Connect with us

News

A Gout Drug Used For Nearly A Decade Found To Increase Risk Of Death After The Trial’s Primary Endpoint

Published

on

Febuxostat, a gout drug that has been in use for nearly a decade, was found to significantly increase the risk of death, even though it did not raise the risk of the trial’s primary endpoint, a combined rate of fatal and nonfatal adverse cardiovascular events, according to research presented at the American College of Cardiology’s 67th Annual Scientific Session.

It is unusual for a clinical trial to reveal an increased risk of death without also showing a heightened risk of other cardiovascular outcomes such as nonfatal heart attack and stroke. The findings, which showed an uptick in deaths after patients had been taking Febuxostat for two years or longer, call into question the safety of long-term Febuxostat use in patients with cardiovascular disease, researchers said.

“This finding was entirely unexpected, and we’re at a loss at this time to explain why this finding was seen,” said William B. White, MD, professor of medicine at the Calhoun Cardiology Center of the University of Connecticut School of Medicine and the study’s lead author.

“The results were consistent across many subgroups; there was no evidence of a relationship with age, sex, race or ethnicity, history of cardiovascular disease, or duration or severity of the gout.”

Gout is a form of arthritis estimated to affect more than 8 million people in the U.S. It is caused by a buildup of urate levels in the body and leads to episodes of intense joint pain due to crystal formation and inflammation. Gout is more common in men and is associated with obesity; many people with gout also have or are at risk for heart disease. Although dietary and lifestyle changes can help manage the disease, many patients require medication called xanthine oxidase inhibitors to prevent flare-ups.

The drug allopurinol has served as the standard treatment for gout since the 1960s, but it can cause kidney problems and severe allergic reactions in some patients. Febuxostat was developed to offer a safer alternative, particularly for gout patients with chronic kidney disease.

Early clinical trials for Febuxostat showed the drug was effective for lowering serum urate but signaled a slightly elevated risk of adverse cardiovascular events. The U.S. Food and Drug Administration (FDA) approved Febuxostat for gout in 2009 under the condition that a robust trial is initiated to assess long-term cardiovascular outcomes.

The FDA-mandated trial, known as CARES, for which results are being reported now for the first time, was designed to assess whether Febuxostat was noninferior to allopurinol in terms of a composite primary endpoint that included death from cardiovascular causes, nonfatal heart attack, nonfatal stroke and unstable angina leading to urgent revascularization (a procedure to open blocked arteries). Researchers also examined rates of each of these outcomes separately, as well as other markers of cardiovascular and kidney health.

The trial enrolled more than 6,000 patients at 320 centers in North America. All study participants had gout as well as established cardiovascular disease, such as a previous heart attack, stroke, hospitalization for chest pain (unstable angina), peripheral arterial disease, or both diabetes and small vessel disease. Half of the patients were randomly assigned to receive febuxostat and half received allopurinol; neither the patients nor their doctors knew which drug they had received.

Participants continued taking their assigned medication while researchers tracked their health outcomes for more than 2.5 years on average and as long as 6.5 years in some patients.

By the end of the trial, 656 primary endpoints had occurred. Patients taking allopurinol and Febuxostat experienced the composite primary endpoint at nearly the same rate. These results met the study’s threshold for noninferiority, indicating that Febuxostat was not inferior to allopurinol. However, when the researchers examined each endpoint separately, they found those randomized to take Febuxostat had a 34 percent higher rate of death from cardiovascular causes and a 22 percent higher rate of death from any cause.

A high proportion of patients (45 percent) elected to stop taking their assigned drug before the study ended. In patients who stopped taking Febuxostat early, the elevated risk of death was diminished. Overall, however, more patients died after discontinuing their assigned medication than while taking the drug.

Researchers were unable to identify the reason for the surprising—and seemingly contradictory—findings. White said the results of previous tests in animal models and cell cultures do not point to any biological mechanisms that would explain how febuxostat might cause cardiovascular harm.

While the increased risk of death was consistent across subgroups of patients based on demographic factors and health conditions, there were two differences noted regarding medication use. Among patients receiving Febuxostat, those who did not regularly take aspirin and those who regularly took nonsteroidal anti-inflammatory drugs (NSAIDs) faced a higher risk of death compared with those taking aspirin or not taking NSAIDs. Researchers cautioned that the study was not designed to assess potential medication interactions, however.

“It is important to be careful when interpreting these findings; it doesn’t necessarily indicate there’s an interaction between these drugs and Febuxostat,” White said.

“It might have been that these patients had more active gout with more flares, for example.”

The researchers plan to continue to explore the data to determine whether the results may yield insights on the optimal treatment for gout in patients who have both cardiovascular disease and chronic kidney disease. In the approximately 50 percent of patients with a history of chronic kidney disease in the CARES trial, mortality was roughly equal among those taking Febuxostat and those taking allopurinol.

In addition, White said ongoing studies being conducted in Europe may help shed light on the potential risks and benefits of febuxostat in patients who have cardiovascular risk factors but who do not have established cardiovascular disease.

The trial was funded by Takeda Pharmaceuticals U.S.A. Inc., maker of febuxostat.

This study was simultaneously published online in the New England Journal of Medicine at the time of presentation.

News

Parents, Kids Spend More Time Discussing How To Use Mobile Technology Than Talking About Content

Published

on

ANN ARBOR—Most parents would agree that one of the of the biggest modern parenting challenges is monitoring a child’s online activity.

A new study appearing in the Journal of Child and Family Studies found that parents spend more time talking with kids about the mechanics of using their mobile devices than they do about what their kids watch and download on those devices.

The findings came from a small, recent study of 75 children and their families, led by researcher Sarah Domoff, then a postdoctoral fellow at University of Michigan Center for Human Growth and Development. The children wore recording devices at home, which recorded talking, conversations or other sounds nearby, as well as audible screen media use.

Domoff, now an assistant professor at Central Michigan University, said the findings revealed some concerning trends in how families and children communicate about media today. Specifically, the researchers observed minimal conversation about the content of programming that children were watching.

Additionally, they learned that other family members appear to play an important role when content is discussed. Children––not parents––initiated most conversations about content, and older siblings played a much bigger role than parents in content mediation for younger siblings. Also, the study found that children as young as toddlers were exposed to multiple media sources at one time, or media multitasking.

Other findings include:

  • Negotiations and conflict are common among parents and children.
  • Parallel family media use is common, meaning different family members use their own devices at the same time.

“One of the most challenging aspects of parenting today is being aware of what children are exposed to online, particularly content delivered via mobile devices,” Domoff said.

“Thus, it is critical that parents utilize privacy settings and restrictions to protect children from certain content. Ideally, this would occur before the child received their own mobile device.”

Domoff recommends developing a family media plan. In 2016, The American Academy of Pediatrics released a tool that helps families set different goals and media use rules based on individual needs, she said.

It’s also troubling that some apps downloaded by children include advertising or request in-app purchases, she said. Parents can identify these apps by using Common Sense Media’s app review.

Parents can also recruit older children to help younger siblings make good content choices.

The study aimed to identify themes of parental mediation and family communication around mobile media devices. There’s a dearth of scientific data in this area compared to television and video games, but studies show that parental mediation leads to better outcomes for children.

Continue Reading

News

Internet Therapy Apps Reduce Depression Symptoms

Published

on

BLOOMINGTON, Ind. — In a sweeping new study, Indiana University psychologists have found that a series of self-guided, internet-based therapy platforms effectively reduce depression.

The work, which reviewed 21 pre-existing studies with a total of 4,781 participants, was published in the November issue of the Journal of Medical Internet Research. The study was led by Lorenzo Lorenzo-Luaces, an assistant professor of clinical psychology in the IU Bloomington College of Arts and Sciences’ Department of Psychological and Brain Sciences.

In the past several years, many internet-based apps and websites have made claims to treat depression. The subjects of the IU study were specifically those applications that provide treatment with cognitive behavioral therapy, a form of psychotherapy that focuses on changing thought patterns and behavior to alleviate symptoms of depression and other mental disorders.

Previous studies had examined the effectiveness of individual internet-based cognitive behavioral therapy apps, or iCBT, using a range of methods. Until this study, however, no review had examined whether the effects of these treatments were inflated by excluding patients with more severe depression or additional conditions such as anxiety or alcohol abuse.

“Before this study, I thought past studies were probably focused on people with very mild depression, those who did not have other mental health problems, and were at low risk for suicide,” Lorenzo-Luaces said.

“To my surprise, that was not the case. The science suggests that these apps and platforms can help a large number of people.”

For Lorenzo-Luaces, internet-based cognitive behavioral therapy apps are an important new tool for addressing a major public health issue: that individuals with mental health disorders like depression far outnumber the mental health providers available to treat them.

“Close to one in four people meet the criteria for major depressive disorder,” he said.

“If you include people with minor depression or who have been depressed for a week or a month with a few symptoms, the number grows, exceeding the number of psychologists who can serve them.”

People with depression are also expensive for the health care system, he added.

“They tend to visit primary-care physicians more often than others,” Lorenzo-Luaces said.

“They have more medical problems, and their depression sometimes gets in the way of their taking their medication for other medical problems.”

By conducting a “meta-regression analysis” of 21 studies, Lorenzo-Luaces and collaborators decisively determined that internet-based therapy platforms effectively alleviate depression. A central question was determining whether previous studies distorted the strength of these systems’ effects by excluding people with severe depression.

The conclusion was that the apps worked in cases of mild, moderate and severe depression.

Many of the studies in the analysis compared use of internet-based cognitive behavioral therapy apps to placement on a wait list for therapy or the use of a “fake app” that made weak recommendations to the user. In these cases, the iCBT apps worked significantly better.

“This is not to say that you should stop taking your medication and go to the nearest app store,” added Lorenzo-Luaces, who said both face-to-face therapy and antidepressants may still prove to be more effective than the iCBT apps alone.

“People tend to do better when they have a little bit of guidance,” he said. But he added that a 10- to 15-minute check-in may be sufficient for many people, freeing health care providers to see more patients.

App-based therapy also has an advantage in situations where access to face-to-face therapy is limited due to logistical barriers, such as long distances in rural areas or inflexible work schedules.

“ICBT apps take the methods we have learned and make them available to the many people who could benefit from them,” Lorenzo-Luaces said.

“It’s an exciting development.”

 

Continue Reading

News

New Study Finds Employee Incentives Can Lead To Unethical Behavior In The Workplace

Published

on

Considering end-of-year bonuses for your employees? Supervisors be forewarned, a new study finds that while incentive rewards can help motivate and increase employee performance it can also lead to unethical behavior in the workplace.

“Goal fixation can have a profound impact on employee behavior, and the damaging effects appear to be growing stronger in today’s competitive business landscape,” says Bill Becker, co-author of the study and associate professor of management in the Pamplin College of Business at Virginia Tech.

The study, “The effects of goals and pay structure on managerial reporting dishonesty,” provides valuable insight into the relationship between pay structures and motivation.

Findings suggest that setting compensation goals can increase dishonesty when managers are also paid a bonus for hitting certain targets.

“These unintended negative consequences can lead to dishonesty, unethical behavior, increased risk-taking, escalation of commitment, and depletion of self-control,” says Becker.

The study points to observations of unethical behaviors in the workplace that include employees falsifying or manipulating financial reporting information as well as time and expense reports.

For example, service professionals such as auditors, contractors, lawyers, and consultants who report hours billed against a target budget is often based on a fixed contract price.

“This causes potential for both under-reporting and over-reporting costs, which can undermine organizational objectives and negatively impact the interest of the firm,” says Becker.

“Using purely monetary incentives is almost always a double edged sword.”

Continue Reading

Like Us on Facebook

Trending Posts

News23 hours ago

Parents, Kids Spend More Time Discussing How To Use Mobile Technology Than Talking About Content

ANN ARBOR—Most parents would agree that one of the of the biggest modern parenting challenges is monitoring a child’s online...

News23 hours ago

Internet Therapy Apps Reduce Depression Symptoms

BLOOMINGTON, Ind. — In a sweeping new study, Indiana University psychologists have found that a series of self-guided, internet-based therapy...

News23 hours ago

New Study Finds Employee Incentives Can Lead To Unethical Behavior In The Workplace

Considering end-of-year bonuses for your employees? Supervisors be forewarned, a new study finds that while incentive rewards can help motivate...

News23 hours ago

Trying To Get People To Agree? Skip The French Restaurant And Go Out For Chinese Food

Why sharing a plate leads to better negotiation outcomes? Here’s a new negotiating tactic: enjoy a family-style meal with your...

News23 hours ago

Review Confirms Food Cravings Can Be Reduced

BATON ROUGE, LOUISIANA — Food craving, the intense desire to eat certain foods, can sabotage efforts to maintain healthy eating habits...

News2 days ago

Study Points To Optimal Blood Pressure Treatment For Stroke Patients

Aggressive treatment of hypertension in stroke patients could do more harm than good in the long term, according to a new...

News2 days ago

Study Identifies A Key Cellular Mechanism That Triggers Pneumonia In Humans

The situation is relatively common, especially in winter. You come down with the flu, which lasts longer than usual. A...

Trending