of the study.


The study also did not find that any of these three biomarkers were correlated, indicating that these processes occur independently in the brain. Future studies will need to look at whether these three variables can serve as independent predictors of dementia, and whether processes other than Aβ deposition play a role in the development of AD and dementia, the authors wrote.


 “There is a wide range of pathology severity, and subjects considered to be ‘negative’ for a biomarker can still carry pathology, which could be of sufficient severity to cause a clinical syndrome. However, there are many subjects ‘positive’ for AD pathology that can remain [cognitively normal],” they concluded. “Therefore, these findings suggest that the events leading to clinical dementia may be more complex and heterogeneous than previously thought.”


For more coverage of Alzheimer’s and dementia research, browse our archives here: