Patient safety merits new review for modified medical devices, physician says

For patient safety, the U.S. Food and Drug Administration (FDA) should require that clinical data be submitted as part of a more rigorous re-evaluation of medical devices that are modified after approval, according to UC San Francisco physician scientists in a commentary published online March 24, 2014 in the Annals of Internal Medicine. According to authors Rita Redberg, MD, UCSF professor of medicine, and UCSF second-year medical student Sarah Zheng, such a requirement could prevent deaths due to insufficiently tested device modifications.

"The need for rapid approval of design improvements to marketed devices must be weighed against the possibility of introducing unknown risks to patient health from such modifications," the authors wrote in their commentary.

In addition, Redberg said, "A requirement that post-marketing clinical data, including adverse events, be collected and deposited into a public data base would allow for the best identification of patients who could benefit from a device, without slowing market entry."

The growing medical device industry is expected to generate $228 billion in sales by 2015 for technologies ranging from orthopedic knee replacements to cochlear implants, to infusion pumps. Many devices are invasively installed within the body, and the potential complications when they fail can be great.

Examples of avoidable outcomes, according to Redberg and Zheng, include hundreds of failures and five deaths arising from use of the modified Sprint Fidelis defibrillator electrical lead wire made by Medtronic, Inc., prompting a recall, and a similar recall of defibrillator leads marketed by St. Jude Medical, Inc., after 227,000 had been implanted in patients.

The FDA evaluates safety and effectiveness of new, high-risk medical devices before they are marketed, through a process known as premarket approval (PMA). This procedure involves the submission and review of clinical-trials data. However, modifications of existing devices may be approved without additional clinical data, through a less rigorous procedure called a PMA supplement.

"Companies often submit changes to a device one supplement at a time instead of submitting multiple changes in a single application," Redberg and Zheng stated in the commentary. "As a result, each submitted modification is evaluated separately, a process that makes it difficult, if not impossible, to take into account the cumulative effects and interactions of multiple modifications."

The Medtronic and St. Jude Medical devices were modified multiple times through PMA supplements without additional clinical data submission, the authors noted.

Clinicians may favor use of a device based on original research on a much earlier version, with no knowledge of substantial, untested modifications that have been made to the currently available device, they said.

The authors advocated for clear labeling of devices to highlight modifications to physicians and alert them to unevaluated risks.

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The above story is based on materials provided by University of California - San Francisco. The original article was written by Jeffrey Norris. Note: Materials may be edited for content and length.

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Robotic arm probes chemistry of 3-D objects by mass spectrometry

When life on Earth was first getting started, simple molecules bonded together into the precursors of modern genetic material. A catalyst would have been needed, but enzymes had not yet evolved. One theory is that the catalytic minerals on a meteorite's surface could have jump-started life's first chemical reactions. But scientists need a way to directly analyze these rough, irregularly shaped surfaces. A new robotic system at Georgia Tech's Center for Chemical Evolution could soon let scientists better simulate and analyze the chemical reactions of early Earth on the surface of real rocks to further test this theory.

In a proof-of-concept study, scientists selected a region for analysis on round or irregularly-shaped objects using a 3-D camera on a robotic arm, which mapped the 3-dimentional coordinates of the sample's surface. The scientists programmed the robotic arm to poke the sample with an acupuncture needle. The needle collected a small amount of material that the robot deposited in a nearby mass spectrometer, which is a powerful tool for determining a substance's chemical composition.

"You see the object on a monitor and then you can point and click and take a sample from a particular spot and the robot will go there," said Facundo Fernandez, a professor in the School of Chemistry and Biochemistry, whose lab led the study. "We're using an acupuncture needle that will touch very carefully on the surface of the object and then the robot will turn around and put the material inside of a high resolution mass spectrometer."

The research was published online February 28 in the journal Analyst, a publication of the Royal Society of Chemistry. The work was supported by a National Science Foundation (NSF) Major Research Instrumentation Program (MRI) grant and by the National Science Foundation (NSF) and NASA Astrobiology Program, under the NSF Center for Chemical Evolution.

Mass spectrometry is a powerful tool for analyzing surface chemistry or for identifying biological samples. It's widely used in research labs across many disciplines, but samples for analysis typically have to be cleaned, carefully prepared, and in the case of rocks, cut into thin, flat samples. The new robotic system is the first report of a 3-D mass spectrometry native surface imaging experiment.

"Other people have used an acupuncture needle to poke a sample and then put that in mass spec, but nobody has tried to do a systematic, three-dimensional surface experiment," Fernandez said. "We are trying to push the limits."

To show that the system was capable of probing a three-dimensional object, the researchers imprinted ink patterns on the surfaces of polystyrene spheres. The team then used the robotic arm to model the surfaces, probe specific regions, and see if samples collected were sufficient for mass spectrometry analysis. The researchers were able to detect inks of different colors and create a 3-D image of the object with sufficient sensitivity for their proof-of-principle setup, Fernandez said.

The research was the result of collaboration between Fernandez's group, which specializes in mass spectrometry, and Henrik Christensen's robotics group in the College of Computing. Christensen is the KUKA Chair of Robotics and a Distinguished Professor of Computing. He is also the executive director of the Institute for Robotics and Intelligent Machines (IRIM) at Georgia Tech.

"The initial findings of this study mark a significant step toward using robots for three-dimensional surface experiments on geological material," Christensen said. "We are using the repeatability and accuracy of robots to achieve new capabilities that have numerous applications in biomedical areas such as dermatology."

"It doesn't happen very often that a group in mass spectrometry will have a very talented robotics group next to them," Fernandez said. "If we tried to learn the robotics on our own it could take us a decade, but for them it's something that's not that difficult."

Christensen's team loaned a Kuka KR5 sixx R650 robot to Fernandez's lab for the study. Afterwards, Fernandez's lab purchased their own robot from Universal Robots. They have also upgraded to a new mass spectrometer capable of resolution nearly eight times higher than the one used in the study. They will soon begin replicating early Earth chemistry on rocks and analyzing the reaction products with their robotic sampling system.

"We really want to look at rocks," Fernandez said. "We want to do reactions on rocks and granites and meteorites and then see what can be produced on the surface."

The technology could also be applied to other research fields, Fernandez said. For example, the robot-mass spec combo might be useful to dermatologists who often probe lesions on the skin, which have distinct molecular signatures depending on if the lesion is a tumor or normal skin tissue.

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Cancer treatment revolution potential with new drug

A revolution in cancer treatment could soon be underway following a breakthrough that may lead to a dramatic improvement in cancer survival rates.

A new study at the University of Warwick, published today in the journal Angewandte Chemie International Edition, has developed a new drug that can manipulate the body's natural signalling and energy systems, allowing the body to attack and shut down cancerous cells.

Called ZL105, the drug is a compound based on the precious metal iridium. The study has found ZL105 could potentially replace currently used anticancer drugs, which become less effective over time, cause a wide-range of side-effects and damage healthy cells as well as cancerous.

Commenting on the breakthrough, University of Warwick researcher and study co-author Dr Isolda Romero-Canelon said "The energy-producing machinery in cancer cells works to the limit as it attempts to keep up with quick proliferation and invasion. This makes cancer cells susceptible to minor changes in the cell 'power-house'. Our drug pushes cancer cells over the limit causing them to slow and shut down, whilst normal cells can cope with its effects."

Preliminary data indicate that the novel drug may be ten times more effective in treating ovarian, colon, melanoma, renal, and some breast cancers, according to data obtained by the US National Cancer Institute. The researchers now aim to expand the study to cancers that are inherently resistant to existing drugs and to those which have developed resistance after a first round of chemotherapy treatments.

Study co-author Professor Peter J. Sadler said "Existing cancer treatments often become less effective after the first course, as cancer cells learn how they are being attacked. The drug we have developed is a catalyst and is active at low doses. It can attack cancer cells in multiple ways at the same time, so the cancer is less able to adapt to the treatment. This means the new drugs could be much more effective than existing treatments."

"Platinum-based drugs are used in nearly 50% of all chemotherapeutic regimens, exert their activity by damaging DNA and cannot select between cancerous and non-cancerous cells, leading to a wide-range of side-effects from renal failure to neurotoxicity, ototoxicity, nausea and vomiting.

"In contrast, the new iridium-based drug is specifically designed not to attack DNA, but to have a novel mechanism of action, meaning that it could not only dramatically slow down and halt cancer growth, but also significantly reduce the side effects suffered by patients" argues Professor Sadler.

This research could also lead to substantial improvements in cancer survival rates. "Current statistics indicate that one in every three people will develop some kind of cancer during their life time, moreover approximately one woman dies of ovarian cancer every two hours in the UK according to Cancer Research UK .It is clear that a new generation of drugs is necessary to save more lives and our research points to a highly effective way of defeating cancerous cells" said Dr Romero-Canelon.

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'Glue' holding together skin cells, other epithelial tissue more active than realized

The strong mechanical attachments -- the "glue" -- that hold together the cells of the skin and the other epithelial tissues of the body are the adherens junctions.

These junctions are responsible for maintaining the shape and integrity of the sheets of epithelial cells that line such body cavities as the digestive tract, as well as the surfaces of structures such as the heart. Defects in the proteins of these attachments have been implicated as potential contributors to the development and spread of cancer.

Recent research on Drosophila flies, combined with previous studies in cell cultures, are challenging the traditional view that adherens junctions maintain tissue integrity by passively resisting disruptive forces.

In studies with Drosophila embryos, the Princeton University lab of Nobel laureate Eric Wieschaus, Ph.D., has uncovered the first evidence in living organisms that adherens junctions actively respond to mechanical cues by remodeling their own position and intensity, which in turn restructures the cells.

Mo Weng, Ph.D., postdoctoral fellow in the lab, used live imaging and quantitative image analysis of fixed and live embryos to determine that these changes depend on mechanical force mediated by the motor protein myosin and precede the changes in the distribution of cell polarity proteins, such as Bazooka, that are responsible for spatial organization of the cells.

Understanding the regulation and functioning of adherens junctions sheds light on the organization of multi-cellularity -- from cell-cell contacts to the remodeling of tissues and organs during life.

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Fewer children at risk for deficient vitamin D

Under new guidelines from the Institute of Medicine, the estimated number of children who are at risk of having insufficient or deficient levels of vitamin D is drastically reduced from previous estimates, according to a Loyola University Chicago Stritch School of Medicine study.

The study, led by Holly Kramer, MD, MPH, and Ramon Durazo-Arvizu, PhD, is published online ahead of print in the Journal of Pediatric Endocrinology and Metabolism.

New Institute of Medicine guidelines say most people get sufficient vitamin D when their blood levels are at or above 20 nanograms per milliliter (ng/mL). The Pediatric Endocrine Society has a similar guideline. However, other guidelines recommend vitamin D levels above 30 ng/mL.

Loyola researchers studied vitamin D data from a nationally representative sample of 2,877 U.S. children and adolescents ages 6 to 18 who participated in the National Health and Nutrition Examination Survey.

The study found that under the Institute of Medicine guidelines, 10.3 percent of children ages 6 to 18 are at risk of inadequate or deficient vitamin D levels. (This translates to an estimated 5.5 million children.)

By comparison, a 2009 study in the journal Pediatrics, which defined sufficient vitamin D levels as greater than 30 ng/mL, found that an estimated 70 percent of people ages 1 to 21 had deficient or insufficient vitamin D levels.

Under previous guidelines, millions of children who had vitamin D levels between 20 and 30 ng/mL would have needed supplementation. Under the Institute of Medicine guidelines, children in this range no longer need to take vitamin D supplements.

The new study found that children at risk of vitamin D deficiency under the Institute of Medicine guidelines are more likely to be overweight, female, non-white and between the ages of 14 and 18.

The Institute of Medicine's new vitamin D guidelines are based on nearly 1,000 published studies and testimony from scientists and other experts. The IOM found that vitamin D is essential to avoid poor bone health, such as rickets. But there have been conflicting and mixed results in studies on whether vitamin D can also protect against cancer, heart disease, autoimmune diseases and diabetes. Moreover, excessive vitamin D can damage the kidneys and heart, the IOM found.

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Twenty-five percent of breast cancer survivors report financial decline due to treatment

Four years after being treated for breast cancer, a quarter of survivors say they are worse off financially, at least partly because of their treatment, according to a new study led by University of Michigan Comprehensive Cancer Center researchers. In addition, 12 percent reported that they still have medical debt from their treatment.

Financial decline varied significantly by race, with Spanish-speaking Latinas most likely to be impacted. Debt was reported more frequently in English-speaking Latinas and Blacks, the study found. Results appear in the Journal of Clinical Oncology.

"As oncologists, we are proud of the advances in our ability to cure an increasing proportion of patients diagnosed with breast cancer. But as treatments improve, we must ensure that we do not leave these patients in financial ruin because of our efforts," says study author Reshma Jagsi, M.D., D.Phil., associate professor of radiation oncology at the University of Michigan Medical School.

The researchers surveyed women in Detroit and Los Angeles who had been diagnosed with early stage breast cancer, based on data obtained from the National Cancer Institute's Surveillance, Epidemiology and End Results population-based registry. Women were surveyed about nine months after diagnosis and again about four years later, with 1,502 women responding to both surveys.

The surveys asked about patients' perceptions of whether they were worse off financially since their diagnosis, and whether that has caused long-term challenges. For example, patients were asked if they had altered their medical care because of financial concerns, by skipping medication or by missing a doctor's appointment or a mammogram. Other questions looked at broader hardships, such as going without health insurance, having utilities turned off or moving out of their home.

Blacks and English-speaking Latinas were more likely than Whites to have experienced one of these issues. Other factors that made a woman more likely to experience these hardships include age under 65, household income under $50,000, part-time work at diagnosis, reduced work hours after diagnosis, lack of substantial prescription drug coverage, breast cancer recurrence, and undergoing chemotherapy.

"These patients are particularly vulnerable to financial distress," Jagsi says. "We need to ensure appropriate communication between patients and their doctors regarding the financial implications of a cancer diagnosis and treatment decisions to help reduce this long-term burden."

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