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Invisible repair: Optical coherence tomography shows an artery immediately, six months, and two years after a stent is put in place. At six months, a small amount of tissue has created a bridge between two of the stent’s ribs; after two years, the bridge and the struts have largely disappeared.
Credit: Abbott

An absorbable coronary stent shows promise in early trials.

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Long gone: Imaged via ultrasound two years after surgery, this artery shows no trace of the bioabsorbable stent used to prop it open.
Credit: Abbott

MIT Technology Review, April 2, 2009, by By Lauren Gravitz — Coronary stents have revolutionized the treatment of heart disease, but they leave metal scaffolding inside arteries that can occasionally cause immune reactions and blood clots, and interfere with future surgeries. A new, fully absorbable stent could one day help prevent problems like these. The stent, made by Abbott Laboratories in Illinois, just finished its first test–a two-year trial involving 30 patients–and now, after a few adjustments, the company is launching its next phase of clinical tests.

Surgeons use stents to open blocked arteries, but the devices can cause complications. The materials used incite an immune response, and damage to the artery wall can trigger the formation of blood clots that, once dislodged, can cause stroke or other damage in a process called late stent thrombosis. Over the past few years, these complications have decreased with the widespread use of anticlotting therapies and drug eluting stents coated with immune suppressants. But some cardiologists still liken the use of metal stents to leaving a cast in place once a person’s broken limb has healed.

Abbott’s new bioabsorbable everolimus-eluting stent, or BVS, is made up of two layers of a biodegradable polymer: one that contains the immunosuppressant drug everolimus, the other forming a longer-lasting backbone. Over time, the body breaks down and absorbs the polymer, ultimately leaving nothing behind. For its initial test run, the stent was placed in patients with just a single narrowed or blocked artery. According to research published this month in The Lancet, the stent appeared to be almost completely absorbed after two years, with no instances of cardiac death, no known cases of stent thrombosis, and no evidence that the arteries had begun to re-narrow.

“It really looks like the stent did its job of stopping re-narrowing, it was safe, and it disappeared,” says John Ormiston, lead researcher of the Lancet study and an interventional cardiologist at Mercy and Auckland City Hospitals in New Zealand. “We have hope that the long-term chance of thrombosis will be very low.”

Because the stent was tested on so few people, however, and because those patients had very simple problems, it is difficult to know whether it will match the long-term success of its metal predecessors. “It certainly appears to work in patients with simple lesions, but it won’t get widespread use unless it works in more-complex patients,” Ormiston says.

“If you have a stent that’s bioabsorbable, could return a vessel to its native condition and protect it from late-stent thrombosis, that’s an inherently appealing concept, especially when you talk about the fact that we’re implanting about a million patients per year here in the U.S.,” says Gregg Stone, director of cardiovascular research and education at New York-Presbyterian Hospital and the Columbia University Medical Center.

“Phase A of the project was really a proof of concept, but I think the concept was very successful” says Stone, who is on Abbott’s BVS advisory board. “Why have a permanent, metallic prosthesis if you don’t have to?”

“I think it’s a wonderful concept,” says Frederic Resnic, the director of the Cardiac Catheterization Laboratory at Brigham and Women’s Hospital in Boston. “But the bar to prove that it is more than just a niche product is going to be very high, because you’re going to have to meet or exceed the results of 2009 drug-eluting stents, and it’s very hard to demonstrate that level of safety and efficacy.”

Abbott is not quite there yet. For a second trial, launching now, the company is using a slightly modified version of the earlier stent; it is easier to store (the first had to be kept at -20 degrees Celsius to prevent the polymer from cracking) and has slightly thicker, stronger struts to help maintain the arterial opening and better prevent re-narrowing. This trial will still be limited to patients with simple lesions and will be only slightly larger than the first, with planned enrollment of 80 people in Europe, Australia, and New Zealand.

Because metal stents have proven to be so effective, some question whether a bioabsorbable version is worth the research investment, especially since the bar to prove both safety and efficacy is set so high, and since there’s not yet proof that the disappearing stent doesn’t leave scarred tissue in its wake. But Ormiston and Stone point to the fact that their patients’ arteries appear to have restored elasticity and that eroding stents don’t prevent the branching-off of new vessels, unlike the metal ones. Plus, they note that patients often have to return for a second stent placement–if the first stent has been absorbed, it can’t get in the way of a second surgery.

These are all distant possibilities, however, and will remain so until patients with more-complex conditions have been treated successfully. “The current study is far from definitive from a clinical perspective,” Resnic says. “Large prospective clinical trials will be necessary to demonstrate that this bioabsorbable platform is as safe and effective as existing [and future iterations of] commercially available drug-eluting stents.” But, he adds: “if perfected, I believe it would naturally replace permanent metallic implants.”

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Improving EHRs: Isaac Kohane, top, and Kenneth Mandl say that the designers of electronic health records (EHRs) could learn something from the iPhone.
Credit: Bachrach Photography, Joon Lee

Open programs to third-party developers, say two tech-savvy physicians.

MIT Technology Review, April 2, 2009, by Emily Singer — Thanks to the $19 billion designated for health-care information technology in the recent stimulus bill, electronic health records (EHRs) have garnered a great deal of attention in the past few weeks. The bill sets aside $17 billion in incentives for physicians and hospitals that use qualifying EHRs beginning in 2011, and $2 billion for the development of standards and best-practice guidelines over the next two years.

The bill does little to specify the types of technology that health-care providers must use, leaving the details to a newly appointed national coordinator for health information technology. Given the amount of money at stake, both EHR vendors and the medical community are anxious to see exactly how these details will unfold over the next two years. In an article in the current issue of the New England Journal of Medicine, physicians Kenneth Mandl and Isaac Kohane outline their prescription for creating an effective EHR system. Their approach is modeled on successful IT products outside of health care, including the iPhone and Facebook, which rely on innovative applications from third-party programmers. Mandl and Kohane propose what they call a platform approach, in which EHR vendors sell a flexible, basic platform that is designed to work with components from other vendors, much as the iPhone works with applications made by a myriad of third-party developers.

Mandl and Kohane, both members of the Harvard/MIT Health Sciences and Technology Program at Children’s Hospital Boston, spoke with Technology Review about why their approach is crucial in digitizing health care.

Technology Review: Why should EHRs be more like the iPhone?

Isaac Kohane: On the iPhone, if you don’t like how an application does a particular task–managing a to-do list, for example–you can download one of ten other available task-management software systems. That’s because Apple created a market for third parties to create new applications. Consequently, better applications are being developed, creating a competitive market.

TR: How does that compare with health-care IT systems?

IK: The contrast is stark. Most existing programs are these big monolithic applications designed to solve all the challenges and tasks that developers conceived there to be at a hospital or doctor’s office. If the practitioner doesn’t like a specific thing, they can’t replace it. They either have to tough it out and deal with a system that doesn’t fit their needs, spend lots of money and more time with the vendor to customize the application, or throw out the whole system and start again. We know from the iPhone and Facebook and their widgets that this just isn’t necessary.

Kenneth Mandl: We have to assume that we don’t know what functionality we [will] want five years from now. We need to build a system that will evolve with our thinking, with our science, and with our health-care system.

TR: Would patients benefit from this kind of approach? Will we soon be able to view lots of different test results on our iPhones, for example?

IK: Yes! The platform model will greatly ease the ability for vendors of personal health records to offer connectivity or subscription services on hospital or practice platforms. This will accelerate access to the patient, including on the iPhone.

TR: What kind of third-party applications are you thinking about?

IK: Genetic testing in clinics has been available for more than 20 years, yet studies show that most doctors don’t know how to order and interpret such tests. Few EHRs support any genetic testing or interpretation of genetic tests. If you had a platform model, a number of companies, including some of the existing [direct-to-consumer] ones, could build applications to order tests and provide interpretation.

TR: The aim of the stimulus bill, obviously, is to stimulate the economy. Will this approach help?

IK: We see this as being stimulating to the economy, because it allows scores of companies to develop business plans around these applications. The basic platforms could be sold by existing vendors but be designed to load third-party applications. It would create a much larger ecosystem of competing, evolving health-care applications driven to meet the different niches of health-care practice. Urban and rural practices, for example, don’t need the same kind of support.

TR: Does the recent stimulus legislation move us in the right direction or the wrong direction?

IK: The legislation is not specific enough to endorse the platform approach or argue against it. The concern is that the money has to be spent awfully fast. If nothing particularly innovative is done soon, it’s the shovel-ready applications [which would likely closely resemble existing EHR programs] that will be implemented, and those are monolithic. We would argue that one of the most important things government could do is propose rapid adoption of a platform model that would allow third-party applications.

TR: Recent studies suggest that very few hospitals and physicians’ offices are using EHRs. How will that affect implementation efforts over the next two years?

KM: You can look at low adoption rates as a glass half empty or half full. The empty view is that we have not been successful in getting the technology out there. But we are looking at the glass as half full. There are lots of offices out there that are ready for something completely new.

Medscape.com, April 2, 2009, by Allison Gandey — Inadequate vitamin D may represent an underrecognized source of nociperception and impaired neuromuscular functioning, say researchers.

“Physicians who care for patients with chronic, diffuse pain that seems musculoskeletal — and involves many areas of tenderness to palpation — should strongly consider checking vitamin-D level,” Michael Turner, MD, from the Mayo Clinic in Rochester, Minnesota, said in a news release issued Friday.

“For example,” he added, “many patients who have been labeled with fibromyalgia are, in fact, suffering from symptomatic vitamin-D inadequacy. Vigilance is especially required when risk factors are present, such as obesity, darker pigmented skin, or limited exposure to sunlight.”

Dr. Turner was lead investigator of a study published in the journal Pain Medicine in November 2008. The work suggests a correlation between inadequate vitamin-D levels and the amount of narcotic medication taken by chronic pain patients.

Required Nearly Twice As Much Pain Medication

The researchers found that patients who had inadequate vitamin-D levels and required narcotic pain medication were taking much higher doses — nearly twice as much — as those with adequate levels. These patients also reported worse physical function and worse overall health perception.

Dr. Turner told Medscape Neurology & Neurosurgery his group was surprised by the finding. “We didn’t anticipate that the difference would be so high.”

The investigators retrospectively studied 267 patients admitted to the Mayo Comprehensive Pain Rehabilitation Center. They compared serum 25-hydroxyvitamin-D levels at the time of admission with other parameters such as the amount and duration of narcotic pain medication used, self-reported levels of pain, emotional distress, physical functioning, health perception, and demographic information such as sex, age, diagnosis, and body-mass index.

Patients with vitamin-D levels below 20 ng/mL were considered to have inadequate amounts. The prevalence of low vitamin D was 26% (95% CI, 20.6% – 31.1%).

Among patients using opioids, the mean morphine-equivalent dose for the inadequate vitamin-D group was 133.5 mg/day compared with 70.0 mg/day for the adequate group (P = .001). The mean duration of opioid use for the inadequate and adequate groups was 71.1 months and 43.8 months, respectively (P = .023).

The researchers also observed a link between increasing body-mass index and decreasing levels of vitamin D.

Inadequate Vitamin D May Create or Sustain Pain

The preliminary results suggest that inadequate vitamin D may play a role in creating or sustaining chronic pain. During an interview, Dr. Turner suggested that patients with inadequate vitamin D may benefit from cholecalciferol 50,000 international units dosed according to the level of deficiency.

But he urged caution for patients with calcium- or phosphate-processing disorders. “Increasing vitamin-D levels could be problematic in patients with kidney failure or stones or primary hyperparathyroidism or sarcoidosis. This doesn’t preclude increasing levels, but it might warrant discussion with an endocrinologist,” he said.

For patients with adequate vitamin D looking to maintain levels, he recommends10 to 15 minutes of sun exposure with no sunscreen on the trunk and arms and legs 3 times a week.

Sun Exposure or Diet and Supplements?

It is a recommendation often made by proponents of vitamin D but hotly contested by the American Academy of Dermatology. The academy recommends that vitamin D be obtained from a healthy diet and supplements and not from unprotected exposure to ultraviolet (UV) radiation.

“Unprotected UV exposure to the sun or indoor tanning devices is a known risk factor for the development of skin cancer,” dermatologists write in the academy’s position statement.

Dr. Turner and his team conclude: “Prospective trials utilizing a repeated-measures design are warranted to assess the effects of vitamin-D repletion on pain outcomes and physiological measures of neuromuscular functioning among patients with chronic pain and comorbid vitamin-D inadequacy.”

The researchers have disclosed no relevant financial relationships.

………………………………………

Prevalence and clinical correlates of vitamin D inadequacy among patients with chronic pain.

Turner MK, Hooten WM, Schmidt JE, Kerkvliet JL, Townsend CO, Bruce BK.

Department of Physical Medicine and Rehabilitation, Mayo Graduate School of Medicine, Rochester, Minnesota 55905, USA.

OBJECTIVE: Vitamin D inadequacy is associated with medication refractory musculoskeletal pain and neuromuscular dysfunction. This vitamin deficiency could subsist as an unrecognized comorbid condition among patients with chronic pain. The primary objective of this study was to determine the prevalence and clinical correlates of vitamin D inadequacy in patients seeking treatment for chronic pain. DESIGN: Retrospective case series. SETTING: Multidisciplinary pain rehabilitation center at a tertiary referral medical center. PATIENTS: The study involved 267 chronic pain patients admitted from February to December 2006. INTERVENTION: Serum 25-hydroxyvitamin D (25[OH]D) was drawn at admission. OUTCOME MEASURES: Patients with serum 25[OH]D levels < or=20 ng/mL were considered to have inadequate levels and those with levels >20 ng/mL were considered to have adequate levels. Upon admission, opioid intake was documented and patients completed the Short Form-36 Health Status Questionnaire. RESULTS: The prevalence of vitamin D inadequacy was 26% (95% confidence interval, 20.6-31.1%). Among patients using opioids, the mean morphine equivalent dose for the inadequate vitamin D group was 133.5 mg/day compared with 70.0 mg/day for the adequate group (P = 0.001). The mean duration of opioid use for the inadequate and adequate groups were 71.1 months and 43.8 months, respectively (P = 0.023). Opioid users with inadequate levels reported worse physical functioning (P = 0.041) and health perception (P = 0.003) than opioid users with adequate levels. CONCLUSION: The prevalence and clinical correlates identified in this pilot study provide the basis for the assertion that vitamin D inadequacy may represent an under-recognized source of nociception and impaired neuromuscular functioning among patients with chronic pain.

The New York Times, April 1, 2009, by John Markoff, MENLO PARK, Calif. — Members of an informal global alliance of computer security specialists who have been trying to eradicate a malicious software program known as Conficker said Tuesday that they were seeing early attempts by the program to communicate with a control server. The researchers said they were uncertain if it had been successful.

The Conficker software, which has spread aggressively around the globe since October and is designed to lash together infected machines into a powerful computer known as a botnet, has touched off widespread concern.

Computer security researchers who have examined a recent version of the program, called Conficker C, have said it was set to try to download commands from a server at an unknown Internet location on Wednesday. There was no certainty about the intent of the program, which could be used to send e-mail spam, distribute malicious software or generate a potentially devastating “denial of service” attack on Web sites or networks.

The choice of April Fool’s Day by the program’s authors, who are unknown, has led to speculation that the program might be a hoax. But a variety of computer security executives and law enforcement officials have pointed out that the program, which has spread to at least 12 million computers, could inflict genuine harm. Consensus among security specialists on Tuesday was that it was likely to take several days before the program’s intent could be determined.

A group of computer security specialists has tried to make it impossible for Conficker’s authors to download instructions to infected computers. While they were doing so, the authors began distributing the C version of the program. It was intended to begin contacting 50,000 Internet domains on Wednesday.

In response, the researchers have created a system that will allow them to trap all of the attempted botnet communications. That has involved a global effort, including monitoring the domains of 110 countries.

A spokeswoman for the Conficker Cabal, a security working group organized by Microsoft and other computer security companies, said on Tuesday that the group had no new information to report about the activity of the malicious program.

“All we are saying is ‘patch and clean, patch and clean,’ ” said Nicole Miller, a Microsoft spokeswoman, referring to the process of disinfecting and protecting machines infected by the software, which targets Windows-based computers.

Separately, I.B.M. said that Mark Yason, a company researcher, had decoded Conficker’s internal communication protocol. The company said that will make it easier for security teams to detect and interrupt the program’s activities.

Earlier this year Microsoft offered a $250,000 reward for information leading to the arrest of Conficker’s author or authors.