Engineers and physiologists at Northwestern University in Chicago developed an algorithm to improve the way health and wellness apps on smartphones track a user’s physical movements. Professor of physical medicine and rehabilitation Konrad Kording, with colleagues Stephen Antos and Mark Albert, published an advance version of their findings online in the Journal of Neuroscience Methods (paid subscription required).
The Northwestern team tackled the problem of smartphone users carrying their phones in different places during the day, depending on their activity at the time or what they’re wearing. The place owners carry their phones, however, can have an impact on the effectiveness of health and wellness apps that use built-in accelerometers for tracking physical activity.
In the study, researchers asked 12 healthy volunteers to carry a smartphone with an activity tracking app in designated carrying places (e.g. belt, pocket, or purse), while engaging in specified activities. The data were collected to highlight the variations in recording physical activity among those conditions second-by-second during the day. That same method was used to record physical activity with smartphones by two people with Parkinson’s disease.
The data collected were used to construct an algorithm to adjust the apps readings for different phone-carrying locations and activities. That algorithm is based on a hidden Markov model, a statistical technique used to associate heterogeneous sources with specified outcomes; “hidden” in this case refers to the changes from one state or condition to another, not the properties of the model.
Tests of the algorithm show it can help improve activity tracking of healthy individuals, and has the potential at least, to be used with Parkinson’s patients. “I believe we will have apps running on smart phones,” says Kording in a university statement, “that will know exactly what we’re doing activity-wise and will warn us of diseases before we even know that we have those diseases.”
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(National Institutes of Health)
A psychologist at University of Missouri in Columbia found the design of software used by physicians influences their choice of diagnostic tests when admitting new patients to hospitals, with implications for the quality of patient care and health care costs. Victoria Shaffer in Missouri’s Department of Health Sciences, with Adam Probst from Baylor Scott & White health system and Raymond Chan from Children’s Mercy Hospitals and Clinics in Kansas City, published their findings in a recent issue of the journal Health Psychology (paid subscription required).
Shaffer and colleagues investigated the way physicians interact with electronic health systems, specifically when ordering lab tests, in this case for pediatric patients at the time of their admission to a hospital. The study examined three ways software often used in the admissions process automatically presents the choice of tests to physicians:
- Opt-in, where no tests are selected, and the admitting physician must choose one or more tests from a list.
- Opt-out, where all test choices are marked, and the physician must turn off the selections not considered relevant.
- Expert recommendations, where a few tests are pre-selected based on judgments of experts in pediatrics.
In the study, 72 providers at a pediatric hospital were asked to review six fictitious cases, with two cases randomly assigned to each type of software design, and the order of the cases varied each time.
The results show the clinicians using software with the opt-out design ordered three more lab tests on average than their medical colleagues using opt-in or expert-recommendations software. Physicians using the expert-recommendations design, however, ordered more tests than colleagues ordering tests with the opt-in system.
The way lab tests are chosen with software, says Shaffer and associates, has financial impacts. They estimate that the opt-out design with all choices pre-selected as the default adds an extra $71 in costs per patient. The expert-recommendations design with just a few pre-set choices may result in fewer tests selected, but also the need to get experts to agree on the recommended choices, which also adds costs to the software.
The results indicate, however, that having at least some pre-set selections increases the likelihood tests recommnded by pediatric experts would be selected. “Essentially we found that including default selections, either with the opt-out method or the recommended method,” says Shaffer in a university statement, “increased the quality of lab tests the clinicians ordered. That is, clinicians ordered more tests recommended by pediatric experts with these methods.”
Shaffer believes software can be better designed if the IT experts and end-users — this case, medical professionals — work together more in the design process. “A wide variety of methods exist that could improve medical lab test ordering software,” notes Shaffer, “and would ensure that only the most appropriate, relevant lab tests for patients are ordered while saving money in the long run.”
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Lymphocyte (National Cancer Institute)
The U.S. Food and Drug Administration on Friday approved an antibody designed to treat chronic lymphocytic leukemia, when taken with chemotherapy. Obinutuzumabm — developed and marketed as the brand name Gazyva by the biotechnology company Genentech, a division of Roche in South San Francisco, California — is the first drug designated as a breakthrough therapy approved by FDA.
Chronic lymphocytic leukemia is a cancer of the blood and bone marrow, where blood stem cells become abnormal white blood cells or lymphocytes that do not adequately fight infection. The growth of these abnormal lymphocytes, also known as leukemia cells, usually happens slowly and crowds out healthy blood cells, leading to easier bleeding, infections, and anemia.
National Cancer Institute says chronic lymphocytic leukemia is the second most common form of leukemia, expected to strike some 15,700 people in the U.S. in 2013, causing nearly 4,600 deaths. The disease occurs most often among middle age or older adults.
Gazyva is an engineered antibody designed to target a marker called CD20 on the surface of leukemia cells that attacks leukemia cells at that marker. The antibody also works by recruiting the body’s remaining healthy immune system cells to attack leukemia cells at the CD20 marker.
FDA based its approval on a late-stage clinical trial of 356 participants with untreated chronic lymphocytic leukemia that tested Gazyva taken with the chemotherapy drug chlorambucil (marketed as Leukeran by GlaxoSmithKline) compared to chlorambucil given alone. Patients receiving Gazyva and chlorambucil had an average progression-free survival of 23 months, compared to 11 months for chlorambucil alone.
Likewise, says Genentech, three-quarters (76%) of the trial participants receiving Gazyva and chlorambucil responded to the drugs, compared to about a third (32%) responding to chlorambucil alone. Some 28 percent of the patients receiving Gazyva and chlorambucil responded completely — showing no evidence of cancer — for a period of time compared to about 1 percent for patients receiving chlorambucil alone.
The most common adverse events from Gazyva were reactions to the injections (chlorambucil is an oral drug), low platelet counts, and low counts of some white blood cells, although infection rates were not higher among the patients receiving Gazyva. The company plans to report more results from the same clinical trial also testing Gazyva with other engineered antibodies, at a meeting of the American Society of Hematology in December.
FDA designated Gazyva a breakthrough therapy in May 2013. A breakthrough therapy is granted to treatments that address serious conditions and have at least preliminary evidence showing the drug is a substantial improvement over current therapies on at least one clinical outcome. The agency says it is the first approval granted to a breakthrough-designated drug or biologic.
FDA also granted priority review to the therapy in July 2013, which is given to new drugs or biologics that offer significant improvements in safety or effectiveness in treating, preventing, or diagnosing disorders compared to those currently in practice. In addition, FDA designated Gazyva an orphan product, since it treats a rare disease.
Hat tip: FirstWord Pharma
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(Yale School of Medicine/Wikimedia Commons)
A new challenge on InnoCentive is looking for new ways to encourage physicians to prescribe anticoagulant drugs other than the commonly used warfarin for decreasing the formation of blood clots in people with atrial fibrillation. The competition has a total purse of $7,500 and a deadline of 27 November 2013.
InnoCentive in Waltham, Massachusetts conducts open-innovation, crowd-sourcing competitions for corporate and organization sponsors. The sponsor of this competition, however, is not disclosed. InnoCentive calls this kind of competition an ideation challenge that requires a written proposal typically of about two pages.
Atrial fibrillation is the most common form of irregular heartbeat, where rapid and disorganized signals cause the upper part of the heart, the atria, to contract very fast and irregularly. As a result, blood is not pumped completely into the the bottom part of the heart, the ventricles, and pools in the atria. The lack of proper blood flow raises the risk of clots forming, causing stroke or heart failure.
Warfarin, marketed under the brand names Coumadin and Jantoven, is a medication prescribed to decrease the body’s ability to form blood clots by blocking the formation of clotting factors based on vitamin K, which also prevents bleeding. While warfarin decreases the blood’s tendency to clot, it does not completely stop clotting. As a result, patients taking warfarin have their blood tested regularly to measure the time needed for blood to clot, and to keep that time within an acceptable target range.
Warfarin has other shortcomings, including an extended time needed for the drug to take effect, numerous food and drug interactions, and higher incidents of internal bleeding. Because of these shortcomings, other anticoagulants that target other coagulation factors, recently entered the U.S. market: dabigatran (Pradaxa, made by Boehringer Ingelheim), rivaroxaban (Xarelto, by Bayer HealthCare and Janssen Research & Development, a division of Johnson & Johnson), and apixaban (Eliquis by Pfizer and Bristol-Myers Squibb).
In this challenge, the sponsor is seeking new ways of modifying the customary behavior of prescribing warfarin for atrial fibrillation, and switching to the new anticoagulants. The sponsor is particularly interested in a new strategy to help physicians better understand the problems with warfarin, and advantages to patients of the newer alternatives.
Ideation challenges, says InnoCentive, are used to generate new ideas, something like an extended brain-storming session to find a breakthrough solution. Participants in an ideation challenge may submit to the competition ideas of their own, ideas from others to which the contestants have rights to submit and authority to convey to the sponsor, or ideas in the public domain with no restrictions. Confidential information should not be revealed in proposals.
The total purse for the challenge is $7,500 with at least one award no smaller than $5,000 and no individual awards any less than $1,000. The sponsor will review the entries and notify participants of the status of their proposals.
By participating in the challenge, contestants are granting to the sponsor a royalty-free, perpetual, and non-exclusive license to use any information included in their proposals.
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Emery Brown (Mass. Institute of Technology)
Engineers at Massachusetts Institute of Technology and medical researchers at Massachusetts General Hospital in Boston developed and tested in lab animals a system connecting the brain to a drug infusion device that automatically controls anesthesia drugs administered to patients in a drug-induced coma. The team led by MIT engineering professor Emery Brown, who is also on the faculty at Harvard Medical School, describe their system online in yesterday’s issue of the journal PLoS Computational Biology.
In some cases of traumatic brain injury, patient are placed in a drug-induced coma to allow swelling in the brain to subside and give time for healing. During that time, the patient must be continuously monitored to keep the brain at the proper level of sedation, which with current technology requires frequent checks and adjustments by trained staff, for hours or sometimes days at a time.
Emery and colleagues previously analyzed electrical waves generated by the brain and measured by an electroencephalogram (EEG) during various states, such as when awake, asleep, or under anesthesia. When in a medically-induced coma, the patient’s brain is quiet for several seconds, followed by short bursts of energy, and staff monitoring the patient need to control the flow of anesthesia drugs in response to the EEG readings to minimize these energy bursts.
While anesthesiologists regularly use computerized equipment, there is no system yet approved by FDA to completely control the administration of anesthesia drugs based on the patient’s brain activity. The MIT/Mass. General team aimed to fill that gap by providing the ability to both monitor EEG activity and control the anesthesia.
The system is based on a connection between the brain, monitored by an EEG, and a drug infusion pump, controlled by algorithms on a computer that adjust the flow of the drug propofol at a precise target level of activity. The connection makes it possible to change drug flow second-by-second to keep it within those target levels.
The MIT/Mass. General team tested the system with rodents, first determining individual target levels for each tested rodent, then inducing and maintaining comas in each animal. The researchers report a performance error for the brain-machine interface of 3.6 percent.
The system can quickly increase the depth of the coma if needed, which the researchers say would be impossible for a human monitor to do accurately. An administrator can also program the controller to bring out a patient from a comatose state, if needed by doctors to perform tests.
Brown says a system of this kind could make it possible to maintain a medically-induced coma with lower doses of anesthetic drugs and reduce the need for constant monitoring by trained nurses, with benefits for overall staffing at hospital intensive care units. “We’re now in discussions with the FDA for approval to start testing this in patients,” says Brown in a Mass. General statement. Mass. General also applied for a patent on the technology.
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(National Institute on Aging, NIH)
Myelin Repair Foundation in Saratoga, California is collaborating with drug development company Bionure Inc. in Barcelona, Spain to evaluate Bionure’s compound BN201 as a therapy candidate for multiple sclerosis. Financial aspects of the agreement were not disclosed.
Multiple sclerosis is a condition where the immune system attacks the central nervous system and damages the fatty, protective substance around nerve fibers known as myelin, as well as nerve cells themselves. Scar tissue from the damaged myelin, known as sclerosis, distorts the nerve signals sent to and from the brain and spinal cord, causing symptoms ranging from mild numbness to loss of vision or paralysis.
Bionure develops therapies for multiple sclerosis and other neurological disorders, by licensing research discoveries from university and research institute labs, and devising candidates through preclinical and early clinical stages. The company says it uses technologies such as systems biology and combinatorial chemistry to discover promising compounds and non-animal lab models for initial testing.
BN201 is a compound developed at Bionure as a potential treatment for acute optic neuritis associated with multiple sclerosis and severe relapses of the disorder. Optic neuritis is inflammation of the optic nerve that transmits visual information from the eye to the brain, leading to pain and temporary vision loss, and is considered an indicator of multiple sclerosis.
Myelin Repair Foundation will evaluate BN201′s capabilities to protect nerve fibers and encourage the restoration of myelin lost as a result of multiple sclerosis. The foundation is expected to test BN201 in its Translational Medicine Center lab, which opened in 2012. Work at the lab, says the foundation, is designed to ensure consistent cell cultures, assays, animal models, and human test tissue to improve the odds of successful clinical trials.
In August, Myelin Repair Foundation began a collaboration with biopharmaceutical company Gencia Corp. in Charlottesville, Virginia to evaluate its candidates for myelin repair. Gencia develops biologics and small molecule compounds to treat disorders of the central nervous system, as well as diseases related to inflammation and genetic disorders.
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Suzanne Ildstad (University of Louisville)
The global pharmaceutical company Novartis, based in Switzerland, is licensing research conducted at University of Louisville to help transplant patients better tolerate donated kidneys. Financial aspects of the agreement between Novartis and the Louisville biotechnology company Regenerex LLC, the original licensee and completed last month, were not disclosed. Regenerex is the company founded by Suzanne Ildstad, the Louisville faculty member who led the research.
The agreement provides Novartis with an exclusive global license to Regenerex’s facilitating cell therapy platform, as well as further collaboration between Novartis, Regenerx, and the university’s Institute for Cellular Therapeutics, where Ildstad serves as director.
With facilitating cell therapy, the kidney donor also provides blood-forming bone marrow stem cells that are enriched and processed to better help the recipient’s immune system accept the donor kidney. The recipient also undergoes radiation and chemotherapy to temporarily suppress his or her bone marrow, making room for the donated facilitating cells.
After the donated kidney is transplanted, the donor’s enriched stem cells are grafted into the recipient’s bone marrow, to create a greater tolerance in the recipient’s immune system for the donated tissue. That tolerance makes it possible for the recipient to decrease the need for anti-rejection drugs.
An early-stage clinical trial of the technique reported last year showed five of eight test recipients were able to reduce and finally end their taking of all immunosuppression drugs after one year. An intermediate-stage trial aiming to enroll 30 patients in Louisville and at Northwestern Memorial Hospital in Chicago is now recruiting participants.
Novartis’s interest in facilitating cell therapy extends beyond kidney transplants, with potential applications to its cell therapies for acute lymphoblastic and chronic lymphocytic leukemia, as well as expanding the benefits of umbilical cord blood stem cells. In addition, Regenerex is developing therapies for sickle cell disease, supported by Small Business Technology Transfer grants from National Institutes of Health.
Ildstad joined the Louisville faculty in 1998, under Kentucky’s Bucks for Brains program that aims to generate economic activity from university research. Under Bucks for Brains — officially known as the Research Challenge Trust Fund — state funds are matched by private donations. Since 1998, Kentucky’s legislature appropriated some $400 million to the program, with one-third of that amount allocated to University of Louisville.
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E coli bacteria magnified (USDA Agricultural Research Service/Wikimedia Commons)
Researchers at University of Copenhagen in Denmark and University of British Columbia in Canada developed and tested in the lab a substance they say quickly and effectively kills multiple types of bacteria, including those resistant to current antibiotics. The team led by Copenhagen’s Henrik Franzyk and UBC’s Robert Hancock published their findings last week in the journal Chemistry & Biology (paid subscription required).
The new substance, called host defense peptidomimetic 4 or HDM-4 is generated from natural antimicrobial peptides in the body, formed as part of the human immune system. Lead author and doctoral candidate Rasmus Jahnsen worked on optimizing this type of antibacterial substance to develop a new class of antibiotics.
Jahnsen, in a University of Copenhagen statement, says the peptide both kills bacteria and supports the body’s natural immune defenses against infection. “The killing mechanism involves destabilizing the bacterial membrane and binding onto the bacteria’s DNA, which in both cases results in the death of the bacteria,” says Jahnsen. “We have also shown that the substance can activate the human body’s own immune cells, strengthening its defense against bacteria during infection.”
In tests with lab cultures, the researchers found HDM-4 exhibited lethal antibacterial power against E. coli and other gram-negative bacteria, the kind of microbe causing pneumonia, blood stream, and surgical site infections in health care settings. HDM-4 was also effective in killing biofilms, collections of bacteria that form complex communities. Because of its ability to both penetrate the bacteria and attack its DNA suggests HDM-4 would less likely lead to a resistant form than a traditional single-target antibiotic.
The published research, Jahnsen notes, represents early-stage lab tests and more work lies ahead. “We hope that in collaboration with partners we can conduct a series of tests in the near future to show that the substance can actually combat an infection in a mammal,” he says. “If we achieve the same results in animals, we will have a potential sensation on our hands.”
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Timothy Platts-Mills (UNC-Chapel Hill)
Medical researchers at University of North Carolina in Chapel Hill found some three in 10 clinical trials having 500 or more participants remain unpublished, with results from the vast majority of unpublished studies not made available on ClinicalTrials.gov, the U.S. government’s database. Findings from the team led by emergency medicine professor Timothy Platts-Mills were reported online in the British Medical Journal.
ClinicalTrials.gov is the largest registry of clinical studies with more than 154,000 entries from 185 countries. The database was established in 1997 and is maintained by National Library of Medicine at National Institutes of Health (NIH). Trial sponsors are required by the 1997 law to register their studies with the site, which sponsors then update as the studies proceed. In 2007, Congress expanded ClinicalTrials.gov’s functions, requiring trial sponsors to submit summary results, with penalties ranging from withholding of NIH grant funding to fines of $10,000 a day.
Platts-Mills and colleagues searched clinical studies listed in ClinicalTrials.gov for studies registered prior to January 2009, with a planned or actual enrollment of 500 or more participants — an arbitrary number, but one for which a study would be considered beyond the pilot stage. The researchers also focused on randomized trials, where participants are assigned at random to different test or control groups, since results of studies conducted under these conditions would more likely meet journals’ criteria for publication.
The team then searched three databases of research publications — PubMed, Google Scholar, and Embase — between April and November 2012 to find published studies with results of clinical trials. The returns from the publications search with clinical trial data were then compared to the results of the ClinicalTrials.gov search.
The Chapel Hill team found 585 registered randomized clinical trials with 500 or more participants, about three-quarters of which (77%) were late-stage or post-marketing trials, with a total planned or actual enrollment of more than 990,000. Of those 585 studies, 171 or about three in 10 (29%) did not have published results. The non-published studies enrolled nearly 300,000 participants.
About one-third (32%) of the industry-funded trials were among those where results were not published, compared to less than two in 10 (18%) of the studies financed by government or other sources. Of the 171 non-published trials, the vast majority — 133 or 78 percent — had no results posted on ClinicalTrials.gov.
Legal requirements aside, the researchers say sponsors of clinical trials have an ethical obligation to publish the results of their studies. This principle is embodied in the US Federal Policy for the Protection of Human Subjects, also known as the Common Rule. “A substantial number of study participants,” say the authors, “were exposed to the risks of trial participation without the societal benefits that accompany the dissemination of trial results.”
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H1N1 virus (U.S. Centers for Disease Control)
NanoBio Corporation in Ann Arbor, Michigan received a new contract from National Institute of Allergy and Infectious Diseases, part of National Institutes of Health, for development of a pandemic influenza vaccine and adjuvant to boost the immune response of that vaccine. The initial contract value is $5.5 million, but the company says it would be eligible for another $5 million if all options under the contract are exercised.
NanBio is a spin-off company from the University of Michigan Nanotechnology Institute for Medicine and Biological Sciences, founded in 2000. The company develops anti-infection compounds and vaccines using its technology that creates oil-in-water emulsions of nanoscale (150 to 400 nanometer) droplets, stabilized with surfactants. The nanoscale emulsions, says the company, can quickly penetrate skin pores and hair shafts to fight infections, or in this case, boost a flu vaccine’s potency.
Funds from this contract will be used for research and development on NanBio’s NanoVax-Panflu product that combines an engineered antigen producing antibodies targeting pandemic influenza with a nano-emulsion adjuvant to boost the immune response of the antigen. The company says this vaccine, administered as a nasal spray, has the potential for protecting against infection both on mucus membranes (e.g., in the nose) and the overall immune system.
The contract, says the company, includes an option to extend the R&D effort to a nanoscale emulsion adjuvant for a vaccine for HIV infections. The option would cover a test of engineered virus-like particles resembling HIV combined with nano-emulsion adjuvant.
In a statement, NanBio’s CEO David Peralta says the company recently completed studies of vaccines enhanced with nano-emulsion (NE) adjuvants for respiratory syncytial virus that affects the lungs and respiratory tract, as well as type 2 genital herpes, viruses that both enter the body through mucosal sites. “The results of these studies,” says Peralta, “very clearly demonstrate the ability of the NE adjuvant to elicit mucosal immunity and the important role this type of immunity plays in protecting against disease.”
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