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A Blood Test Can Predict Dementia. Trouble Is, There’s No Cure

Nobel prizewinner Koichi Tanaka says the predictive blood test for Alzheimer’s disease he and colleagues spent almost a decade developing is a double-edged sword.

Without medications to stave off the memory-robbing condition, identifying those at risk will do nothing to ease the dementia burden and may fuel anxiety. But used to identify the best patients to enroll in drug studies, the minimally invasive exam could speed the development of therapies for the 152 million people predicted to develop the illness by 2050.

 

“We must be cautious on how the test is used because there’s no curative treatment,” Tanaka said in an interview at Kyoto, Japan-based Shimadzu Corp., where he’s worked for 36 years. The 59-year-old engineer, who shared the Nobel for chemistry in 2002, said he hopes the test he helped pioneer will one day be administered routinely, but right now it belongs in the hands of drug developers and research laboratories.

 
 

More than a century after the telltale signs of Alzheimer’s were first seen under a microscope, and billions of dollars in research spending by Roche Holding AGEli Lilly & Co.Eisai Co. and other companies, there’s still no drug slow down the disease.

 

In the absence of medical breakthroughs, the worldwide cost of dementia is projected double to $2 trillion by 2030.

 

Nature Study

“There are many reasons why drugmakers have failed to develop a cure for Alzheimer’s disease, but it’s too late to start treatment when patients already show symptoms,” Tanaka said.

In a study published in Nature in January last year, Tanaka and colleagues showed it was possible to use a novel biomarker discovered by his lab to accurately quantify minute traces of amyloid-beta from a teaspoonful of blood, and gauge the progression of Alzheimer’s — allowing identification of people likely to develop dementia over the coming decades.

Previously, the brain changes that occur long before Alzheimer’s symptoms appear could only be reliably assessed by magnetic resonance imaging (MRI) and positron-emission tomography (PET) scans, and from measuring amyloid and another errant protein called tau in spinal cord fluid — methods that are expensive and, in the case of a spinal tap, invasive.

“Our finding overturned the common belief that it wouldn’t be possible to estimate amyloid accumulation in the brain from blood,” Tanaka said. “We’re now being chased by others, and the competition is intensifying.”

Roche, Quanterix

About a dozen companies and research groups from around the world, including Roche, Spain’s Araclon Biotech SL, and Lexington, Massachusetts-based Quanterix Corp., are pursuing blood-based diagnostic tools for Alzheimer’s and other neurodegenerative diseases.

“These blood tests are very important to that aim of trying to get these groups identified and ready to go into trials, and make them faster and less expensive,” said Christopher Rowe, a neurologist who heads molecular imaging research at the Austin Hospital in Melbourne. “That, in turn, is the greatest hope for having a significant impact on the epidemic.”

 

Risky Endeavor

Estimated cost of developing a drug through to regulatory approval

The global Alzheimer’s disease diagnostics and therapeutics market is predicted to reach $11.1 billion in 2024 from $7.5 billion last year, ResearchAndMarkets.com said in March.

 
 

‘Exceptional Accuracy’

“You really get exceptional accuracy,” said Bateman, whose lab studies the causes, diagnosis and treatments of Alzheimer’s disease. “I could see that easily becoming a clinical standard.”

Shimadzu Corp.'s Nobel-winning Researcher Koichi Tanaka Interview

Shimadzu’s AXIMA series mass spectrometer.

Photographer: Shoko Takayasu/Bloomberg

Both the Shimadzu and Washington University groups use an analytical technique called mass spectrometry that can search for a particular compound based on its specific molecular weight and charge. The method was found to be 90% accurate when it was checked against brain scans, Tanaka and colleagues said in their Nature paper.

Tanaka likens the approach to fishing with bait that only a specific fish will take. It enabled him to more precisely quantify amyloid in blood than an older, antibody-based method, he said.

New digital technology has bolstered the antibody-based test, with Quanterix using it to detect the errant proteins associated with the start of Alzheimer’s disease, as well as neurofilament light chain — a marker of neurological injury that can be elevated by conditions including concussion, Parkinson’s and multiple sclerosis.

“There’s an incredible opportunity to transform brain health by understanding your neuro baseline,” said Kevin Hrusovsky, Quanterix’s chief executive officer.

‘Game-Changing’

Several drugmakers are trying to get tests for neurofilament light chain validated clinically as a complementary diagnostic tool because they will enable patients’ responses to medications to be monitored in real time, providing an early signal of efficacy, Hrusovsky said. “There’s a lot of evidence that this is going to be game-changing,” he said.

Roche is evaluating the use of Elecsys, which tests cerebrospinal fluid for signs of Alzheimer’s, in blood plasma, the Swiss company said in an emailed response to questions.

Shimadzu Corp.'s Nobel-winning Researcher Koichi Tanaka Interview

Tanaka is a senior fellow at Shimadzu.

Photographer: Shoko Takayasu/Bloomberg

Shimadzu finished analyzing amyloid levels in blood-serum samples from 2,000 patients in March, Tanaka said. The company is preparing to offer the service in the U.S. this year before extending it to Europe and China.

“One thing we are looking into is running prospective cohort studies targeting people who have started to build up amyloid in the brain and see whether anything — food, exercise — can intervene to slow the progression of the disease,” the Nobel laureate said. “There are many things to be done.”

— With assistance by Jason Gale, and Tim Loh

HOW D’OXYVA CAN HELP?

Breathing in additional oxygen improves the function of blood vessels in the brains of people with chronic obstructive pulmonary disease (COPD), according to research published in Experimental Physiology [published online July 5, 2018]. Exp Physiol. doi: 10.1113/EP086994.].  The study revealed that possibly because of lower brain oxygen levels as a result of problems with blood supply from brain blood vessels, patients are at higher risk of dementia. 

Another research published in the Journal of Alzheimer’s & Dementia says improving cerebral microcirculation and metabolism leads to the regression of dementia and cognitive impairment and causes long-term ALZHEIMER’S DISEASE remission. https://www.alzheimersanddementia.com/article/S1552-5260(16)31871-4/fulltext

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation and oxygenation. Based on years of experience, D’OXYVA has continued developing microcirculation therapy. This process, unique to D’OXYVA, has demonstrated triggering protective physiological functions in the body: vasodilation and vasoconstrictions in the vessels, catalyzing vessel structure growth (angiogenesis), autoregulation of local blood supply in tissues and organs, neuroreceptor signaling in the brain and balancing blood pH, among other critical functions.

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Analysis: Has Trump actually done anything about drug prices?

Did you know the annual average cost of insulin per diabetic is about $6,000 and the monthly dosing of the 10 most advertised drugs is between about $500 and $17,000 in the States? Have you considered D’OXYVA’s immediate and significant benefits and advantages?

The administration has turned public anger at the pharmaceutical industry into real action — but has also left many meaningful opportunities on the table.

 

Donald Trump’s promise of sweeping health-care reform has not come to pass. While the president campaigned heavily on assurances to “repeal and replace Obamacare” on “day one” with an unspecified plan for every American to have affordable health care, his claims have now been diluted to a focus on “drug prices.”

One of his first comments on the release of the Mueller report was that it was a distraction from the need to “get back to infrastructure, get back to cutting taxes, get back to lowering prescription drug prices.”

Trump’s calls to action have been interspersed with claims of victory. In March of last year, Trump promised, “You’ll be seeing drug prices falling very substantially in the not-too-distant future, and it’s going to be beautiful.” Just 10 months later, in his 2019 State of the Union address, this had ostensibly already happened: “As a result of my administration’s efforts, in 2018 drug prices experienced their single largest decline in 46 years.”

Drug prices are still increasing. While growth in spending on drugs has slowed in recent years, total national spending continues to grow. Americans spend more than anyone else in the world. The average person spends $1,025 per year on medication — an inflation-adjusted increase of elevenfold since 1960.

Still, the cost of drugs accounts for only about 10 percent of the country’s health expenditures, and this trend has been steady for almost two decades. Exorbitant as drug prices are, a relatively small 24 percent of people say they have any “difficulty affording medications.” It is medical bills that cause much more angst and financial hardship, and are now the leading cause of bankruptcy in the United States. Slowing the growth of pharmaceutical costs would put only a small dent in the much bigger problem.

The focus on drug pricing is also curious as an ideological outlier for Trump. Among goals that have included protecting the fossil-fuel industryderegulating big banks, and handing out corporate tax cuts, the president could be expected to celebrate the $1.1 trillion pharmaceutical sector and the many jobs it provides. Instead, at least rhetorically, here he has chosen to side with consumers.

So what has Trump actually done about drug prices?

Last year, the administration did indeed lay out some proposals in a “blueprint’’ that included a long list of niche policy bullet points. Most notable among them were efforts at transparency and simplification: eliminating some rebates paid out by drug companies that obscure the price of drugs, using international comparisons for pricing Medicare drugs, and requiring drug companies to include prices in advertising.

It would be difficult to attribute any recent changes in drug prices to these measures, though, because they have not actually taken effect yet.

In the past two weeks, the issue started to come to a boil. The Congressional Budget Office projected that limiting rebates would not result in lower list prices, and would actually increase federal spending on drugs over the next decade by $170 billion. In the wake of that setback, the administration forged ahead with an announcement on Wednesday that the requirement to disclose drug prices in TV commercials would be implemented in July.

This may be the most noticeable single move the administration has made on the issue. In its news release, the Department of Health and Human Services cites the fact that the 10 most commonly advertised drugs have list prices ranging from $488 to $16,938 per month or course of treatment. Sharing this number would hypothetically encourage companies to lower their prices. Though if the requisite two-minute listing of gruesome side effects didn’t render ads ineffective, a price tag might not either—especially when it’s not the price that most consumers end up paying.

Patchwork regulation of this sort has historically failed to contain the pharmaceutical industry, which has continued to find ways to pass costs on to consumers and remain, consistently, extremely profitable. This is in part because of a system in which several layers of middlemen and reimbursement schemes serve to keep costs hidden from both patients and doctors, and fully apart from most decision making. While the advertising-disclosure requirement is a move toward cultural consciousness of cost, it has traditionally been market competition that has led to real price decreases. At a time when Trump’s executive orders are projected to leave fewer people with comprehensive health insurance, gestures at price transparency are unlikely to render them able to afford drugs out of pocket. Though drug prices are a popular talking point, if the overall goal were actually keeping American people alive and well, it would require a systemic reform of the health-care system.

In contrast to the drugs, which are integral to our existence and the functioning of our bodies and our understanding of ourselves, the system by which we procure them is opaque and foreign to most people, even though everyone is constantly paying for drugs. Part of every American’s paycheck goes to Medicare, the largest buyer of drugs. And everyone is familiar with the drugstore itself, a sort of microcosm of the country’s drug-pricing problem.

Many of the largest pharmacy chains, such as Walgreens and CVS, explicitly brand themselves as bastions of health and/or wellness. Yet the pharmacy itself is always at the back of the store. Four of the top five most prescribed drugs in the U.S. are used to treat elements of metabolic syndrome — the constellation of high blood pressure, diabetes, and heart disease that is strongly tied to what we eat. But in order to get these medications, you have to walk past two aisles of candy (one seasonal). This is not to mention an onslaught of magazine covers of extremely thin, young people with eerily white teeth.

You can buy a whitening system for your teeth, too. And the coffee to stain them back. And the sleep aids to counteract the caffeine. If there is a unifying philosophy to drugstores, it is that they sell things that have a potential to produce profit. At the back of the store, the drugs that constitute some of the few products that are essential to life — such as insulin — are often not cheap. An annual supply of insulin in the U.S. costs more than any other country, around $6,000. What’s more, from 2012 to 2016, the price roughly doubled — a textbook case of the pharmaceutical industry inexplicably increasing prices.

Insulin was the subject of congressional hearings last month that included the three biggest makers: Sanofi, Eli Lilly, and Novo Nordisk. Pharmaceutical companies traditionally justify high prices based on the costs of developing new drugs. In the case of insulin, the innovation that would justify such costs is not obvious. These companies did not invent or reconceptualize insulin. Some changes have been made to how long various insulin formulations last in the body, but there has been no revolution; the drug is an analogue of the hormone produced in the pancreas, similar to the insulin that was taken initially from pigs and given to humans a century ago.

Just before the hearing, Sanofi and Eli Lilly announced they would lower insulin prices (for some patients). Representatives called them out for only acting once called out. Joseph Kennedy was exasperated at the fact that this happened only after “15 years of global outcry.”

The drug companies gave a new, karmic defense: that others were now unfairly profiting off of them. They blamed high consumer costs on rebates being paid to a new layer of middlemen known as pharmacy benefit managers (PBMs). The three dominant PBMs—Express Scripts, OptumRx, and CVS Health—were also present at the hearing, seated shoulder to shoulder with the pharmaceutical companies, with each industry blaming the other for high prices while in fact both were profiting. As a group, PBMs spent $1.5 millionin lobbying in the first quarter of this year, an all-time high. This is a fraction of the pharmaceutical industry’s $9.9 million spent in the same quarter. That very lobbying practice is a potential target to truly rein in drug costs that Trump has not pursued.

Whether or not the plan to ban some rebates comes to pass may matter little. Such rebates — which Secretary of Health and Human Services Alex Azar, a former Eli Lilly executive, has called “a hidden system of kickbacks to middlemen” — are already a shrinking part of PBM profits. As in most large industries, corporations often look seven or eight steps ahead of potential regulatory impediments and preemptively create new revenue streams. As the CBO report put it, prices would not come down for patients because, rather than lowering list prices, drug companies would negotiate with PBMs using an alternative process known as “chargebacks.”

Without getting too far into the details about how all this matters to those of us in line at the pharmacy, as we’re assaulted by some Bruno Mars song and forced to stare at Red Bull and discount Peeps, the semantics of drug pricing are important. Even the oft-repeated phrase drug prices is less straightforward than it seems. First, there’s a list price, which is like the sticker price on a car: traditionally not what most people actually expect to pay. (Though under the more and more common high-deductible plans supported by the Trump administration, more people are paying the full list price.) In many cases, insurers and PBMs negotiate prices that are radically different from the list price. A net price is what’s actually paid to pharmaceutical companies after rebates. The complexity is an element of the 10-dimensional chess that is not entirely unintentional, and serves to thwart attempts at price transparency.

Even drugstore receipts could serve as an imperfect analogy for the convoluted system of drug prices. If you’ve ever been to a CVS, you know that the receipts areaccompanied by a scroll of coupons as long as a large dog. Sometimes there are coupons for $5 off any item — meaning a $5 bag of almonds is free. If you used all these coupons diligently, and then calculated prices accordingly, it could be difficult to get an accurate picture of costs and profits. Then imagine that the coupons were even more dramatic and numerous, and sometimes you got one that was $1,000. How would that affect the very idea of price?

Ultimately the most meaningful measurement of trends may be total national spending on prescription drugs, which has clearly increased. Though the rate of growth slowed in 2018, prices are simply not falling. The White House justified the president’s State of the Union claims by citing a 2018 report from its council of economic advisors, as well as data from the consumer price index for prescription drugs that showed a decline in list prices in January 2019 compared with the year prior. Without knowing how rebates changed—PBMs are notoriously secretive about this—it’s difficult to know what that means.

Even looking at list prices alone, more than 3,000 drugs went up, while only 117 went down. A report by the Associated Press found that 46 name-brand drugs decreased in price, but 4,412 increased. These sorts of analyses highlight the power of a few, intergalactically priced outliers — like the $700,000 hepatitis medication Sovaldi — to shift averages. The majority of drugs are considered “small molecule,” and in the generic market, which constitutes some 90 percent of drugs, people tend to take little issue with their prices.

Cholesterol-lowering statin medications, for example, are sometimes cited as how the market is “supposed” to work: A discovery is made, and a company takes in huge profits for a few years to reward the risk of investment in clinical trials. The artificial monopoly period ends after seven years, generic manufacturers move in and create identical products, and the price drops accordingly (in many cases). That process—a mix of free-market and governmental control—has made significant treatments available at reasonable costs to most Americans. Monopoly expirations have saved buyers about $65 billion over the past five years. The generic market accounts for an ever-greater percentage of prescriptions, and the Trump administration has made continued efforts to expand that.

The public perception that many or most drugs are maliciously overpriced comes largely from the minority of cases of brand-name drugs for which companies have consistently raised prices far beyond inflation — just because they can. Other wealthy countries have a system that reimburses drug companies based on the value of their product. The U.S. stands alone in allowing manufacturers to charge whatever they like. As in the yacht industry, this market-based approach gives producers an incentive to maximize profit, not to maximize the number of consumers.

To that end, the other potentially significant effort the Trump administration has made is a continuation of Barack Obama–era initiatives to accelerate the approval of generic drugs and increase competition among drugmakers. But there’s scant evidence yet that the approvals have had that effect. For unclear reasons, many of the generics haven’t actually gone to market.

Single-source issues sometimes plague the generic market, too, as with the lifesaving EpiPen’s overnight jump from $57 to $317. This is also where the now-incarcerated former pharmaceutical CEO Martin Shkreli (the “pharma bro”) caused havoc when he increased the price of a 50-year-old, lifesaving antibiotic for HIV patients several-thousand-fold overnight. These and other drugs should be cheap—they are off-patent and not expensive to produce. Fortunately, this kind of profiteering happens mostly at small scales. Rarely are abuses so egregious and ostentatious, and public ire so clearly directed at a single, unrepentant character.

Even still, Shkreli went to prison for securities fraud; the pricing itself was not illegal. Had he increased the price of the drug more quietly, and said with somber resolve that it was an unfortunately necessary move in order to be able to invest in future research and development, he would likely be a free man in the company of other extremely wealthy executives.

This is where Trump’s tough rhetoric may have had some effect on prices. When the president professes to hold drug companies accountable, even if it never comes to pass, they may be less likely to call attention to themselves with a spurious 400 percent price increase. Still, the Band-Aid approach is not satisfactory to those who insist on a fair, predictable, market-driven system. As Senator Chuck Grassley put it during the insulin hearing: “It shouldn’t take months of bad press, persistent public outcry, and increasing congressional scrutiny to get a company to charge a fair price. That’s not how a functioning marketplace works.”

Increasing generic competition, even sprinkled with public shaming, still leaves a growing hole in the regulatory framework around the newest way that pharmaceutical companies are making money: specialty medicines, or “orphan drugs,” with small potential markets but much greater potential for profit. For example, the FDA recently approved a $375,000drug to help treat a rare disorder called Lambert-Eaton myasthenic syndrome. A gene-therapy drug whose makers say it can cure spinal muscular atrophy is expected to hit the market soon at a cost of $2 million. Manufacturers justify these prices based on smaller markets and the fact that the drugs can sometimes have actual lifesaving value.

This space also includes drugs known as “biologics,” defined vaguely by the size and complexity of the molecule. Relative to traditional, small-molecule drugs, biologics are also more customized to specific consumer populations. Imagine an aisle at the pharmacy where your name is on the sign overhead, next to “juice.” Such specificity would be a marked change from the age-old business model for drugs where everyone lines up at identical, cookie-cutter drugstores to receive cookie-cutter drugs in slightly different doses and colors. More targeted drugs have smaller markets but a higher likelihood of helping any given person. Biologics constitute just 1 percent of the pharmaceutical market but have exploded to 30 percent of spending. This is in part because they enjoy an especially long artificial monopoly period of 12 years. If a person wanted to have a talking point about addressing drug prices, this could be a place to start.

Democrats in Congress have, drafting legislation that would decrease that period to seven years. Rather than embracing this bipartisan move, Trump has gone the opposite direction. His new iteration of NAFTA, the United States–Mexico–Canada Agreement, is protective of the pharmaceutical industry, forbidding Congress from shortening patent monopolies.

The tension that undermines any cohesive progress on drug prices is evident in Trump’s populist rhetoric, which swings between protecting and demonizing American pharmaceutical corporations. On a global scale, he depicts the industry as a victim. Domestically, it is ripping people off. As he put it in his State of the Union: “I am asking the Congress to pass legislation that finally takes on the problem of global freeloading, and delivers fairness and price transparency for American patients.”

The mention of freeloading is an apparent reference to the fact that pharmaceutical companies charge much lower prices in international markets. Though as Azar described in October, this is because the companies take advantage of Medicare’s inability to negotiate. Companies charge higher prices to the U.S. government because, frankly, they can. HHS has proposed implementing a pricing system that accords with international standards, but in Azar has also warned that this may simply cause drug companies to stop selling their products internationally rather than lowering their prices in the U.S.

As Trump briefly acknowledged, if the country really wanted to rein in the pharmaceutical industry, and to see more Americans provided with effective drugs at affordable prices, the approach would have to be systemic, not a patchwork of publicly shaming the worst abuses after they have occurred. It could mean asking who, really, is “freeloading.”

Sharing in the Shkreli outrage in 2015, Hillary Clinton laid out a plan to allow Medicare to negotiate lower drug prices. This was an initial component of Obamacare, too, that didn’t make it to law. The long-standing arrangement has been simply that a pharmaceutical company names its price, and then it has some 60 million potential consumers for whom the program (taxpayers) must pay that price. In the case of insulin, for example, Grassley questioned why the magnanimous price-lowering announcement did not include a discount for patients in federal programs. “If Sanofi can reduce the price to patients for insulin while still making a profit, I can’t imagine a legitimate reason taxpayers shouldn’t be charged the same price,” he said.

Allowing Medicare to negotiate prices with drug companies is an approach widely endorsed by Democrats and, historically, Republicans. It has bipartisan support of 92 percent among Americans. It was also endorsed in a recent report from the National Academies of Sciences, Engineering, and Medicine. The Trump administration made a partial gesture in this direction last year, announcing that it would allow Medicare Advantage plans (those paid for by the government but administered by private insurance companies) to negotiate prices with drug companies. But the administration has not pursued negotiation on behalf of the the much larger Medicare pool, despite Trump’s branding as an advocate of deal making. A bill allowing such negotiations was introduced by Democrats again in February but remains unheard.

Instead, in April, the Department of Commerce proposed limiting the government’s ability to take action against monopolies by removing an existing allowance for intervention in cases of exorbitant drug prices. It’s part of a 1980 law known as Bayh-Dole, which established the current system in which federally funded research institutions license discoveries to privatized pharmaceutical corporations, which then develop marketable products. Ownership of patents for drugs based on discoveries made using federal funds remains with the academic institutions, not the government. But the academy can exclusively license intellectual property rights to drug companies and get royalty payments. The grant funding is part of a $38 billion federal budget line for the National Institutes of Health. So in a sense, the public not only pays for the discovery on which new medicines are based, but also then pays for the resulting products at a price that the industry picks.  

If Trump wanted to rally populist support around the problem of drug prices, he could call attention to the fact that tax dollars are used to develop drugs. They are then advertised under tax-exempt auspices in television commercials that pitch consumers directly, a practice that almost no other country permits. Then, it is tax dollars that go to buying the drugs from the corporations — with Medicare as the single largest purchaser. A profitable industry relying on a federal funding pipeline may not have been the vision of the senators who wrote the law, but one thing they did foresee was the potential for price gouging. The law includes a clause that gives the government “march-in rights” when a company using a taxpayer-funded discovery is not made available to the public “on reasonable terms.’’

In such cases — which have never actually happened — the government could override a patent and license someone else to market a drug. Though these rights have never been used, the potential for this intervention has served as a check on pharmaceutical companies. Some Democratic members of Congress wrote to Trump after he put the pharmaceutical industry on his list of targets in 2017, urging him to use this allowance to create specific guidelines as to what would constitute unreasonable terms, and what sorts of actions the government would take. But instead of acting on it, or even using it as a threat, the Trump administration is moving to eliminate it.

The overall effect of weighing what has actually been done with what could have been done leaves little hope that drug prices are indeed the priority Trump claims. The administration has made a series of reasonable gestures without meaningfully threatening the pharmaceutical industry, much less overhauling the health-care system. This sort of middle-ground approach to tinkering with the status quo is at odds with the burn-it-all-down ethos of the Trump campaign.

At the same time, the ongoing rise in support by some Democrats for single-payer health care — which in some models would eliminate private insurance companies altogether — could lead to the spread of such a philosophy to other highly profitable and widely disliked sectors. The presidential candidate Elizabeth Warren has introduced legislation that would let the government manufacture generic drugs. In some cases it could conceivably be less expensive for the government to pay the entire cost to develop a drug — from discovery through distribution — than to give monopolies to an industry that sells your discoveries back to you.

This shifting of the public-private partnership further toward the former would be at a far end of an ideological spectrum, where allowing Medicare to negotiate with drug companies is somewhere in the middle. In any approach, the overarching goal is to reward the sort of innovation that actually benefits the health of the population, as opposed to the innovation that optimizes the bottom line of each middleman profiting from taxpayer-funded innovations. Minimizing drug costs will ultimately be about tying reimbursement to value, rewarding innovation that meets consumer needs rather than keeping consumers in need. A market-driven approach will only work if companies have an incentive to treat diabetes rather than to sell as much insulin as is maximally profitable.

In some dream scenario, vendors of diabetes medications would even have some incentive not to also line their aisles with candy.

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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Circularity Enters Talks to Close Institutional Financing Round, Announces Phase 3 Clinical Research and Human Trials of Diabetic Foot Ulcer Treatment and Microcirculation at Multiple Sites in Seven Countries

Published in PRWeb

Los Angeles, CA May 8, 2019.

Circularity Healthcare is emerging from a successful conference on Microcirculation in Maastricht, the Netherlands, organized by the European Society for Microcirculation (ESM-EVBO.) The company secured multiple new high-quality research projects that are planned to start in the near future in the United States, Canada, France, Germany, Holland, Sweden, and Hungary. In addition, management secured several high-profile commercial deals at the event, including one of the top equine groups in Europe.

The new studies will demonstrate the effectiveness of Circularity’s D’OXYVA (deoxyhemoglobin vasodilator) device. D’OXYVA is a novel non-invasive transdermal (over-the-skin) technology, which is the leader in the field of microcirculation and microvascular therapy in terms of the depth and breadth of the clinical evidence obtained by Circularity over the past six years. The clinical work has demonstrated outsized benefits results, laying the groundwork for a broad range of existing and potential commercial applications.

 

Prof. Ito Puruhito presents the Efficacy of Transdermal CO2 administration using D’OXYVA medical device to treat diabetic foot ulcers during a lunch symposium sponsored by Circularity Healthcare.
 

 

The company also announced at the Microcirculation event that it has recently appointed a leading global clinical research organization (CRO) called the Professional Education and Research Institute, Inc. (PERI) to launch a phase 3 human clinical trial. The trial will be performed under the leadership of Prof. David G. Armstrong, a world renowned expert in diabetic foot classification, treatments, and limb salvage. Dr. Armstrong has assembled an expert team with his colleagues at MIT, Yale, Harvard, and other top global research institutions to carry out the clinical trial at multiple sites, with the goal of obtaining FDA approval for applying D’OXYVA to treat and close diabetic foot ulcers.

“I look forward to this opportunity to conduct highly important and truly groundbreaking research with distinguished scientists. Our company’s institutional funding round under negotiations with a number of large private equity and corporate venture capital funds is focused around financing this critical new research, as well as translating our existing results into general practice at the bedside and in-home health care,” stated Circularity CEO, Norbert Kiss. “We may end up with a larger funding round than originally planned, sourced from multiple funds. This can only be a benefit, as it will provide additional resources for our teams to carry out Circularity’s mission to transform the delivery of critical health care with real measurable results to multiple massive patient populations that are currently underserved and in need of what D’OXYVA can provide.”

 

Prof. Ito Puruhito standing beside his presentation poster gallery.

 

Circularity’s Business Development Officer and CFO, Dr. Paul Kirkitelos added, “All the latest scientific evidence in microcirculation is pointing to the need for the underlying benefits D’OXYVA is already delivering to patients on a regular basis. Our path forward is to collect additional data to support the applications we have already studied and bring it to the scientific, medical, and consumer communities for the benefit of millions of diabetics suffering from chronic wounds and amputations with a high mortality rate. The partnership we have recently launched with Airgas in the US provides an outstanding distribution channel to allow us to meet the enormous current demand for Circularity’s products. We anticipate this demand will continue to grow considerably in the foreseeable future.”

Circularity Healthcare’s presence at the latest 3rd Joint International Microcirculation – ESM-EVBO 2019 – Conference in Maastricht, The Netherlands was a success. “Attending this kind of event is a great way to get top professionals in the Microcirculation scientific and medical field discover Circularity’s mission, giving people opportunity to interact with our brand which definitely impacts customer acquisition rates positively. It was also a great platform to build many relationships. Such distinguished long-term relationships are especially helpful as these connections can be the first step to improving our access both to repeat and new customers in a variety of markets,” said Jennifer Boadilla-Pelaez, Circularity’s Senior Sales and Marketing Manager and Creative Director.

 

Maastricht City Hall dinner function

 

Prof. Ito Puruhito said during his presentation at the event, “I am supporting the adoption of D’OXYVA in the university and hospitals in Surabaya and across Indonesia to benefit as many of our people as possible.”

Download Prof. Puruhito’s presentation delivered at the conference and get access to additional free educational material. (Warning: images of open wounds are included.) You can watch the 15-minute video recording of the presentation by simply registering your email, name, and occupation at this link.

Advertisement banners at the event.

 

About Circularity Healthcare

Circularity Healthcare, LLC, headquartered in Los Angeles, California in the U.S., is an emerging world leader in proprietary circulatory health and noninvasive delivery technologies, committed to helping significantly improve lives by developing, manufacturing, and marketing medical, pharmaceutical, and consumer health products. Circularity specializes in groundbreaking noninvasive technologies for affordable and portable transdermal delivery systems, and is pursuing regulatory approvals worldwide for device usage as a treatment of disease states related to cardiovascular and microcirculatory blood flow, immunological and autonomic nervous system disorders.

 

About ESM (European Society for Microcirculation)

The European Society for Microcirculation was founded in Hamburg in 1960 following a first meeting of interested scientists in Lund, Sweden in 1959, and now has 500-600 regular members. The aims of the Society are to advance understanding of the microcirculation by bringing together clinicians and scientists from a wide range of specialists, but including physiology, vascular biology, genetics and biophysics.

Since 1980, the Society has its own journal, the Journal of Vascular Research, an international publication of growing impact, through which the worldwide scientific community is informed of the Society’s endeavors.

 

About EVBO (European Vascular Biology Organization)

EVBO was launched in 2006, after discussion between European vascular biologists who recognized that there is a need for a democratic society to provide a united focus and forum for vascular biologists in Europe, primarily by organizing conferences but also by maintaining and enhancing an interactive network of researchers; evolving from the experience of the previous European Vascular Biology Association and building on the achievements of the FP6 European Vascular Genomics Network (EVGN).

 

About Professional Education and Research Institute, Inc. (PERI)

Professional Education and Research Institute (PERI), a global clinical research organization, was established in 2005 as a premier CRO with a goal to work closely with our sponsors throughout the world to manage Phase I through IV clinical trials in the most efficient and cost effective manner possible, while maintaining the highest standards in good clinical practice and human protection.

PERI offers top-quality facilities with a staff including regulatory and pharmacovigilance specialists, clinical research coordinators, as well as specialists in statistical analysis and data management.

 

About Airgas

Airgas, an Air Liquide company, is a U.S. supplier of industrial, medical and specialty gases, as well as hard goods and related products; one of the largest U.S. suppliers of safety products; and a leading U.S. supplier of ammonia products and process chemicals. Headquartered in Radnor Township, Pennsylvania.

 

For more information, please visit http://www.circularityhealthcare.com or http://www.doxyva.com or doctors (Rx only) visit http://www.doxyvaforwound.com and send your general inquiries via the Contact Us page. For specific inquiries contact Circularity Customer Care at info@doxyva.com info@circularityhealthcare.com or by phone toll free at 1-855-5DOXYVA or at 1-626-244-8090.

 

Forward-Looking Information

This press release may contain forward-looking information. This includes, or may be based upon, estimates, forecasts and statements as to management’s expectations with respect to, among other things, the quality of the products of Circularity Healthcare, LLC, its resources, progress in development, demand, and market outlook for non-invasive transdermal delivery medical devices. Forward-looking information is based on the opinions and estimates of management at the date the information is given and is subject to a variety of risks and uncertainties that could cause actual events or results to differ materially from those initially projected. These factors include the inherent risks involved in the launch of a new medical device, innovation and market acceptance uncertainties, fluctuating components and other advanced material prices, new federal or state governmental regulations, the possibility of project cost overruns or unanticipated costs and expenses, uncertainties relating to the availability and costs of financing needed in the future and other factors. The forward-looking information contained herein is given as of the date hereof and Circularity Healthcare, LLC assumes no responsibility to update or revise such information to reflect new events or circumstances, except as required by law. Circularity Healthcare, LLC makes no representations or warranties as to the accuracy or completeness of this press release and shall have no liability for any representations (expressed or implied) for any statement made herein, or for any omission from this press release.

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Study of Microcirculation of Patients with Varicose Veins of Lower Limbs

Abstract

Varicose veins of lower limbs have always caused, because of their rate, highest social spendings. Those patients who have trophic disturbances often need surgical treatment even after surgical intervention. This condition becomes worse in Southern Europe countries because of environmental and climatic factors.

INTRODUCTION

Varicose veins of lower limbs have always caused, because of their rate,highest social spendings. Those patients
who have trophic disturbances often need surgical treatment even after surgical intervention. This condition becomes worse in Southern Europe countries because of
environmental and climatic factors.
It is therefore necessary to improve diagnostic methods in order to prevent trophic disturbances.
In order to reach this target, our Institute studies all patients affected by varicose disease not only by doppler
c.w. but also by microcirculatory methods, such as Videocapillaroscopy and Reflected Light Rheography on medial malleolus.

MATERIALS AND METHODS

Thirty patients (24 females and 4 males) suffering from varicose veins of lower limbs at 2nd or 3rd stage of Widmer
classification, were studied by Reflected Light Rheography and Videocapillaroscopy on medial malleolus of both legs.
In order to avoid any interference, capillaroscopy was ever made before RLR; in the same way, no drugsduring the
period of study were administered. In the patients with only one affected leg, the other leg gave useful comparison parameters.

RESULTS

In the group of 30 patients the following parameters were evaluated: Venous network, refilling time (TO), venous drain capability (dr), capillaries density and morphology. About rheographic parameters we found TO equal to 12+-3 seconds and dr equal to 100+-50 mV (mean values). In the group of patients at 2nd Widmer stage, TO was equal to 16+-3 seconds and dr was equal to the patients at 3d Widmer stage TO respectively, equal to 8+-2 seconds About capillaroscopic parameters, capillaries density in all subjects; formation” pictures, espectively, (13,3%) patients.

CONCLUSIONS

The study of microcirculation by Capillaroscopy and Rheography, in the patients suffering from varicose veins of lower limbs, was with no doubt useful to demonstrate that any stage of venous disorders causes different microcirculatory alterations. In fact, we found “”halo formation· pictures in patients with more pathological rheographic parameters (TO less than 10 seconds) and nearly all these patients suffered from varicose disease at 3rd stage of Widmer classification. Furthermore, microcirculatory alterations were more evident in patients with trophic disturbances and elder venous disease.

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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How does transdermal non-invasive CO2 infusion at the thumb cause improved blood circulation and cellular O2 levels in the foot?

How does transdermal non-invasive CO2 infusion at the thumb cause improved blood circulation and cellular O2 levels in the foot?

ABOUT THE AUTHOR

Judy Delp Ph.D.

Job Description

Professor of Biomedical Sciences

 

Education

B.S. Rockhurst University, Kansas City, Missouri

Ph.D. University of Missouri

 

Memberships

American Physiological Society

American Microcirculatory Society

American Heart Association

Toriyama et al.17 studied the effect of CO2 bathing in 83 limbs with critical ischemia and achieved limb salvage in 83% without surgery. They concluded that peripheral vasodilation from CO2 bathing resulted from an increased parasympathetic and decreased sympathetic activity. In the current study, treatment with transdermal CO2 in a localized area produced a sustained, remote vasodilation, and a lowering of systemic blood pressure.
 
These findings share some similarity with the hemodynamic changes that occur following an acute bout of exercise, in which both neural and vascular components contribute to a sustained decrease in vascular resistance and blood pressure that persists after cessation of exercise18. In the current study, the period of sustained vasodilation seen in response to transdermal CO2 was heightened in diabetic patients.
 
Interestingly, in hypertensive individuals, the period of post-exercise hypotension is of greater magnitude and duration as compared to that of normotensive individuals 18, 19. Paradoxically, the current findings in diabetic patients exposed to transdermal CO2 as well as previous findings in hypertensive patients post-exercise, imply that sensitivity to signals that mediate these cardiovascular responses increases in patients with pre-existing cardiovascular dysfunction19.
 
A sustained decrease in systolic blood pressure occurs post-exercise and here, following application of transdermal CO2, suggesting that neural mechanisms contribute to the observed reduction in systemic vascular resistance. The roles of efferent sympathetic nerve activity18-20, afferent nerve activity from muscle 21-24, and the baroreceptor reflex20, 23 in mediating post-exercise hypotension remain controversial.
 
Neural mechanism(s) could contribute to changes in skin SPP and systolic blood pressure induced by exposure to transdermal CO2. Future studies will need to monitor heart rate, heart rate variability, and sympathetic nerve activity during and after transdermal CO2 in order to more fully assess the role of the autonomic nervous system in mediating the sustained increases in SPP and systolic blood pressure reported in this initial study.
 
Vascular conductance increases in both active muscle and inactive vascular beds following a bout of dynamic exercise 25, 26, suggesting that circulating factors contribute to this period of sustained systemic vasodilation. Vasodilation occuring independently of neural regulation constitutes more than 50% of the increase in systemic vascular conductance that occurs post-exercise; however, the mechanisms that underlie the post-exercise vasodilation have remained elusive.
 
Studies that have employed blockade of nitric oxide or evaluation of circulating nitric oxide metabolites have shown that the post-exercise vasodilatory response does not rely on circulating nitric oxide availability27, 28. A recent study by New and colleagues28 indicates that the nadir of post-exercise hypotension coincides with the peak of appearance of lipid hydroperoxides in venous blood, suggesting that reactive oxygen species with known vasodilatory properties29-32 contribute to the exercise-induced decrease in systemic vascular resistance. In the current study, transdermal CO2 was applied to the thumb, and a significant increase in SPP was measured at the toe.
 
Thus, a similar circulating vasodilatory stimulus may contribute to the remote, sustained vasodilation created by local transdermal application of CO2. Further investigations will need to focus on the identification of the mechanisms involved in both the local and remote factors that contribute to the sustained hemodynamic changes produced by exposure of the skin to CO2.
 
Recently, studies have documented that episodes of brief, non-damaging ischemia occurring in a tissue can induce systemic protection against ischemia-reperfusion injury in a remote organ. This phenomenon, termed remote ischemic conditioning, has been demonstrated to confer protection against ischemic events in the myocardium33-35, brain36, and kidney37, 38.
 
Although shown to be effective in various clinical and pre-clinical models 34, 35, 38-40, the mechanism(s) of remote protection have not been clearly identified. Both neural and humoral mechanisms have been proposed to contribute to the protection against ischemic damage afforded by remote ischemic conditioning38, 39, 41-43.
 
Basalay et al.41 have shown that when remote ischemic conditioning is applied before induction of myocardial ischemia, sensory nerves and recruitment of a parasympathetic neural pathway are involved in reduction of infarct size. In contrast, application of remote ischemic conditioning after myocardial ischemia also afforded protection against infarction, but was not altered by vagotomy or peripheral denervation41.
 
Remote ischemic conditioning has also been demonstrated to improve perfusion of transplanted kidneys, suggesting that remote conditioning confers protection that does not rely on intact neural circuitry38. Recently, Michelsen and colleagues42 have demonstrated that dialysate of human plasma from subjects who underwent either ischemic preconditioning or exercise preconditioning reduced infarct size in rabbit hearts, indicating that release of a humoral factor, possibly acting on opioid receptors, contributes to the cardioprotective effects of ischemic and exercise preconditioning.
 
Other reports in the literature have also shown evidence of a humoral substances that mediate protection against ischemia when remote ischemic conditioning is applied; however, these substance(s) remain to be identified. Application of transdermal CO2 produces a remote vasodilation that may be mediated through release of a circulating humoral agent.
 
Future investigations will need to focus on assessment of plasma samples during and following transdermal CO2 application.
This pilot study demonstrated an increase in measures of remote skin microvascular function with D’OXYVA, a simple commercially-available device to deliver transdermal CO2. The effects of the treatment were evident at all periods up to and including the last test period, 240 minutes post-exposure.
 
Although the sample size was small in this study, a clear increase in SPP and SPP/SBP ratio and a decrease in SBP and DBP continued for 4 hours post-treatment. The differences in skin perfusion and blood pressure responses detected between diabetic and non-diabetic subjects will require further examination in larger studies.
 
Click below to access Prof. Judy Delp’s Presentation on Transdermal Delivery of Carbon Dioxide Boosts Microcirculation.
 

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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7 Subtle Signs That Prove You’re Not As Healthy As You Think You Are

When you say healthy, it often brings to mind an image of person that exercises all the time and only eats nutritious food while avoiding junk like candy and fast food. However, it actually demands so much more than that. Truth is, being truly healthy means that one should have a sense of “physical, mental, and social wellbeing, and the resources to live a full life.”

Of course, we don’t always think of it that way. In fact, in most cases, eating heathy and pairing it with consistent exercise is more than enough. However, while being classified as “overweight” or “underweight” is an obvious sign of being unhealthy, there are also other not-so-obvious signs — ones that you may be ignoring. And ones that may mean you’re not as healthy as you believe you are. Below are some of them.

  1. Snoring – You may think it’s just an embarrassing act, but it can also indicate that you’re not that healthy. In fact, snoring is linked to a variety of health conditions, including sleep apnea, heart disease, and even stroke.
  2. Constant skin breakouts – Skin breakouts are also a sign of general unhealthiness, and unfortunately, there’s no single cause. However, thanks to face mapping, we can now easily adjust our lifestyle based on where we get breakouts. Chin acne for example, means we have to eat healthier, while forehead acne means we need better sleep and hygiene.
  3. The white of your eyes aren’t as white – This one is more subtle, but basically, if your eyes are a tad yellowish, it indicates that you may have complications in your bile ducts, gall bladder, liver or pancreas. There’s also red eyes, which come from lack of sleep and exhaustion.
  4. Your nails have an odd color and texture – A yellowish color in your nails is believed to be caused by fluid build-up and inadequate circulation in the body.
  5. Being gassy – Excessive gas can be signs of an irritable bowel syndrome, lactose intolerance, and celiac disease.
  6. Constant exhaustion – This one is obvious, but continuous exhaustion means that you may have iron deficiency, too little exercise, and even dehydration.
  7. Your urine doesn’t have a pale color – The color, smell, and density of urine can reveal what’s going on in our body. And in this case, having urine that has a darker color or has a strong scent means that you should probably get yourself checked by a doctor ASAP.

Reference: https://www.medicaldaily.com/7-subtle-signs-prove-youre-not-healthy-you-think-you-are-432551

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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“People are dying”: Diabetics rationing insulin amid rising drug prices

Drug manufacturers were grilled Wednesday about the skyrocketing price of insulin, which has doubled in the last five years and led some patients to ration the life-saving drug. One study finds the underuse of insulin could affect nearly 40 million people with diabetes by 2030.

“Nobody cared or nobody understood that without this next vial of insulin, I wouldn’t live to see another week,” said 28-year-old Kristen Whitney Daniels.

She started rationing her insulin after she was kicked off her parents’ insurance plan two years ago.

“I can’t really explain how isolating and how terrifying it is,” she said.

She’s now a patient at the Yale Diabetes Center, where a recent Journal of American Medical Association study found one in four patients reported “cost-related underuse.” Dr. Kasia Lipska treats patients at the clinic, and was the study’s lead author. She testified on Capitol Hill last week.

  • Woman says her son couldn’t afford his insulin – now he’s dead
  • Eli Lilly rolling out half-price insulin. Diabetics say it’s not enough

“This vial of insulin cost just $21 when it first came on the market in 1996. It now costs $275,” she said.

Some drug makers are already reacting to the outrage. On Wednesday, Sanofi announced it will cut the price of insulin for uninsured patients and those who pay cash to $99 per month. But that doesn’t eliminate advocate concerns.

“People are dying from lack of access to a drug that has been around for almost a century. I think it’s unconscionable,” Lipska said.

Insulin manufacturers told CBS News they’ve taken steps to address prices, including offering free medication to people who quality.

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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Circularity Healthcare Presenting D’OXYVA Diabetic Wound Healing Microcirculation Therapy Clinical Evidence and Sponsoring the 3rd International Microcirculation Conference – ESM-EVBO 2019

It is with our great pleasure to announce that we were invited by the organizers to participate in the 3rd joint ESM-EVBO 2019 and become a sponsor.

The 2019 ESM-EVBO (European Society for Microcirculation – European Vascular Biology Organization) Conference will be held on April 15-18 and hosted at the MECC in Maastricht, The Netherlands.

The conference focuses on advancing scientific research and medicine in all areas of vascular biology/medicine. Biennially, the ESM-EVBO hosts a four-day conference, where vascular enthusiasts from biology, preclinical and clinical research groups, and opinion leaders gather to share new fundamental scientific insights and current pre-clinical advances. Its network now has over 500 members worldwide, including representation in over 30 countries.

Besides being accepted into the poster sessions, Circularity is sponsoring the international symposium on Microcirculation.

Prof. Ito Puruhito, a distinguished thoracic vascular surgeon at Airlangga University, in Surabaya, Indonesia has been conducting several successful human clinical studies with D’OXYVA at the university over the past few years, and he is presenting some of his latest clinical evidence on diabetic foot ulcer treatment with D’OXYVA on April 17, 2019: http://esm-evbo2019.org/program/lunch-symposium/.

Want to stay updated on this event and what will happen next? Register your email for free now and follow the news about groundbreaking health discoveries!

About ESM (European Society for Microcirculation)

The European Society for Microcirculation was founded in Hamburg in 1960 following a first meeting of interested scientists in Lund, Sweden in 1959, and now has 500-600 regular members. The aims of the Society are to advance understanding of the microcirculation by bringing together clinicians and scientists from a wide range of specialists, but including physiology, vascular biology, genetics and biophysics.

Since 1980, the Society has its own journal, the Journal of Vascular Research, an international publication of growing impact, through which the world wide scientific community is informed of the Society’s endeavors.

 

About EVBO (European Vascular Biology Organization)

EVBO was launched in 2006, after discussion between European vascular biologists who recognized that there is a need for a democratic society to provide a united focus and forum for vascular biologists in Europe, primarily by organizing conferences but also by maintaining and enhancing an interactive network of researchers; evolving from the experience of the previous European Vascular Biology Association and building on the achievements of the FP6 European Vascular Genomics Network (EVGN).

 

About Circularity Healthcare

Circularity Healthcare, LLC, headquartered in Los Angeles, California in the U.S., is an emerging world leader in proprietary circulatory health and noninvasive delivery technologies, committed to helping significantly improve lives by developing, manufacturing, and marketing medical, pharmaceutical, and consumer health products. Circularity specializes in groundbreaking noninvasive technologies for affordable and portable transdermal delivery systems, and is pursuing regulatory approvals worldwide for device usage as a treatment of disease states related to cardiovascular and microcirculatory blood flow, immunological and autonomic nervous system disorders.

HOW D’OXYVA CAN HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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Have you heard of Tere’s inspiring diabetic story?

“My Doctor told me I have less than a year to live if I won’t let them amputate my leg, but I didn’t let them . . . here’s how I am still alive now!”

When doctors initially told 60-year-old Theresa “Tere” Schaufer that she had diabetes, she went into denial for 20 years.

“I was diagnosed with diabetes 20 years ago, and only when my doctor told me that they needed to cut my leg, did I realize that my diabetes was serious,” she says.

 

A major contributing factor

“Doctors told me the only way to survive this fight was to amputate my leg,” Schaufer says.  

She acknowledges that she had lived an unhealthy lifestyle for many years. Working in a restaurant as a cashier, she did very little exercise, ate fast food and drank sodas on a regular basis.

“If the doctor tells you you’re a diabetic, don’t ignore it. Don’t get to where I am. The sooner you accept things, the better it is for your health.”

Only after her doctor advised amputation did she realize the seriousness of her situation. Schaufer’s lifestyle had a hugely negative impact on controlling her diabetes. 

 

It was very painful!

Schaufer had puss from underneath her foot and necrotic toe. “After the doctor examined my foot, it was like decaying,” she says. “I couldn’t handle the pain. It was excruciating!” She was given less than a year to live because of her poor lifestyle.

 

I started to accept the situation.

Schaufer finally accepted her fate as a diabetic after the doctor told her that her leg would have to be amputated.

“I saw it coming. The pain was terrible. I could no longer handle it. At this point I was prepared; whatever came had to be.”

 

Unexpected turn of events

“I was browsing a support page I found on the web and read about a colleague’s experience with the microcirculation therapy she had tried. She noted that it had an amazing effect on her diabetic foot ulcer,” Schaufer says.

Right there on the support page, the woman raved, “There is this new technology you can buy online, D’OXYVA, which was voted one of the Top 10 Diabetes Care Solution Providers 2018! I didn’t have to amputate my leg because of this amazing product. In just four weeks, I can see my diabetic foot ulcer improving!”

“I read these words, and it gave me the hope I’d been praying for,” noted Schaufer.

She only had a month before her scheduled amputation, and without hesitation, she used the remaining days to try out D’OXYVA. She ordered the product online and closely collaborated with their in-house support.

“I was under D’OXYVA therapy for one month, taking it twice a day, once in the morning and once before bed as advised. It was very easy to use and non-invasive. In the first few days, I was skeptical as I wasn’t seeing any improvements, but I continued anyway and followed their suggested therapy guide,” Schaufer explains.

 

Thankful for D’OXYVA

When it was time for her to go back to her doctor and give her consent to amputate, her doctor was shocked to see her leg.

“What happened?” Those were the exact words my doctor asked upon seeing my leg after only a month. “Your wounds seemed to be healing from the inside,” my doctor said.

After a thorough check-up and the usual diagnostic check of my foot’s PI (perfusion index), he said the words that I never expected to hear. “We don’t need to amputate your leg anymore, but you need to continue whatever you’ve been doing for the past month.”

I then introduced him to D’OXYVA, and he was amazed by how this product had saved me.

 

Helping others

“I’m on my third month of D’OXYVA therapy, and it does amazing things for my health! I don’t think I have thanked D’OXYVA enough for this chance to live longer. I wouldn’t have the outlook on life that I have now,” Schaufer continues cheerfully.    

She is now also leading a healthy life. “This changed how I live my life, and I will continue sharing my experience as much as I can to help others.”

Schaufer often spends time with other “to-be-amputees” struggling to deal with their situation. “God gave me my situation to help others,” she maintains.

One of the ladies she counselled remarked how Schaufer had helped her tremendously. “She told me that I gave her her life back,” Schaufer says, breaking into tears.

“I’m in a way thankful for what I have been through with my diabetes because, without it, I wouldn’t have stumbled across my strength and my ability to help others.”

HOW CAN D’OXYVA HELP?

D’OXYVA is the only fully noninvasive, completely painless transdermal (over-the-skin) microcirculatory solution that has been clinically tested to significantly improve microcirculation.

The improvement of microcirculation, i.e., blood flow to the smallest blood vessels, benefits one’s health, immune system and overall sense of well-being in a variety of ways.

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Impaired Tissue Perfusion

What is Impaired Tissue Perfusion?

Ineffective tissue perfusion is a state in which an individual has a decrease in oxygen resulting in failure to nourish the tissues at the capillary level.

Tissue perfusion is a critical parameter for tissue survival and function, and both relative and absolute perfusion assessments are highly relevant for both diagnosis and evaluation of the therapy response.

Sometimes situations occur where this exchange of gases between the blood and the cells is disrupted, meaning the cells (and ultimately the tissues and organs) stop getting adequate oxygen supply. The body can’t function without oxygen, so obviously this is a problem. When tissues don’t receive enough oxygen through the capillaries, this is called ineffective tissue perfusion.

Many conditions can disrupt the exchange of oxygen and carbon dioxide, but diabetes, obesity, anemia, high blood pressure, and coronary artery disease are some of the more common risk factors that can cause ineffective tissue perfusion. We can further classify the type of ineffective tissue perfusion based on the part of the body affected. For example, there’s renal (meaning kidney), cerebral (meaning brain), cardiopulmonary (meaning heart and lungs), gastrointestinal (meaning digestive tract), and peripheral (meaning affecting the extremities) ineffective tissue perfusion.

Common Risk Factors

Small arteries in diabetic subjects, whether hypertensive or normotensive, exhibit severe hypertrophic remodeling, and histological analysis of skeletal muscle biopsy samples reveals capillary rarefaction in subjects with type 2 diabetes. Histological capillary density is inversely related to fasting plasma glucose and fasting insulin levels and positively related to insulin sensitivity in nondiabetic individuals. Microvascular permeability to large molecules such as albumin is increased in diabetes, a process that is linked to hyperglycemia and ROS

In humans, coronary flow reserve is significantly lower in obese than in nonobese subjects, and capillary recruitment is reduced in nondiabetic obese individuals compared with lean control subjects. Even in a sample of healthy children (11 to 14 years of age), microvascular function was negatively correlated with adiposity. Thus, obesity appears to have an independent effect on microvascular function.

Coronary flow reserve decreases progressively with age in subjects without coronary artery disease, from approximately 4 at 30 years to 3 at 65 years of age, largely due to increased basal myocardial blood flow.

Tobacco smoking acutely impairs capillary recruitment, and thus hyperemic blood flow increases in skin and coronary flow reserve is reduced in established smokers. Coronary flow reserve in smokers can be improved by administration of antioxidant vitamin C, which suggests that smoking-related oxidative stress is an important mechanism.

Individuals with hypercholesterolemia without coronary artery disease have reduced coronary flow reserve, and coronary flow reserve is inversely correlated with LDL cholesterol. A reduction in coronary flow reserve can be detected in healthy young men (mean age 31 years) with familial hypercholesterolemia, which suggests that microvascular abnormality is detectable early in the atherosclerotic process.

Given the relationships between individual cardiovascular risk factors with measures of microvascular status, it is not surprising that the overall Framingham risk score is inversely correlated with skin capillary recruitment, maximal skin capillary density, and coronary flow reserve.

Defining Characteristics

Ineffective Tissue Perfusion is characterized by the following signs and symptoms:

  • Abnormal arterial blood gases
  • Altered respiratory rate outside of acceptable parameters
  • Bronchospasms
  • Capillary refill >3 seconds
  • Chest pain
  • Chest retraction
  • Dyspnea
  • Dysrhythmias
  • Nasal flaring
  • Sense of “impending doom”
  • Use of accessory muscles
  • Altered mental status
  • Behavioral changes
  • Changes in motor response
  • Changes in pupillary reactions
  • Difficult in swallowing
  • Extremity weakness or paralysis
  • Speech abnormalities
  • Abdominal distention
  • Abdominal pain or tenderness
  • Hypoactive or absent bowel sounds
  • Nausea
  • Altered sensations
  • Altered skin characteristics (hair, nails, moisture)
  • Cold extremities
  • Dependent, blue, or purple skin color
  • Diminished arterial pulsations
  • Edema
  • Positive Homan’s sign
  • Skin discolorations
  • Skin temperature changes
  • Skin color pale on elevation, color does not return on lowering the leg
  • Slow healing of lesions
  • Weak or absent pulses
  • Altered blood pressure outside of acceptable parameters
  • Elevation in BUN/creatinine ratio
  • Hematuria
  • Oliguria or anuria

Damage, Complications, and Prognosis

Microvascular abnormalities that lead to impaired tissue perfusion appear to represent a generalized condition that affects multiple tissues and organs. For example, in hypertension, coronary flow reserve is correlated with the media:lumen ratios of small arteries in biopsies of subcutaneous fat. Dilatation of venules in the retina independently predicts progression of cerebral small-vessel disease, and in diabetes, reduced coronary flow reserve predicts the occurrence of retinopathy.

Impaired tissue perfusion may be involved in target-organ damage and complications that involve several vascular beds. For the coronary microcirculation, an obvious example associated with both hypertension and diabetes is the occurrence of myocardial ischemia and angina in the presence of angioscopically normal epicardial coronary arteries, also known as cardiac syndrome X. Impaired myocardial perfusion may also be an important factor in the development of hypertensive heart failure and may lead to localized ischemia and disturbed patterns of electrical activity that constitute a substrate for serious arrhythmias. In the case of renal disease, glomerular and peritubular capillary rarefaction has been noted in different animal models and in human progressive renal disease, and it precedes the development of impaired perfusion and chronic hypoxia. It has been suggested that hypoxia may be the common factor linking many forms of progressive renal disease.

Microvascular abnormality is also a predictor of prognosis. In hypertensive patients, the media:lumen ratio of peripheral small arteries is a strong independent predictor of cardiovascular events. Among individuals with normal or minimally diseased coronary arteries, reduced coronary flow reserve is an independent predictor of cardiovascular events within the next decade. Finally, in patients with chest pain and angiographically normal arteries, coronary flow reserve <3 is associated with a 6-fold increase in all-cause mortality risk compared with coronary flow reserve >3 during 8.5 years of follow-up.