Praxbind Gains Full FDA Approval as Pradaxa Reversal Agent

If you are on Pradaxa, this is worth reading....

Final Phase 3 study data had demonstrated that Praxbind immediately reversed the anticoagulant effect of Pradaxa

Boehringer Ingelheim announced that the Food and Drug Administration (FDA) has granted full approval for Praxbind (idarucizumab) for use in patients treated with Pradaxa (dabigatran etexilate mesylate) when reversal of anticoagulant effects is needed for emergency surgery/urgent procedures or in life-threatening or uncontrolled bleeding. 

Praxbind was initially granted accelerated approval by the FDA in October 2015; continued approval was pending results from the Phase 3 RE-VERSE AD trial (N=503). The latest analysis included findings from patients requiring urgent procedures/emergency surgery (eg, surgery for an open fracture after a fall) or patients with either uncontrolled or life-threatening bleeding complications (eg, intracranial hemorrhage, severe trauma after car accident). The primary endpoint was the degree of reversal of the anticoagulant effect of Pradaxa achieved by Praxbind within 4 hours. 

The final study data, published in July 2017, demonstrated that Praxbind immediately reversed the anticoagulant effect of Pradaxa. Complete reversal was seen within 4 hours in the majority of patients, as measured by ecarin clotting time (ECT 82%) or diluted thrombin time (dTT 99%). In addition, there was a low rate of thrombotic events and no new safety events were reported. 

Innovative, Affordable Home Care Model Boosts Cantata’s Bottom Line

Real, thoughtful coordination is less expensive and more effective.....

Cantata, a Chicago-area senior housing and care provider, is achieving success with its Take2 home care model, increasing margins even as clients are paying less for services.

Take2 was piloted in 2014, rolled out on a wider scale in 2016, and now serves about 60 people after a record month for new sign-ups in March, Cantata CEO John Larson said last week at the LeadingAge Illinois annual meeting and expo near Chicago. Cantata is a not-for-profit organization that offers an array of senior services; its campus-based housing, located about 15 miles southwest of downtown Chicago, includes independent living, assisted living and enhanced care.

The cost of personal care is already steep for consumers, and rates are only going up as tightening labor markets and changing laws increase costs for providers. At the same time, turnover is rampant in home care and a worker shortage is set to get worse as the baby boomer generation ages.

Take2 is a neighborhood-based system, in which caregivers drive around a designated area for the duration of their shifts, dropping in on clients to provide services in short bursts of about 20 minutes. Some of these drop-ins are scheduled and others are done on-demand, as clients have needs that arise and they alert the Take2 staff.

Currently, the service area is roughly six square miles around the Cantata campus. The organization has two people handling the program logistics and six to eight roving caregivers. They work regularly scheduled shifts, around the clock.

Take2 provides a wide array of services, including bathing and dressing assistance, light housekeeping, medication reminders, home maintenance and pet care. It does not provide companion care, given that the caregivers come in to perform specific tasks and then leave, moving on to the next house.

At the outset, the Cantata team had some doubts about the model. For instance, some people feared that clients would constantly be calling for help, and caregivers would be frantically trying to field requests and get from house to house.

“Our team said, it’ll be like a video game,” Larson said.

Those fears did not come to pass. In fact, clients request on-demand services infrequently, and the care team has been able to keep visits brief while maintaining 95% customer satisfaction and good health outcomes. For instance, as of October 2016, with 125 clients served, there had been only three falls with injury and two 30-day hospital readmissions.

There is a learning curve, however. Explaining the system and setting client expectations are important.

“We rarely if ever say, you’ll have a bath at 9:30,” Larson said. “We say … you’ll get hygiene in the morning.”

Similarly, there was skepticism about helping people with toileting on a schedule, but that has also not been a stumbling block. It is not unusual to have a toileting schedule in an assisted living setting, Larson noted.

A Stunning Breakthrough in the Fight Against a Devastating Blood Disease

Beta thalassemia is one of the most common genetic diseases in the world, affecting an estimated three hundred thousand people, with another sixty thousand born every year. (Evolutionary biologists speculate that the gene has survived for so long because, like the sickle-cell mutation, it may confer resistance to malaria.) Beta thalassemia is prevalent in Africa, Asia, the Middle East, and, especially, the Mediterranean. Its name comes from the Greek words thalassa, meaning “sea,” and haema, meaning “blood.” In many countries, including England, Greece, Iran, Saudi Arabia, and Taiwan, couples are screened for the disorder before they conceive, so that they know the chances of their child inheriting it. Once a patient shows symptoms of beta thalassemia, treatment is essentially palliative, consisting of regular transfusions of red blood cells from healthy donors. But with these life-saving transfusions come large amounts of iron, which builds up in the liver, heart, and other organs, amplifying the damage of the disease itself. At Hadassah, few of the patients with the severe form of beta thalassemia lived into adulthood. The years before death were typically marked by broken bones, recurrent infections, and overwhelming fatigue.

Now, a little more than four decades after I cared for these young patients, science is on the cusp of curing the disease. This week, the New England Journal of Medicine published a landmark paper on beta thalassemia by researchers in the United States, France, Australia, and Thailand. Twenty-two patients with the condition, treated at six centers around the world, underwent so-called gene therapy, a process in which the normal variant of a gene is inserted into the patient’s DNA, compensating for the abnormal one. In this case, the researchers retrieved immature stem cells from each patient’s bone marrow—the body’s blood factory—and isolated them in the laboratory. Next, they used an otherwise harmless virus to infect the cells with a copy of the normal globin gene. They cleared the patient’s marrow of diseased cells using chemotherapy, then reintroduced the genetically altered cells into the bloodstream—what is known as an autologous transplant. The cells found their own way back into the marrow.

The researchers’ hope was that the modified stem cells would mature into red blood cells and produce robust amounts of healthy hemoglobin. That hope was realized. Nine of the twenty-two patients suffered from severe beta thalassemia, and, after treatment, the number of blood transfusions they required fell by seventy-four per cent. Three of the nine no longer need any transfusions at all. The same is true of twelve of the thirteen patients with the less severe version of the disease. So far, the subjects of the trial have been observed for a maximum of forty-two months, but they will be monitored long into the future, to insure that the benefits of the therapy persist and cause no serious side effects. One early concern—that the procedure could disrupt the DNA of the stem cells, potentially triggering leukemia—has not, fortunately, come to fruition.

What We Know And Don’t Know About Memory Loss After Surgery

Thanks and a hat tip to RoAnne Chaney. Illuminating article; Completely altered my understanding of the issues.....

“He never got back to his cognitive baseline,” Cole continued, noting that his father was sharp as a tack before the operation. “He’s more like 80 percent.”

The old man likely has postoperative cognitive dysfunction (POCD) — a little-known condition that affects a substantial number of older adults after surgery, Cole said.

Some patients with POCD experience memory problems; others have difficulty multitasking, learning new things, following multistep procedures or setting priorities.

“There is no single presentation for POCD. Different patients are affected in different ways,” said Dr. Miles Berger, a POCD specialist and assistant professor of anesthesiology at Duke University School of Medicine.

Unlike delirium — an acute, sudden-onset disorder that affects consciousness and attention — POCD can involve subtle, difficult-to-recognize symptoms that develop days to weeks after surgery.

Most of the time, POCD is transient and patients get better in several months. But sometimes — how often hasn’t been determined — this condition lasts up to a year or longer.

Mechanisms at work. What’s responsible for POCD? The drugs administered during anesthesia or the surgery itself? Currently, the evidence implicates the stress of surgery rather than the anesthesia.

“Most surgery causes peripheral inflammation,” Eckenhoff explained. “In young people, the brain remains largely isolated from that inflammation, but with older people, our blood-brain barrier becomes kind of leaky. That contributes to neuroinflammation, which activates a whole cascade of events in the brain that can accelerate the ongoing aging process.”

At Mount Sinai, Deiner has been administering two-hour-long general anesthesia to healthy seniors and evaluating its impact, in the absence of surgery. Older adults are getting cognitive tests and brain scans before and after. While findings haven’t been published, early results show “very good and rapid cognitive recovery in older adults after anesthesia,” Deiner said. The implication is that “the surgery or the medical conditions surrounding surgery” are responsible for subsequent cognitive dysfunction, she noted.

Advice. Currently, most patients are not told of the post-surgical risk of POCD during the process of informed consent. That should change, several experts advise.

“Beyond question, patients should be informed that the ‘safety step’ of not undergoing surgery is theirs to choose,” wrote Dr. Kirk Hogan, professor of anesthesiology at the University of Wisconsin-Madison School of Medicine and Public Health, in an article published earlier this year. “Each patient must determine if the proposed benefits of a procedure outweigh the foreseeable and material risks of cognitive decline after surgery.”

People with Misophonia Find Background Chewing Sounds so Annoying it Affects Their Ability to Learn

Research in clinical settings shows that some people with mental health problems experience extreme distress when hearing non-speech vocal sounds, like coughs and chewing noises, a phenomenon called “misophonia”. Now research from Amanda Seaborne at the University of California, Santa Barbara, and Logan Fiorella at the University of Georgia, published in Applied Cognitive Psychology, suggests that this issue exists in the broader population, and that people sensitive to these sounds perform poorly in their presence.

Seventy-two undergraduates sat in a cubicle and read a technical text about migraines for six minutes, before reporting what they remembered, answering questions on the text, and finally completing a questionnaire about their misophonia sensitivity (they rated how distressing they found sounds like “rustling papers, sneezing, chewing gum, tapping, eating crunchy foods, and heavy breathing”). For half the participants, a nearby cubicle contained a confederate working for the researchers who chewed gum loudly throughout the experiment. Participants in this condition who scored higher on the misophonia questionnaire performed worse at the comprehension measures than lower scorers.

Interestingly, the reverse pattern was found for the participants in the quiet control condition, with the more sound-sensitive students performing slightly better – perhaps because these conditions were the ones in which they naturally thrive. So misophonia seems to have an impact in non-clinical contexts (none of the rating scores reached clinical levels of sensitivity), although we can’t say whether its origin is in a subtle neurological difference or a psychological preoccupation. But it’s a good reminder that by honouring the expectations in designated quiet spaces, we may be helping others more than we know.

What You Don’t Know About Sepsis Could Kill You

I was at Coachella when I got the call.

“Alex? Can you hear me?”

Music from Father John Misty blared over my mom’s voice. “Sort of,” I said, curling up on the ground like an ailing arachnid and pressing my phone closer.

“I have something serious to tell you,” she said.

I knew that voice. It was the tone of a doctor who’s seen death up close. It was the sound of a wife and mother bearing unthinkable news. It was the noise from my nightmares reverberating into reality.

“Dad is in the ICU. He’s in serious condition.”

I bolted upright. “Is he stable?”

“He is at the moment, but the nurse said that these things are very touch and go.”

Touch and go? I felt sick. My arms trembled like pylons in an earthquake. “Should I come home?”

“I think you have to ask yourself if you want to be here to see him. He could die from this.”

The next hour was the worst of my life. I don’t remember large chunks of it. What I do remember haunts me. I remember running away from the stage repeating “Oh no oh no oh no.” I have a flash memory of dry heaving into a potted palm tree. I recall sobbing uncontrollably in the car. And as much as I’d like to, I can’t forget having a meltdown while packing my suitcase — crying, yelling, and pounding my fists on the ground like a five-year old.

My dad was dying of sepsis. And I felt helpless, 200 miles away at a concert in Palm Springs.

You might not have heard of sepsis. You’re not alone — almost half the population hasn’t either.

Sepsis is the body’s extreme reaction to an infection. The immune system essentially backfires and triggers inflammatory responses throughout the body. The infection can start anywhere — pneumonia, the skin, or a UTI. Sepsis is considered severe sepsis when organs exhibit signs of malfunctioning, like difficulty breathing or abnormally high heart rate. Septic shock takes hold when blood pressure drops to a critical low, even with treatment and intravenous fluids.

Interview With Gut Microbiome Expert Prof. Sarkis Mazmanian

How much progress have we made in understanding the link between our gut microbiome and neurodegeneration?

The field is still relatively young, but it has gained a lot of attention and momentum of late. This has been supported by the emergence of new technologies, especially advances in genomic sequencing and bioinformatics. We are now at a stage in the field where we can look into the basic biology of the microbiome and start asking questions about how it relates to diets, diseases, lifestyles and populations.

The connection to neurodegeneration is in its infancy. We have a few flashbulbs that have gone off in the dark, but we are far from having a clear picture. Our laboratory was one of the first to link Parkinson’s disease to the microbiome. This has gotten a lot of popular press, some of which has been hype and I worry about that long term because it makes promises to society that we don’t know yet if we can keep.

We are interested in learning whether the microbiome tells us anything that we can use to treat neurodegenerative conditions, and also to understand the causes of disease. am hopeful that future research advances may result in ways to improve the health of people suffering from neurodegeneration.

What is your take on claims made that certain probiotics or gut cleaning solutions can help people with Parkinson’s disease?

The knowledge just isn’t there to know what approach will be effective, there is no science behind most commercially available products. We understand so little about the biology of disease, let alone its connection to the microbiome, that anyone who tells you that they have evidence suggesting that they can target the microbiome to help treat any neurodegenerative condition, is guesswork at best.

However, probiotics that are sold commercially are generally safe, so there isn’t much harm being done. But long-term these approaches may not be viable and we need more evidence-based probiotics to validate the link between the microbiome and neurodegeneration.

Hepatitis C Treatments Reduce Transplants

This is not a surprise, but the discussion up to this point has largely been on the cost of the Hep C cures... .

Therapies also appear to reduce liver-related mortality.

Since use of direct acting antiviral combination therapies for hepatitis C virus (HCV) infection became widespread, the need for liver transplantation for patients with the infection has plummeted, researchers reported here.

In 2007, HCV infection was listed as the reason for 23.87% of all liver transplants in Europe, and that remained constant through 2014 when the impact of direct acting antiviral medications began to hit, said Chiara Mazzarelli, MD, of A.O. Ospedale Niguarda Ca'Granda, Milan, Italy.

After that, the proportion dropped sharply each year, to the point that in 2017 about 10.6% of transplants were performed for HCV (P<0.0001).

"In contrast, the demand for livers for patients with NASH (nonalcoholic steatohepatitis) is increasing," Mazzarelli said in her late-breaker presentation at the International Liver Conference, sponsored by the European Association for the Study of the Liver. Liver transplantation for alcohol-related cirrhosis and for hepatitis B infection has remained consistent across the 11-year study period, she said.

She indicated that the reduction in transplantation observed among European patients would likely be similar in the United States and North America.

"In Europe the percentage of liver transplantations performed because of hepatitis C virus infection is rapidly declining," Mazzarelli said at a press conference. "This trend is expected to continue with the increasing access to direct acting antiviral therapy. For the first time after many years, survival of hepatitis C virus transplant recipients is improving thanks to the advent of direct acting antivirals."

"This important study does put into perspective the impact of treatment and shows that treatment can result in really relevant outcomes," said press conference moderator Markus Cornberg, MD, of Hannover Medical School in Germany.

How Growing Inequality Is Altering The Long-Term Care Policy Battlefield, While Tightening The Financing Knot

For many years, long-term care (LTC) policy makers have tended to fall into two warring camps: those favoring expanded social insurance, and those wanting tighter Medicaid eligibility criteria to incentivize people to plan for and buy LTC insurance. Both sides have warned of looming financial catastrophe as the Baby Boomers move into retirement and more than double the population needing care. Disagreement has resulted in a policy stalemate. 

The vanguard of the Boomer generation is less than 10 years away from beginning to drive up demand for LTC, and the country is unprepared to pay for it. It’s time that the policymakers stepped out of the old trenches. The war they’ve been fighting is largely obsolete.

Both progressives who supported the Community Living Assistance Services and Supports (CLASS) Act (a federal LTC insurance program quickly repealed after passage due to its financial instability), and those more inclined to market-based solutions tend to share a middle-to-upper-middle class perspective that has not been sensitive to major shifts in the economic strata below them. Many assume there is a stable American middle class that could either be sufficiently taxed to expand government programs or incentivized to pre-finance LTC of a variety and a quality level above a typical nursing home—which is what is now universally available to Americans through Medicaid after exhausting virtually all their assets. 

Two developments now challenge this orthodoxy. The most obvious is the collapse of the market for LTC insurance, which Conservatives held out as the alternative for middle class reliance on Medicaid. More important, but until recently less understood, is the phenomenon economist Joseph Stiglitz calls the “hollowing out” of the American middle class. A growing body of research reveals trends including a long period of wage stagnation; significantly less likelihood of earning as much as one’s parents; and diminishing lifetime earnings for cohorts entering the workforce since the late 1960s.

A Single Concussion Can Increase Your Chances Of Developing Dementia

The link between head injuries and dementia has just grown stronger: A new study of 2.8 million people in Denmark, including those who had and had not experienced a traumatic brain injury (TBI) in their lifetime, found that those with at least one TBI had a 24 percent increased risk of dementia, on average. The average diagnosis age was 81.

The NHS emphasize that this is about increased risk after receiving a TBI, however. The absolute risk of developing dementia throughout your lifetime is very small. Of this sample, only 5.1 percent of those that had a TBI developed dementia, compared to 4.5 percent of non-TBI people that also developed dementia.