Day: 12/10/2022

Can AI Drive More Diversity in Drug Development?

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Artificial intelligence could help improve diversity, equity, and inclusion in clinical trials and drug development by overcoming some traditional human bias in these areas, but we’re not there yet, experts say. The technology could also assist doctors with data insights to make diagnosis and treatment more precise. 

It starts with quality. Artificial intelligence (AI) relies on large amounts of data to create algorithms – or computer instructions – to develop best practices and predictions. But the instructions are only as good as the data used to create them. And people are the ones creating the data.

“Underpinning the development of AI technologies are people, and those people have their own biases,” says Naheed Kurji, the chair of the board for the Alliance for Artificial Intelligence in Healthcare. “As a result, the algorithms will have their own biases.”

Technology that uses speech to diagnose disease is an example. 

“There are many cases, examples where companies have failed to recognize the differences in speech across different cultures,” says Kurji. When technology is based on speech patterns of a limited demographic, “then when that model is applied in the real world to a different demographic with a different accent, that model fails.”

“As a result, it’s not representative.”

Another example is genetic and genomic data. 

“Give or take, 90-plus percent of genetic and genomic data has originated from people of European descent. It’s not from people from the continent of Africa, Southeast Asia, Asia, or South America,” says Kurji, who is also president and CEO of Cyclica Inc., a data-driven drug discovery company based in Toronto. 

Therefore, “a lot of research that has been done on that level of data is inherently biased,” he says. 

To Be Fair 

Creating data that takes diversity, equity, and inclusion of people and cultures around the world into account is not a hopeless challenge. But it will take time, experts say. Once that is achieved, AI should be closer to being free of human and systemic biases.

Greater awareness is essential. 

“The solution to the problem comes from people inherently understanding that the bias exists,” Kurji says, and then only including fair and balanced data that passes a diversity test.

Choosing More Wisely?

Another promising avenue for AI is streamlining the drug development process, narrowing down potential drug candidates, and making clinical trials more cost-effective. 

“If the source data has challenges and limitations, then that the AI is going to just keep propagating those limitations,” agrees Sastry Chilukuri, co-CEO of the data-driven clinical trial company Medidata and founder and president of Acorn AI. “The source data has to get more representative and has to get more equitable for the AI to reflect what’s happening.”

When it comes to human or systemic bias in drug development, “it would be too much of a simplification to say AI or machine learning can fix it,” says Angeli Moeller, PhD, head of data and integrations generating insights at Roche in Berlin. “But responsible use of AI and machine learning can help us identify biases and find ways to mitigate any negative effects it might cause.”

Silent Partners?

At the same time AI aims to streamline drug development, the technology also can help make all doctors better at their jobs, experts say. AI would, for instance, help by spreading knowledge and expertise far and wide, sharing best practices from doctors with a lot of experience in more complex patients. This would help guide those who treat only a few such patients each year. 

The surgical volumes in New York City or in Delhi could be as high as hundreds of patients a year, Chilukuri says. “But if you go to interiors of the U.S. like Nebraska, the surgeon just doesn’t see that much volume.” 

AI could help doctors “by providing the kind of tools that allow them to be able to deliver the same top-notch care to all of their populations at lot faster,” he says.

Boosting Efficiency 

AI could help target therapy by using data to identify patients at highest risk. The technology also could improve some bottleneck areas in medicine, such as the time it takes to interpret radiology images, Kurji says. 

There is an AI company “whose entire business model is not to replace your radiologist but to make radiologists better,” he notes. One of company’s aims is “to prevent death or severe ailment from radiology scans that get missed or that get stacked on the pile and just don’t get acted on fast enough for that patient.” 

Radiologists are so busy, they may have only 30 seconds or less to interpret each scan, says Chilukuri. AI can flag a lesion of potential concern, but it can also compare an image to past scans on the same patient. This view afforded by AI does not just apply to radiology but across data-driven areas of medicine. 

Advancing Personalized Medicine

AI could also guide a personal approach to surgery, “because it’s not like humans come in small, medium and large,” Chilukuri says. The technology could help surgeons determine exactly where to operate on an individual patient.

Moeller agrees that AI holds potential for boosting personalized medicine.  Slideshow

Emerging Trends in Health Technology

“AI can help with diagnosis and risk prediction, which can mean earlier interventions,” says Moeller, who’s also vice chair of the Alliance for Artificial Intelligence in Healthcare board.  “If you look, for instance, at a diabetic patient, what is the likelihood that he or she might develop eye problems from diabetic macular edema?”

The technology could also help with getting a look at the big picture. 

“Machine learning can look for patterns in a population that might not be in your medical textbook,” Moeller says. 

Beyond diagnosis and treatment, AI also could help with recovery by customizing rehabilitation for each patient, Chilukuri predicts. 

“It’s not like every person is going to rehab the exact same way. So, you have highly individualized AI plans that allow you to actually stay on track and predict where you’re going.”

Source: WebMD

New Alzheimer’s Drug Shows ‘Modest’ Success, And Risks

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photo of medical research

Widely anticipated data from a phase 3 trial of a new Alzheimer’s disease treatment suggests the drug “modestly” relieved cognitive problems in patients early into the disease — but at a cost.

In the trial, adverse events among patients taking the drug, lecanemab, were common compared with placebo, including leaking blood vessels ; and a news report this week linked a second death to the drug.

Moving forward, “longer trials are warranted to determine the efficacy and safety of lecanemab in early Alzheimer’s disease,” Christopher H. van Dyck, MD, of the Yale School of Medicine in New Haven, CT, and colleagues write.

The full trial findings were presented at the 15th Clinical Trials on Alzheimer’s Disease conference, and were also published  Nov. 29 in the New England Journal of Medicine.

Endpoints Met 

The phase 3 trial of lecanemab has been closely watched in Alzheimer’s circles, especially considering positive early data released in September, reported by Medscape Medical News at that time.

The FDA is expected to decide whether to approve the drug in January. The agency has approved only one other similar treatment, the highly controversial and expensive aducanumab (Aduhelm).

For the new 18-month, randomized, double-blind trial, researchers enrolled 1,795 patients ages 50 to 90 with early Alzheimer’s.. All were randomly assigned to receive either a placebo or intravenous lecanemab.

The study ran from 2019 to 2021. The participants (52% women, 20% non-White) were recruited in North America, Europe, and Asia. 

Those on the experimental drug scored 27% better on a Alzheimer’s rating scale compared to those on the placebo. 

The study authors did not speculate about how this difference would affect the day-to-day life of patients who took the drug, although it does refer to “modestly less decline” of cognition/function in the lecanemab group.

Concerning Adverse Event Data

With respect to adverse events, deaths occurred in both groups (0.7% in those who took lecanemab and 0.8% in those who took the placebo). The researchers did not attribute any deaths to the drug. However, the journal Science reported Nov. 27 that a 65-year-old woman who was taking the drug as part of a clinical trial “recently died from a massive brain hemorrhage that some researchers link to the drug.”

The woman, the second person “whose death was linked to lecanemab,” died after suffering a stroke. Science summarized a case report as saying that the drug “contributed to her brain hemorrhage after biweekly infusions of lecanemab inflamed and weakened the blood vessels.”

Eisai, which sponsored the new trial, told Science that “all the available safety information indicates that lecanemab therapy is not associated with an increased risk of death overall or from any specific cause.”

Cautious Optimism

In separate interviews with Medscape Medical News, two Alzheimer’s specialists who weren’t involved in the study praised the trial and described the findings as “exciting.” But they also highlighted its limitations.

Alvaro Pascual-Leone, MD, PhD, professor of neurology at Harvard Medical School
and chief medical officer of Linus Health, said the study represents impressive progress after 60-plus trials examining what are known as anti-amyloid monoclonal antibodies. “This is the first trial that shows a clinical benefit that can be measured,” he said. 

However, it’s unclear whether the changes “are really going to make a difference in people’s lives,” he said. The drug is likely to be expensive due to the large investment needed for research, he added, and patients will have to undergo costly testing such as PET scans and spinal taps. 

Howard Fillit, MD, co-founder and chief science officer at the Alzheimer’s Drug Discovery Foundation, noted that the trial reached its primary and secondary endpoints and had what he called a “modest” effect on cognition.

However, the drugmaker will need to explore the adverse effects, he said, especially in patients with atrial fibrillation who take anticoagulants. And, he said, medicine is still far from the ultimate goal — fully reversing cognitive decline. 

Rave Reviews from the Alzheimer’s Association

In a statement, the Alzheimer’s Association raved about lecanemab and declared the FDA should approve lecanemab on an accelerated basis. The study “confirms this treatment can meaningfully change the course of the disease for people in the earliest stages of Alzheimer’s disease…,” the association said, adding that “it could mean many months more of recognizing their spouse, children and grandchildren.”

The association, which is also a staunch supporter of aducanumab, called on the Centers for Medicare and Medicaid Services to cover the drug if the FDA approves it. The association’s statement did not address the drug’s potential high cost, the adverse effects, or the 2 reported deaths. 

Source: WebMD

Where Did All the Monkeypox Go?

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Mpox questions answered by Demetre “Doctor D” Daskalakis

Photo of Dr. D over a background of the monkey pox virus.

Within months of first hearing about monkeypox spreading outside of endemic areas, Demetre Daskalakis, MD, MPH, was appointed deputy coordinator of the White House Monkeypox Response Team.

MedPage Today sat down with Daskalakis to discuss the transformation the epidemic has been through, from a rocky start with fear and few answers to now just a trickle of cases of what was recently renamed “mpox” in order to reduce stigma and racism.

Testing, vaccination (Jynneos), treatment (tecovirimat, Tpoxx), community cooperation, and a mass targeted communications campaign that was particularly aimed towards LGBTQ+ communities slowed the virus such that the mpox epidemiology (epi) curve has returned to where it was in June. The Biden administration announced last week that mpox will no longer have health emergency status after January.

That progress was not without many bumps in the road.

Stigma, conspiracy theories, and politics were great enemies of the virus from day one. Mpox Clade IIb is most transmissible during human skin-to-skin contact and thus highly transmissible during sex. The community of men who have sex with men (MSM) accounted for more than 95% of cases; and particularly severe cases were found in people co-infected with HIV.

Daskalakis had both pandemic experience as former senior lead on equity in COVID-19 data and engagement for the New York City Department of Health and Mental Hygiene and an “in” with the LGBTQ+ community from his work in HIV prevention and his transparency about being a gay man.

Daskalakis is a self-described “queer health warrior.” As the founder of the Men’s Sexual Health Project, he went to sex clubs and bathhouses to test men for HIV and other sexually transmitted diseases (STDs) to help direct them to treatment. For mpox, that meant getting vaccine to gay events, testing and treating in STD clinics, and meeting people “where they were.” He also tackled equity challenges, particularly in reaching Black and Hispanic communities, and challenges educating health professionals about potential stigma.

Not shying away from a fight with stigma, Daskalakis playfully took part in a campaign endorsing NYC’s promotion of open conversation about sex and drugs between patients and their doctors, posing shirtless for the “Bare it all” campaign, baring his muscles, tattoos, and a big smile.

His bold strokes as a doctor and as a communicator have been both applauded and criticized.

“Don’t be jealous because he also looks better than you with his shirt off,” David Holland, MD, an infectious disease specialist at Emory University in Atlanta, tweeted in response to negative comments about images of Daskalakis clad in a leather harness. “He’s a brilliant scientist, tireless public servant, and has always worked right on the front lines, including this amazing ad campaign.”

The conversation with Daskalakis that follows has been lightly edited, mainly for length. It occurred before the virus was renamed mpox.

What did you carry forward from the HIV and COVID-19 outbreaks into the monkeypox outbreak?

Daskalakis: From the monkeypox perspective, I think that the lessons we learned from the COVID-19 pandemic are that complications are expected; they’re not surprising. You learn that in HIV, and you learn that in COVID. So really, it’s critical to take a proactive intentional path when doing public engagement and addressing the issues right from the start.

With that said, it still didn’t work perfectly for monkeypox.

We still have inequities, and we still have challenges. Some of that is just based on logistics. When you don’t have enough vaccine at the beginning of the outbreak, it’s really a challenge. But I feel like the strategy of trying to increase vaccine [supply] is one of those important equity interventions, along with moving to do testing quicker — that’s a lesson from COVID-19.

I definitely think the messaging is less about the details of what you say and more about the fact that you [as the government-appointed person leading this] need to have humility in terms of what you know and what you don’t know. And so, I feel like that is my mantra from COVID-19 actually, and also for monkeypox: Risk messaging is of critical importance; and being able to sort of say “I know this” and “I don’t know this” and “what I know today is going to be different tomorrow,” that changes everything.

The data show that people are still getting infected after they get the vaccine. Does that reflect the vaccine or behavior?

Daskalakis: None of that is surprising. No vaccine is 100%. We are going to learn more about the vaccine efficacy as we go forward, but I think definitely that post-vaccination infections are to be expected.

It’s not good harm-reduction to expect or to tell people to change their behaviors for life for a virus that is like this.

I always go back to thinking about early HIV and having the desire for people to change their behavior for HIV. It worked for a while. But you would have to get people to change their behaviors for a couple of generations to get rid of HIV. This one [monkeypox], you don’t have to change behaviors for generations; it’s for a few months. Once you build your force field of immunity with vaccines, people can make their own informed decisions about their risk. If I’m still willing to accept any risk, I may cool some of the things I would normally do, but if I’m willing to accept more risk I may not. But I will have some confidence that I have some level of protection. That’s harm reduction. That’s the way to do this.

The second dose of vaccine brings you to a higher level of protection based on lab data. I’m not a vaccine efficacy expert, but we tend to see the epi curve going down. It shows you whatever we have done so far with behavior, and people who have had infections are immune, all those things come together to really get us to a place where we’re controlling this outbreak.

Will we see this virus eradicated?

Daskalakis: I think a long tail is what we can expect. This outbreak went straight up, and it’s going down. Do I think we’re going to get to zero next week? No. Will we have weeks when we get to zero? I think yeah. Not quite yet.

This is where we have to ante up and move faster with the vaccine, because it’s working. We’ve seen some softening in vaccine demand, and so we just need to sort of get the word out and keep magnifying it. This is not the time to back off. The more protection we can get during this peaceful lull, the better we are in long-term infections.

What are the long-term effects of monkeypox infection?

Daskalakis: Definitely there is some concern about long-term scarring, like skin scarring. There’s the potential for scarring in places you don’t want to scar, that can cause urethral and rectum stricture.

But we know this virus is not going to recur. Once it’s gone, it’s gone. We have to watch carefully — there are so many post-viral syndromes people have. It’s super important for us to see longitudinally what happens to folks.

What has been your biggest challenge working in the White House?

Daskalakis: When Bob [Robert Fenton, White House national monkeypox response coordinator] and I started the job, President Biden said, “I really want you to make sure we’re improving the health of men that have sex with men, and especially those of color.”

I was like, “Yes, sir!” I can’t believe I signed up for this. It wasn’t in my bingo cards to be in the White House, so if this is what the boss says, well this is great. This is what I want to do. Let’s do it!

So the biggest challenge has been the normal outbreak stuff — trying to be as transparent as I can with what we know and what we don’t know. Sometimes it’s fraught with complications. What do we know enough about to say? And what don’t we know enough about to say?

In terms of signing up to get what the community needs, I can say with confidence that the Biden administration strategy worked, as demonstrated by our epi curve. But I feel like the fact that the foundation of the response was engagement with the community just tells you that that’s where it all starts.

Do you know of any other country that has approached the epidemic the way the U.S. did, by reaching out to vaccinate the MSM community at gay pride events?

Daskalakis: One of the biggest successes is San Francisco, where they made the magic happen [getting the number of cases down to zero quickly]. The bottom line is getting vaccines out. One of the most important events in my opinion was Black Pride in Atlanta, where we gave 5,000 vaccines and 4,200 injections were administered.

We really try to take strategies to improve equity programmatically but also by addressing some of the important barriers that are experienced, like people saying “I don’t want this mark on my forearm” [out of concern for stigma]. So we worked with the FDA and the CDC and we were able to move to other sites that people can receive vaccine, like the upper back.

I feel like we are kind of unicorns in this. It shows that this is the way to do it.

Did it take too long to decide monkeypox was “like” an STD?

Daskalakis: I feel like we can say with great certainty that monkeypox has been transmitted with close physical contact associated with sex.

From the programmatic perspective, we’re treating it with a syndemic strategy, and the way we’re doing it using sexually-transmitted infection and HIV resources signals so much about the right way to control the outbreak.

It’s really more the “how” than the semantics of it. Every state is able to decide if they want to move it into an STD category. So, for example, New York did that; for some 90-day period, they are calling this an STD, so that there is access to resources already there.

Our signal is to use the HIV infrastructure to address this, and people responded really well to that.

Is there ongoing funding for monkeypox?

Daskalakis: There’s no specific funding that’s been allocated for monkeypox. We sent a supplemental request that wasn’t funded. We need a longitudinal plan.

You’ve advocated home testing. How would home testing affect the ongoing surveillance and statistics on monkeypox?

Daskalakis: I come from that HIV space, where sometimes you have to give up something to be able to make movement in other things. People that are going to order home tests are going to be motivated to action in other ways. And so thinking about HIV home testing, which was the grandparent of COVID-19 home testing, this really shows us how you reach people you’re not going to reach when you have lab-based, provider-only testing.

When you look at the HIV home testing data from the CDC, 26% of the people that ordered a home test had never been tested before. That is way higher than what you would expect.

It’s a “power to the person on the street” issue for me. That’s so important, that if you’re not going to build a testing center where people will come, then if you can get the test to them — even if it causes a little bit of a pause in data or difficulty understanding the data — that home-based testing ends up becoming really important. I feel pretty strongly that you can’t hold the operational and programmatic things that you know can improve your outcomes hostage for perfect data.

The reality is that a multiplex test in the lab is really important for monkeypox, like a point-of-care test. As seen with secondary syphilis, for example, people tend to come to point of care because they’ve got something going on.

For people that may be symptomatic but don’t need to go get clinical care for monkeypox, who don’t want to go into an environment where “Oh! I have to disclose my sexuality, or this disease potentially discloses in some people’s minds my gender identity,” I think there’s high utility in that.

Cognitive Decline Tied to Midlife Diet

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Impact of ultra-processed foods is small but important, prospective study suggests

A photo of a mature man on a couch with a bowl of potato chips on his chest, beer in hand.

Middle-age people who ate more ultra-processed foods — white bread, candy bars, cookies, frozen meals, and soda, for example — were modestly more likely to have subsequent cognitive decline, a prospective study in Brazil showed.

Adults who got 20% or more of their daily calories from ultra-processed foods (UPFs) showed a 28% faster rate of global cognitive decline over 8 years, albeit with a small linear association (β -0.004, 95% CI -0.006 to -0.001, P=0.003), reported Natalia Gomes Gonçalves, PhD, of the University of São Paulo Medical School in Brazil, and co-authors.

That group also showed a 25% faster rate in executive function decline, again with a small linear correlation (β −0.003, 95% CI -0.005 to 0.000, P=0.01), the researchers wrote in JAMA Neurology.

“Intact cognitive function is key to successful aging,” they wrote. “Therefore, despite the small effect size of the association between UPF consumption and cognitive decline, our findings are meaningful to cognitive health.”

The results echoed findings published earlier this year that linked ultra-processed foods with dementia risk. Notably, risk was projected in that study to drop sharply when swapping junk food for unprocessed or minimally processed foods.

“Middle age is an important period of life to adopt preventive measures through lifestyle changes, since the choices we make at this age will influence our older years,” Gomes Gonçalves said in an email to MedPage Today.

“This does not mean that older adults will not have benefits if they adopt a healthier lifestyle,” she added. “Research has shown over and over again that we benefit from healthy choices at any age.”

A diet of 20% or more of ultra-processed foods is common, she noted. “Considering a person who eats a total of 2,000 kcal a day, 20% of daily calories from ultra-processed foods are about two 1.5-ounce Kit Kat bars, or five slices of bread, or about a third of an 8.5-ounce package of chips,” Gomes Gonçalves wrote.

In the U.S., 58% of daily calories come from ultra-processed foods. In the U.K. and Canada, that figure is 47-48%; in Brazil, it’s 30%.

Gomes Gonçalves and colleagues analyzed ultra-processed food consumption at baseline and subsequent cognitive decline among 10,775 people in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Participants were public servants ages 35 to 74 recruited in six Brazilian cities from 2008 to 2019.

The researchers assessed food and drink intake over the 12 months prior to baseline with a validated food frequency questionnaire that included 114 items. Foods were classified by their extent of industrial processing using the NOVA classification system.

Cognitive evaluations included immediate and delayed word recall, word recognition, phonemic and semantic verbal fluency tests, and the Trail-Making Test part B, which were conducted over a median follow-up of 8 years. Individuals were tested up to three times every 4 years.

Mean age at baseline was 51.6 years. About 55% of participants were women, 53% were white, and 57% had at least a college degree. Total daily calorie intake averaged 2,856 kcal, with 27% (785 kcal) from ultra-processed foods. The researchers grouped the percentage contribution of ultra-processed food into quartiles (0-19.9%, 20-26.7%, 26.8-34.1%, and 34.2-72.7%), comparing the lowest-intake group against all others combined.

Age modified the effect between ultra-processed foods and cognitive function. People younger than 60 who ate 20% or more of their daily calories as ultra-processed foods showed faster global cognition decline than their same-age counterparts who consumed less junk food (β -0.006, 95% CI -0.009 to -0.003, P<0.001).

“The interesting thing about the NOVA classification system is that it classifies foods based on the industrial processing they go through,” Gomes Gonçalves observed. “To make healthier choices, one can dedicate more time to cooking meals from scratch at home.”

“For example, instead of buying frozen pizza, one could buy separate ingredients, make homemade dough, and use fresh ingredients as toppings,” she noted. “It’s possible to make healthier food choices within our means even if our access to healthy food is limited. We just need to dedicate the time and energy.”

Attrition is a concern for a long-term study, the researchers acknowledged. People under age 55 didn’t have a cognitive assessment during their second visit due to study design. The findings relied on self-reported data from food frequency questionnaires, which may be subject to bias and misreporting.

source:Medscape.com

Small Spot a Source of Mysterious Abdominal Pain in Adolescent Girl

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Case highlights a clinically diagnosed condition often misdiagnosed in adults and teens alike

A photo of a nauseous teen girl with a hand on her mouth, the other on her stomach.

A 15-year-old girl presented to the emergency department (ED) after 3 days of pain in her lower left abdomen, with no precipitating factors or visceral symptoms, reported Kazuki Iio, MD, and Yu Ishida, MD, of the Tokyo Medical University Hachioji Medical Center, in a case report published in JAMA.

She told clinicians the pain had developed slowly over the previous 3 days, but otherwise she felt fine. Her appetite was not affected, she said, nor did she have any nausea, bloating, diarrhea, or blood in her stool.

On questioning, she noted that over the past 2 years, she had periodically experienced the same symptoms, which lasted about 1 week each time.

Asked about her medical history, she reported taking an oral contraceptive. She had never been pregnant, undergone abdominal surgery, or experienced any abdominal injuries.

Findings of a medical workup from 1 year before presentation, including laboratory tests, upper endoscopy, colonoscopy, and an abdominal CT scan, were all normal.

The ED intake physical showed normal vital signs and body mass index. Abdominal examination showed no rigidity or guarding; however, clinicians identified a 1-cm point of significant tenderness in the left lower abdomen.

On palpation, the patient noted worsening pain in this small spot when she raised her head and tightened her stomach muscles. She experienced loss of sensation in the affected area when clinicians applied an alcohol gauze pad, and pinching the skin caused her severe pain.

Clinicians considered several diagnoses, including post-herpetic neuralgia, celiac artery compression syndrome, and acute intermittent porphyria, before concluding that the symptoms were due to anterior cutaneous nerve entrapment syndrome (ACNES).

Iio and Ishida explained that post-herpetic neuralgia was unlikely given the absence of a rash or “dermatomal distribution of abdominal pain.” The patient’s abdominal pain did not suggest celiac artery compression syndrome symptoms, which tend to be epigastric and worsen after eating, they noted. “And acute intermittent porphyria typically causes diffuse abdominal pain.”

“The key to the correct diagnosis was recognition that the 1-cm point of maximal tenderness was localized to the outer rim of the rectus abdominis muscle,” they wrote.

The patient was given a subfascial injection of 5 mL of 1% lidocaine under ultrasound guidance into the 1-cm area of maximal abdominal tenderness. “One hour later, the patient reported a decrease in pain from 9 to 0 on a numeric pain rating scale that ranges from 0 (no pain) to 10 (worst pain imaginable),” the authors reported. On follow-up 9 months later, the patient said she remained free of any recurrences of abdominal pain.

Discussion

ACNES is an abdominal wall disorder that is four times more common in females than males, and is usually diagnosed at a median age of 40 to 50 years, Iio and Ishida noted. However, it can occur at any age, they added, “and the incidence increases during adolescence.”

ACNES patients typically experience abdominal pain below the level of the umbilicus, often on the right side. A retrospective study of over 1,100 patients showed that up to 50% of patients with ACNES reported visceral symptoms such as nausea, bloating, abdominal swelling, and loss of appetite.

The condition is widely presumed to be “related to compression and irritation of the intercostal nerve endings that pass through the rectus abdominis muscle and innervate the oblique muscles,” Iio and Ishida explained. “Abdominal muscle spasm results in progressive nerve entrapment, which perpetuates the pain.”

Approximately one in three patients report a prior event thought to give rise to the condition, including surgery, trauma, or injury; pregnancy; and influenza infection; however, it occurs without provocation in 75% of adolescents affected. Interestingly, oral contraceptive use has also been implicated in ACNES, according to at least one report.

The estimated incidence of ACNES in the general population is one in 1,800 to 2,000 individuals, and the condition accounts for 2% of ED presentations for acute abdominal pain, the authors noted.

Still, diagnosis takes time, they said, with a median of 18 months after symptom onset. Other data suggest that diagnosis can take more than 5 years in about 10% of patients with ACNES, since patients are often misdiagnosed with irritable bowel syndrome, fibromyalgia, complex regional pain syndrome, or rheumatoid arthritis.

ACNES diagnosis is “based on history and characteristic clinical findings in patients who have abdominal pain in an area of 1 cm or less at the lateral border of the rectus abdominis muscle,” Iio and Ishida noted. The only role of blood tests and imaging is to help exclude other reasons for the abdominal pain.

As in this patient’s case, “a positive Carnett test, defined as increased pain with head lifting and tensing of the abdominal muscles while the point of maximal tenderness is palpated, was reported in 87% of 1,116 patients with ACNES,” they wrote.

Other research suggests that if the cause of the pain is visceral, such as cholecystitis, pain may decrease with this maneuver.

Physical exam findings characteristic of ACNES include:

  • Sensory disturbances at the painful abdominal area (78%)
  • Positive pinch sign (78%)
  • Positive Carnett sign (87%)
  • Positive response to a modified rectus sheath block (>50% pain reduction; 81%)

Diagnosis can be confirmed if pain is reduced by at least half after 5 to 10 mL of local anesthetic (lidocaine) is injected (with or without ultrasound guidance) into the affected area, Iio and Ishida noted.

A single injection of lidocaine achieves immediate pain reduction in 86% of patients, they added, citing other data showing that a single injection was associated with persistent pain relief in 10% to 20% of patients. Recurrent abdominal pain affects most patients, however, and is generally managed with “up to 2 additional injections of lidocaine.”

Another study suggested that about half of patients with ACNES had a decrease in abdominal pain following pulsed radiofrequency therapy, with 8% remaining pain-free at 15-month follow-up.

Finally, patients whose pain persists in spite of multiple lidocaine injections may get relief with neurectomy — the surgical removal of intercostal nerve branches, the authors noted.

Source: Medscape

Aging U.S. Population a Challenge for Oncologists

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Older patients will have different care goals, preferences, geriatric oncologist says

By 2030 the entire Baby Boomer generation — now estimated by the U.S. Census Bureau to number over 73 million people — will be older than 65.

“This is really important for us who care for individuals with cancer because the peak incidence of cancer diagnosis is in the eighth decade of life,” explained Tullika Garg, MD, MPH, a specialist in geriatric oncology at Penn State Health in Hershey, Pennsylvania, during a session at the Society of Urologic Oncology annual meeting. “It is also the second leading cause of death in people who are 85 and older.”

Urologic oncologists are not going to be immune from the demographic trends, she noted, adding that the incidence of genitourinary cancers is going to increase precipitously in older adults in the next few years.

Garg emphasized that oncologists should realize that older cancer patients are going to be different from their younger counterparts — particularly in terms of age-related conditions, as well as treatment goals and preferences — pointing to results from the GOSAFE (Geriatric Oncology Surgical Assessment and functional rEcovery) study, which assessed 977 geriatric patients prior to undergoing cancer surgery, and found that:

  • 20% had difficulty walking
  • 10% had a history of one or more falls
  • 37% were taking more than five medications
  • 31% had decreased food intake prior to surgery
  • 66% screened positive for frailty

These conditions actually inform why geriatric cancer patients have different goals and preferences, Garg said. “They’re worried how cancer treatment will impact their current geriatric conditions.”

For example, she added, results from a survey of 226 patients ages 60 and older who had a limited life expectancy due to cancer, congestive heart failure, or chronic obstructive pulmonary disease showed that if the outcome from treatment was survival, but with severe functional impairment or cognitive impairment, 74.4% and 88.8% of these patients, respectively, would not choose treatment.

Quoting the late geriatric oncologist Arti Hurria, MD — “Our patients want to know if they are treated, just how sick they are going to get, they want to know if they will be able to continue to function, and if their memory will be intact” — Garg noted that “ultimately between the combination of geriatric conditions and goals and healthcare preferences, our goal is to balance under- and overtreatment in this population.”

However, older adults are a heterogenous group, she said. “And we don’t have great data on how to make these decisions, and our clinical trial data are largely based on younger, healthier patients. We have to find ways to evaluate our patients — figure out who is fit, and then tailor care to what their needs are.”

Furthermore, she pointed out that traditional pre-treatment evaluations focus on chronological age, “which we know is not a great marker of fitness.”

Garg suggested that oncologists should consider adopting the concept of the Geriatric 5 Ms — representing mind, mobility, medications, multicomplexity, and matters to me — to help determine a patient’s fitness for treatment.

“One thing I would really like to do more in my own practice — and I think something which is really important for all of us — is to do cognitive screening,” she said. “Cognitive impairment really impacts the ability to provide good informed consent for surgery, and also impacts a patient’s risk of delirium in the postoperative period.”

Finally, Garg suggested that oncologists use frailty screening tools such as the Geriatric 8 questionnaire and the TUG (Timed Up & Go) test, assess patients’ risks of chemotherapy toxicity with tools such as the Cancer and Aging Research Group’s chemotoxicity calculator, and cultivate relationships with geriatricians.

She also advised oncologists to be mindful of ageism, and their own individual biases regarding age.

“My patients have taught me a lot about what is important to them, and they do worry about their cancer,” Garg said. “Certainly they care about the other non-traditional outcomes I talked about — but they do worry about their cancer, and our goal is to get them whatever treatment we can provide that is tailored to all of their goals and preferences.”

source: Medscape

Adding Gut Health Supplement Helped Kids With Obesity Lose More Weight

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Small trial saw metabolic benefits with daily butyrate added to standard of care

A photo of a white capsule between a child’s fingers next to a white bottle.

Children with obesity saw therapeutic benefits with the addition of a daily oral butyrate supplement to standard of care, the randomized Butyrate Against Pediatric Obesity (BAPO) trial showed.

In an intention-to-treat analysis of 54 participants, supplementation with oral sodium butyrate 20 mg/kg body weight per day led to a higher rate of decreases of ≥0.25 SD scores for body mass index (BMI) compared with placebo at 6 months (96% vs 56%, P<0.01), reported Roberto Berni Canani, MD, PhD, of the University of Naples in Italy, and colleagues.

This translated into a number needed to treat of only 2, the group noted in JAMA Network Open.

BMI dropped down to an average of 26.53 from a baseline of 29.55 in the butyrate group, while the placebo group only dropped down to 28.71 from a baseline of 29.47.

In the per-protocol analysis of 48 participants, several other significant metabolic benefits were seen in those taking butyrate compared with placebo:

  • Waist circumference: -5.07 cm (95% CI -7.68 to -2.46)
  • Insulin level: -5.41 μU/mL (95% CI -10.49 to -0.34)
  • Homeostatic model assessment of insulin resistance: -1.14 (95% CI -2.13 to -0.15)
  • Ghrelin level: -47.89 μg/mL (95% CI -91.80 to -3.98)
  • MicroRNA221 relative expression: -2.17 (95% CI -3.35 to -0.99)
  • Interleukin-6 level: -4.81 pg/mL (95% CI -7.74 to -1.88)

There were no differences in changes in serum glucose, cholesterol, LDL-C, HDL-C, and triglyceride levels seen between the butyrate and placebo groups.

All participants engaged in similar diets, with both groups cutting out around 500 calories per day by 6 months. Canani’s group also noted a shift in macronutrient intake, marked by lower carb and fat intake but more grams of fiber per 1,000 calories consumed.

These benefits seen with butyrate can be traced back to its beneficial impact on the gut microbiome (GM), the researchers explained.

“Plant foods are fermented by GM to produce the antiobesogenic short-chain fatty acid butyrate,” they wrote. “Although butyrate dietary intake could be increased by the consumption of dairy products, its main source is derived by GM fermentation of nondigestible carbohydrates.”

“A low intake of dietary substrates for butyrate production and a low number of butyrate-producing bacteria may contribute to obesity,” they added. “This evidence suggests the potential of butyrate for treating obesity.”

Those in the butyrate group took up to 800 mg/day of sodium butyrate for 6 months, while the placebo group took cornstarch capsules. Both groups received standard-of-care treatment for pediatric obesity in Italy, which involved the Mediterranean diet using the reference of the Italian Society of Human Nutrition plus at least 60 minutes of daily aerobic activity paired with a reduction in sedentary behaviors.

There were a few drawbacks to butyrate supplementation, as two children reported mild nausea and headaches while taking it, though these symptoms dissipated over the first 4 weeks of the study.

“The lower adherence rate and higher frequency of mild adverse effects observed in patients treated with butyrate suggest that the unpleasant organoleptic features of this compound may limit its clinical application,” Canani and colleagues noted, adding that the “development of new butyrate-based compounds free of these unpleasant features is advocated for a more effective therapeutic action of butyrate against pediatric obesity.”

This study, conducted from November 2020 through December 2021, included 54 participants ages 5 to 17 (mean age 11, 57% girls) treated at the Tertiary Center for Pediatric Nutrition at the University of Naples. Median baseline BMI was 27.3 in the placebo group and 30.4 in the butyrate group.

Of note, four participants in the butyrate group didn’t adhere to treatment versus only two in the placebo group.

Source: Medscape.com