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Friday, November 30, 2018

Three Common Dementia Screens Faulty, Inaccurate


Three brief cognitive assessments often used in primary care settings to identify patients with cognitive impairment who could benefit from a full diagnostic workup for dementia are often inaccurate, new research shows.
The three tests are the Mini–Mental State Examination (MMSE), which assesses orientation to time and place and the ability to remember words; the Memory Impairment Screen (MIS), which focuses on the ability to remember words; and Animal Naming (AN), which involves naming as many animals as possible in 60 seconds.
“Our study found that all three tests often give incorrect results that may wrongly conclude that a person does or does not have dementia,” study author David Llewellyn, PhD, of the University of Exeter Medical School, United Kingdom, said in a news release.
The study also found that each test has a different pattern of biases, so people are more likely to be misclassified by one test than another, depending on factors such as their age, education, and ethnicity.
“While these results are at first concerning, knowing the specific limitations for each test will help clinicians decide which is the most appropriate for their patient,” lead author Janice Ranson, doctoral researcher in clinical epidemiology at the University of Exeter Medical School, told Medscape Medical News.
“There are many available brief tests, which all have some limitations and biases, and there is currently not strong enough evidence to suggest one particular test is best for everyone. From our findings, it appears that the best test depends on the clinical context and patient characteristics,” said Ranson.
The study was published online November 28 in Neurology Clinical Practice, a journal of the American Academy of Neurology.

Huge Need for Better Tests

The study included 824 adults (mean age, 82 years) from the population-based Aging, Demographics and Memory Study (ADAMS) who underwent a comprehensive workup for dementia. The workup included physical examination, genetic testing for the APOE gene, psychological testing, and comprehensive memory and thinking tests. On the basis of these results, 35% of the patients were found to have dementia, and 65% were found not to.
Armed with this information, the researchers then had participants take the three brief cognitive assessment tests. They found that 35.7% of participants were wrongly classified by at least one test, 13.4% were misclassified by two or more tests, and 1.7% were misclassified by all three tests. Overall dementia misclassification rates for the MMSE, the MIS, and the AN were 21%, 16%, and 14%, respectively. These rates included both false positive and false negative results.
Years of education predicted higher rates of false negative results (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.07 – 1.40) and lower rates of false positive results (OR 0.77; 95% CI, 0.70 – 0.83) on the MMSE.
Nursing home residency predicted lower rates of false negative results (OR, 0.15; 95% CI, 0.03 – 0.63) and higher rates of false positive results (OR, 4.85; 95% CI, 1.27 – 18.45) on the AN.
Across all tests, not having an informant (such as a family member or friend) weigh in on the patient’s memory was associated with increased risk for misclassification.
“Each test is biased in different ways, so the accuracy of each test varies with the characteristics of the patient,” said Ranson.
“There is clearly great potential for improvement of this initial stage in the diagnostic pathway for dementia. We desperately need more accurate and less biased ways of detecting dementia swiftly in clinic,” he added.
This reinforces that we don’t have one simple test.Dr Steven DeKosky

“Not Surprising”

Reached for comment, Steven DeKosky, MD, McKnight Brain Institute, Florida Alzheimer’s Disease Research Center, Gainesville, said he’s not surprised by the data.
“We have known about this for a long time, and kudos to this group for doing this careful analysis of all three tests. The fact that only 1.7% of the cases were misdiagnosed when all three tests were used is testimony to the fact that the diagnosis is proportional to the amount of time that you spend testing a patient,” said DeKosky, a fellow of the American Academy of Neurology.
“Everybody is looking for the one test that will tell you whether the patient has Alzheimer’s disease or whether they are impaired, and the human brain is a little too complicated for that.
“Dementia and cognitive impairment of normal aging are multidimensional, continuous processes, and we are trying to nail a state out of what is a bunch of declining lines or stable lines of cognition. This reinforces that we don’t have one simple test. There will always be some people that are missed if you use just one test,” said DeKosky.
He said the study also highlights the importance of having the patient’s partner provide information on whether there is memory loss or not.
“Patients will often tell you that they don’t have memory loss, which is either their denial or possibly loss of insight because they are developing one, or because they just don’t want to believe it. So often, the partner is a more accurate source,” said DeKosky.
The study was supported by the Halpin Trust, the Mary Kinross Charitable Trust, the Engineering and Physical Sciences Research Council, and the UK National Institute for Health Research. The study authors and Dr DeKosky have disclosed no relevant financial relationships.
Neurol Clin Pract. Published online November 28, 2018. Abstract

McKesson to move corporate HQS from SF to Las Colinas, Texas

McKesson Corporation announced the relocation of its corporate headquarters from San Francisco, California to Las Colinas, Texas, effective April 1, 2019, expanding upon its presence in the Dallas area. “We are excited to strengthen our presence in Texas and make Las Colinas our official global headquarters,” said John H. Hammergren, chairman and chief executive officer, McKesson Corporation. “Governor Abbott and the Irving/Las Colinas community have provided tremendous support since we opened our Las Colinas campus last April. Making this move will improve efficiency, collaboration and cost-competitiveness, while providing an exceptional work environment for our employees.” McKesson’s Las Colinas campus is already a key hub for the company. Employees at the North Texas location perform vital functions for the company in areas such as operations, information technology, finance and accounting, marketing and sales, administration and support, purchasing, and project management. As previously announced on April 25, 2018, McKesson launched a multi-year strategic growth initiative, inclusive of plans to optimize the company’s operating and cost structures. The company expects these initiatives and actions will generate approximately $300M-$400M in annual pre-tax gross savings that will be substantially realized by the end of Fiscal 2021.
https://thefly.com/landingPageNews.php?id=2830717

Amgen, UCB say FDA to review EVENITY


Amgen and UCB announced the U.S. Food and Drug Administration Bone, Reproductive and Urologic Drugs Advisory Committee, or BRUDAC, will review data supporting the Biologics License Application for EVENITY for the treatment of osteoporosis in postmenopausal women at high risk for fracture at a meeting on Jan. 16, 2019. “After a fracture, postmenopausal women with osteoporosis are five times more likely to fracture in the subsequent year, and these fractures can be life-changing. Yet these patients often remain undiagnosed and untreated and could benefit from a potential new bone forming therapy that has been shown to reduce their risk of fracture within the first year,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen. “We look forward to discussing the efficacy and safety data from our EVENITY clinical program with the members of the Committee.” “We are currently seeing a large gap in the management and treatment of osteoporosis, especially in the post-fracture setting, with an estimated 77 percent of women aged 67 or older remaining undiagnosed and untreated in the first six months after a fracture.4 This is a stark reminder of the need to improve post-fracture care and reduce the risk of future fractures,” said Dr. Pascale Richetta, head of bone and executive vice president, UCB. “We believe EVENITY has the potential to help postmenopausal women with osteoporosis who are at high risk for fracture, and we look forward to the interactions with the members of the Committee.”
https://thefly.com/landingPageNews.php?id=2830703

Akari Therapeutics ‘encouraged’ by new Coversin data


Akari Therapeutics announced recent developments and supporting data which underscore the differentiation of Coversin. “We are encouraged by new data that demonstrates the potential for improved patient comfort and ease of use. Alongside this focus on patient convenience we continue to develop Coversin as a differentiated treatment by means of its combined complement C5 and LTB4 inhibitory activity with early data readouts of our bullous pemphigoid and atopic keratoconjunctivitis trials expected in first quarter 2019,” said Clive Richardson, Interim Chief Executive Officer of Akari Therapeutics. New data showing Coversin can be concentrated to 150mg/ml at low viscosity validates the enhanced convenience of the auto-injector pen across Akari subcutaneous program – currently PNH, thrombotic microangiopathy and BP. New highly concentrated formulation with small volume and water-like viscosity allows ease of administration and increasing patient comfort. Single cartridge to contain seven days of dosing which is stable at room temperature allowing patients to carry drug with them. A second eculizumab-resistant patient with PNH has now received more than six months of Coversin therapy treatment. Resistant to eculizumab because of a known C5 polymorphism. Previously transfusion-dependent and has now been transfusion independent for five months. New pharmacokinetic data for PAS Coversin supports once weekly dosing. Preclinical data investigating the half-life of PAS Coversin in three species supports potential for once weekly dosing in man.
https://thefly.com/landingPageNews.php?id=2830707

Qiagen, NeoGenomics to accelerate diagnostics for cancer meds


Qiagen (QGEN) and (NEO) announced a master service agreement to accelerate the availability of companion diagnostics that enable precision medicine for cancer patients. The partnership between Qiagen and NeoGenomics, a provider of cancer-focused genetic testing services, will ensure day-one patient access to FDA-approved molecular tests paired with newly approved drugs for cancer. Building on the FDA’s modernized regulatory approach to advanced diagnostics, especially next-generation sequencing, or NGS, tests, the collaboration with NeoGenomics will allow Qiagen and pharmaceutical partners to streamline the development and launch of targeted drugs and companion diagnostics to guide treatment decisions. The partnership offers pathways leading to introduction of FDA-approved companion diagnostics simultaneously with launch of new therapies. Qiagen and NeoGenomics will discuss their efforts to expedite access for precision medicine solutions at the American Society of Hematology, or ASH.
https://thefly.com/landingPageNews.php?id=2830709

FDA authorizes Meridian Bioscience’s cytomegalovirus test


The U.S. Food and Drug Administration announced that it has permitted marketing of a new diagnostic test to aid in detecting a type of herpes virus called cytomegalovirus in newborns less than 21 days of age. The Alethia CMV Assay Test System is used as an aid in the diagnosis of congenital CMV infection by detecting CMV deoxyribonucleic acid from a saliva swab. The FDA granted marketing authorization of the Alethia CMV Assay Test System to Meridian Bioscience.
https://thefly.com/landingPageNews.php?id=2830701

Better bandage promotes powerful healing


A new device powered by energy harvested from the body’s natural motions accelerates wound healing by delivering gentle electric pulses to an injury site.
Credit: Sam Million-Weaver
A new, low-cost wound dressing developed by University of Wisconsin-Madison engineers could dramatically speed up healing in a surprising way.
The method leverages energy generated from a patient’s own body motions to apply gentle electrical pulses at the site of an injury.
In rodent tests, the dressings reduced healing times to a mere three days compared to nearly two weeks for the normal healing process.
“We were surprised to see such a fast recovery rate,” says Xudong Wang, a professor of materials science and engineering at UW-Madison. “We suspected that the devices would produce some effect, but the magnitude was much more than we expected.”
Wang and collaborators described their wound dressing method today (Nov. 29, 2018) in the journal ACS Nano.
Researchers have known for several decades that electricity can be beneficial for skin healing, but most electrotherapy units in use today require bulky electrical equipment and complicated wiring to deliver powerful jolts of electricity.
“Acute and chronic wounds represent a substantial burden in healthcare worldwide,” says collaborator Angela Gibson, professor of surgery at UW-Madison and a burn surgeon and director of wound healing services at UW Health. “The use of electrical stimulation in wound healing is uncommon.”
In contrast with existing methods, the new dressing is much more straightforward.
“Our device is as convenient as a bandage you put on your skin,” says Wang.
The new dressings consist of small electrodes for the injury site that are linked to a band holding energy-harvesting units called nanogenerators, which are looped around a wearer’s torso. The natural expansion and contraction of the wearer’s ribcage during breathing powers the nanogenerators, which deliver low-intensity electric pulses.
“The nature of these electrical pulses is similar to the way the body generates an internal electric field,” says Wang.
And, those low-power pulses won’t harm healthy tissue like traditional, high-power electrotherapy devices might.
In fact, the researchers showed that exposing cells to high-energy electrical pulses caused them to produce almost five times more reactive oxygen species — major risk factors for cancer and cellular aging — than did cells that were exposed to the nanogenerators.
Also a boon to healing: They determined that the low-power pulses boosted viability for a type of skin cell called fibroblasts, and exposure to the nanogenerator’s pulses encouraged fibroblasts to line up (a crucial step in wound healing) and produce more biochemical substances that promote tissue growth.
“These findings are very exciting,” says collaborator Weibo Cai, a professor of radiology at UW-Madison. “The detailed mechanisms will still need to be elucidated in future work.”
In that vein, the researchers aim to tease out precisely how the gentle pulses aid in healing. The scientists also plan to test the devices on pig skin, which closely mimics human tissue.
And, they are working to give the nanogenerators additional capabilities — tweaking their structure to allow for energy harvesting from small imperceptible twitches in the skin or the thrumming pulse of a heartbeat.
“The impressive results in this study represent an exciting new spin on electrical stimulation for many different wound types, given the simplicity of the design,” says Gibson, who will collaborate with the team to confirm the reproducibility of these results in human skin models.
If the team is successful, the devices could help solve a major challenge for modern medicine.
“We think our nanogenerator could be the most effective electrical stimulation approach for many therapeutic purposes,” says Wang.
And because the nanogenerators consist of relatively common materials, price won’t be an issue.
“I don’t think the cost will be much more than a regular bandage,” says Wang. “The device in itself is very simple and convenient to fabricate.”
This research was supported by grants from the National Institutes of Health (R01EB021336 and P30CA014520).
Story Source:
Materials provided by University of Wisconsin-Madison. Original written by Sam Million-Weaver. Note: Content may be edited for style and length.

Journal Reference:
  1. Yin Long, Hao Wei, Jun Li, Guang Yao, Bo Yu, Dalong Ni, Angela LF Gibson, Xiaoli Lan, Yadong Jiang, Weibo Cai, Xudong Wang. Effective Wound Healing Enabled by Discrete Alternative Electric Fields from Wearable NanogeneratorsACS Nano, 2018; DOI: 10.1021/acsnano.8b07038