Artists' Brushstrokes May Offer First Hints of Brain Disease

News Picture: Artists' Brushstrokes May Offer First Hints of Brain Disease

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THURSDAY, Dec. 29, 2016 (HealthDay News) — An artist’s work may reveal early signs of progressive brain disease, a new study suggests.

Researchers examined the brushstrokes in nearly 2,100 paintings from seven famous artists.

Two (Salvador Dali and Norval Morrisseau) had Parkinson’s disease, two (James Brooks and Willem de Kooning) had Alzheimer’s disease, and three (Marc Chagall, Pablo Picasso and Claude Monet) had no known neurodegenerative disorders.

The results showed clear patterns of change in the works of the artists with neurodegenerative disorders, compared to those with no brain diseases.

“Art has long been embraced by psychologists an effective method of improving the quality of life for those persons living with cognitive disorders,” study author Alex Forsythe said. Forsythe is a senior lecturer and director of studies in applied psychology at the University of Liverpool in England.

“We have built on this tradition by unpicking artists ‘handwriting’ through the analysis of their individual connection with the brush and paint. This process offers the potential for the detection of emerging neurological problems,” she said in a university news release.

The study was published Dec. 29 in the journal Neuropsychology.

— Robert Preidt

Copyright © 2016 HealthDay. All rights reserved.

SOURCE: University of Liverpool, news release, Dec. 29, 2016

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What Else is in the 21st Century Cures Act?

WASHINGTON — When most people think about the 21st Century Cures Act, they think about curing cancer and Alzheimer’s disease, and curbing the nation’s opioid epidemic. But the nearly 1,000-page healthcare spending bill, which President Obama signed in mid-December, also aims to reform the nation’s fragmented mental health system, improve access to electronic health data, and ensure that underrepresented individuals are included in important health research.

Mental Health

Approximately 13 million people in the U.S. have a serious mental illness or substance use disorder, according to the American Psychiatric Association (APA), which applauded the 21st Century Cures Act, calling its reforms to mental health a “huge step forward.”

The Cures Act included efforts to promote evidence-based treatments, strengthen mental health parity, and bolster the mental health workforce. The bill also established a grant program focused on early intervention for those showing warning signs of a potentially serious mental illness.

Earlier this year, Congress took aim at the Substance Abuse and Mental Health Services Administration (SAMHSA), saying that the agency had failed patients with serious mental health problems.

One almost immediate change the bill makes is to establish a new assistant secretary for Mental Health and Substance Abuse to oversee SAMHSA, explained Andrew Sperling, director of legislative advocacy for the National Alliance on Mental Illness.

Speaking in a phone interview with MedPage Today that included a public relations official, Sperling said he anticipates that Rep. Tom Price (R- Ga. ), the newly appointed Secretary of Health and Human Services, will have “a great deal of influence” in selecting that individual.

Better Integration, Better Care

The 21st Century Cures Act also designates a new Interdepartmental Serious Mental Illness Coordinating Committee, charged with summarizing advances in diagnosing and treating serious mental illness in a written report to congress. The committee — which includes members from SAMHSA, the Department of Defense, the Health Resources and Services Administration (HRSA), and other federal health agencies — will also be required to evaluate the impact of federal programs on important public health outcomes (i.e., rates of suicide, preventable emergency room visits, and homelessness).

Other key mental health-related provisions of the bill include the following:

  • Authorizing a grant program for assertive community treatment for adults with serious mental illness;
  • Authorizing a grant program to enable local governments to improve crisis intervention among emergency responders, clinicians, and law enforcement and funding to build registries of available inpatient psychiatric beds;
  • Establishing policies to create new residency programs to train future primary care doctors and psychiatrists about integrating mental and physical health;
  • Designating a nationwide hotline and online tool for improving access to mental health and substance use providers; and
  • Enhancing grant programs that offer behavioral health services for homeless and justice-involved individuals.

Also, the Cures Act, while not amending the Health Insurance Portability and Accountability Act (HIPAA), does outline the circumstances by which clinicians can share information with family members when a loved one is in crisis. “We hope this will ease the chilling environment around disclosure of information to family members,” by providing clinicians with greater clarity regarding when they can disclose, Sperling said.

With regard to mental health parity — equal access and coverage from insurers for mental health issues compared with physical concerns — most states have not been aggressively auditing insurers, an APA representative told MedPage Today.

However, the Cures Act calls for a standardized approach to auditing, and, on a federal level, requires the Department of Labor to periodically publish reports to showcase the volume of cases the agency has pursued.

Efforts to ensure more consistency and transparency could produce a “sentinel effect,” said the APA official. The more that insurers believe they risk being audited, the more likely they are to take internal compliance seriously.

Electronic Health Records

The Cures Act also strengthens efforts to improve and enforce health information interoperability.

Beginning in January 2018, vendors’ relative interoperability will be evaluated, and by 2019, those not in compliance will lose certification, explained Mandy Long, chair of the Electronic Health Records Association (EHRA) Clinician Experience Workgroup for the Healthcare Information and Management Systems Society (HIMSS), speaking in a phone interview with MedPage Today during which a public relations official was present.

“There are real teeth to [the language in the bill], and [the penalties] grow over the course of a couple of years,” said Long, who is also vice president of product management at Modernizing Medicine, an EHR and practice management software company in Boca Raton, Fla.

She noted that vendors who engage in data blocking can be fined up to $1 million per violation.

Long, whose daughter has Turner syndrome, also spoke as the parent of an ill child about the challenge of keeping specialists in different hospitals current with her daughter’s health status and tests. “We call it the ‘patient’s Bible’ — that binder that patients create for themselves, or their parents create [of various medical records] — we lug it from visit to visit or, God forbid, if we end up in an emergency situation; it’s awful and frequently out of date.”

Long said she believes the bill’s requirements to promote a scalable integration structure will have benefits for patients as well as industry.

The College of Healthcare Information Management Executives (CHIME) offers more specifics on the health IT provisions of the bill related to information blocking, interoperability standards, and hardship exemptions for decertified EHRs.

Superbugs, Vaccinations, and Equity in Research

Other elements of the bill include provisions to fight superbug infections, such as allowing the FDA to require manufacturers or reusable medical devices to share their cleaning instructions and verify that such methods work. The Cures Act also creates new requirements for the National Institutes of Health to encourage scientists studying similar topics to collaborate, with the goal of increasing the volume of data on underrepresented populations (i.e., women, children, and minorities).

Finally, the bill aims to raise maternal vaccination rates through efforts to prevent vaccine shortages and by incentivizing drugmakers to develop new vaccines for pregnant women. In addition, the act encourages pediatric drug development by allowing products given a “rare pediatric disease designation” from the FDA before 2020 the chance to be considered for a voucher until 2022.


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Longer Survival with Androgen Therapy in AML

Action Points

  • Note that this randomized trial of norethandrolone maintenance therapy among older individuals treated with chemotherapy for acute myeloid leukemia (AML) found that the androgenic agent successfully prolonged disease-free survival.
  • There were no cases of prostate cancer reported in either arm of the study.

Androgen maintenance therapy for acute myeloid leukemia (AML) led to significantly longer survival in older patients, a randomized trial showed.

Among patients in complete remission 1 year after chemotherapy induction, those assigned to androgen maintenance therapy had a twofold improvement in disease-free survival (DFS) at 5 years as compared with no maintenance therapy (P=0.002). The 5-year overall survival also was significantly higher in patients who received either of two doses of norethandrolone for 2 years after achieving remission (P=0.008).

All outcomes relevant to prognosis favored the patient group that received androgen maintenance therapy, Norbert Ifrah, MD, of University Hospital Center in Angers, France, and coauthors reported online in the Journal of Clinical Oncology.

“In choosing to add androgens to post-remission therapy, we expected to improve DFS, which was achieved, yet a beneficial effect was finally observed for EFS and OS. This beneficial effect was intriguingly time-dependent and became significant only among patients who had failed to relapse during the first year of therapy.”

A time-dependent analysis of covariates identified hyperleukocytosis (WBC count >30 x 109/L at diagnosis) as an additional prognostic factor.

“These data suggest that for the non-negligible population of elderly patients with AML with a WBC count <30 x 109/L at diagnosis, the addition of androgens could become a valid cost-effective maintenance therapy,” the authors concluded.

In an accompanying editorial, however, Joseph G. Jurcic, MD, director of the Hematologic Malignancies Department of Columbia University Medical Center in New York City, said that although intriguing, the data must be considered in the context of uncertainty surrounding the role of maintenance therapy in AML. Chemotherapy-based approaches to maintenance have yielded limited benefit, but studies of molecularly targeted agents have been more promising, he explained. Moreover, the lomustine-based induction chemotherapy is not favored by many experts in the field, the intensive postremission therapy may be difficult for many older patients to tolerate, and the androgen preparation used in the study is not widely available.

“Before [the approach is] considered standard of care, the generalizability of the findings should be demonstrated with a more commonly used chemotherapy backbone and more readily available androgen formulations, particularly because other preparations have not produced clinical benefit,” Jurcic wrote.

“Future studies must also include careful correlative studies to elucidate the effects of androgens on normal and leukemic progenitors. These data provide proof of principle that maintenance strategies can improve outcomes in AML and support further investigation of this approach.”

AML is a disease of older individuals, as more than 70% of patients are over 60 at diagnosis. Older patients with AML have a poor prognosis, owing in part to low tolerance to intensive chemotherapy regimens. Additionally, Ifrah and co-authors noted, older patients with AML often have unfavorable prognostic features, such as poor-risk cytogenetics and multidrug resistance phenotype.

Older patients have a higher treatment-related mortality, lower rate of complete remission after induction therapy, and briefer duration of remission, as compared with younger patients with AML. The 5-year overall survival for older patients with AML is 15% or less, the researchers continued.

The rationale for androgen maintenance therapy in AML came from a long successful clinical experience in the treatment of aplastic anemia, which led to small, single-center preliminary clinical trials in AML. Subsequent in vitro studies showed that androgens inhibited proliferation of leukemia cell lines, providing additional rationale to evaluate the agents in AML.

Ifrah and his co-investigators in the French GOELAMS (Groupe Ouest Est d’Etude des Leucémies et Autres Maladies du Sang) cooperative group performed the multicenter clinical trial to evaluate two weight-based doses of norethandrolone (10 or 20 mg) as maintenance therapy in older patients with AML. The trial involved 330 patients ≥60 with newly diagnosed AML.

All patients received induction therapy with idarubicin, cytarabine, and lomustine, and those who attained complete or partial remission received additional treatment with alternating courses of idarubicin-cytarabine and methotrexate-mercaptopurine. Patients who remained in complete remission at 1 year (N=247) were randomized to 2 years of norethandrolone maintenance therapy or no maintenance.

The primary endpoint was DFS. Secondary endpoints included EFS, overall survival, and safety.

The authors reported that 52 patients (16%) died during induction therapy, most often as a result of sepsis (N=23).

After a median follow-up of 1.2 years from the start of induction therapy (4.6 years among patients alive at last follow-up), the patients assigned to androgen maintenance had a 5-year DFS rate of 31.2% versus 16.2% for patients who received no maintenance therapy.

Relapses occurred in 146 patients (64 in the maintenance arm and 82 without maintenance), and 32 patients died in complete remission — 16 in each arm.

Patients assigned to androgen maintenance therapy had 5-year EFS and overall survival rates of 21.5% and 26.3%, respectively, compared with 12.9% and 17.2% in the group that received no maintenance therapy.

Analysis of postremission toxicity showed no difference between the treatment groups with respect to rehospitalization, need for transfusion, or grade 3/4 toxicities. The authors reported that secondary cancers occurred in 11 patients on androgen maintenance and 16 in the no-maintenance arm, and no patient in either arm developed prostate cancer.

The study was supported by University Hospital Center of Grenoble in France.

Ifrah disclosed relationships with Celgene, Sanofi, Novartis, Pfizer, Chugai, and Alexion Pharmaceuticals. One or more coauthors disclosed relationships with Novartis, Amgen, Merck Sharp & Dohme, Celgene, Pfizer, Chugai, Sunesis Pharmaceuticals, Mundipharma, Roche, Janssen-Cilag, GlaxoSmithKline, Cell Therapeutics, Sanofi, Alexion, and Celgene.

Jurcic disclosed relationships with Novartis, Bayer, Amgen, Alexion Pharmaceuticals, Seattle Genetics, Sunesis Pharmaceuticals, Celgene, Astellas, Actinium Pharemaceuticals, Daiichi Sankyo, Forma Therapeutics, Kura, and Syros Pharmaceuticals.

  • Reviewed by
    F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner


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Antipsychotic Drugs May Up Risk of Early Death in Alzheimer's Patients

News Picture: Antipsychotic Drugs May Up Risk of Early Death in Alzheimer's Patients

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TUESDAY, Dec. 27, 2016 (HealthDay News) — Taking antipsychotic drugs significantly increases the risk of premature death among Alzheimer’s patients, a new study indicates.

Researchers analyzed data from almost 58,000 people in Finland diagnosed with Alzheimer’s disease between 2005 and 2011.

Slightly more than a quarter of the Alzheimer’s patients took antipsychotic drugs. The study found they had a 60 percent higher risk of death than those who didn’t take the drugs.

The risk of death was highest when patients first started taking antipsychotics, but the increased risk persisted with long-term use of the drugs.

Patients who took two or more antipsychotic drugs at the same time were nearly twice as likely to die early than those who took one antipsychotic.

Although the study found an association between antipsychotic drug use and a higher risk of dying, it cannot prove a cause-and-effect link.

But, the researchers — led by Marjaana Koponen, a doctoral student from the School of Pharmacy at the University of Eastern Finland — said their findings support previous studies. The first warnings about increased risk of death among Alzheimer’s patients taking antipsychotics were issued more than 10 years ago.

The new study confirms current recommendations that antipsychotic drugs should be used only for the most difficult behavioral symptoms of dementia, such as agitation and aggression, and that length of use should be limited, the researchers said.

Also, patients should be given the lowest possible doses, and should not be given two or more antipsychotics at the same time.

The study was published recently in the Journal of Alzheimer’s Disease.

— Robert Preidt

Copyright © 2016 HealthDay. All rights reserved.

SOURCE: University of Eastern Finland, news release, December 2016

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TSRI scientists develop new approach for understanding diverse effects of endocrine-disruptors

Breast cancer researchers from the Florida campus of The Scripps Research Institute (TSRI) have developed a novel approach for identifying how chemicals in the environment–called environmental estrogens–can produce infertility, abnormal reproductive development, including “precocious puberty,” and promote breast cancer.

Environmental estrogens work by binding to the estrogen receptor, a protein in cells that guides sexual maturation and reproduction. The new research shows how high-resolution imaging techniques could give scientists a window into how exposure to these chemicals may impact public health.

This research method could also be used to speed up the discovery of new drugs for breast cancer and many other diseases, added study senior author Kendall Nettles, associate professor at TSRI.

The study was published online ahead of print in the journal Cell Chemical Biology.

Taking Snapshots of a Crucial Receptor

Environmental estrogens control the estrogen receptor’s activity by changing its shape, which can mimic the effects of estrogen. These chemicals can also block receptor activity, as seen with the breast cancer therapy tamoxifen.

These changes are often exceedingly small, in the sub-ångström range (one ångström is equal to one ten-billionth of a meter). In fact, changes to even a single atom in a chemical or endocrine therapy drug can often drive widely divergent outcomes, but the resolution of the typical crystal structure does not allow visualization of these small changes.

Nettles calls the approach in the new study “super-resolution x-ray crystallography.”

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X-ray crystallography is a technique that produces a snapshot of the receptor’s 3-D atomic structure. Like the images produced by photography or microscopy, x-ray crystal structures have a certain resolution, or level of detail, that can be visualized. With optical microscopy, super-resolution imaging–a discovery for which researchers were awarded the Nobel Prize in 2014–can be achieved by combining many images to produce a sharper picture.

Nettles and his colleagues reasoned that they could use a similar approach with x-ray crystallography to compare molecular snapshots, or structures, and better understand how estrogenic chemicals control receptor activity.

Developing a Framework for Drug Design

They found that by combining data about structural disturbances from many structures with activity profiles of their ligands (the estrogenic chemicals), researchers can identify the sub-ångström details that determine endocrine disruption.

“Our novel approach offers a framework for understanding the diverse effects of environmental estrogens and other endocrine disruptors, furthering efforts to develop improved breast cancer therapies,” said TSRI Research Associate Jerome C. Nwachukwu, first author of the study. “This approach can also be applied to other allosteric receptors.”

Super-resolution x-ray crystallography can also be applied to the large groups of receptors that comprise the targets for most known drugs. With structure-based drug design, chemists can use this new approach to visualize how to modify drug-candidate chemicals to promote the desirable therapeutic profile.


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A new strategy to fight prostate cancer

A new study led by scientists from the Florida campus of The Scripps Research Institute (TSRI) sheds light on a signaling circuit in cells that drives therapy resistance in prostate cancer. The researchers found that targeting the components of this circuit suppresses advanced prostate cancer development.

The study, led by TSRI Associate Professor Jun-Li Luo, was published online ahead of print in the journal Molecular Cell.

A New Strategy to Fight Prostate Cancer

Prostate cancer—which, according to the American Cancer Society, affects one in six American men—is the second-leading cause of death after lung cancer in American men.
Currently, the most effective treatment of advanced prostate cancer is to deprive the cancer of what feeds it—androgen hormones, such as testosterone. Unfortunately, almost all patients eventually develop resistance to this therapy, leaving doctors with no options to counteract the inevitable.

The new study shows that a “constitutively active” signaling circuit can trigger cells to grow into tumors and drive therapy resistance in advanced prostate cancer. A cell signal pathway with constitutive activity requires no binding partner (ligand) to activate; instead, the signaling circuit continually activates itself.

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This signaling circuit, which is composed of the protein complex IκBα/NF-κB (p65) and several other molecules, controls the expression of stem cell transcription factors (proteins that guide the conversion of genetic information from DNA to RNA) that fuel the aggressive growth of these resistant cancer cells.

“The fact that the constitutive activation of NF-kB in the circuit is independent of traditional activation opens the door for potential treatment options,” said Luo.

Targeting Other Signaling Components Shows Promise

NF-kB plays important roles in cancer development, and it is regarded as one of the most important targets for cancer therapy. However, the use of NF-kB inhibitors in treating cancer is complicated by severe side effects related to immunosuppression caused by indiscriminate inhibition of NF-kB in normal immune cells.

Luo noted that targeting the other non-IκBα/NF-κB components in this signaling circuit would avoid the suppression of NF-κB in normal immune cells while keeping the potent anti-cancer efficacy.

In addition to IκBα/NF-κB, the signaling circuit includes the microRNA miR-196b-3p, Meis2 and PPP3CC. While miR-196b-3p promotes tumor development, Meis2, which is an essential developmental gene in mammals, can disrupt the circuit when overexpressed. The protein PPP3CC can inhibit NF-κB activity in prostate cancer cells.

“Disrupting this circuit by targeting any of its individual components blocks the expression of these transcription factors and significantly impairs therapy-resistant prostate cancer,” said TSRI Research Associate Ji-Hak Jeong, the first author of the study.


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Burger King, Tim Hortons to curb antibiotics used in chicken

By Tom Polansek and Lisa Baertlein

Restaurant chains Burger King and Tim Hortons plan to switch to chicken raised without antibiotics considered “critically important” to human medicine, their owner said on Wednesday, making it the latest company to ditch the drugs over health concerns.

Restaurant Brands International Inc, which owns both chains, said it aims to make the change in U.S. stores in 2017 and in Canada in 2018.

An estimated 70 percent of antibiotics that are important to fighting human infections and ensuring the safety of invasive procedures such as surgeries are sold for use in meat and dairy production.

Concern has been growing among scientists, public health experts, consumers and shareholders that the overuse of such drugs is contributing to rising numbers of life-threatening human infections from antibiotic-resistant bacteria dubbed “superbugs.”

“We believe that it is important to reduce the use of antibiotics important for human medicine in order to preserve the effectiveness of antibiotics in both veterinary and human medicine,” Restaurant Brands said.

The company did not immediately respond to requests for further comment.

The U.S. Centers for Disease Control and Prevention estimates that at least 2 million people in the United States are infected with drug-resistant bacteria each year and that 23,000 die as a direct result.

Officials with health advocacy group As You Sow said they have been working with Restaurant Brands on its antibiotics policy for more than a year. In February, the group withdrew a shareholder proposal calling on the company to develop a stricter policy after Restaurant Brands agreed to address the issue before the end of 2016.

Austin Wilson, environmental health program manager for As You Sow, said the company’s new plan represented progress. Still, he said it was “disappointing, since it is weaker than the standards set in the last year or two by Tyson, McDonald’s and Wendy’s.”

McDonald’s Corp has already removed all antibiotics important to human medicine from its U.S. chicken supply chain, and Wendy’s Co said in August it would quit using chickens raised with antibiotics important to human health by 2017.

Tyson Foods Inc, the biggest U.S. chicken processor, has said it intends to stop using all antibiotics important to human medicine to raise its chickens in 2017.

Restaurant Brands is only eliminating drugs that are “the most critical in human medicine” from its supply, Wilson said.

Yum Brands Inc’s KFC stands out as the last major chicken chain to make a move on curbing antibiotic use.

KFC has far more restaurants than any other fast-food chicken chain and is second in sales behind Chick-fil-A, which has committed to finishing its switch to chicken raised without any antibiotics by the end of 2019.

As You Sow has filed a shareholder proposal requesting that Yum phase out harmful antibiotics from its meat supply in a bid to prompt changes at KFC.

(Reporting by Lisa Baertlein and Tom Polansek; Editing by Frances Kerry and Lisa Shumaker)

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Slovakia reports outbreak of severe bird flu: OIE

Slovakia has confirmed an outbreak of the highly pathogenic H5 bird flu virus, the World Organisation for Animal Health (OIE) said on Thursday, citing a report from the country’s agriculture ministry.

The disease was detected among laying hens in a backyard in the capital Bratislava. It killed 64 out of 65 birds exposed to the virus, with the remaining animal slaughtered, the report posted by the OIE said.

The report did not indicate what strain of H5 bird flu was found.

Europe has seen the H5N8 strain of bird flu spread in recent weeks, while in Asia different strains of the disease have prompted the culling of millions of poultry birds.

(Reporting by Gus Trompiz; Editing by Adrian Croft)

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