New Compound Promising for Knee Osteoarthritis

A novel study has shown that intra-articular therapy with high‐purity synthetic trans‐capsaicin (CNTX‐4975) was associated with significant relief of knee pain in patients with chronic knee osteoarthritis (OA).

The TRIUMPH study was a double‐blind, phase II study in adults (45–80 years) with stable knee osteoarthritis. Patients were given an intra‐articular injection of placebo, CNTX‐4975 0.5 mg, or CNTX‐4975 1.0 mg. The primary efficacy endpoint was area under the curve (AUC) for change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain with walking scores at week 12.

A total of 172 subjects were enrolled and at week 12, greater decreases in WOMAC pain scores were observed with CNTX‐4975 versus placebo.

• CNTX-4975 0.5 mg: LSMD −0.79, P=0.0740
• CNTX-4975 1.0 mg: LSMD −1.6, P<0.0001
• Efficacy continued till week 24 in the 1.0 mg group (LSMD −1.4, P=0.0002)

Adverse events were similar in the placebo and 1.0‐mg groups.

Knee pain from knee OA may be effectively and safely managed with this new investigational compound, CNTX‐4975, and is thought to be mediated by sustained desensitization of nociceptors (pain sensory fibers).

Jack Cush, MD, is the director of clinical rheumatology at the Baylor Research Institute and a professor of medicine and rheumatology at Baylor University Medical Center in Dallas. He is the executive editor of RheumNow.com. A version of this article first appeared on RheumNow, a news, information and commentary site dedicated to the field of rheumatology. Register to receive their free rheumatology newsletter.

• Primary Source

  Arthritis & Rheumatology

  Source Reference: Stevens RM, et al “Randomized, Double‐Blind, Placebo‐Controlled Trial of Intra‐articular CNTX‐4975 (trans‐capsaicin) for Pain Associated With Osteoarthritis of the Knee” Arthr Rheumatol 2019; DOI: 10.1002/art.40894.

https://www.medpagetoday.com/rheumatology/arthritis/79312

Novel 5-minute workout improves blood pressure, may boost brain function

A volunteer demonstrates Inspiratory Muscle Strength Training at the University of Colorado Boulder.

Credit: CU Boulder

Could working out five minutes a day, without lifting a single weight or jogging a single step, reduce your heart attack risk, help you think more clearly and boost your sports performance?

Preliminary results from a clinical trial of Inspiratory Muscle Strength Training (IMST), presented this week at the Experimental Biology conference in Orlando, suggest “yes.”

“IMST is basically strength-training for the muscles you breathe in with,” said Daniel Craighead, a postdoctoral researcher in the the University of Colorado Boulder Integrative Physiology department who is leading the study. “It’s something you can do quickly in your home or office, without having to change your clothes, and so far it looks like it is very beneficial to lower blood pressure and possibly boost cognitive and physical performance.”

Developed in the 1980s as a means to wean critically ill people off ventilators, IMST involves breathing in vigorously through a hand-held device — an inspiratory muscle trainer — which provides resistance. Imagine sucking hard through a straw which sucks back.

During early use in patients with lung diseases, patients performed a 30-minute, low-resistance regimen daily to boost their lung capacity.

But in 2016, University of Arizona researchers published results from a trial to see if just 30 inhalations per day with greater resistance might help sufferers of obstructive sleep apnea, who tend to have weak breathing muscles.

In addition to more restful sleep, subjects showed an unexpected side effect after six weeks: Their systolic blood pressure plummeted by 12 millimeters of mercury. That’s about twice as much of a decrease as aerobic exercise can yield and more than many medications deliver.

“That’s when we got interested,” said principal investigator Professor Doug Seals, director of CU Boulder’s Integrative Physiology of Aging Laboratory.

Systolic blood pressure, which signifies the pressure in your vessels when your heart beats, naturally creeps up as arteries stiffen with age, leading to damage of blood-starved tissues and higher risk of heart attack, cognitive decline and kidney damage.

While 30 minutes per day of aerobic exercise has clearly been shown to lower blood pressure, only about 5 percent of adults meet that minimum. Meanwhile, 65 percent of mid-life adults have high systolic blood pressure.

“Our goal is to develop time-efficient, evidence-based interventions that those busy mid-life adults will actually perform,” said Seals, who was recently awarded a $450,000 National Institute of Aging grant to fund the clinical trial of IMST involving about 50 subjects.

Craighead presented preliminary results Sunday and Monday at Experimental Biology 2019 showing that:

With about half the tests done, the researchers have found significant drops in blood pressure and improvements in large-artery function among those who performed IMST with no changes in those who used a sham breathing device that delivered low-resistance.

The IMST group is also performing better on certain cognitive and memory tests.

When asked to exercise to exhaustion, they were also able to stay on the treadmill longer and keep their heart rate and oxygen consumption lower during exercise.

Some cyclists and runners have already begun to use commercially-available inspiratory muscle trainers to gain a competitive edge.

But Seals and Craighead stress that their findings are preliminary and curious individuals should ask their doctor before considering IMST.

That said, with a high compliance rate (fewer than 10 percent of study participants drop out) and no real side-effects, they’re optimistic.

“High blood pressure is a major risk factor for cardiovascular disease, which is the number one cause of death in America,” said Craighead. “Having another option in the toolbox to help prevent it would be a real victory.”

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Story Source:

Materials provided by University of Colorado at Boulder. Note: Content may be edited for style and length.

https://www.sciencedaily.com/releases/2019/04/190408161643.htm

The Value of Providing Smokers With Free E-Cigarettes

Bottom Line: Studies show that e-cigarette use facilitates quitting smoking. The provision of e-cigarettes to smokers for at least a period of time, without financial charge, may well be something that public health services should consider. 

The Royal College of Physicians and Public Health England have both indicated the likely benefit of switching to the exclusive use of vaping devices for those smokers who are unable or unwilling to quit smoking combustible tobacco products. The issue that we address within this paper is whether the encouragement and assistance to smokers to switch to non-combustible tobacco products should include the free provision of those products for at least a restricted period of time.

Few studies have investigated the rates of smoking cessation and smoking reduction that are associated with the provision of free e-cigarettes to smokers. In this study, e-cigarettes were given to a sample of adult smokers. After 90 days:

• The complete abstinence rate was 36.5%, up from 0% at baseline.
• The frequency of daily smoking reduced from 88.7% to 17.5%.
• The median consumption of cigarettes/day reduced from 15 to five.
• The median number of days per month that participants smoked also reduced from 30 to 13 after 90 days.

On the basis of these results, there may be value in smoking cessation services and other services ensuring that smokers are provided with e-cigarettes at zero or minimal costs for at least a short period of time.

The study shows that use of e-cigarettes supported smokers’ efforts in quitting and reducing smoking over a 90-day period. The abstinence levels increased from baseline to day 30, and continued to rise throughout the study duration (90 days). The finding suggests that the use of vaping may have additional benefits with longer use—i.e., a proportion of smokers quit smoking within the first month of use, but a larger proportion needed more than two months to make the switch, and gradually quit over a longer period.

Read the full report here.

https://www.realclearpolicy.com/public_affairs/2019/01/08/the_value_of_providing_smokers_with_free_e-cigarettes_110976.html

How tech will put hospitals out of business

Internet 2.0, smart tech, big data, machine learning and artificial intelligence—these are all the building blocks of our digital future.

Someday soon, cars will drive by themselves, refrigerators will inform you when you need more milk (and order it for you) and a plethora of connected devices will collect data that will make them work more efficiently and effectively for us.

This digital revolution will touch everything—including the hospital.

 

Smart tech has already revolutionized medical care: Robots perform surgery, handheld devices collect data from sensors attached to patients and upload them to patient record databases and hospitals use location tech to quickly find staff, supplies and more. But the application of smart tech is still at its beginning stage.

The "next big thing" in hospital care, many experts believe, will be providing care not at the hospital but at home.

This is not home care, experts who see this trend forming emphasize. Instead, it's home-based hospital standard care with access to all the advanced equipment and expert caregivers that patients would get in the hospital itself.

Advanced communications tech, internet of things devices, the ability of physicians or nurses to remotely monitor every aspect of a patient's condition—all those are creating conditions that will enable patients to rest, recuperate and recover in familiar surroundings with access to family and friends. The "next big thing" in hospital care, many experts believe, will be providing care not at the hospital, but at home.

The hospital as we know it—a medical center crammed full of patients, beds, equipment, medical staff and service workers, and much more—is an expense society can't really afford anymore.

 

Hospitals, as they exist today, are about a century old, and in that time have turned into the focal point of medical care. If you're sick, you go to the doctor, who prescribes a plan to treat the condition. If that doesn't work, the doctor may send you to a hospital for tests or treatment—and if you're sick enough, you're treated in the hospital, with drugs, surgery or whatever else your prognosis requires.

That initial treatment, or series of treatments, is usually followed by a recovery period, which can be lengthy. Chronically ill patients may find themselves in the hospital for months at a time, while medical staff try to come up with new ways of treating them. Most of the day patients are left to their own devices, with nurses or LPNs coming around to their vital signs—all of which, of course, are measured using digital tools.

Meanwhile, costs climb, insurance companies pay out, patients are frustrated or depressed at being institutionalized—and are at risk of contracting a hospital-acquired infection—and another individual who needs treatment may not be able to get it, because the hospital is already likely to be running at full capacity.

If, indeed, much of a patient's time is spent in recovery or convalescence—and the data are being digitally read and recorded anyway—why not use the communications technology at our disposal to set up a temporary “mini-hospital” at a patient's home? This is the next leap in the burgeoning telemedicine movement: The physical hospital can focus on intensive care and surgical operations, while other functions will be replaced by advanced home care with medical staff in constant touch remotely.

In the event of a medical emergency, staff will be alerted immediately—and an ambulance, itself a mini-hospital on wheels, will be dispatched with qualified staff aboard to conduct the necessary actions to stabilize the patient. If need be, it will bring them back to the physical hospital for further treatment.

And the data hospitals will have on their virtual patients will enable medical staff to intervene even before that emergency. Big data, crunched and processed, combined with advanced machine learning and AI, is already being used to predict patient events. Patients will benefit not just from analysis of their own data, but from the analysis of the many other patients who are being treated for the same or similar conditions, as analytics systems parse the huge body of data and examine treatment patterns and outcomes, determining which patterns are likely to work best in each specific case.

Indeed, this will revolutionize hospital care as we know it within the coming decade. Other industries—retail, banking, finance and others—have long used digital tools to enable clients and businesses to collaborate and connect, anytime and anywhere. Those tools are now available to the medical industry—and given the constantly ballooning costs of care, the hospital is a perfect candidate for its own digital revolution.

https://www.fiercehealthcare.com/hospitals-health-systems/industry-voices-how-tech-will-put-hospitals-out-business

Ketamine cultivates new nerve cell connections in mice

Ketamine banishes depression by slowly coaxing nerve cells to sprout new connections, a study of mice suggests. The finding, published in the April 12 Science, may help explain how the hallucinogenic anesthetic can ease some people’s severe depression.

The results are timely, coming on the heels of the U.S. Food and Drug Administration’s March 5 approval of a nasal spray containing a form of ketamine called esketamine for hard-to-treat depression (SN Online: 3/21/19). But lots of questions remain about the drug.

“There is still a lot of mystery in terms of how ketamine works in the brain,” says neuroscientist Alex Kwan of Yale University. The new study adds strong evidence that newly created nerve cell connections are involved in ketamine’s antidepressant effects, he says.

While typical antidepressants can take weeks to begin working, ketamine can make people feel better in hours. Scientists led by neuroscientist Conor Liston suspected that ketamine might quickly be remodeling the brain by spurring new nerve cell connections called synapses. “As it turned out, that wasn’t true, not in the way we expected, anyway,” says Liston, of Cornell University.

Newly created synapses aren’t involved in ketamine’s immediate effects on behavior, the researchers found. But the nerve cell connections do appear to help sustain the drug’s antidepressant benefits over the longer term.

To approximate depression in people, researchers studied mice that had been stressed for weeks, either by being restrained daily in mesh tubes, or by receiving injections of the stress hormone corticosterone. These mice began showing signs of despair, such as losing their taste for sweet water and giving up a struggle when dangled by their tails.

Three hours after a dose of ketamine, the mice’s behavior righted, as the researchers expected. But the team found no effects of the drug on nerve cells’ dendritic spines — tiny signal-receiving blebs that help make new neural connections. So the creation of new synapses couldn’t be responsible for ketamine’s immediate effects on behavior, “because the behavior came first,” Liston says.

When the researchers looked over a longer time span, though, they found that these new synapses were key. About 12 hours after ketamine treatment, new dendritic spines began to pop into existence on nerve cells in part of the mice’s prefrontal cortex, the brain area responsible for complex thinking. These dendritic spines seemed to be replacing those lost during the period of stress, often along the same stretch of neuron.

To test if these newly created spines were important for the mice’s improved behavior, the researchers destroyed the spines with a laser a day after the ketamine treatment. That effectively erased ketamine’s effects, and the mice again exhibited behavior resembling depression, including struggling less when held by their tails. (The mice kept their regained sugar preference.)

Research on humans has also suggested that depressed people have diminished synapses, says Ronald S. Duman, a neuroscientist at Yale University not involved in the study. The new work adds more support to those findings by showing that destroying new synapses can block ketamine’s behavioral effects. “That’s a huge contribution and advance,” Duman says.

https://www.sciencenews.org/article/ketamine-new-nerve-cell-connections-mice-depression?tgt=nr

In Medicare-For-All Debate, Insurers Bet They’re Loved More Than Bernie

Health insurance executives are increasingly betting that Americans like private coverage more than health benefits that would only be administered by the government given public statements by CEOs and information pushed by their lobbyists.

As presidential hopeful U.S. Sen. Bernie Sanders and some Democrats push a single payer version of Medicare for All that would replace the private healthcare system, health insurers are countering with more aggressive responses, touting their worth to U.S. consumers and patients. Insurers are touting their businesses and noting Americans are buying what they have to offer backed by polls and surveys saying consumers are satisfied.

Take UnitedHealth Group’s CEO, who led off the company’s 80-minute first quarter earnings call this past week talking for several minutes about the benefits of the private insurer’s role working with the government in administering U.S. healthcare benefits.

“The best system is one which is informed, engaged and aligned, where people, their doctors and the private and public sectors work together to improve or sustain individual health, while improving the performance of health systems – for everyone,” UnitedHealth Group CEO David Wichmann said.

And other health insurance CEOs are also speaking out, talking about the expense of Medicare for All and doubting whether it will even happen given how entrenched the private sector is. More than 20 million Americans are now enrolled in private Medicare Advantage plans and most U.S. Medicaid beneficiaries get coverage from a private insurer that contracts with states,reports show.

On the day Centene CEO Michael Neidorff announced the proposed acquisition of WellCare Health plans, he talked about a 10-year cost of Medicare for All of more than $25 trillion and touted insurer efforts to expand benefits in partnership with the government. “We cannot afford it,” Neidorff said on a conference call March 27.

Centene, which already provides coverage for 2 million individually insured Americans under the Affordable Care Act, administers Medicaid benefits and would have an expanded role in Medicare Advantage once the WellCare Health Plan deal closes.

“We have to look at the practical, the political and everything I saw said: This is a great transaction,” Neidorff said. “It put two great companies together in a very meaningful way serving a lot of audiences that you can never do enough to serve.”

Both politicians and health insurers tout studies and polls showing people like both Medicare for All and private coverage.

America’s Health Insurance Plans, which lobbies for most large health insurers including Centene, Cigna and Anthem, released a survey last year showing more than 70% of Americans “satisfied” with their “employer-provided health coverage.”

Meanwhile, other research published by independent organizations shows Americans tend to be satisfied with their private and employer coverage but that could be waning a bit.

The Kaiser Family Foundation, which has monthly tracking polls and other surveys rating the public’s perception of health coverage, showed 83% of Americans rated their employer-based coverage as “excellent” or “good” and 17% said it was “not so good” or “poor,” in a 2016 survey. In 2010, 92% said their employer coverage was “excellent” or “good” and just 7% said it was “not so good” or “poor.”

“Overall, a majority of these individuals rate their coverage favorably, but we did find a slight decrease in favorability from 2010 to 2016,” says Ashley Kirzinger, associate director of Kaiser’s polling team.

https://www.forbes.com/sites/brucejapsen/2019/04/20/in-medicare-for-all-debate-insurers-bet-theyre-loved-more-than-bernie/#a3e11ec2889c

Anti-Inflammatory Add-On May Be Beneficial for Depression

Anti-inflammatory add-on treatment is beneficial for patients with major depressive disorder (MDD) or depressive symptoms, according to a meta-analysis published in the May issue of Acta Psychiatrica Scandinavica.

Ole Köhler-Forsberg, from Aarhus University Hospital in Denmark, and colleagues performed a systematic review of randomized clinical trials (RCTs) studying antidepressant treatment effects and side effects of pharmacological anti-inflammatory interventions in adults with MDD or depressive symptoms. Data were included for 36 RCTs, of which 13 investigated nonsteroidal anti-inflammatory drugs (4,214 patients), nine cytokine inhibitors (3,345 patients), seven statins (1,576 patients), three minocyclines (151 patients), two pioglitazones (77 patients), and two glucocorticoids (59 patients).

The researchers found that compared with placebo, anti-inflammatory agents improved depressive symptoms as an add-on in patients with MDD (standardized mean difference [SMD], −0.64) and as monotherapy (SMD, −0.41). Response and remission were improved with an anti-inflammatory add-on (risk ratios, 1.76 and 2.14, respectively). A trend toward increased risk for infections was seen; a high risk for bias was observed in all studies.

“What’s persuasive is that we’ve found that several of the anti-inflammatory drugs have what can be characterized as a medium to a large effect on depression and depressive symptoms, in particular because the results build on almost 10,000 people who have participated in the placebo-controlled studies with anti-inflammatory treatment,” a coauthor said in a statement. “The results from the meta-analysis are particularly promising not only because of an effect of the anti-inflammatory medicine on its own but also due to the supplementary effect when the anti-inflammatory medicine is given simultaneously with the antidepressants that are used today.”

Abstract/Full Text

https://www.physiciansbriefing.com/psychiatry-16/depression-news-176/anti-inflammatory-add-on-may-be-beneficial-for-depression-745140.html