Could your arthritic knee be destroying brain cells?

Well, yeah, could be.  Not really a big surprise – inflammation associated with knee arthritis (chronic knee pain) shows accelerated brain cell aging.  Not a surprise because we know that inflammation is the route of all bad things… though it’s a necessary part of normal function as well.  Controlled inflammation (i.e. regular exercise) is good for you.  Uncontrolled inflammation is bad for you.  This article talks about a single specific gene, but there are a multitude of genes that impact inflammation.  We look at these – managing the response to inflammation with this guidance can be both very helpful and likely has more long-term impact than we probably even know.  

Opportunities for better health abound – Limitless Healing is our tagline!

FROM MEDSCAPE INTERNAL MEDICINE / BY MEGAN BROOKS

Chronic Pain Linked to Accelerated Brain Aging

The consequences of chronic musculoskeletal pain (CMP) may extend well beyond physical discomfort, potentially leading to faster aging of the brain, new research showed.

Using structural MRI data from more than 9000 adults with knee osteoarthritis (KOA) from the UK Biobank, investigators developed a brain age model to compare an individual's brain age with their chronological age. Those with KOA showed a much faster rate of brain aging than healthy individuals.

The acceleration in brain aging was largely driven by the hippocampus and predicted memory decline and incident dementia during follow-up. Researchers identified a gene highly expressed in glial cells as a possible genetic factor for accelerated brain aging.

"We demonstrate the accelerated brain aging and cognitive decline in chronic musculoskeletal pain, in particular knee osteoarthritis, and provide a neural marker for early detection and intervention," co-first author Jiao Liu, PhD candidate, Chinese Academy of Sciences, Beijing, China, told Medscape Medical News.

"We are interested to know how to slow down the aging brain in chronic musculoskeletal pain patients. Proper exercise and lifestyle may reduce the risk," Liu said.

Common Condition

CMP affects more than 40% of the world's population and has been shown to have a harmful impact on cognitive function, although the exact mechanisms remain unclear. Prior research suggests that inflammatory markers associated with brain aging are higher in patients with CMP, suggesting a link between brain aging and CMP.

To investigate further, researchers explored patterns of brain aging in healthy cohorts and cohorts with four common types of CMP — chronic knee pain, chronic back pain, chronic neck pain, and chronic hip pain.

Using their brain age model, investigators observed significantly increased brain aging, or "predicted age difference," only in individuals with KOA (P < .001). The observation was validated in an independent dataset (P = .020), suggesting a pattern of brain aging acceleration specific to KOA.

This acceleration was primarily driven by key brain regions involved in cognitive processing, including hippocampus and orbitofrontal cortex, and was correlated with longitudinal memory decline and dementia risk.

These data also suggest that the SLC39A8 gene, which is highly expressed in glial cells, might be a key genetic factor underpinning this acceleration.

"We not only revealed the specificity of accelerated brain aging in knee osteoarthritis patients, but importantly, we also provided longitudinal evidence suggesting the ability of our brain aging marker to predict future memory decline and increased dementia risk," corresponding author Yiheng Tu, PhD, also with Chinese Academy of Sciences, Beijing, China, said in a news release.

A Future Treatment Target?

Commenting on this research for Medscape Medical News, Shaheen Lakhan, MD, PhD, neurologist, and researcher based in Miami, Florida, noted that in this study, people with KOA showed signs of "faster brain aging on scans. Think of it as your brain wearing a disguise, appearing older than its actual years," Lakhan said.

"Inflammation, a key player in osteoarthritis, might be playing a double agent, wreaking havoc not just on your joints but potentially on your memory too. Researchers even identified a specific gene linked to both knee pain and faster brain aging, hinting at a potential target for future treatments," he added.

"Importantly, the increased risk of cognitive decline and dementia associated with chronic pain is likely one of many factors, and probably not a very high one on its own," Lakhan noted.

The "good news," said Lakhan, is that there are many "well-established ways to keep your brain sharp. Regular exercise, a healthy diet, and staying mentally stimulated are all proven strategies to reduce dementia risk. Think of chronic pain management as another tool you can add to your brain health toolbox."

Good way to get unhealthy-- Eat late and eat fast

A very good summary article of lots of little tidbits about eating and issues.  

Eating fast leads to a bunch of problems.  While eating slow leads to lower calories for those not-so-heavy, it may not make any difference if you’re already obese.  But eating late (evening or lots later in the day) has substantially increased risks of weight gain.  Even time restricted eating is better if you make your eating window earlier in the day.

The article even suggests a truly radical concept:  Eat only if you are hungry, don’t if you’re not!  RADICAL!

FROM MEDSCAPE INTERNAL MEDICINE / by john watson

Speedy Eating and Late-Night Meals May Take a Toll on Health

You are what you eat, as the adage goes. But a growing body of evidence indicates that it's not just what and how much you eat that influence your health. How fast and when you eat also play a role.

Research now indicates that these two factors may affect the risk for gastrointestinal problems, obesity, and type 2 diabetes (T2D). Because meal timing and speed of consumption are modifiable, they present new opportunities to change patient behavior to help prevent and perhaps address these conditions.

Not So Fast

Most people are well acquainted with the short-term gastrointestinal effects of eating too quickly, which include indigestion, gas, bloating, and nausea. But regularly eating too fast can cause long-term consequences.

Obtaining a sense of fullness is key to staving off overeating and excess caloric intake. However, it takes approximately 20 minutes for the stomach to alert the brain to feelings of fullness. Eat too quickly and the fullness signaling might not set in until you've consumed more calories than intended. Research links this habit to excess body weight.

The practice also can lead to gastrointestinal diseases over the long term because overeating causes food to remain in the stomach longer, thus prolonging the time that the gastric mucosa is exposed to gastric acids.

A study of 10,893 adults in Korea reported that those with the fastest eating speed (< 5 min/meal) had a 1.7 times greater likelihood of endoscopic erosive gastritis than those with the slowest times (≥ 15 min/meal). Faster eating also was linked to increased risk for functional dyspepsia in a study involving 89 young-adult female military cadets in Korea with relatively controlled eating patterns.

On the extreme end of the spectrum, researchers who performed an assessment of a competitive speed eater speculated that the observed physiological accommodation required for the role (expanding the stomach to form a large flaccid sac) makes speed eaters vulnerable to morbid obesity, gastroparesis, intractable nausea and vomiting, and the need for gastrectomy.

The risk for metabolic changes and eventual development of T2D also appear to be linked to how quickly food is consumed.

Two clinical studies conducted in Japan — a cohort study of 2050 male factory workers and a nationwide study with 197,825 participants — identified a significant association between faster eating and T2D and insulin resistance. A case-control study involving 234 patients with new onset T2D and 468 controls from Lithuania linked faster eating to a greater than twofold risk for T2D. And a Chinese cross-sectional study of 7972 adults indicated that faster eating significantly increased the risk for metabolic syndrome, elevated blood pressure, and central obesity in adults.

Various hypotheses have been proposed to explain why fast eating may upset metabolic processes, including a delayed sense of fullness contributing to spiking postprandial glucose levels, lack of time for mastication causing higher glucose concentrations, and the triggering of specific cytokines (eg, interleukin-1 beta and interleukin-6) that lead to insulin resistance. It is also possible that the association is the result of people who eat quickly having relatively higher body weights, which translates to a higher risk for T2D.

However, there's an opportunity in the association of rapid meal consumption with gastrointestinal and metabolic diseases, as people can slow the speed at which they eat so they feel full before they overeat.

A 2019 study in which 21 participants were instructed to eat a 600-kcal meal at a "normal" or "slow" pace (6 minutes or 24 minutes) found that the latter group reported feeling fuller while consuming fewer calories.

This approach may not work for all patients, however. There's evidence to suggest that tactics to slow down eating may not limit the energy intake of those who are already overweight or obese.

Patients with obesity may physiologically differ in their processing of food, according to Michael Camilleri, MD, consultant in the Division of Gastroenterology and Hepatology at Mayo Clinic in Rochester, Minnesota.

"We have demonstrated that about 20%-25% of people with obesity actually have rapid gastric emptying," he told Medscape Medical News. "As a result, they don't feel full after they eat a meal and that might impact the total volume of food that they eat before they really feel full."

The Ideal Time to Eat

It's not only the speed at which individuals eat that may influence outcomes but when they take their meals. Research indicates that eating earlier in the day to align meals with the body's circadian rhythms in metabolism offers health benefits.

"The focus would be to eat a meal that syncs during those daytime hours," Collin Popp, PhD, MS, RD, a research scientist at the NYU Grossman School of Medicine in New York, told Medscape Medical News. "I typically suggest patients have their largest meal in the morning, whether that's a large or medium-sized breakfast, or a big lunch."

A recent cross-sectional study of 2050 participants found that having the largest meal at lunch protected against obesity (odds ratio [OR], 0.71), whereas having it at dinner increased the risk for obesity (OR, 1.67) and led to higher body mass index.

Consuming the majority of calories in meals earlier in the day may have metabolic health benefits, as well.

A 2015 randomized controlled trial involving 18 adults with obesity and T2D found that eating a high-energy breakfast and a low-energy dinner leads to reduced hyperglycemia throughout the day compared with eating a low-energy breakfast and a high-energy dinner.

Time-restricted eating (TRE), a form of intermittent fasting, also can improve metabolic health depending on the time of day.

A 2023 meta-analysis found that TRE was more effective at reducing fasting glucose levels in participants who were overweight and obese if done earlier rather than later in the day. Similarly, a 2022 study involving 82 healthy patients without diabetes or obesity found that early TRE was more effective than mid-day TRE at improving insulin sensitivity and that it improved fasting glucose and reduced total body mass and adiposity, while mid-day TRE did not.

A study that analyzed the effects of TRE in eight adult men with overweight and prediabetes found "better insulin resistance when the window of food consumption was earlier in the day," noted endocrinologist Beverly Tchang, MD, an assistant professor of clinical medicine at Weill Cornell Medicine with a focus on obesity medication.

Patients May Benefit From Behavioral Interventions

Patients potentially negatively affected by eating too quickly or at late hours may benefit from adopting behavioral interventions to address these tendencies. To determine if a patient is a candidate for such interventions, Popp recommends starting with a simple conversation.

"When I first meet patients, I always ask them to describe to me a typical day for how they eat — when they're eating, what they're eating, the food quality, who are they with — to see if there's social aspects to it. Then try and make the recommendations based on that," said Popp, whose work focuses on biobehavioral interventions for the treatment and prevention of obesity, T2D, and other cardiometabolic outcomes.

Tchang said she encourages her patients to be mindful of hunger and fullness cues.

"Eat if you're hungry; don't force yourself to eat if you're not hungry," she said. "If you're not sure whether you're hungry or not, speak to a doctor because this points to an abnormality in your appetite-regulation system, which can be helped with GLP-1 [glucagon-like peptide 1] receptor agonists."

Adjusting what patients eat can help them improve their meal timing.

"For example, we know that a high-fiber diet or a diet that has a large amount of fat in it tends to empty from the stomach slower," Camilleri said. "That might give a sensation of fullness that lasts longer and that might prevent, for instance, the ingestion of the next meal."

Those trying to eat more slowly are advised to seek out foods that are hard in texture and minimally processed.

A study involving 50 patients with healthy weights found that hard foods are consumed more slowly than soft foods and that energy intake is lowest with hard, minimally processed foods. Combining hard-textured foods with explicit instructions to reduce eating speed has also been shown to be an effective strategy. For those inclined to seek out technology-based solution, evidence suggests that a self-monitoring wearable device can slow the eating rate.

Although the evidence is mounting that the timing and duration of meals have an impact on certain chronic diseases, clinicians should remember that these two factors are far from the most important contributors, Popp said.

"We also have to consider total caloric intake, food quality, sleep, alcohol use, smoking, and physical activity," he said. "Meal timing should be considered as under the umbrella of health that is important for a lot of folks."

That's not Teen Spirit... That's an upcoming trauma reaction

It doesn’t Smell(s) Like Teen Spirit --  but it does smell like an upcoming PTSD episode.  At least that’s what a couple of highly trained dogs would tell you.  

This article is a testament to the creativity and ingenuity of some folks who are willing to experiment with innate talents.  Dogs have crazy sensitive noses, and people smell funny at times.  Turns out that you can have dogs differentiate certain chemicals (VOCs – volatile organic compounds), and identify people who are (in this case) experiencing a trauma reaction (think PTSD flashback).  What’s really interesting is the presumed difference between the dog’s sensitivities – one to shame, the other to anxiety.  

Anyway, I thought this is a cool thing that points to some interesting possibilities.  VOC sensors are getting pretty sophisticated, so maybe there’ll be a device that one could wear to detect the buildup of these chemicals to signal the individual so they could avoid disaster.

Just thinking out loud…

FROM MEDSCAPE INTERNAL MEDICINE / BY PAULINE ANDERSON

Dogs Able to Sniff Out PTSD, Other Trauma, in Human Breath

Dogs can detect stress-related compounds in the breath of people experiencing early signs of trauma, including those with posttraumatic stress disorder (PTSD), a new proof-of-concept study suggested.

The research provides evidence that some service dogs with PTSD can be trained to detect episodes of pending distress through a person's breath and perhaps prompt the individual to use coping skills to manage the episode.

"Ours is the first study to demonstrate that at least some dogs can detect putative stress-related volatile organic compounds in human breath that are associated with PTSD symptoms," study author Laura Kiiroja, PhD candidate, Department of Psychology and Neuroscience, Faculty of Science, Dalhousie University, Halifax, Nova Scotia, Canada, told Medscape Medical News.

The study was published online on March 28, 2024, in Frontiers of Allergy.

Heightened Sense of Smell

The lifetime prevalence of PTSD is about 8% in the general population, but data show it can reach 23% in veterans. In addition, many more trauma-exposed individuals experience subthreshold symptoms.

Research is investigating the application of dogs' sense of smell, which is up to 100,000 times more sensitive than humans', to detect cancers, viruses, parasites, hypoglycemia, and seizures in humans.

There is also some evidence that dogs can detect putative stress-related volatile organic compounds (VOCs) such as isoprene and monoterpenes from the human body through urine, sweat, and breath, with the greatest success achieved with breath.

The new study included 26 mostly civilian "donors" (mean age, 31 years; 18 females) who had experienced various types of trauma but had no severe mental illness. More than 50% met the criteria for PTSD.

Participants were recruited from a study examining neurocognitive mechanisms underlying the potential links between trauma and cannabis use. However, participants in the dog study abstained from using cannabis for at least 12 hours prior to the study experiments.

Breath Donors

Breath samples were collected via disposable medical-grade face masks at baseline and during ensuing experiments. In total, 40 breath sample sets were collected.

Two female companion dogs — Ivy, a red golden retriever, and Callie, a German shepherd/Belgian Malinois mix — were trained to identify target odors from the samples.

The animals were tested to determine whether they were able to discriminate between breath samples collected from these same "breath donors" during a relatively relaxed state and during induced stress testing which is known as the alternative forced choice discrimination test.

The dogs' ability to discern trauma cues from breath samples of various individuals was tested by presenting one sample (baseline or trauma cue) at a time. The researchers used signal detection theory to evaluate the sensitivity and specificity of dogs in detecting human stress VOCs.

Investigators found the dogs had about a 90% accuracy rate across all sample sets in the discrimination experiment and 74% and 81% accuracy for Ivy and Callie, respectively, in the detection experiment.

"Our study contributed to the evidence showing that not only are dogs able to detect some physical health conditions in humans but also that some mental health conditions alter the released VOCs in a way that is detectable by dogs," Kiiroja said.

Emotion Detectors

At baseline and during each cue exposure, donors reported their affect using the Positive and Negative Affect Schedule. Ivy's performance correlated with the donors' self-reported anxiety, and Callie's performance correlated with the donors' self-reported shame.

Based on these correlations, the researchers speculate Ivy detected VOCs that likely originated from the sympathetic-adrenomedullary axis, which involves adrenaline and noradrenaline.

VOCs detected by Callie likely originated in the hypothalamus-pituitary-adrenal axis, which involves cortisol and corticosterone. These two endocrine subsystems play a major role in reestablishing homeostasis in response to a stressor.

The results suggest some service dogs could alert to upcoming intrusion and hyperarousal symptoms even before physical signs manifest and before the person is even aware of the situation, said Kiiroja.

"This would enable earlier distraction and reminders to use skills learned in psychotherapy; this would have a better likelihood of increasing the efficacy of these skills and preventing further escalation of the arousal," she said.

Most breath samples likely included both early and late stress VOCs, as the breath donors wore the trauma mask for a relatively long time, the authors noted. Future studies should test dogs' olfactory acuity on samples collected minutes after the trauma cue, they added.

Another limitation is that all donors were regular cannabis users, so the results may not generalize to others. However, the fact the dogs demonstrated their detection ability even with cannabis users makes the proof-of-concept "more stringent," Kiiroja said.

The goal of the study was to see if some dogs are capable of detecting stress VOCs from people with trauma histories in response to trauma cues, so the small number of dogs in the study isn't a limitation, the authors noted.

'Wonderful Work'

Commenting on the findings, Elspeth Ritchie, MD, chair of psychiatry, MedStar Washington Hospital Center, Washington, DC, described the research as "wonderful work." Ritchie, who was not a part of this study, has also studied PTSD supports dogs.

The study is yet another illustration of the "amazing things dogs can do…not just for veterans but for people with mental illness." They can be a source of comfort and help people manage their anxiety.

Training PTSD service dogs can be expensive, with some well-accredited organizations charging about $50,000 for an animal, Ritchie said. Training a dog to detect VOCs could also be costly, she added.

Although such research has increased in recent years, it's unclear how it would be applied in practice. Identifying funding for this sort of study and designing trials would also be challenging, Ritchie added.

"The idea is good, but when you try to operationalize it, it gets tricky," she said.

The fact that all donors in the study used cannabis is a confounding factor and raises the question of what else might confound the results, Ritchie added.

Ritchie emphasized that although ideally veterans would learn to recognize the onset of stress symptoms themselves, a dog could serve as a valuable companion in this process. "That's precisely why this research should progress," she said.

Obesity Drugs are going to break the bank? Not the whole story. (Part Two)

But that’s not the whole story!  Treating obesity, proactively avoiding end-stage terrible disease states, could save real money.  I’ve attached another analysis that suggests that paying upfront may have real benefits for the patients, and the society in general.  The attached article is dense – I’ve only attached it for the economists and healthcare nerds.

It speaks to what is at the heart of what I’ve believed is a huge problem in how determining what is covered – the cost of care does not include societal cost.  As such, we only get a snapshot of true costs.  It’s like saying I don’t want to fix my car’s steering because it’s too expensive and the car is old.  Meanwhile, the chances that an accident only hurts the driver is quite small.  If you look at the whole picture, the upfront cost is easily justified.  

The whole Ozempic/Wegovy/Moujaro/Zepbound thing is still in its infancy.  It’ll get more complicated before it’s settled.  I’ll say it is a good choice for many, but, as usual, it depends.

I always try to look at the big picture – your big picture and not focus on little stuff that ends up not that important.  

If you have any questions, please give me a call.

FROM USC Schaeffer / BY Darius Lakdawalla, Bryan Tysinger, PhuongGiang Nguyen, Alison Sexton Ward & Dana Goldman

A new USC Schaeffer Center white paper finds the value to society of Medicare coverage for new classes of weight loss drugs would equal nearly $1 trillion over ten years.

Obesity is one of the United States’ most urgent health issues—and also one of the most treatable. Yet because Medicare and most private insurers do not cover weight-loss medications and many devices, just 1% of eligible patients receive treatments.  

“Obesity is a leading risk factor for mortality in the U.S.,” says Darius Lakdawalla, director of research at the USC Schaeffer Center for Health Policy & Economics and co-author of the study. “Our modeling shows that new treatments generate substantial benefits to Medicare and its beneficiaries. Developing strategies for unlocking that value should be a priority for policymakers.” Lakdawalla is also a professor at the USC Mann School of Pharmacy & Pharmaceutical Sciences and the USC Price School of Public Policy.

Leveraging the Schaeffer Center’s Future Adult Model, an economic-demographic microsimulation model, the researchers estimated the benefits of treating Americans suffering from obesity and the cost-offsets that Medicare and society could accrue if laws were changed to allow Medicare to cover anti-obesity medications. 

Coverage for new obesity treatments could generate approximately $175 billion in cost offsets to Medicare in the first 10 years alone. By 30 years, cost offsets to Medicare would increase to $700 billion.

The positive impacts extend beyond Medicare: society could reap as much as $100 billion per year (or $1 trillion over 10 years) of social benefit in the form of reduced healthcare spending and improvements in quality of life from reduced disability and pain if all eligible Americans were treated.

Models show the ripple effects of obesity on the healthcare system

Despite safe and effective treatments, federal law currently prohibits Medicare from paying for most forms of obesity procedures and medications. Legislation has been introduced, including the bipartisan Treat and Reduce Obesity Act, that would expand Medicare Part D’s prescription benefits to include FDA-approved drugs for chronic weight management.

Researchers discovered that most of the cost savings to Medicare—more than 60%—would flow to Medicare Part A, which covers hospital, hospice, nursing facility and home care.  This could significantly help Medicare, which risks becoming insolvent by 2028.

“Because obesity is associated with many chronic conditions that significantly impact patients’ lives—and Medicare’s costs—reducing obesity rates has a ripple effect in the prevalence of other conditions,” says Alison Sexton Ward, one of the co-authors of the paper and research scientist at the USC Schaeffer Center.

The researchers find that if all Americans eligible for obesity treatments gained access, the prevalence of obesity in the Medicare population would fall by 53% after the first decade.  In addition, the researchers show that treating obesity will reduce the incidence of many related diseases, including diabetes (a 5.5% reduction in prevalence after 10 years), hypertension (1.2%) and heart disease (1.7%).

Covering obesity treatments reduces health disparities

Improving access to obesity medications could also enhance health equity, since obesity disproportionately affects Black, Hispanic and lower-income communities. More than half of the Black Medicare population has obesity and three-fourths have hypertension.

“Black and other historically marginalized communities have been disproportionately burdened by obesity,” says one of the paper’s co-authors, Bryan Tysinger, director of health policy simulation at the USC Schaeffer Center and assistant research professor at the USC Price School.

Medical breakthroughs that simplify healthcare and reduce patient effort can reduce disparities, but only if access is prioritized.

Outcomes-based pricing models would ensure access

New obesity treatments promise substantial benefits to patients if policymakers can solve the problem of how to pay for them.  The researchers point to outcomes-based valuation models, including a novel pricing approach that allows for real-world evaluation of the treatments while also encouraging broad coverage.  

“About half the decline in U.S. deaths from coronary heart disease over the past 50 years can be attributed to new drugs to lower cholesterol and blood pressure,” says one of the paper’s co-authors, Dana Goldman, co-director of the USC Schaeffer Center and dean of the USC Price School. “Now imagine if Congress had prohibited coverage for these lifesaving drugs.  Novel pricing solutions can ensure access for all patients who would benefit from these important new anti-obesity treatments.”  

Chronic UTIs are awful -- but there's hope!

Don’t know what a UTI is?  This article might not be for you, but I’ll bet someone you know cares about this subject intimately!  

UTI is short for Urinary Tract Infections.  Some people (vastly more women) get UTIs constantly, are in pain as a result, have their lifes disrupted interminably and need to take antibiotics regularly, predictably screwing up a whole bunch of other stuff in their systems.  Not good.  

This article reports a cool possible solution – a pineapple flavored sublingual (under the tongue) spray of inactivated bacteria (commonly found in UTIs) daily for 3 months.  And then…Voilà!  54% of the population tested were UTI-free for 9 years!! The entire group averaged 4.5 years without a UTI.  WOW.

Of course, we’re in America, so who knows how long it will be before we see this as a real option.  But there’s hope!!

FROM MEDSCAPE UK / ANDREW R. SCOTT

Recurrent UTI Patients Find Long-Term Ally in Oral Vaccine

Results from the first long-term follow-up study of an oral vaccine for recurrent urinary tract infections (UTIs) suggest that it “could be a gamechanger for UTI prevention,” according to consultant urologist Bob Yang, who co-led the trial.

“It’s very exciting… for us it was almost magical,” said Yang, who works with the Royal Berkshire NHS Foundation Trust. Speaking to Medscape News UK, he explained that the trial, whose results are being presented at the European Association of Urology Congress (EAU) in Paris from 5 to 8 April 2024, was built on initial impressive results he and colleagues had found in private, off-licence use with a small number of patients.

Results from the first long-term follow-up study of an oral vaccine for recurrent urinary tract infections (UTIs) suggest that it “could be a gamechanger for UTI prevention,” according to consultant urologist Bob Yang, who co-led the trial.

“It’s very exciting… for us it was almost magical,” said Yang, who works with the Royal Berkshire NHS Foundation Trust. Speaking to Medscape News UK, he explained that the trial, whose results are being presented at the European Association of Urology Congress (EAU) in Paris from 5 to 8 April 2024, was built on initial impressive results he and colleagues had found in private, off-licence use with a small number of patients.

‘Dramatic’

“The results were dramatic,” Yang said. “We had women who were coming month after month with infection after infection, despite all treatment, often with last-line antibiotics. And [after using the vaccine] they came back and said what have you done to us? We are infection-free.” 

The vaccine, called Uromune, was developed by Immunotek S.L. in Spain. It is composed of inactivated whole bacteria commonly associated with UTIs: Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, and Enterococcus Faecalis. It is administered by two sprays of a pineapple flavoured suspension under the tongue every day for 3 months.

The vaccine has been used, largely off-licence, in some countries for several years, with short-term efficacy already supported by published trials in which Yang and his colleagues participated. But they wanted to more fully investigate if an initial vaccination regime could safely and effectively give long-lasting protection for people who experience recurrent UTIs.

Long-Term Results

That led to the 9-year follow-up, which investigated safety and long-term efficacy in 89 patients (72 women and 17 men) aged 18 to 87 (average age 56) with recurrent UTIs. These patients were originally treated privately at the Urology Partnership Reading, UK. 40% of the participants also had repeat doses of the vaccine after 1 or 2 years.

Forty-eight participants (54%) remained UTI-free during the 9-year follow up period, with an average UTI-free period for the entire cohort of 4.5 years. In terms of safety, Yang said no adverse effects or other concerns were identified.

Yang explained to Medscape News UK that one key purpose of the presentation to the EAU Congress was to subject the results to some initial peer review and feedback. Formal and full publication should then follow by the end of 2024.

‘Exciting’

Jennifer Rohn, professor of renal medicine and head of the Centre for Urological Biology at University College London, who was not involved in the research, told Medscape News UK: "These results are exciting and suggest that preventing UTI may be one viable strategy in our fight against an infection that afflicts around 400 million people each year, mostly women, and which antibiotics struggle to control in up to 30% of those many cases.”

Rohn added that vaccination is a particularly attractive strategy in an era when bacterial infections are becoming increasingly resistant to antibiotics. “Although people often consider UTI to be a trivial infection, there are already about a quarter of a million UTI deaths annually associated with antibiotic resistance, and this number is expected to rise,” she said. 

While acknowledging the promise of the study, Rohn did point out that it contained a relatively small number of patients who self-reported their symptoms, so she feels that larger studies will be welcome. “Also, we have to keep in mind that it was performed on individuals with relatively simple recurrent UTIs, and further work is needed to understand whether it will be as effective in complicated or chronic UTI," she said.

Next Steps

Among ongoing efforts by various researchers to address the efficacy in more complex situations, Yang said that he has won funding to test the Uromune vaccine on spinal injury patients, who can experience more complicated UTIs. This will initially proceed as a small prospective trial, then be followed by a large randomised controlled trial.

Yang also pointed out that, although many other bacteria can cause UTIs in addition to the four most common ones specifically targeted by the vaccine, these other infections also seemed covered by the vaccine. “The reason for that is likely because a lot of these gram-negative bacteria share a common lipopolysaccharide outer layer… so you get a broad-spectrum response,” along with other non-targeted effects on the immune system, he suggested.

Meantime, however, the vaccine remains unlicensed in the UK, and Yang emphasised that it would be very difficult for GPs to use it off-licence, so the next steps will be to try to move forward towards regulatory approval in the UK.

“Once this treatment gets licensed it will be revolutionary for GPs,” Yang said. While emphasising that the approval will be a slow process, he feels that the emerging data, including these recent results, are steadily feeding in the evidence that will be required.

Here we go again.... EXERCISE is GOOD for you

I’ve said it before, and you can bet I’ll say it again – EXERCISE is GOOD for you.  Right – you knew that.  Again, it’s the single best thing you can do to improve your overall health and longevity, as long as you do it intelligently.  So what’s new?

 The article says “Regular Exercise Linked to Better Sleep”.  Cool – but what are the details (that’s where the devil is, after all)?  

Thousands of people in 9 countries over 10 years have 30-50% better sleep when people who did exercise more than 30 minutes twice a week were compared to those who were inactive (which was 37% of the population tested!).

As usual, there’s loads of limitations to this report – two questionnaires 10 years apart and drawing conclusions from that.  But it does support that getting up and moving actually is important and has real health benefits.

GET UP!  MOVE!  

Talk soon.

FROM MEDSCAPE MEDICAL NEWS / BY BATYA SWIFT YASGUR

Regular Exercise Linked to Better Sleep

TOPLINE:

Over time, exercising at least twice a week is associated with significantly fewer insomnia symptoms and better sleep duration, new research shows.

METHODOLOGY:

• The study included 4339 adults aged 39-67 years (48% men) from 21 centers in nine countries participating in the third follow-up to the European Community Respiratory Health Survey (ECRHS III).

• Participants responded to questions about physical activity, insomnia symptoms, sleep duration, and daytime sleepiness at 10-year follow-up.

• Being "physically active" was defined as exercising with a frequency of at least twice a week for ≥ 1 hour per week.

• The main outcome measures were insomnia, sleep time, and daytime sleepiness in relation to physical activity.

TAKEAWAY:

• From baseline to follow-up, 37% of participants were persistently inactive, 25% were persistently active, 20% became inactive, and 18% became active.

• After adjusting for age, sex, body mass index, smoking history, and study center, persistently active participants were less likely to report difficulties with sleep initiation (adjusted odds ratio [aOR], 0.60; 95% CI, 0.45-0.78), with short sleep duration of ≤ 6 hours/night (aOR, 0.71; 95% CI, 0.59-0.85) and long sleep of ≥ 9 hours/night (aOR, 0.53; 95% CI, 0.33-0.84), compared with persistently nonactive subjects.

• Those who were persistently active were 22% less likely to report any symptoms of insomnia, 40% less likely to report two symptoms, and 37% less likely to report three symptoms.

• Daytime sleepiness and difficulties maintaining sleep were found to be unrelated to physical activity status.

IN PRACTICE:

"This study has a long follow-up period (10 years) and indicates strongly that consistency in physical activity might be an important factor in optimizing sleep duration and reducing the symptoms of insomnia," the authors wrote.

SOURCE:

Erla Björnsdóttir, of the Department of Psychology, Reykjavik University, Reykjavik, Iceland, was the co-senior author and corresponding author of the study. It was published online on March 25 in BMJ Open.

LIMITATIONS:

It's unclear whether individuals who were active at both timepoints had been continuously physically active throughout the study period or only at those two timepoints. Sleep variables were available only at follow-up and were all subjectively reported, meaning the associations between physical activity and sleep may not be longitudinal. Residual confounders (eg, mental health and musculoskeletal disorders or chronic pain) that can influence both sleep and exercise were not explored.

Red LEDs/Laser are all the rage. Do they do anything?

I’m sure you’ve seen the advertisements – Red light facemasks for skin rejuvenation, Red light helmets for fighting baldness, Red light wands for spot skin treatments, lasers for everything.  They must be good, right?

Turns out we’re back to my two favorite words:  IT DEPENDS.  

Let’s back up – why should we even consider these options?  

Let’s start with a little basic science and a thought experiment (don’t worry – it won’t hurt!)

You probably didn’t know that chlorophyll (stuff that makes plants green) and hemoglobin (the stuff that makes blood red) only differ in their central atom (cation) – magnesium for plants, iron for animals.  In plants, that molecule takes energy from the sun and allows the plant to store energy as growth (think vegetables).  In animals, that molecule (as commonly described) allows oxygen to be delivered to cells.  

But, there’s another part to this story.

Ever say “I need to go get some sun, so I can RECHARGE”?  There is evidence to show that going out in the sun does more than increase your Vitamin D levels – it actually (literally) charges your battery.  If we think of the body as kind of a battery, the whole analogy above starts to make more sense.  This has broad implications that we can discuss at another time.

So what if hitting the body with the appropriate light energy could deliver important inputs to push the body to do more restoration or the like, pushing energy into the system to do more of what would be good for it?  Not that far-fetched.  

The caveats are, of course, what kind of energy is right?  How it’s delivered, how intense, how long, over what area, etc., etc.  It can get pretty complicated, pretty fast.  

I have a pre-programmed handheld high-powered laser that allows me to treat all kinds of issues with very positive results, ranging from pain control to viral therapies.  We could even develop a protocol to treat your issues!  

Happy to have a conversation to discuss what FeldMed might have to offer to help bring you along the road to Limitless Healing!

FROM NATIONAL GEOGRAPHIC / BY LEAH WORTHINGTON

In the mid-1960s, a Hungarian physician named Endre Mester shined a low-power laser on the shaved skin of a mouse. Though he was testing for impacts on tumor growth, he observed an unexpected side effect—the red light seemed to stimulate hair regrowth and, in later studies, wound healing.

Sixty years later, this accidental discovery has found its way into a booming market for clinical procedures and at-home devices using light-emitting diodes (LEDs).

Also possible with cold lasers, "low level" or "low power" light therapy requires a certain power level (measured in milliwatts per centimeter) to be effective, without the damaging heat of high-powered lights. From face and full-body masks to portable wands, low-level light therapy products promise all sorts of anti-aging, rejuvenating, and wound-healing benefits. 

“There’s a lot of hype in the industry,” says Daniel Barolet, a dermatological laser therapy researcher and clinician, and an adjunct professor at McGill University.

But are these devices—which can cost hundreds, even thousands of dollars—worth the price? Experts discuss the benefits and limitations of light therapy, and what consumers should know before making the investment. 

In the decades since Mester’s groundbreaking mice trials, research and development of phototherapy has taken off—with promising results.

Today, LED light therapy, or “photobiomodulation” (PBM) as it’s more accurately known, uses gentle, low-level light within the visible spectrum—typically blue, red, or near-infrared—to stimulate natural physiological processes. Or, as Barolet says, PBM just means “using light to give our cells a little nudge in the right direction.”

For much of human history, we would have gotten these benefits directly from the sun—but now we’re spending more time inside, with often cool-toned indoor lighting.

“When we're using photobiomodulation, we just cut the bad UV rays. We're just using the healing stuff,” Barolet says. “It’s biomimicking, but you harness what’s good for your skin, and you delete what’s not good for your skin.”

Light therapy devices found in clinics are generally more powerful, producing better and faster results. But for those who want to do their treatment at home, there’s a market full of options. 

While the exact mechanisms are not yet fully understood, PBM therapy has been shown to produce a range of positive effects. Blue light, for instance, can be used to treat acne and may mitigate other skin disorders by reducing inflammation. When blue light is absorbed by the skin, it activates the production of toxic free radicals which, over the course of several days, kill off the acne-causing P. acnes bacteria.

Glynis Ablon, a dermatologist and associate clinical professor at UCLA, says she’s seen dramatic effects in her patients undergoing blue light therapy. “What they'll notice, just from these LEDs alone, is that their acne gets better, that the level of inflammatory lesions reduces, that their overall skin just starts to look better.”

Red and near-infrared light, on the other hand, have longer wavelengths that can target the skin cells or travel deeper into the body. When light in this range penetrates the cells, Barolet says, it “kicks off a chain reaction” in the mitochondria. This metabolic process produces several important molecules, including ATP and nitric oxide, that are critical for basic bodily functions like energy production and healthy blood flow. 

The application of red and near-infrared light has a domino effect, stimulating collagen production and blood circulation. On a surface level, this can speed healing of wounds, such as burns or ulcers, and even reduce signs of aging, like wrinkles and brown spots.

While the skin is the largest and most visible organ in the body, all cells theoretically can enjoy a boost from red or near-infrared light therapy.

Generally speaking, the tissues that will improve the most are those in a state of depletion or disorder—such as sunburnt skin—according to Alexander Wunsch, a physician and photobiology expert. Of course, light therapy isn’t a panacea for treating skin or any other conditions. 

“There is real science to it and it does work clinically,” says Zakia Rahman, a clinical professor of dermatology at the Stanford School of Medicine, “but it’s not going to have the level of dramatic effect that more aggressive treatments in a medical setting would have.” 

Still, LEDs have distinct benefits—they’re non-invasive, pain-free, and essentially harmless. Prolonged exposure to blue light, which is near the UV spectrum, may cause skin damage, aging or irritation, but long-term research is still limited. With red and near-infrared, the only potential concerns are for those with sun allergies or highly sensitive eyes, according to Barolet.

“Think of photobiomodulation like your morning cup of coffee…but with light,” Barolet says. “It's like a wake-up call that gets all those tiny cellular processes up and running, helping the body to repair, rejuvenate, and energize itself.”

Clinics around the world offer PBM therapy for all sorts of cosmetic and medical purposes. Office devices are generally more powerful, producing better and faster results. But for those who want to do their treatment at home, there’s a market full of options. 

When it comes to choosing an LED device, experts agree that the most meaningful factor to consider is the output intensity.

“There’s a lot of scams out there…most of the time, energies are very, very low,” Ablon says. For red light, she looks for devices that emit 105 milliwatts per centimeter, but for blue light, the intensity can be lower. “If it’s somewhere in that 40 range, I’m ok, but if it ends up being 10, it’s probably not doing anything.”

Barolet also warns consumers to avoid devices that promote “a rainbow” of lights, such as green, yellow, and purple. When it comes to health, he says, the only wavelengths proven to be effective are red, near-infrared, and blue.

At-home light treatment can be performed with a variety of devices, including a shield-like mask (left) and wand (right).

It’s important to note that not all LED products on the market have been greenlit by the FDA. Wunsch advises consumers to look for 510(k) Clearance, “which gives you at least the information that this device has been evaluated”—though not tested—by the FDA for safety and effectiveness.

Barolet notes that, while the research supporting light therapy is robust, scientists are still perfecting their “recipe”—the ideal wavelengths, dosage, intensity, and proximity—for different health goals. In some cases, LED therapy works best in concert with other interventions, like pairing red light treatment with anti-aging cream, he says. While not a replacement for products like sunscreen or prescription retinoids, Rahman says that LEDs “can work well in your entire skin regimen.”

Ultimately, whether undergoing a clinical procedure or using at-home masks, experts advise people to stay the course of the treatment and not expect immediate results. While wound healing can happen faster, Wunsch says, the effects on healthy, normally aging skin can be slow and cumulative.  “You have to invest in the compliance in the first phase, and you will get your rewards in five or ten years.”

Study Throws Wet Blanket on Intermittent Fasting / Time Restricted Eating?

Everybody has heard of intermittent fasting / time restricted eating, right?  If not, it’s when you spend more time NOT eating than you do eating (think overnight fast – hence, Break-FAST).  It’s pretty clear that there are significant benefits to NOT eating for over 12 hours – the body has time to clear stuff out and potentially rebuild while not digesting food.  

The new study shows that when you push the NOT EATING window to 16 hours, you may be asking for trouble.  While the study is observational and has many limitations, the results are approaching astounding.  Risks of dying are significantly increased between 90 and 300%, depending on your baseline conditions.  If you’ve got cancer, the 8 hour or less feeding window translated to a 3 times greater risk of dying.  YIKES!

While I’m a big proponent of time restricted eating, I have always cautioned against the extremes here.  I’ve always thought that, on average, the optimal feeding window is around 10 hours – a 14 hour overnight fast (stop eating at 8, breakfast at 10).   For women, anything more than that seems to regularly make them feel worse.  Guys can tolerate longer, but this study has to make one wonder if that’s a good idea.  

As usual, the right answer will fall into the “it depends” category.  Individualized approach is always the best, but these data are hard to ignore, despite their limitations.

FROM MEDSCAPE / BY MEGAN BROOKS

Intermittent Fasting Linked to Higher CVD Death Risk

A new study raises a cautionary note on time-restricted eating (TRE), a type of intermittent fasting that is gaining popularity.

The observational analysis of over 20,000 US adults showed that those who limited their eating to a period of less than 8 hours per day had a higher risk for cardiovascular mortality compared with peers who ate across the typical 12-16 hours per day. This was the case in the overall sample and in those with cardiovascular disease (CVD) or cancer.

Lead author Victor Wenze Zhong, PhD, cautioned that the findings "require replication and we cannot demonstrate 8-hour TRE causes cardiovascular death in this observational study."

"However, it's important for patients, particularly those with existing heart conditions or cancer, to be aware of the positive association between an 8-hour eating window and cardiovascular death," Zhong, professor and chair, Department of Epidemiology and Biostatistics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China, told theheart.org | Medscape Cardiology. 

The results (Abstract P192) were presented March 18 at the American Heart Association (AHA) Epidemiology and Prevention | Lifestyle and Cardiometabolic Health Scientific Sessions 2024.

'Provocative' Results 

Short-term randomized controlled trials have suggested that 8-hour TRE may improve cardiometabolic risk profiles, but the potential long-term effects of this eating pattern are unknown. 

The observation that TRE may have short-term benefits but long-term adverse effects is "interesting and provocative" and needs further study, Christopher D. Gardner, PhD, professor of medicine at Stanford University in California, who wasn't involved in the study, said in a conference statement, and he agreed that much more research is needed. 

The researchers analyzed data on dietary patterns for 20,078 adults (mean age, 48 years; 50% men; 73% non-Hispanic White) who participated in the 2003-2018 National Health and Nutrition Examination Surveys (NHANES). All of them completed two 24-hour dietary recall questionnaires within the first year of enrollment. Deaths through the end of 2019 were determined via the National Death Index.

During a median follow-up of 8 years, there were 2797 deaths due to any cause, including 840 CV deaths and 643 cancer deaths. 

In the overall sample, compared with an eating duration of 12-16 hours, 8-hour TRE was significantly associated with an increased risk for CV mortality (hazard ratio [HR], 1.91; 95% CI, 1.20-3.03).

This association was also observed in adults with CVD (HR, 2.07; 95% CI, 1.14-3.78) and adults with cancer (HR, 3.04; 95% CI, 1.44-6.41). 

Other eating durations were not associated with CV mortality, except for eating duration of 8 to less than 10 hours in people with CVD (HR, 1.66; 95% CI, 1.03-2.67). 

No significant associations were found between eating duration and all-cause or cancer mortality in the overall sample and CVD/cancer subsamples, except that eating duration of more than 16 hours was associated with a lower risk for cancer mortality in people with cancer (HR, 0.47; 95% CI, 0.23-0.95).

Quality More Important Than Timing 

Zhong noted that the study doesn't address the underlying mechanisms driving the observed association between 8-hour TRE and CV death. 

"However, we did observe that people who restricted eating to a period less than 8 hours per day had less lean muscle mass compared with those with typical eating duration of 12-16 hours. Loss of lean body mass has been linked to higher risk of cardiovascular mortality," Zhong said. 

"Based on the evidence as of now, focusing on what people eat appears to be more important than focusing on the time when they eat. There are certain dietary approaches with compelling health benefits to choose, such as DASH diet and Mediterranean diet," Zhong told theheart.org | Medscape Cardiology.

Intermittent fasting is "certainly an interesting concept and one on which the potential mechanisms underlying the improvements in short outcome studies and preclinical studies in animals are strongly being pursued," Sean Heffron, MD, cardiologist at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, New York, NY, who wasn't involved in the study, told theheart.org | Medscape Cardiology. 

Heffron expressed skepticism about the study results calling them "far from complete" and noted that data on diet was based on only 2-day diet records without correction for confounding variables. 

Heffron also noted that the restricted diet group has more smokers and more men. "I would "strongly anticipate that once appropriate corrections are made, the findings will no longer persist in statistical significance," Heffron said.

He emphasized the need for more rigorous research before making clinical recommendations. When patients ask about intermittent fasting, Heffron said he tells them, "If it works for you, that's fine," but he doesn't provide a recommendation for or against it. 

Vitamin D -- it's not about COVID anymore

Vitamin D has been the source of some controversy for some time now.  Years ago there was debate about whether we should measure it at all (still some camps out there holding to that) because it wasn’t shown to relate to any clear diseases, increased risk, or if supplementing it made a difference.  More recently, COVID demonstrated that those with low vitamin D levels were more likely to end up in the Intensive Care Unit (86% of ICU COVID patients had low levels – under 29), and thus more likely to die.  Lots of people argued that supplementing vitamin D as prophylaxis against serious illness (including myself) was a good idea, but conventional evaluations of that didn’t yield confirmatory results (some studies were poorly done, but others were done well).  It makes for a bit of a morass when you’re trying to decide what to do.  For the record, my normal vitamin D level (25-OH to be specific) tends toward the low side, so I supplement daily.  

Now we have a review of small group of sedentary, nonsmoking Spaniards who had a bunch of metabolic parameters measured and compared.  What it showed was an inverse relationship between Vitamin D levels and virtually every cardiovascular risk factor you can think of . In other words, Vitamin D goes down, everything else bad goes up.  Their argument is that we could measure Vitamin D levels as an easy way to monitor cardiovascular risk.  Of course, in the US, to have the Vitamin D levels paid for by insurance companies, you have to be diagnosed with a Vitamin D disorder!  Ahhh, the beauty of American medicine.

By the way, I measure Vitamin D in everyone regularly.   It’s inexpensive to supplement, easy to avoid the virtually unheard of problems associated with excessive Vitamin D, and it just might avoid problems in the 300 or so mechanisms for which Vitamin D is essential.  

Concerned about your cardiovascular risks?  We have cutting edge approaches to evaluating and managing those risks, and establishing the presence of real issues before they become problems.  Let’s discuss your situation – first conversation is complementary.

From medscape / by Shrabasti Bhattacharya

Low Vitamin D Levels May Signal CVD Risk in Young Adults

TOPLINE:

Circulating levels of serum 25-hydroxyvitamin D (25[OH]D) may be a marker of cardiovascular disease (CVD) risk in healthy young adults, small study finds.

METHODOLOGY:

• A secondary analysis of the Activating Brown Adipose Tissue Through Exercise (ACTIBATE) trial assessed the association between serum 25(OH)D levels and CVD risk factors.

• The cross-sectional study used baseline data of in 177 healthy sedentary adults ages 18-25 years (65% women; all White individuals), who were recruited between October 2015 and December 2016 from Granada, a region in the south of Spain.

• Study participants were nonsmokers, led a sedentary lifestyle, and did not have a prior history of CVD or chronic illnesses.

• The CVD risk factors included anthropometrical and body composition profiles, glucose and lipid metabolism, liver, and pro- and anti-inflammatory biomarkers.

• 25(OH)D serum concentrations were measured with a competitive chemiluminescence immunoassay and defined as deficient (< 20 ng/mL), insufficient (21-29 ng/mL), or normal (> 30 ng/mL).

TAKEAWAY:

• The vitamin D levels correlated inversely with body mass index (BMI; standardized regression coefficient [β], −0.177; P = .018), fat mass index (β, −0.195; P = .011), and systolic blood pressure (β, −0.137; P = .038), after adjusting for sex.

• Glucose metabolism markers (serum glucose and insulin concentrations, insulin/glucose ratio, and homeostatic model assessment of insulin resistance index) also correlated inversely with vitamin D levels.

• The trend was similar for liver markers serum γ-glutamyl transferase and alkaline phosphatase) and the anti-inflammatory marker interleukin-4.

• BMI, waist/hip ratio, fat mass index, blood pressure, and levels of glucose, insulin, triglycerides, and liver markers were higher in the 44 participants with vitamin D deficiency vs 41 participants with normal vitamin D levels.

IN PRACTICE:

"Collectively, these findings support the idea that 25(OH)D concentrations may be used as a useful marker of CVD status, which can be easily monitored in young individuals," the authors wrote.

SOURCE:

This study was led by first author Francisco J. Amaro‑Gahete, MD, PhD, from the Department of Physiology, Faculty of Medicine, University of Granada, Spain, who also holds positions in other institutions. It was published online on January 4, 2024, in the Journal of Endocrinological Investigation.

LIMITATIONS:

This study could not establish causal relationships due to its cross-sectional design. The results might not apply to younger or older people from different locations and ethnic backgrounds. The gold standard method for analyzing vitamin D levels, liquid chromatography–mass spectrometry, was not used in this study.

DISCLOSURES:

This study was supported by the Spanish Ministry of Economy and Competitiveness, Spanish Ministry of Education, AstraZeneca HealthCare Foundation, and other sources. The authors declared no conflicts of interest.

Itching can be a real *itch

Itching is a real problem for many people.  We all get an itch periodically, and if you’re lucky, you scratch it and it goes away. 

SIDE NOTE: Itching is on of human’s most noxious – worst – stimuli.  We scratch because the pain induced from scratching is less problematic for us than the itch.

There are, however, people who have a chronic itch.  This article discusses some of the treatment options they try, and I have to laugh a bit.  The expert is from John Hopkins Itch Center – clearly one of the premier institutions in the world, and yet, there is NO discussion of identifying and removing the cause of said itch!  The symptoms and the world is a better place – UNTIL THE NEXT TIME!  Seriously?

There are some conditions that, even in conventional medicine, are known to cause itch – allergic reactions, thus you take an anti-histamine.  But it can be much more that allergies.

Let’s think about how the body handles stuff that no longer belongs in the body – waste products of all kinds.  If something is supposed to be disposed of through the bowels or the kidneys, but the system isn’t up to that (for any number of reasons we won’t go into here), the body will try an alternative path.  That path could be through the skin (think sweating).  But it that “stuff” isn’t supposed to go through the skin, the body might react – sometimes with a rash, but sometimes simply with an itch.  If you can “open up” the correct path (colon or kidney for example), you can get the rash to go away.  I have plenty of folks for whom this approach works and works well.  

My logo is about coming out of the box – I suggest the box discussed here is still a bit too small.

FROM MEDSCAPE MEDICAL NEWS / By Damian McNamara

Think Outside the Traditional Toolbox to Treat Itch

"Itch may not be as sexy as Mohs surgery or aesthetic procedures," but treating it is important and meaningful to patients, particularly those who've found little relief previously, Shawn G. Kwatra, MD, said at the annual ODAC Dermatology, Aesthetic & Surgery Conference.

Chronic itch is common, with presentations that range from annoying to debilitating. There are many over-the-counter and prescription treatments patients can and likely have tried by the time they seek a dermatologist for help.

In doctors' defense, it can be highly challenging to know which approach is optimal for each individual with pruritus, added Kwatra, associate professor of dermatology at Johns Hopkins University, Baltimore, Maryland.

Cooling agents, topical capsaicin, topical anesthetics like pramoxine 1%, various forms of lidocaine, strontium, opioid modulators like naltrexone, oral Janus kinase inhibitor (JAK) inhibitors, and medical marijuana are among some of the "outside the box" tools in Kwatra's itch toolbox.

Often a Medical Puzzle

Frequently, patients come to the dermatologist complaining of itch, "but you don't see much on their skin." After a trial of antihistamines, and some topical steroids, the doctor might put up their hands and think: I tried, but I don't know what else to do. "This actually happens a lot," said Kwatra, who is also director of the Johns Hopkins Itch Center.

This means itch can frustrate providers as well. But for patients, the impact on their quality of life can be on the same level as recovering from a stroke or living with heart failure, Kwatra said. Finding relief for their itch is where "we can make a big difference for patients."

Consider Cooling Agents

Many of these therapies are inexpensive and widely available. Cooling agents like menthol, camphor, or calamine can reduce activity of the transient receptor potential (TRP) channels in the skin associated with itch. This ion channel also senses temperature, pressure, and other sensations.

Another option is topical capsaicin, which works through the same ion channels. It binds to the TRPV1 receptors in sensory nerve fibers and causes desensitization. Initially, four to six applications a day are required to reduce itch. After that, patients can apply the medication less frequently. "You have to tell folks we know it's going to work, but it's going to burn a lot initially," Kwatra said. "In real world practice, I'm not using it often."

A 1.8% capsaicin patch, approved for treating postherpetic neuralgia, can be used to treat pruritus as well. "You put the patch on for one hour and you can have a true clinical response," he noted.

Another option for itch relief, the topical anesthetic pramoxine 1%, "is probably underutilized for our patients," Kwatra said. Pramoxine 1% works fast — as quickly as 2 minutes — and lasts up to 8 hours and is well-tolerated with low toxicity, he added. The agent is applied three to four times a day and relieves itch by reducing the transmembrane permeability of sodium ions on the skin. "This is something widely available and cheap."

Lidocaine, another topical anesthetic, is available compounded, over the counter, and as a spray or patch. "I would be careful before you use high doses, like 10%" because of tolerability issues, Kwatra cautioned. He generally starts with lower concentrations.

Topical strontium is really interesting as a strategy, Kwatra said. Strontium is a soft, white metal that competes with calcium for receptor binding. There are over-the-counter formulations available as a scalp solution or lotion, which, he said, "are ways to go with more episodic itching."

Topical oatmeal can also relieve itch in some patients. "There is actually some good scientific evidence for topical oatmeal preparations," he said.

Steroid-Sparing Novel Topicals

Topical ruxolitinib (a JAK inhibitor approved for atopic dermatitis and vitiligo); topical roflumilast (a phosphodiesterase-4 inhibitor) and topical tapinarof (an aryl hydrocarbon receptor agonist), both approved for treating psoriasis; and the atopic dermatitis drug crisaborole fall into this category of topicals with potential for treating itch, he said, noting that use for treating itch is off label.

Off-label use of biologic agents are also possible treatment options for itch, dupilumab and tralokinumab, both US Food and Drug Administration (FDA)–approved for treating atopic dermatitis. Emerging agents that may prove useful for treating itch include lebrikizumab, nemolizumab, amlitelimab, and rocatinlimab, he said.

In terms of oral therapies, the FDA has approved two oral JAK inhibitors for atopic dermatitis, abrocitinib and upadacitinib, which could prove useful for itch as an off-label indication, according to Kwatra.

Naltrexone Off Label

An emerging therapeutic concept for treating itch is using an opioid antagonist like naltrexone. Morphine causes more itch, so the theory is a reversal agent might help reduce it. The challenge is that naltrexone only comes as a 50 mg tablet, "and I find the high dose makes people nauseous and vomit," he added.

Don't Forget Devices

He referred to a "great paper" that he said has been "totally overlooked," published in 2001, which evaluated a device that stimulates C fibers in the skin to reduce itch. In the study, 19 patients used the device to treat local areas 20 minutes daily for 5 weeks. Punch biopsies of the affected areas were taken at baseline and after treatment. Mean itch ratings decreased from 78% to 42%, and the number of immunoreactive nerve fibers in the epidermis decreased by 40% at the end of treatment.

"Electrical neurostimulation is better for localized pruritus. There is limited case series evidence, but it's something to think about," Kwatra said.

He and his colleagues also have a case study in press that explored the use of injected botulinum toxin to relieve recalcitrant, chronic itch in a 65-year-old man "who failed everything."