Wednesday, 15 February 2017

NeuroBreak: Marathon Pauses DMD Drug Launch; Another Alzheimer's Failure

Marathon is "temporarily pausing" the launch of its Duchenne muscular dystrophy drug deflazacort (Emflaza) after a public outcry over the planned $89,000 annual price tag on its old steroid drug, which sells for $1,000 to $1,600 a year in the U.K. and Canada. In an open letter to the DMD community, the company emphasized its plans to increase access to the drug and to re-invest profits in Duchenne research.

Another experimental Alzheimer's drug bites the dust. Lundbeck said its 5HT6 antagonist idalopirdine -- which targeted disease symptoms, not progression -- failed two phase III trials, raising questions for Axovant's similar candidate intepirdine. (Reuters)

See and hear Mount Sinai's Fred Lublin, MD, talk about the landscape for treating progressive multiple sclerosis in an exclusive MedPage Today video.

Acorda's inhaled levodopa passed a phase III test, paving the way to an NDA submission with the FDA. (Endpoints News)

This clinic falsely told more than 50 people they had Alzheimer's disease, a lawsuit alleges. (Associated Press)

SAGE reported some early positive results for its depression candidate. (TheStreet)

The FTC says the supposed memory-enhancing product Prevagen is a hoax. (NBC News)

Adding a comprehensive management plan to memantine therapy boosts the efficacy of the drug 10-fold, according to Barry Reisberg, MD, of NYU Langone Medical Center, and colleagues. That plan involves caregiver training, a residence assessment, therapeutic home visits, and caregiver support groups. (Dementia & Geriatric Cognitive Disorders)

Opioids are driving an increase in cocaine-related deaths. (American Journal of Public Health)

Non-pharmaceutical therapies such as heat and massage should be first-line treatments for low back pain, according to new guidelines from the American College of Physicians. (MedPage Today)

The FTC is suing Shire over "citizen petitions" it sent to FDA to block generic competition to its ADHD drugs. (BioPharmaDive)

Small-town Kentucky pharmacies thrive selling opioid painkillers. (Kaiser Health News)

Neurocrine and Bial -- the Portuguese company at the center of the deadly FAAH inhibitor trial -- announced a licensing agreement for the development and commercialization of opicapone in North America. (Press Release)

Axovant is moving ahead to late-stage trials of nelotanserin following a successful phase II trial in Lewy body dementia. (Endpoints News)

2017-02-14T12:00:00-0500
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New insight into role of cell protein in learning ability and AIDS-related dementia

Researchers from the University of California (UCLA) and Cardiff University have made a breakthrough in the understanding of AIDS-related dementia, discovering the role of a neuron protein which was also found to affect learning abilities in healthy subjects.

Professor Kevin Fox who led the work at Cardiff University's School of Biosciences said: "Our work represents a major change in the understanding of how AIDS-related dementia works.

"Armed with the new knowledge that the CCR5 protein in neurons affects learning and plays a major role in AIDS-related dementia, we can now look at ways to suppress it for treatment of the disease and investigate whether its reduction can also benefit other forms of dementia and even aid recovery for stroke victims."

The new research started out as a random behavioural screen of mice at UCLA, revealing some mutant mice had better memory than others. Further tests revealed the mice with better memory lacked CCR5 proteins in their neurons. Conversely, animals that over-expressed CCR5 protein were slower to learn, revealing the impact of CCR5 on neurons and their ability to code memories.

The team already knew that the CCR5 protein was the receptor that AIDS uses to infect immune cells and that AIDS patients suffer from dementia. Having witnessed the link between CCR5 and learning in their behavioural screen of mice, they reasoned that activation of the protein in neuron cells by HIV infection might decrease neuron function and learning. When they introduced to the brain the part of HIV that attaches to CCR5 they found that learning and memory was decreased in normal mice, implying that HIV is likely to produce AIDS-related dementia by increasing the natural levels of CCR5 activity and restraining the cells from their usual plasticity function, resulting in a failure to code memories properly.

"I am still amazed that mice without CCR5 can have much better memory than normal mice. It is really exciting that drugs that inhibit CCR5, already on the market, could potentially be used to treat all sorts of memory deficits!" said Alcino Silva, professor of neurobiology and psychiatry at UCLA's David Geffen School of Medicine and Semel Institute for Neuroscience and Human Behavior.

Dr Stuart Greenhill, part of the Cardiff University team, added: "With the available CCR5 drugs on the market this work could have broad and immediate applicability across a range of neurological diseases."

Approximately 30% of HIV-positive adults and 50% of HIV-positive infants suffer from cognitive deficits - a significant clinical problem associated with HIV infection. It was previously thought that AIDS-related dementia was caused by the effects of HIV on immune cells, affecting the brain indirectly by attacking the immune system and creating inflammation.

"Our findings signal a major turnaround on how we imagine treating cognitive problems associated with AIDS," said UCLA scientist Miou Zhou.

Article: CCR5 is a suppressor for cortical plasticity and hippocampal learning and memory, Miou Zhou Stuart Greenhill Shan Huang Tawnie K Silva Yoshitake Sano Shumin Wu Ying Cai Yoshiko Nagaoka Megha Sehgal Denise J Cai Yong-Seok Lee Kevin Fox Alcino J Silva, eLife, doi: 10.7554/eLife.20985, published 20 December 2016.

Gut bacteria may play a role in Alzheimer's disease

New research from Lund University in Sweden has shown that intestinal bacteria can accelerate the development of Alzheimer's disease. According to the researchers behind the study, the results open up the door to new opportunities for preventing and treating the disease.

Because our gut bacteria have a major impact on how we feel through the interaction between the immune system, the intestinal mucosa and our diet, the composition of the gut microbiota is of great interest to research on diseases such as Alzheimer's. Exactly how our gut microbiota composition is composed depends on which bacteria we receive at birth, our genes and our diet.

By studying both healthy and diseased mice, the researchers found that mice suffering from Alzheimer's have a different composition of gut bacteria compared to mice that are healthy. The researchers also studied Alzheimer's disease in mice that completely lacked bacteria to further test the relationship between intestinal bacteria and the disease. Mice without bacteria had a significantly smaller amount of beta-amyloid plaque in the brain. Beta-amyloid plaques are the lumps that form at the nerve fibres in cases of Alzheimer's disease.

To clarify the link between intestinal flora and the occurrence of the disease, the researchers transferred intestinal bacteria from diseased mice to germ-free mice, and discovered that the mice developed more beta-amyloid plaques in the brain compared to if they had received bacteria from healthy mice.

"Our study is unique as it shows a direct causal link between gut bacteria and Alzheimer's disease. It was striking that the mice which completely lacked bacteria developed much less plaque in the brain", says researcher Frida Fåk Hållenius, at the Food for Health Science Centre.

"The results mean that we can now begin researching ways to prevent the disease and delay the onset. We consider this to be a major breakthrough as we used to only be able to give symptom-relieving antiretroviral drugs."

The research is a result of an international collaboration between Associate Professor Frida Fåk Hållenius and doctoral student Nittaya Marungruang, both at the Food for Health Science Centre in Lund, and a research group at the Ecole Polytechnique Federale de Lausanne in Switzerland. The collaboration has now expanded to include researchers from Germany and Belgium in connection with receiving a SEK 50 million EU grant.

The researchers will continue to study the role of bacteria in the development of Alzheimer's disease, and test entirely new types of preventive and therapeutic strategies based on the modulation of the gut microbiota through diet and new types of probiotics.

Article: Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota, T. Harach, N. Marungruang, N. Duthilleul, V. Cheatham, K. D. Mc Coy, G. Frisoni, J. J. Neher, F. Fåk, M. Jucker, T. Lasser & T. Bolmont, Scientific Reports 7, doi:10.1038/srep41802, published online 8 February 2017.

NeuroBreak: Spinraza's $750K Price Tag; Bial Skipped PD Data

Biogen set the price of its new spinal muscular atrophy drug Spinraza at $750,000 for the first year, and half that for each year thereafter, totaling $1.5 million over 3 years. (Endpoints News)

Bial didn't check pharmacodynamic data on lower doses of its FAAH inhibitor before ramping up to the dose that was tied to one death and several hospitalizations in a French clinical trial. (Nature)

Andrew Josephson, MD, of the University of California San Francisco, officially takes the helm at JAMA Neurology, calling for collaboration with JAMA Psychiatry as the fields of neuroscience, neurology, and psychiatry continue to blend together.

Welders be wary: exposure to manganese-containing welding fumes may cause a dose-dependent progression of Parkinsonism, especially upper limb bradykinesia, limb rigidity, and impairment of speech and facial expression, according to a study of 886 trade union workers. (Neurology)

Could saunas be good for the brain? One study from Finland suggests so. (New York Times)

Surgery may be a good option for patients with nonlesional neocortical epilepsy, with about 60% pf patients achieving long-term seizure freedom in a small South Korean study. (JAMA Neurology)

CSF levels of soluble CD27 may predict which patients with clinically isolated syndrome will progress to multiple sclerosis. (JAMA Neurology)

2017-01-03T14:30:00-0500
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Morning Break: Docs Sue over Immigration Ban; Solanezumab's Last Gasp?

At least two physicians who were denied entry back into the U.S. have sued government officials to be allowed to come back to their jobs: Dr. Amer al Homssi of Chicago, and Dr. Suha Abushamma of the Cleveland Clinic. (ABC, ProPublica)

The New England Journal of Medicine has published several policy papers on Trump's immigration executive order, including this one on its detrimental effects on medical training and healthcare, and another on denying visas to doctors in the U.S.

And the American Medical Association has weighed in, sending a letter to Homeland Security Secretary John Kelly arguing that the order will hurt patients in the U.S. (Reuters)

A 4-month-old Iranian girl with a heart condition won't be able to fly to the U.S. for a surgical consultation any longer, even though her grandparents and uncle are U.S. citizens. (Fox)

Eli Lilly has scrapped EXPEDITION PRO, a phase III trial of its twice-failed Alzheimer's drug solanezumab. (Endpoints News)

The March for Science has set a date: April 22, Earth Day. (Scientific American)

President Trump's longtime physician tells the New York Times that The Donald has had pharmaceutical assistance in maintaining his luxurious signature coiffure. And STAT reports that Trump is keeping Obama's White House doctor for now.

The U.S. Preventive Services Task Force's days may be numbered if Tom Price is confirmed as HHS secretary. (ProPublica)

The drug industry doesn't really want to blow up the FDA. (STAT News)

If pharma does bring back American jobs, as Trump has urged, it would reverse a 5-year trend of sending them offshore. (Endpoints News)

Google blocked searches from Britain's NHS, mistaking the high volume of traffic for a cyber-attack. (The Register)

The "frugal wanderlust" or the "accidental retiree"? Physician identifies colleagues who are most likely to retire early. (KevinMD)

Medical professionals can expect these trends in 2017. (Health Affairs)

Medicare Advantage payments to insurers could rise by 0.25% this year, according to a new CMS proposal. (Reuters)

Abbott said it won FDA approval for the first molecular Zika test that can be used with whole-blood samples.

Morning Break is a daily guide to what's new and interesting on the Web for healthcare professionals, powered by the MedPage Today community. Got a tip? Send it to us: MPT_editorial@everydayhealthinc.com.

2017-02-02T09:35:00-0500
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Morning Break: Obamacare Out? No $$ for Gun Violence Studies; FDA and E-Cigs

Obamacare repeal resolution introduced as 115th Congress opens. (Reuters)

AMA asks Congress not to repeal without replacement plan. (STAT)

And can Republicans repeal the law without upending the insurance market causing millions to lose coverage? (Kaiser Health News)

MedPage Today's Shannon Firth details the perilous repeal landscape here.

Pesticide that killed four children in Texas was "black market."(KFDA-TV). How common are pesticide deaths? (CNN)

A federal judge slashed by half a jury's billion-dollar damage award to people claiming injury from a Johnson & Johnson hip implant. (Reuters)

French authorities to ban Vitamin D supplement linked to baby's death. (International Business Times UK)

"Gun violence research was the least-researched cause of death and the second-least funded cause of death after falls," according to new study. Authors say study supports treating gun violence as public health crisis. (NPR)

Pharma R&D returns hit 6-year low. (Drug Discovery)

New book The Telomere Effect makes a case for how healthy lifestyle may "actually lengthen your telomeres -- and perhaps your life." (STAT)

Scientists find that the intestine's mesentery is a single piece of tissue, qualifying it for designation as an organ in its own right. (Discover)

Some people are "non-responders" to workouts. But new research shows non-responders may successfully switch from one form of exercise to another. (The New York Times)

The FDA will hold a 2-day meeting to explore reports of exploding batteries in e-cigarettes. (AP)

"American Children Deserve a Better Death," writes Eleanor Cummins. "Here's one way we can give it to them." (Slate)

What paint can tell us: Liverpool researchers found evidence of cognitive decline in brush strokes of great artists. (Medgadget)

Morning Break is a daily guide to what's new and interesting on the Web for healthcare professionals, powered by the MedPage Today community. Got a tip? Send it to us: MPT_editorial@everydayhealthinc.com.

2017-01-04T09:15:00-0500
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Does Living by a Busy Road Boost Dementia Risk?

Action Points

  • Living near a noisy major road may cause more mental health problems than just sleep deprivation, with dementia more common in people who lived close to a major road than those who lived further away from the road.
  • Note that although the study did not find a link between living near a major road and Parkinson's disease or multiple sclerosis.

Living near a high-traffic road may cause more mental health problems than just sleep deprivation, according to Canadian researchers.

In a population-based cohort in Ontario, dementia, but not Parkinson's disease or multiple sclerosis (MS), was more common in people who lived close to a major road than those who lived further away from the road, reported Hong Chen, MD, of Public Health Ontario in Canada, and colleagues.

Compared with people who lived at least 300 meters from a major roadway, those who lived 201-300 m (adjusted HR 1.00, 95% CI 0.99-1.01), 100-200 m (HR 1.02, 95% CI 1.01-1.03), 50-100 meters (HR 1.04, 95% CI 1.02-1.05), and less than 50 meters (HR 1.07, 95% CI 1.06-1.08) had an increase in incidence of dementia, they wrote online in the Lancet.

According to Chen, "increasing population growth and continuing urbanization globally has placed many people close to heavy traffic. With the widespread exposure to traffic and growing population with dementia, even a modest effect from near-road exposure can pose an enormous public health burden.

"Quantitatively speaking, our study estimated that 7%-11% of dementia cases in patients who live near major roads were attributable to traffic exposure alone," he explained to MedPage Today.

In an accompanying editorial, Lilian Calderón-Garcidueñas, MD, of the University of Montana in Missoula, and Rodolfo Villarreal-Ríos, of the Universidad del Valle de México in Mexico City, wrote that the study "opens up a crucial global health concern for millions of people."

Chen's group used Ontario's Registered Persons Database -- a registry of all residents who have ever had health insurance -- to determine the incidence of dementia, Parkinson's disease, and MS between 2001 and 2012. All participants were ages 20-85 years, Canadian-born, and Ontario residents for 5 years or longer as of April 1, 2001.

They separated the population into two cohorts -- individuals ages 20-50 with MS (n=4.4 million), and individuals ages 55–85 with dementia or Parkinson's disease (n=2.2 million) -- then excluded individuals with any of the three disorders at baseline.

Residential proximity to major roadways (thoroughfare with medium to large traffic capacity with controlled access and intersections) or highways (expressways and primary and secondary highways) was calculated according to six-character postal-code addresses from 1996.

The researchers assessed the associations between traffic proximity and the neurological conditions using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighborhood income. They also conducted several sensitivity analyses, such as adjusting for access to neurologists and exposure to nitrogen dioxide and fine particulate matter.

They identified 243,611 cases of dementia, 31,577 cases of Parkinson's disease, and 9,247 cases of MS from 2001 to 2012.

The associations between proximity to major roadways and dementia risk were strongest among urban residents, especially those who lived in major cities (HR 1.12, 95% CI 1.10-1.14 for people living <50 m from a major traffic road) and who never moved (HR 1.12, 95% CI 1.10-1.14 for people living <50 m from a major traffic road).

Additionally, the researchers concluded that exposure to nitrogen dioxide and fine particulate matter was also linked to higher dementia incidence, but did not account for the full effect.

"Our study suggests that improvements in environmental health policies and land use planning aimed at reducing traffic exposure can have considerable potential for prevention of dementia, which would lead to a broad public health implication," Chen explained to MedPage Today.

He also suggested that changes in transportation emissions and land use policies may help to prevent dementia and improve public health.

The editorialists agreed that policy change is paramount to better health. "The health repercussions of living close to heavy traffic vary considerably among exposed populations, given that traffic includes exposures to complex mixtures of environmental insults ... We must implement preventive measures now, rather than take reactive actions decades from now," they wrote.

Study limitations included the inability to identify undiagnosed cases of the three conditions and the lack of information on medications that may influence risk of dementia.

Additionally, Chen's group noted that because air pollution exposure was estimated at the postal-code level, it may not account accurately for each individual's exposure.

This study was supported by government agencies and grants.

Chen and co-authors disclosed no relevant relationships with industry.

Calderón-Garcidueñas and Villarreal-Ríos disclosed no relevant relationships with industry.

  • Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
2017-01-04T18:30:00-0500
  • Primary Source

    The Lancet
    Source Reference: Chen H, et al "Living near major roads and the incidence of dementia, Parkinson's disease, and multiple sclerosis: a population-based cohort study" Lancet 2017; DOI: 10.1016/S0140-6736(16)32399-6.
  • Secondary Source

    The Lancet
    Source Reference: Calderón-Garcidueñas L and Villarreal-Ríos R "Living close to heavy traffic roads, air pollution, and dementia" Lancet 2017.
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Children of patients with C9orf72 mutations are at a greater risk of frontotemporal dementia or ALS at a younger age

The most common genetic cause of the brain diseases frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) is a mutation in the C9orf72 gene. Researchers from VIB and UAntwerp, headed by Prof. Christine Van Broeckhoven, have demonstrated that if an affected parent passes on this mutation, the children will be affected at a younger age (than the parent). There are no indications that the disease progresses more quickly. These results are published in the international scientific journal JAMA Neurology.

Prof. Christine Van Broeckhoven (VIB-UAntwerp): "This research is based on our team's previous results, which showed that the same C9orf72 mutation leads to both FTD and ALS. As this mutation occurs in a substantial group of ALS and FTD patients, it is important to extract as much knowledge about this mutation and the disease process as possible."

Brain diseases associated with neurodegeneration

Frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two brain diseases associated with neurodegeneration, the abnormally rapid death of brain cells. In FTD, the frontal lobes and temporal lobes are affected first, causing changes in the patient's behavior and personality, or problems with language. Loss of memory functions occurs only later on in the disease. After Alzheimer's disease, FTD is the most common form of dementia in young patients. A fraction of the FTD patients show symptoms consistent with ALS, a disease in which the nerve cells that control the muscles, in the brain and spinal cord, are affected. This causes ALS patients to progressively lose muscle mass, resulting in loss of strength in the limbs and problems with speaking, swallowing, and breathing. ALS is more common without FTD symptoms.

A common hereditary factor

Previous research by Prof. Van Broeckhoven's group demonstrated a genetic link between FTD and ALS, namely a mutation in the same gene C9orf72.

Prof. Christine Van Broeckhoven (VIB-UAntwerp): "The C9orf72 mutation is the most frequent mutation in FTD and ALS. In the Belgian population, 37% of patients with ALS and 25% of patients with FTD can be explained by the presence of this C9orf72 mutation. The C9orf72 mutation is present in 88% of patients with FTD plus ALS." These results dating from 2012 were published in The Lancet Neurology (Gijselinck et al.). The mutation in C9orf72 consists of a repetition of a short DNA sequence GGGGCC which can expand in patients up to several thousands of repetitions. It is not yet known why some patients get FTD and others ALS.

The length of the C9orf72 repeat is determinative for the age of onset of the disease

The age at first presentation of disease symptoms ranges in patients from 29 to 82 years, even in patients from the same family. Until recently, there was no explanation for this high variability. VIB-UAntwerp's researchers demonstrated in 2016 that the age of onset is determined by the number of GGGGCC repeats: the more repetitions, the earlier the age of onset. In C9orf72 families in which the affected parent had a late age of onset and their affected children an earlier age of onset, the researchers provided evidence that the GGGGCC repeat in the C9orf72 gene expanded from a short sequence of repeats (less than 200 repeats) to a long one (more than a thousand) (Gijselinck et al. Molecular Psychiatry 2016).

Dr. Sara Van Mossevelde (VIB-UAntwerp): "In a new clinical study in 36 C9orf72 families, we analyzed the age of onset of the patients in 2 to 4 generations. We found that there was a significant difference in the ages of onset between successive generations. In most families, the children were affected by the disease at a younger age, but there were no indications that the disease was progressing more quickly. We also found that in families with both FTD and ALS patients, if the parent had FTD the child was more likely to have FTD, and a similar principle applied to ALS."

This research was conducted by physician and PhD student Dr. Sara Van Mossevelde under the direction of Prof. Christine Van Broeckhoven in the Research Group Neurodegenerative Brain Diseases at VIB-UAntwerp Center for Molecular Neurology. The project was carried out in close collaboration with neurologists from the Hospital Network Antwerp (ZNA), Antwerp University Hospital (UZA), and the Belgian Neuroscience Consortium.

The identification of the C9orf72 mutation in Belgian FTD and ALS patients was published in The Lancet Neurology (Gijselinck et al. A C9orf72 promoter repeat expansion in a Flanders-Belgian cohort with disorders of the frontotemporal lobar degeneration-amyotrophic lateral sclerosis spectrum: a gene identification study, 2012). The molecular studies of the C9orf72 repeat expansions were published in Molecular Psychiatry (Gijselinck et al. The C9orf72 repeat size correlates with onset age of disease, DNA methylation and transcriptional downregulation of the promoter, 2016)

This research was funded by VIB and the University of Antwerp Research Fund and through external national and international funding from IWT/VLAIO, FWO, FPS Science Policy, and the Foundation for Alzheimer's Research (SAO/FRMA).

Article: Clinical Evidence of Disease Anticipation in Families Segregating a C9orf72 Repeat Expansion, Sara Van Mossevelde, MD; Julie van der Zee, PhD; Ilse Gijselinck, PhD; et al., JAMA Neurology, doi: 10.1001/jamaneurol.2016.4847, published online 13 February 2017.

Morning Break: Flip Flop on Drug Prices; Journal of Alternative Facts; Happy Ending for CCF Doc

On again off again White House support for Medicare negotiating drug prices is on again. "He's for it," says White House spokesman a week after the President called it "price fixing". (NPR)

House Speaker Paul Ryan says Obamacare replacement will pass this year. White House also "optimistic" about that timetable. (Reuters)

Homeless who have benefitted from Obamacare now fear loss of coverage. (NPR)

Lawsuit says Toledo clinic falsely told 50 people they had Alzheimer's. (AP)

Contaminated pot may have killed a cancer patient. (CBS News)

Vatican defends decision to invite Chinese to organ trafficking conference. Up to 90% of deceased Chinese transplant donors are people executed. (AP)

The Cleveland Clinic doctor who wasn't allowed to return to the U.S. because of Trump's immigration ban is now back in the U.S. (ProPublica)

FTC says memory supplement Prevagen is a hoax. (NBC News)

A doctor in California removed a 130-pound benign tumor from a man -- the tumor started out as an ingrown hair.

Medical stories too often have needless use of word "controversial," according to HealthNewsReview.

The "growing and important discipline of alternative facts" now has a journal of its very own. (Retraction Watch, Health Economics)

Harvard Health Policy analyst who studies high deductibles cut back on his own care when his heart problem brought him face-to-face with high price tag of treating his illness. (Washington Post)

STAT reports that two samples of original mold Alexander Fleming used to produce penicillin are going up for auction in London.

Morning Break is a daily guide to what's new and interesting on the Web for healthcare professionals, powered by the MedPage Today community. Got a tip? Send it to us: MPT_editorial@everydayhealthinc.com.

2017-02-08T12:58:34-0500
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Seniors Load Up on Psych Meds (JAMA Internal Medicine)

Older Americans are being over-prescribed, suggested new research finding that the percentage of people over 65 taking three or more mind-altering drugs has more than doubled in the past decade.

What's more, nearly half of these patients were not formally diagnosed with mental health issues, insomnia, or pain conditions.

Researchers found that 1.4% of doctor visits by seniors involved three or more central nervous system-affecting medication in 2013 compared to 0.6% in 2004, meaning 3.68 million doctor visits a year involve older patients taking three or more brain-altering drugs.

The authors said the latest findings are "concerning" as combining multiple drugs such as opioids, antidepressants, tranquilizers, and antipsychotics are associated with serious risks, particularly in seniors.

"We hope that the newer prescribing guidelines for older adults encourage providers and patients to reconsider the potential risks and benefits from these combinations," said lead author Donovan Maust, MD, MS, of the University of Michigan.

2017-02-15T15:30:00-0500
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Tiny Brain Blocks as Marker for Heart Disease Too?

Visible on magnetic resonance imaging (MRI), cortical cerebral microinfarcts were associated with traditional blood markers of cardiac disease, a study showed.

Patients with cortical cerebral microinfarcts were more likely to have a history of cardiac disease as follows, according to the data published online in JAMA Neurology:

  • Atrial fibrillation (RR 1.62, 95% CI 1.20-21.8)
  • Ischemic heart disease (RR 4.31, 95% CI 3.38-5.49)
  • Congestive heart failure (RR 2.05, 95% CI 1.29-3.25)

For the study, on multivariable adjustment by Christopher L. Chen, BMBCh, of National University of Singapore, and colleagues, the number of cortical cerebral microinfarcts that a patient had correlated with elevated NT-proBNP (RR 3.19, 95% CI 2.62-3.90) and hs-cTnT concentrations (RR 4.86, 95% CI 3.03-7.08) as well.

This relationship remained intact whether or not patients showed clinical signs of cardiac disease, the team reported.

Writing in an accompanying editorial, Robert J. Wityk, MD, of Johns Hopkins University School of Medicine in Baltimore, said that the association with biomarkers could be attributable to underlying shared risk factors -- although known cardiovascular risk factors were included in the multivariate model -- or could represent subclinical cardiac disease as a cause of cortical cerebral microinfarcts.

Chen's group recruited 464 participants from two memory clinics in Singapore -- although only 243 individuals had complete blood and MRI data for the analysis. Patients underwent 3-Tesla MRI scanning from 2010 to 2015.

"Until recently, cortical cerebral microinfarcts have not been detectable during life; however, recent advances in MRI techniques have allowed detection of cortical cerebral microinfarcts in vivo," the authors recalled.

"Subsequent studies have found that cortical cerebral microinfarcts were associated with small-vessel (lacunes, white matter hyperintensities, and microbleeds) and large-vessel (cortical infarcts and intracranial stenosis) diseases, which may suggest a heterogeneous origin. Furthermore, the [microinfarcts] were also linked to a history of cardiovascular disease and cognitive dysfunction."

Wityk commented that much of the prior work on cortical cerebral microinfarcts was done on 7-Tesla MRI. "Although 7-T MRI appears to have a good correlation of cortical cerebral microinfarct lesions with neuropathologic findings, even in research centers, 7-T MRI is not as widely available as 3-T MRI," he wrote, suggesting that for the sake of future research, additional studies may be needed to confirm the accuracy of 3-T MRI for detecting cortical cerebral microinfarcts.

The researchers and Wityk reported having no relevant conflicts of interest.

2017-06-02T00:00:00-0400

last updated

  • Primary Source

    JAMA Neurology
    Source Reference: Hilal S, et al "Association between subclinical cardiac biomarkers and clinically manifest cardiac diseases with cortical cerebral microinfarcts" JAMA Neurol 2017; DOI: 10.1001/jamaneurol.2016.5335.
  • Secondary Source

    JAMA Neurology
    Source Reference: Wityk RJ "Cerebral cortical microinfarcts on 3-T magnetic resonance imaging: a new tool in the study of cerebrovascular ischemia" JAMA Neurol 2017; DOI: 10.1001/jamaneurol.2016.5555.
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