Rox Medical’s Coupler Device Shows Promise for Treatment-Resistant Hypertension

Experts claim a new medical device which resembles a twisted paper clip could potentially save the lives of those at greatest risk from stroke, heart attacks and heart failure.

Inserted into the groin, the device controls and lowers the blood pressure of even the most hard-to-treat patients. The coupler creates a chamber between the artery and the vein in the upper thigh which appears to help lower resistance and bring blood pressure down.

According to a report published in the medical journal, The Lancet, the device was effective in two thirds of cases during a study of 83 patients.

It found that those who received the device experienced an immediate reduction in blood pressure; however, one third also developed swelling in their leg which needed treatment.

In the UK, high blood pressure affects one in three adults, creating strain on the vessels carrying blood around the body, and causing them to become clogged up or to weaken. Ultimately, this can lead to significant damage to the heart or brain and can result in death.

One in 20 of those affected suffer from resistant hypertension, which does not respond to medication.

The study, led by researchers Queen Mary University of London and funded by the manufacturers, ROX Medical in California, tested the device on 42 patients with high blood pressure which had not responded to at least three types of drug intervention.

They compared the effects with 35 patients who were given the standard treatment for uncontrolled high blood pressure.

The study found “significant reductions in blood pressure” in the group fitted with the device six months after it was implanted, with fewer hypertensive complications and fewer hospital admissions for high blood pressure emergencies. This cohort of patients were also able to reduce their medication.

However, the device did have some side-effects. In almost a third of patients (29%) swelling developed in the leg in which the coupler was inserted, resulting in the need for another procedure to insert a stent in the vein.

Lead author Dr Melvin Lobo, from Queen Mary University of London, acknowledged there was more to learn about the device:

“We need more research to explore the long-term effects of the coupler, better understand its safety and understand more about how it works within the body.

“We must find better means of treating high blood pressure as drugs do not work for everyone and the coupler is a big step forward in our search for alternative treatment.”

Prof Tom MacDonald, president of the British Hypertension Society, and professor of clinical pharmacology at the University of Dundee, said the device could be “a fantastic thing for patients”.

“It’s another potentially great advance in the treatment of hypertension. It’s not without its problems, but the beauty of it is you can reverse it, and it can be given to people on top of hypertension medication.

“We now need more rigorously controlled studies and a definitive trial before it can be funded for the NHS.”

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Supra-annular design maximizes blood flow. In a comparison, CoreValve has a larger potential orifice area when implanted in a degenerative surgical bioprosthesis.

Best Degree of Oversizing Varies by TAVR Device

Different degrees of oversizing result in varying outcomes between balloon-expandable and self-expanding TAVR devices, shows an observational study published online April 2, 2015, ahead of print in Catheterization and Cardiovascular Interventions.

Although the findings are “simply hypothesis generating,” study coauthor Jonathon Leipsic, MD, of St. Paul’s Hospital (Vancouver, Canada), told TCTMD in an email, they “should at least make operators pause and think about which device may be suited for a given patient’s anatomy and annular geometry.”

Dr. Leipsic and colleagues looked at 368 patients treated at 3 experienced TAVR centers who had undergone 3-dimensional multidetector CT to evaluate annulus geometry, including short and long diameter, annulus perimeter, and area. One-year follow-up was available for 78% of patients.

Patients were assigned to 2 groups based on whether their annular size would only allow for:

• Moderate oversizing (n = 190): 5%-20% by area or 2.5%-9.5% by perimeter, described by the researchers as the favorable Sapien XT (Edwards Lifesciences) zone
• Large oversizing (n = 178): 20.1%-35% by area or 9.6%-16.2% by perimeter, described as the favorable CoreValve (Medtronic) zone

Within the moderate group, 78 patients received Sapien XT and 112 CoreValve. All those implanted with Sapien XT had devices that were oversized moderately, but among the CoreValve recipients, only 15.2% had moderate oversizing and 84.8% had severe oversizing (> 35% by area or > 16.2% by perimeter).

Within the large group, 88 received Sapien XT and 90 CoreValve. All those implanted with CoreValve had large device oversizing, whereas among Sapien XT recipients, only 46.6% had devices that were largely oversized and 53.4% were mildly oversized (< 5% by area or < 2.5% by perimeter).

Differences in Dilatation, Annular Rupture, Major Stroke

Patients in the moderate oversizing group had similar baseline characteristics, irrespective of whether they received Sapien XT or CoreValve. Those in the large oversizing group had a higher mean Society of Thoracic Surgeon score with Sapien XT than with CoreValve (6.7 vs 5.0; P = .002) as well as greater prevalence of chronic renal insufficiency (44.3% vs 18.9%; P < .001).

Most procedural characteristics and clinical outcomes were similar between the 2 device types within the moderate and large oversizing groups. Notably, there were no differences related to the degree of paravalvular leakage.

However, with moderate oversizing, CoreValve procedures were more likely to involve postballoon dilatation and resulted in higher rates of major stroke and the need for pacemaker implantation by 30 days. With large oversizing, Sapien XT cases carried higher risks of annular rupture, conversion to surgery, and acute kidney injury but—as in the moderate group—had a reduced need for pacemaker implantation at 30 days (tables 1 and 2).

“Optimal clinical performance of CoreValve and Sapien XT appears to be reached with different degrees of oversizing,” the researchers conclude. “Certain annular sizes that allow for only moderate or large oversizing, but not both, appear to benefit from a device-specific approach.”

Finding the Best Fit

Dr. Leipsic said the current study is just a starting point. “We need to continue to investigate and learn how to optimally treat each patient now with TAVR,” he noted. “With more devices available and growing experience, we have the opportunity to potentially individualize and optimize device selection.”

Appropriate oversizing, Dr. Leipsic added, can “help ensure the best clinical outcomes possible.”

Today’s clinicians have many resources at their disposal but also face challenges, he explained. “In the early days of TAVR, there were limited devices and limited sizes, thereby limiting the importance of preprocedural imaging. Now, with more [transcatheter heart valve] sizes and next-generation devices, the decisions are much more complicated and need to be taken in the context of many patient-specific factors.”

Study Provides Clarity While Reinforcing Current Practice

In an email with TCTMD, Isaac George, MD, of Columbia University Medical Center (New York, NY), praised the study as being “very informative.

“The sizing algorithms have been proposed before in the past but [their validation] is an important step in achieving better procedural outcomes,” he continued. “[The current study] reinforces our current practice for oversizing but also provides key information about how the performance of the Sapien XT and CoreValve valves [changes] at different sizing. This information could potentially be useful for patients who possess anatomic limitations for oversizing, which can thus guide the choice of valve.”

As the array of devices expands, it will be important to understand advantages and disadvantages, the ramifications of sizing, and the profile for each valve, Dr. George said, adding, “Having the ability to use multiple valves will only enhance our experience.”

While these data are a “good start,” he noted, more rigorous study of sizing will be provided by the PARTNER II and SURTAVI trials.

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Source:Dvir D, Webb JG, Piazza N, et al. Multicenter evaluation of transcatheter aortic valve replacement using either Sapien XT or CoreValve: degree of device oversizing by computed-tomography and clinical outcomes. Catheter Cardiovasc Interv. 2015;Epub ahead of print.

Dementia 'halted in mice brains'

Tweaking the brain's immune system with a drug has prevented mice developing dementia, a study shows.

The team at Duke University, in the US, showed immune cells which start attacking nutrients in the brain may be a trigger for the disease.

They say their findings could open up new avenues of research for a field that has not developed a single drug to slow the progression of the disease.

Experts said the findings offered new hope of a treatment.

The researchers indentified microglia - normally the first line of defence against infection in the brain - as major players in the development of dementia.

They found some microglia changed to become exceptionally adept at breaking down a component of protein, an amino acid called arginine, in the early stages of the disease.

As arginine levels plummeted, the immune cells appeared to dampened the immune system in the brain.

Stopping dementia

In mouse experiments, a chemical was used to block the enzymes that break down arginine.

They showed fewer of the characteristics of dementia such as damaged proteins collecting in the brain and the animals performed better in memory tests.

One of the researchers, Dr Matthew Kan, said: "All of this suggests to us that if you can block this local process of amino acid deprivation, then you can protect the mouse, at least from Alzheimer's disease.

"We see this study opening the doors to thinking about Alzheimer's in a completely different way, to break the stalemate of ideas in Alzheimer's disease."

However, the findings do not suggest that arginine supplements could combat dementia as the boosted levels would still be broken down.

'Hope'

Dr James Pickett, from the Alzheimer's Society said the study was "offering hope that these findings could lead to new treatments for dementia".

He added: "This study in animals joins some of the dots in our incomplete understanding of the processes that cause Alzheimer's disease, in particular around the role played by the immune system."

Dr Laura Phipps, from Alzheimer's Research UK, said the study was "interesting" and shed "more light on the mechanisms of immune system involvement in Alzheimer's".

But she cautioned clinical trials in people were still needed and that "the findings do not suggest that supplementation of the amino acid could mirror the benefits seen in these mice".

Facebook's Mark Zuckerberg hits back in Internet.org India row

Facebook boss Mark Zuckerberg has defended the aims of their Internet.org initiative after several Indian firms decided to pull out of the project.

In a blog post, Mr Zuckerberg argued that Internet.org's basic free services were not incompatible with net neutrality - the principle that all web services should be equally accessible.

"We fully support net neutrality," he wrote. "Universal connectivity and net neutrality can and must co-exist."

But critics were quick to respond.

Writing in the Hindustan Times, India's Save The Internet coalition maintained that Internet.org is "Zuckerberg's ambitious project to confuse hundreds of millions of emerging market users into thinking that Facebook and the internet are one and the same."

Distorting competition?

At the heart of the row is Internet.org's policy of "zero-rating", whereby telecoms providers agree not to pass on the costs of handling the data traffic so that consumers can receive services for free.

Critics argue this has a distorting effect on competition, making it difficult for publishers not signed up to Internet.org to reach the hundreds of millions of poorer people in developing economies who have no internet access at all.

But Facebook disagrees, pointing out that joining Internet.org is free for web publishers and app providers.

"We're open for all mobile operators and we're not stopping anyone from joining," says Mr Zuckerberg. "We want as many internet providers to join so as many people as possible can be connected."

However, India's leading mobile operator Bharti Airtel has also been applying zero-rating to its Airtel Zero service.

This means that consumers can access certain apps for free because the app provider picks up the data bill.

Smaller developers without the resources to do the same are at a commercial disadvantage.

Better than nothing?

Facebook chooses the services offered by Internet.org after consultation with "local governments and the mobile operators" in each country, says Mr Zuckerberg.

It is this hand-picking process that appears discriminatory to many within the industry.

But Mr Zuckerberg believes that "if someone can't afford to pay for connectivity, it is always better to have some access than none at all."

In India, Internet.org has rolled out its free basic services on the Reliance network in Tamil Nadu, Maharashtra, Andhra Pradesh, Gujarat, Kerala and Telangana.

And it has also launched in Indonesia on the Indosat network.

Boycott

This week a number of firms, including travel portal Cleartrip.com and media giant Times Group, withdrew from Internet.org

, claiming that the service conflicts with the principle of net neutrality.

The issue has certainly galvanised the Indian public - more than 800,000 people have sent emails to India's telecom regulator, Telecom Regulatory Authority of India, demanding a free and fair internet.

Indian telecoms companies have been putting pressure on the government to change the way so-called "over-the-top" mobile apps, such as Skype, WhatsApp, and Instagram, are licensed.

Such apps piggyback on the operators' networks and have benefited greatly from the proliferation of smartphones and the explosion in mobile content.

Operators want a bigger slice of the pie.

Wikileaks publishes hacked Sony emails and documents

Wikileaks has published hundreds of thousands of emails and documents from a cyber-attack on Sony Pictures Entertainment last year.

The archive apparently includes Sony conversations with Downing Street and with Hollywood figures.

In November, the entertainment company suffered a cyber-attack weeks before releasing The Interview, a film criticised by the North Korean regime.

Sony said it "strongly condemns" the Wikileaks release.

"We vehemently disagree with WikiLeaks' assertion that this material belongs in the public domain,'' the company said in a statement.

The Wikileaks dump includes more than 170,000 emails and over 20,000 documents.

After November's hack, an unknown organisation published the documents online, but it was not in an easily-searchable form.

Julian Assange, the founder of the website, justified the publication by saying the documents show the inner functioning of a multinational company and are "at the centre of a geo-political conflict".

The attack came just weeks before Sony was set to release the film about a fictional American plot to kill North Korean leader Kim Jong-un.

North Korea denied involvement in the attack but praised it as a "righteous deed".

In December, a group calling itself the "Guardians of Peace" threatened 9/11-type attacks on cinemas showing the movie, spurring Sony to cancel the film's release.

Days later, amidst growing public pressure to show the film, Sony bosses appeared to change their minds and said they would give it a limited Christmas Day release.

In January, the US imposed new sanctions on North Korea in response to the attack. And, in April, President Obama ordered the creation of a programme that would allow the US government to sanction foreign hackers.

Mr Assange is currently seeking refuge at the Ecuadorian Embassy in London after two women in Sweden accused him of rape and sexual assault.

US schools seek refund over $1.3bn iPad project

Schools in Los Angeles are seeking compensation from Apple over a $1.3bn (£870m) iPad-based education project that has gone awry.

They have sent letters to Apple and its project partners seeking refunds.

The project began in 2013 and aimed to give iPads and other computers to about 650,000 students.

It hit problems when students were able to bypass security systems on the tablets and because the computer-based curriculum was incomplete.

Cutting ties

In the letters, the LA Unified School District (LAUSD) said it was "extremely dissatisfied" with the way the project has been handled, according to a report in the LA Times.

The scheme was intended to be a way for poorer pupils to keep up with wealthier peers who already enjoyed access to tablets and other computer-based study aids.

The LA school district initially bought 43,261 iPads loaded with a maths and English curriculum designed by educational and training firm Pearson. A further 77,000 iPads were bought to be used in standardised tests.

Teachers, school heads and administrators were also expected to use the gadgets to improve lessons and the way schools were run.

"While Apple and Pearson promised a state-of-the-art technological solution they have yet to deliver it," said the letters sent to the two firms this week.

Lawyers acting for the school district are also believed to be considering legal action against the two main suppliers. In addition, the schools have cut ties with the firms and do not want them to be involved in any future development.

The letters come after repeated demands from the LA school district that Apple and Pearson improve the way the scheme was being run. In its complaints, the district said only two schools were regular users of the iPad-based curriculum and those that used it intermittently reported frequent problems.

Apple has not responded to requests for comment about the complaints.

In a statement, Pearson said it was "proud of our long history working with LAUSD and our significant investment in this groundbreaking initiative to transform instructional practices and raise expectations for all students".

The statement acknowledged the "challenges" there had been in implementing the project but said it stood by the "quality of our performance".

The Pearson/Apple deal was one part of a $1.3bn programme that included spending $700m on improving internet access at schools.

The superintendent in charge of the LA school district who drew up and oversaw the costly programme resigned after the problems with the scheme came to light.