Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

Meaningful weight loss was seen with the weight loss drugs Wegovy or Ozempic regardless of whether people had previous weight loss surgery, a first-of-its-kind study reveals.

In addition, insurance coverage/expense was the most common issue for people wishing to start the popular medications, known as GLP-1 receptor agonists. Side effects and drug shortages were among the reasons people stopped taking the medication.

Overall, people lost an average of 6% of their total body weight in almost 1 year of taking semaglutide, the class of drugs that includes Wegovy and Ozempic. When researchers compared people who had weight loss surgery with those who had not, total weight loss was almost identical: 5.8% in those who had surgery, vs 6.0% in those who had not.

People in this study lost a lower percentage of their total body weight, compared with people in clinical trials for the drugs, who tended to lose up to 15%, said lead investigator Pourya Medhati, MD, a postdoctoral research fellow at Brigham and Women’s Hospital in Boston.

These results suggest real-world weight loss results may be different than those in carefully controlled research studies. Dr. Medhati presented the findings at Digestive Disease Week® (DDW) 2024 in Washington.

Total weight loss was not significantly different between men and women in the surgery group. But in the nonsurgery group, women lost 6.4%, compared with 4.8% among men, a significant difference.

Dr. Medhati and Ali Tavakkoli, MD, chief of the Division of General and GI Surgery at Brigham and Women’s Hospital, used electronic health records to study 2491 adults prescribed semaglutide between 2018 and 2023 at Brigham and Women’s Hospital. Average age was 51, 74% were White, and 78% were women. A total of 13% had a history of weight loss surgery.
 

Costs, Side Effects, and Other Concerns

The investigators looked at issues around starting and staying on semaglutide in a subgroup of 500 patients. A total of 75 people never started the drug, for example. The majority, 72%, of this group said it was because of insurance coverage or the cost of the medication. Another 19% did not give a reason, and 9% said it was because of side effects.

People with higher body mass indexes and diabetes were less likely to start taking semaglutide, Dr. Medhati said.

Another 100 of the 500 patients started and then stopped semaglutide. Again, insurance coverage and cost were reasons, this time cited by 13%. About 36% stopped because of side effects; 21% pointed to a shortage of semaglutide; and 30% stopped for an unspecified reason.

“Our study highlights the importance of addressing insurance to ensure broader access,” Dr. Medhati said.

The 325 people who stayed on semaglutide lost an average of 8.5% of their total body weight at 50 weeks.
 

Access Remains Unequal

“These medications are incredibly powerful to treat obesity and weight-related disease both for people with a history of bariatric surgery and those without,” said session co-moderator Matthew Kroh, MD, vice chair of innovation and technology in the Department of General Surgery at Cleveland Clinic.

More equitable access to semaglutide and other GLP-1s is needed, he said. “Because the cost is so high and they’re not covered by most insurance plans at this point, people with better financial means have access to these medications,” while others may not.

Dr. Kroh said the findings may only apply to the patients, most of whom were female, White, and middle-aged. But he applauded the researchers for doing the study outside of a clinical trial. “Real-world data will help guide these decisions in the future,” he said.

A version of this article appeared on WebMD.com.

The principle of resilience and survival is crucial for medically significant fungi. These microorganisms are far from creating the postapocalyptic scenario depicted in TV series like The Last of Us, and much work is necessary to learn more about them. Accurate statistics on fungal infections, accompanied by clinical histories, simple laboratory tests, new antifungals, and a necessary One Health approach are lacking. 

The entomopathogenic fungus Ophiocordyceps unilateralis was made notorious by the TV series, but for now, it only manages to control the brains of some ants at will. Luckily, there are no signs that fungi affecting humans are inclined to create zombies.

What is clear is that the world belongs to the kingdom of fungi and that fungi are everywhere. There are already close to 150,000 described species, but millions remain to be discovered. They abound in decomposing organic matter, soil, or animal excrement, including that of bats and pigeons. Some fungi have even managed to find a home in hospitals. Lastly, we must not forget those that establish themselves in the human microbiome.

Given such diversity, it is legitimate to ask whether any of them could be capable of generating new pandemics. Could the forgotten Cryptococcus neoformans, Aspergillus fumigatus, or Histoplasma species, among others, trigger new health emergencies on the scale of the one generated by SARS-CoV-2?

We cannot forget that a coronavirus has already confirmed that reality can surpass fiction. However, Edith Sánchez Paredes, a biologist, doctor in biomedical sciences, and specialist in medical mycology, provided a reassuring response to Medscape Spanish Edition on this point.

“That would be very difficult to see because the way fungal infections are acquired is not from person to person, in most cases,” said Dr. Sánchez Paredes, from the Mycology Unit of the Faculty of Medicine at the National Autonomous University of Mexico.

Close to 300 species have already been classified as pathogenic in humans. Although the numbers are not precise and are increasing, it is estimated that around 1,500,000 people worldwide die each year of systemic fungal infections.

“However, it is important to emphasize that establishment of an infection depends not only on the causal agent. A crucial factor is the host, in this case, the human. Generally, these types of infections will develop in individuals with some deficiency in their immune system. The more deficient the immune response, the more likely a fungal infection may occur,” stated Dr. Sánchez Paredes.

The possibility of a pandemic like the one experienced with SARS-CoV-2 in the short term is remote, but the threat posed by fungal infections persists.

In 2022, the World Health Organization (WHO) defined a priority list of pathogenic fungi, with the aim of guiding actions to control them. It is mentioned there that invasive fungal diseases are on the rise worldwide, particularly in immunocompromised populations.

“Despite the growing concern, fungal infections receive very little attention and resources, leading to a paucity of quality data on fungal disease distribution and antifungal resistance patterns. Consequently, it is impossible to estimate their exact burden,” as stated in the document.

In line with this, an article published in Mycoses in 2022 concluded that fungal infections are neglected diseases in Latin America. Among other difficulties, deficiencies in access to tests such as polymerase chain reaction or serum detection of beta-1,3-D-glucan have been reported there.

In terms of treatments, most countries encounter problems with access to liposomal amphotericin B and new azoles, such as posaconazole and isavuconazole.

“Unfortunately, in Latin America, we suffer from a poor infrastructure for diagnosing fungal infections; likewise, we have limited access to antifungals available in the global market. What’s more, we lack reliable data on the epidemiology of fungal infections in the region, so many times governments are unaware of the true extent of the problem,” said Rogelio de Jesús Treviño Rangel, PhD, a medical microbiologist and expert in clinical mycology, professor, and researcher at the Faculty of Medicine of the Autonomous University of Nuevo León in Mexico.
 

Need for More Medical Mycology Training

Dr. Fernando Messina is a medical mycologist with the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital in Buenos Aires, Argentina. He has noted an increase in the number of cases of cryptococcosis, histoplasmosis, and aspergillosis in his daily practice.

“Particularly, pulmonary aspergillosis is steadily increasing. This is because many patients have structural lung alterations that favor the appearance of this mycosis. This is related to the increase in cases of tuberculosis and the rise in life expectancy of patients with chronic obstructive pulmonary disease or other pulmonary or systemic diseases,” Dr. Messina stated.

For Dr. Messina, the main obstacle in current clinical practice is the low level of awareness among nonspecialist physicians regarding the presence of systemic fungal infections, and because these infections are more common than realized, it is vital to consider fungal etiology before starting empirical antibiotic therapy.

“Health professionals usually do not think about mycoses because mycology occupies a very small space in medical education at universities. As the Venezuelan mycologist Gioconda Cunto de San Blas once said, ‘Mycology is the Cinderella of microbiology.’ To change this, we need to give more space to mycoses in undergraduate and postgraduate studies,” Dr. Messina asserted.

He added, “The main challenge is to train professionals with an emphasis on the clinical interpretation of cases. Current medicine has a strong trend toward molecular biology and the use of rapid diagnostic methods, without considering the clinical symptoms or the patient’s history. Determinations are very useful, but it is necessary to interpret the results.”

Dr. Messina sees it as unlikely in the short term for a pandemic to be caused by fungi, but if it were to occur, he believes it would happen in healthcare systems in regions that are not prepared in terms of infrastructure. However, as seen in the health emergency resulting from SARS-CoV-2, he thinks the impact would be mitigated by the performance of healthcare professionals.

“In general, we have the ability to adapt to any adverse situation or change — although it is clear that we need more doctors, biochemists, and microbiologists trained in mycology,” emphasized Dr. Messina.

More than 40 interns pass through Muñiz Hospital each year. They are doctors and biochemists from Argentina, other countries in the region, or even Europe, seeking to enhance their training in mycology. Regarding fungal infection laboratory work, the interest lies in learning to use traditional techniques and innovative molecular methods.

“Rapid diagnostic methods, especially the detection of circulating antigens, have marked a change in the prognosis of deep mycosis in immunocompromised hosts. The possibility of screening and monitoring in this group of patients is very important and has a great benefit,” said Gabriela Santiso, PhD, a biochemist and head of the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital.

According to Dr. Santiso, the current landscape includes the ability to identify genus and species, which can help in understanding resistance to antifungals. Furthermore, conducting sensitivity tests to these drugs, using standardized commercial methods, also provides timely information for treatment.

But Dr. Santiso warns that Latin America is a vast region with great disparity in human and technological resources. Although most countries in the region have networks facilitating access to timely diagnosis, resources are generally more available in major urban centers.

This often clashes with the epidemiology of most fungal infections. “Let’s not forget that many fungal pathologies affect low-income people who have difficulties accessing health centers, which sometimes turns them into chronic diseases that are hard to treat,” Dr. Santiso pointed out.

In mycology laboratories, the biggest cost is incurred by new diagnostic tests, such as those allowing molecular identification. Conventional methods are not usually expensive, but they require time and effort to train human resources to handle them.

Because new methodologies are not always available or easily accessible throughout the region, Dr. Santiso recommended not neglecting traditional mycological techniques. “Molecular methods, rapid diagnostic methods, and conventional mycology techniques are complementary and not mutually exclusive tests. Continuous training and updating are needed in this area,” she emphasized.
 

Why Are Resistant Fungal Infections Becoming Increasingly Common?

The first barrier for fungi to cause infection in humans is body temperature; most of them cannot withstand 37 °C. However, they also struggle to evade the immune response that is activated when they try to enter the body. 

“We are normally exposed to many of these fungi, almost all the time, but if our immune system is adequate, it may not go beyond a mild infection, in most cases subclinical, which will resolve quickly,” Dr. Sánchez Paredes stated.

However, according to Dr. Sánchez Paredes, if the immune response is weak, “the fungus will have no trouble establishing itself in our organs. Some are even part of our microbiota, such as Candida albicans, which in the face of an imbalance or immunocompromise, can lead to serious infections.”

It is clear that the population at risk for immunosuppression has increased. According to the WHO, this is due to the high prevalence of such diseases as tuberculosis, cancer, and HIV infection, among others.

But the WHO also believes that the increase in fungal infections is related to greater population access to critical care units, invasive procedures, chemotherapy, or immunotherapy treatments.

Furthermore, factors related to the fungus itself and the environment play a role. “These organisms have enzymes, proteins, and other molecules that allow them to survive in the environment in which they normally inhabit. When they face a new and stressful one, they must express other molecules that will allow them to survive. All of this helps them evade elements of the immune system, antifungals, and, of course, body temperature,” according to Dr. Sánchez Paredes.

It is possible that climate change is also behind the noticeable increase in fungal infections and that this crisis may have an even greater impact in the future. The temperature of the environment has increased, and fungi will have to adapt to the planet’s temperature, to the point where body temperature may no longer be a significant barrier for them.

Environmental changes would also be responsible for modifications in the distribution of endemic mycoses, and it is believed that fungi will more frequently find new ecological niches, be able to survive in other environments, and alter distribution zones.

This is what is happening between Mexico and the United States with coccidioidomycosis, or valley fever. “We will begin to see cases of some mycoses where they were not normally seen, so we will have to conduct more studies to confirm that the fungus is inhabiting these new areas or is simply appearing in new sites owing to migration and the great mobility of populations,” Dr. Sánchez Paredes said.

Finally, exposure to environmental factors would partly be responsible for the increasing resistance to first-line antifungals observed in these microorganisms. This seems to be the case with A. fumigatus when exposed to azoles used as fungicides in agriculture.
 

One Health in Fungal Infections

The increasing resistance to antifungals is a clear testament that human, animal, and environmental health are interconnected. This is why a multidisciplinary approach that adopts the perspective of One Health is necessary for its management.

“The use of fungicides in agriculture, structurally similar to the azoles used in clinics, generates resistance in Aspergillus fumigatus found in the environment. These fungi in humans can be associated with infections that do not respond to first-line treatment,” explained Carlos Arturo Álvarez, an infectious diseases physician and professor at the Faculty of Medicine at the National University of Colombia.

According to Dr. Álvarez, the approach to control them should not only focus on the search for diagnostic methods that allow early detection of antifungal resistance or research on new antifungal treatments. He believes that progress must also be made with strategies that allow for the proper use of antifungals in agriculture.

“Unfortunately, the One Health approach is not yet well implemented in the region, and in my view, there is a lack of articulation in the different sectors. That is, there is a need for true coordination between government offices of agriculture, animal and human health, academia, and international organizations. This is not happening yet, and I believe we are in the initial stage of visibility,” Dr. Álvarez opined.

Veterinary public health is another pillar of the aforementioned approach. For various reasons, animals experience a higher frequency of fungal infections. A few carry and transmit true zoonoses that affect human health, but most often, animals act only as sentinels indicating a potential source of transmission.

Carolina Segundo Zaragoza, PhD, has worked in veterinary mycology for 30 years. She currently heads the veterinary mycology laboratory at the Animal Production Teaching, Research, and Extension Center in Altiplano, under the Faculty of Veterinary Medicine and Animal Husbandry at the National Autonomous University of Mexico. Because she has frequent contact with specialists in human mycology, during her professional career she has received several patient consultations, most of which were for cutaneous mycoses.

“They detect some dermatomycosis and realize that the common factor is owning a companion animal or a production animal with which the patient has contact. Both animals and humans present the same type of lesions, and then comes the question: Who infected whom? I remind them that the main source of infection is the soil and that animals should not be blamed in the first instance,” Dr. Segundo Zaragoza clarified.

She is currently collaborating on a research project analyzing the presence of Coccidioides immitis in the soil. This pathogen is responsible for coccidioidomycosis in dogs and humans, and she sees with satisfaction how these types of initiatives, which include some components of the One Health vision, are becoming more common in Mexico.

“Fortunately, human mycologists are increasingly providing more space for the dissemination of veterinary mycology. So I have had the opportunity to be invited to different forums on medical mycology to present the clinical cases we can have in animals and talk about the research projects we carry out. I have more and more opportunities to conduct joint research with human mycologists and veterinary doctors,” she said.

Dr. Segundo Zaragoza believes that to better implement the One Health vision, standardizing the criteria for detecting, diagnosing, and treating mycoses is necessary. She considers that teamwork will be key to achieving the common goal of safeguarding the well-being and health of humans and animals.
 

Alarms Sound for Candida auris

The WHO included the yeast Candida auris in its group of pathogens with critical priority, and since 2009, it has raised alarm owing to the ease with which it grows in hospitals. In that setting, C auris is known for its high transmissibility, its ability to cause outbreaks, and the high mortality rate from disseminated infections.

“It has been a concern for the mycological community because it shows resistance to most antifungals used clinically, mainly azoles, but also for causing epidemic outbreaks,” emphasized Dr. Sánchez Paredes.

Its mode of transmission is not very clear, but it has been documented to be present on the skin and persist in hospital materials and furniture. It causes nosocomial infections in critically ill patients, such as those in intensive care, and those with cancer or who have received a transplant.

Risk factors for its development include renal insufficiency, hospital stays of more than 15 days, mechanical ventilation, central lines, use of parenteral nutrition, and presence of sepsis.

As for other mycoses, there are no precise studies reporting global incidence rates, but the trend indicates an increase in the detection of outbreaks in various countries lately — something that began to be visible during the COVID-19 pandemic.

In Mexico, Dr. Treviño Rangel and colleagues from Nuevo León reported the first case of candidemia caused by this agent. It occurred in May 2020 and involved a 58-year-old woman with a history of severe endometriosis and multiple complications in the gastrointestinal tract. The patient’s condition improved favorably thanks to antifungal therapy with caspofungin and liposomal amphotericin B.

However, 3 months after that episode, the group reported an outbreak of C. auris at the same hospital in 12 critically ill patients co-infected with SARS-CoV-2. All were on mechanical ventilation, had peripherally inserted central catheters and urinary catheters, and had a prolonged hospital stay (20-70 days). The mortality in patients with candidemia in this cohort was 83.3%.
 

Open Ending

As seen in some science fiction series, fungal infections in the region still have an open ending, and Global Action For Fungal Infections (GAFFI) has estimated that with better diagnostics and treatments, deaths caused by fungi could decrease to less than 750,000 per year worldwide.

But if everything continues as is, some aspects of what is to come may resemble the dystopia depicted in The Last of Us. No zombies, but emerging and reemerging fungi in a chaotic distribution, and resistant to all established treatments.

“The risk factors of patients and their immune status, combined with the behavior of mycoses, bring a complicated scenario. But therapeutic failure resulting from multidrug resistance to antifungals could make it catastrophic,” Dr. Sánchez Paredes summarized.

At the moment, there are only four families of drugs capable of counteracting fungal infections — and as mentioned, some are already scarce in Latin America’s hospital pharmacies.

“Historically, fungal infections have been given less importance than those caused by viruses or bacteria. Even in some developed countries, the true extent of morbidity and mortality they present is unknown. This results in less investment in the development of new antifungal molecules because knowledge is lacking about the incidence and prevalence of these diseases,” Dr. Treviño Rangel pointed out.

He added that the main limitation for the development of new drugs is economic. “Unfortunately, not many pharmaceutical companies are willing to invest in the development of new antifungals, and there are no government programs specifically promoting and supporting research into new therapeutic options against these neglected diseases,” he asserted.

Development of vaccines to prevent fungal infections faces the same barriers. Although, according to Dr. Treviño Rangel, the difficulties are compounded by the great similarity between fungal cells and human cells. This makes it possible for harmful cross-reactivity to occur. In addition, because most severe fungal infections occur in individuals with immunosuppression, a vaccine would need to trigger an adequate immune response despite this issue.

Meanwhile, fungi quietly continue to do what they do best: resist and survive. For millions of years, they have mutated and adapted to new environments. Some theories even blame them for the extinction of dinosaurs and the subsequent rise of mammals. They exist on the edge of life and death, decomposing and creating. There is consensus that at the moment, it does not seem feasible for them to generate a pandemic like the one due to SARS-CoV-2, given their transmission mechanism. But who is willing to rule out that this may not happen in the long or medium term?

Dr. Sánchez Paredes, Dr. Treviño Rangel, Dr. Messina, Dr. Santiso, Dr. Álvarez, and Dr. Segundo Zaragoza have declared no relevant financial conflicts of interest. 
 

This story was translated from Medscape Spanish Edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The principle of resilience and survival is crucial for medically significant fungi. These microorganisms are far from creating the postapocalyptic scenario depicted in TV series like The Last of Us, and much work is necessary to learn more about them. Accurate statistics on fungal infections, accompanied by clinical histories, simple laboratory tests, new antifungals, and a necessary One Health approach are lacking. 

The entomopathogenic fungus Ophiocordyceps unilateralis was made notorious by the TV series, but for now, it only manages to control the brains of some ants at will. Luckily, there are no signs that fungi affecting humans are inclined to create zombies.

What is clear is that the world belongs to the kingdom of fungi and that fungi are everywhere. There are already close to 150,000 described species, but millions remain to be discovered. They abound in decomposing organic matter, soil, or animal excrement, including that of bats and pigeons. Some fungi have even managed to find a home in hospitals. Lastly, we must not forget those that establish themselves in the human microbiome.

Given such diversity, it is legitimate to ask whether any of them could be capable of generating new pandemics. Could the forgotten Cryptococcus neoformans, Aspergillus fumigatus, or Histoplasma species, among others, trigger new health emergencies on the scale of the one generated by SARS-CoV-2?

We cannot forget that a coronavirus has already confirmed that reality can surpass fiction. However, Edith Sánchez Paredes, a biologist, doctor in biomedical sciences, and specialist in medical mycology, provided a reassuring response to Medscape Spanish Edition on this point.

“That would be very difficult to see because the way fungal infections are acquired is not from person to person, in most cases,” said Dr. Sánchez Paredes, from the Mycology Unit of the Faculty of Medicine at the National Autonomous University of Mexico.

Close to 300 species have already been classified as pathogenic in humans. Although the numbers are not precise and are increasing, it is estimated that around 1,500,000 people worldwide die each year of systemic fungal infections.

“However, it is important to emphasize that establishment of an infection depends not only on the causal agent. A crucial factor is the host, in this case, the human. Generally, these types of infections will develop in individuals with some deficiency in their immune system. The more deficient the immune response, the more likely a fungal infection may occur,” stated Dr. Sánchez Paredes.

The possibility of a pandemic like the one experienced with SARS-CoV-2 in the short term is remote, but the threat posed by fungal infections persists.

In 2022, the World Health Organization (WHO) defined a priority list of pathogenic fungi, with the aim of guiding actions to control them. It is mentioned there that invasive fungal diseases are on the rise worldwide, particularly in immunocompromised populations.

“Despite the growing concern, fungal infections receive very little attention and resources, leading to a paucity of quality data on fungal disease distribution and antifungal resistance patterns. Consequently, it is impossible to estimate their exact burden,” as stated in the document.

In line with this, an article published in Mycoses in 2022 concluded that fungal infections are neglected diseases in Latin America. Among other difficulties, deficiencies in access to tests such as polymerase chain reaction or serum detection of beta-1,3-D-glucan have been reported there.

In terms of treatments, most countries encounter problems with access to liposomal amphotericin B and new azoles, such as posaconazole and isavuconazole.

“Unfortunately, in Latin America, we suffer from a poor infrastructure for diagnosing fungal infections; likewise, we have limited access to antifungals available in the global market. What’s more, we lack reliable data on the epidemiology of fungal infections in the region, so many times governments are unaware of the true extent of the problem,” said Rogelio de Jesús Treviño Rangel, PhD, a medical microbiologist and expert in clinical mycology, professor, and researcher at the Faculty of Medicine of the Autonomous University of Nuevo León in Mexico.
 

Need for More Medical Mycology Training

Dr. Fernando Messina is a medical mycologist with the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital in Buenos Aires, Argentina. He has noted an increase in the number of cases of cryptococcosis, histoplasmosis, and aspergillosis in his daily practice.

“Particularly, pulmonary aspergillosis is steadily increasing. This is because many patients have structural lung alterations that favor the appearance of this mycosis. This is related to the increase in cases of tuberculosis and the rise in life expectancy of patients with chronic obstructive pulmonary disease or other pulmonary or systemic diseases,” Dr. Messina stated.

For Dr. Messina, the main obstacle in current clinical practice is the low level of awareness among nonspecialist physicians regarding the presence of systemic fungal infections, and because these infections are more common than realized, it is vital to consider fungal etiology before starting empirical antibiotic therapy.

“Health professionals usually do not think about mycoses because mycology occupies a very small space in medical education at universities. As the Venezuelan mycologist Gioconda Cunto de San Blas once said, ‘Mycology is the Cinderella of microbiology.’ To change this, we need to give more space to mycoses in undergraduate and postgraduate studies,” Dr. Messina asserted.

He added, “The main challenge is to train professionals with an emphasis on the clinical interpretation of cases. Current medicine has a strong trend toward molecular biology and the use of rapid diagnostic methods, without considering the clinical symptoms or the patient’s history. Determinations are very useful, but it is necessary to interpret the results.”

Dr. Messina sees it as unlikely in the short term for a pandemic to be caused by fungi, but if it were to occur, he believes it would happen in healthcare systems in regions that are not prepared in terms of infrastructure. However, as seen in the health emergency resulting from SARS-CoV-2, he thinks the impact would be mitigated by the performance of healthcare professionals.

“In general, we have the ability to adapt to any adverse situation or change — although it is clear that we need more doctors, biochemists, and microbiologists trained in mycology,” emphasized Dr. Messina.

More than 40 interns pass through Muñiz Hospital each year. They are doctors and biochemists from Argentina, other countries in the region, or even Europe, seeking to enhance their training in mycology. Regarding fungal infection laboratory work, the interest lies in learning to use traditional techniques and innovative molecular methods.

“Rapid diagnostic methods, especially the detection of circulating antigens, have marked a change in the prognosis of deep mycosis in immunocompromised hosts. The possibility of screening and monitoring in this group of patients is very important and has a great benefit,” said Gabriela Santiso, PhD, a biochemist and head of the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital.

According to Dr. Santiso, the current landscape includes the ability to identify genus and species, which can help in understanding resistance to antifungals. Furthermore, conducting sensitivity tests to these drugs, using standardized commercial methods, also provides timely information for treatment.

But Dr. Santiso warns that Latin America is a vast region with great disparity in human and technological resources. Although most countries in the region have networks facilitating access to timely diagnosis, resources are generally more available in major urban centers.

This often clashes with the epidemiology of most fungal infections. “Let’s not forget that many fungal pathologies affect low-income people who have difficulties accessing health centers, which sometimes turns them into chronic diseases that are hard to treat,” Dr. Santiso pointed out.

In mycology laboratories, the biggest cost is incurred by new diagnostic tests, such as those allowing molecular identification. Conventional methods are not usually expensive, but they require time and effort to train human resources to handle them.

Because new methodologies are not always available or easily accessible throughout the region, Dr. Santiso recommended not neglecting traditional mycological techniques. “Molecular methods, rapid diagnostic methods, and conventional mycology techniques are complementary and not mutually exclusive tests. Continuous training and updating are needed in this area,” she emphasized.
 

Why Are Resistant Fungal Infections Becoming Increasingly Common?

The first barrier for fungi to cause infection in humans is body temperature; most of them cannot withstand 37 °C. However, they also struggle to evade the immune response that is activated when they try to enter the body. 

“We are normally exposed to many of these fungi, almost all the time, but if our immune system is adequate, it may not go beyond a mild infection, in most cases subclinical, which will resolve quickly,” Dr. Sánchez Paredes stated.

However, according to Dr. Sánchez Paredes, if the immune response is weak, “the fungus will have no trouble establishing itself in our organs. Some are even part of our microbiota, such as Candida albicans, which in the face of an imbalance or immunocompromise, can lead to serious infections.”

It is clear that the population at risk for immunosuppression has increased. According to the WHO, this is due to the high prevalence of such diseases as tuberculosis, cancer, and HIV infection, among others.

But the WHO also believes that the increase in fungal infections is related to greater population access to critical care units, invasive procedures, chemotherapy, or immunotherapy treatments.

Furthermore, factors related to the fungus itself and the environment play a role. “These organisms have enzymes, proteins, and other molecules that allow them to survive in the environment in which they normally inhabit. When they face a new and stressful one, they must express other molecules that will allow them to survive. All of this helps them evade elements of the immune system, antifungals, and, of course, body temperature,” according to Dr. Sánchez Paredes.

It is possible that climate change is also behind the noticeable increase in fungal infections and that this crisis may have an even greater impact in the future. The temperature of the environment has increased, and fungi will have to adapt to the planet’s temperature, to the point where body temperature may no longer be a significant barrier for them.

Environmental changes would also be responsible for modifications in the distribution of endemic mycoses, and it is believed that fungi will more frequently find new ecological niches, be able to survive in other environments, and alter distribution zones.

This is what is happening between Mexico and the United States with coccidioidomycosis, or valley fever. “We will begin to see cases of some mycoses where they were not normally seen, so we will have to conduct more studies to confirm that the fungus is inhabiting these new areas or is simply appearing in new sites owing to migration and the great mobility of populations,” Dr. Sánchez Paredes said.

Finally, exposure to environmental factors would partly be responsible for the increasing resistance to first-line antifungals observed in these microorganisms. This seems to be the case with A. fumigatus when exposed to azoles used as fungicides in agriculture.
 

One Health in Fungal Infections

The increasing resistance to antifungals is a clear testament that human, animal, and environmental health are interconnected. This is why a multidisciplinary approach that adopts the perspective of One Health is necessary for its management.

“The use of fungicides in agriculture, structurally similar to the azoles used in clinics, generates resistance in Aspergillus fumigatus found in the environment. These fungi in humans can be associated with infections that do not respond to first-line treatment,” explained Carlos Arturo Álvarez, an infectious diseases physician and professor at the Faculty of Medicine at the National University of Colombia.

According to Dr. Álvarez, the approach to control them should not only focus on the search for diagnostic methods that allow early detection of antifungal resistance or research on new antifungal treatments. He believes that progress must also be made with strategies that allow for the proper use of antifungals in agriculture.

“Unfortunately, the One Health approach is not yet well implemented in the region, and in my view, there is a lack of articulation in the different sectors. That is, there is a need for true coordination between government offices of agriculture, animal and human health, academia, and international organizations. This is not happening yet, and I believe we are in the initial stage of visibility,” Dr. Álvarez opined.

Veterinary public health is another pillar of the aforementioned approach. For various reasons, animals experience a higher frequency of fungal infections. A few carry and transmit true zoonoses that affect human health, but most often, animals act only as sentinels indicating a potential source of transmission.

Carolina Segundo Zaragoza, PhD, has worked in veterinary mycology for 30 years. She currently heads the veterinary mycology laboratory at the Animal Production Teaching, Research, and Extension Center in Altiplano, under the Faculty of Veterinary Medicine and Animal Husbandry at the National Autonomous University of Mexico. Because she has frequent contact with specialists in human mycology, during her professional career she has received several patient consultations, most of which were for cutaneous mycoses.

“They detect some dermatomycosis and realize that the common factor is owning a companion animal or a production animal with which the patient has contact. Both animals and humans present the same type of lesions, and then comes the question: Who infected whom? I remind them that the main source of infection is the soil and that animals should not be blamed in the first instance,” Dr. Segundo Zaragoza clarified.

She is currently collaborating on a research project analyzing the presence of Coccidioides immitis in the soil. This pathogen is responsible for coccidioidomycosis in dogs and humans, and she sees with satisfaction how these types of initiatives, which include some components of the One Health vision, are becoming more common in Mexico.

“Fortunately, human mycologists are increasingly providing more space for the dissemination of veterinary mycology. So I have had the opportunity to be invited to different forums on medical mycology to present the clinical cases we can have in animals and talk about the research projects we carry out. I have more and more opportunities to conduct joint research with human mycologists and veterinary doctors,” she said.

Dr. Segundo Zaragoza believes that to better implement the One Health vision, standardizing the criteria for detecting, diagnosing, and treating mycoses is necessary. She considers that teamwork will be key to achieving the common goal of safeguarding the well-being and health of humans and animals.
 

Alarms Sound for Candida auris

The WHO included the yeast Candida auris in its group of pathogens with critical priority, and since 2009, it has raised alarm owing to the ease with which it grows in hospitals. In that setting, C auris is known for its high transmissibility, its ability to cause outbreaks, and the high mortality rate from disseminated infections.

“It has been a concern for the mycological community because it shows resistance to most antifungals used clinically, mainly azoles, but also for causing epidemic outbreaks,” emphasized Dr. Sánchez Paredes.

Its mode of transmission is not very clear, but it has been documented to be present on the skin and persist in hospital materials and furniture. It causes nosocomial infections in critically ill patients, such as those in intensive care, and those with cancer or who have received a transplant.

Risk factors for its development include renal insufficiency, hospital stays of more than 15 days, mechanical ventilation, central lines, use of parenteral nutrition, and presence of sepsis.

As for other mycoses, there are no precise studies reporting global incidence rates, but the trend indicates an increase in the detection of outbreaks in various countries lately — something that began to be visible during the COVID-19 pandemic.

In Mexico, Dr. Treviño Rangel and colleagues from Nuevo León reported the first case of candidemia caused by this agent. It occurred in May 2020 and involved a 58-year-old woman with a history of severe endometriosis and multiple complications in the gastrointestinal tract. The patient’s condition improved favorably thanks to antifungal therapy with caspofungin and liposomal amphotericin B.

However, 3 months after that episode, the group reported an outbreak of C. auris at the same hospital in 12 critically ill patients co-infected with SARS-CoV-2. All were on mechanical ventilation, had peripherally inserted central catheters and urinary catheters, and had a prolonged hospital stay (20-70 days). The mortality in patients with candidemia in this cohort was 83.3%.
 

Open Ending

As seen in some science fiction series, fungal infections in the region still have an open ending, and Global Action For Fungal Infections (GAFFI) has estimated that with better diagnostics and treatments, deaths caused by fungi could decrease to less than 750,000 per year worldwide.

But if everything continues as is, some aspects of what is to come may resemble the dystopia depicted in The Last of Us. No zombies, but emerging and reemerging fungi in a chaotic distribution, and resistant to all established treatments.

“The risk factors of patients and their immune status, combined with the behavior of mycoses, bring a complicated scenario. But therapeutic failure resulting from multidrug resistance to antifungals could make it catastrophic,” Dr. Sánchez Paredes summarized.

At the moment, there are only four families of drugs capable of counteracting fungal infections — and as mentioned, some are already scarce in Latin America’s hospital pharmacies.

“Historically, fungal infections have been given less importance than those caused by viruses or bacteria. Even in some developed countries, the true extent of morbidity and mortality they present is unknown. This results in less investment in the development of new antifungal molecules because knowledge is lacking about the incidence and prevalence of these diseases,” Dr. Treviño Rangel pointed out.

He added that the main limitation for the development of new drugs is economic. “Unfortunately, not many pharmaceutical companies are willing to invest in the development of new antifungals, and there are no government programs specifically promoting and supporting research into new therapeutic options against these neglected diseases,” he asserted.

Development of vaccines to prevent fungal infections faces the same barriers. Although, according to Dr. Treviño Rangel, the difficulties are compounded by the great similarity between fungal cells and human cells. This makes it possible for harmful cross-reactivity to occur. In addition, because most severe fungal infections occur in individuals with immunosuppression, a vaccine would need to trigger an adequate immune response despite this issue.

Meanwhile, fungi quietly continue to do what they do best: resist and survive. For millions of years, they have mutated and adapted to new environments. Some theories even blame them for the extinction of dinosaurs and the subsequent rise of mammals. They exist on the edge of life and death, decomposing and creating. There is consensus that at the moment, it does not seem feasible for them to generate a pandemic like the one due to SARS-CoV-2, given their transmission mechanism. But who is willing to rule out that this may not happen in the long or medium term?

Dr. Sánchez Paredes, Dr. Treviño Rangel, Dr. Messina, Dr. Santiso, Dr. Álvarez, and Dr. Segundo Zaragoza have declared no relevant financial conflicts of interest. 
 

This story was translated from Medscape Spanish Edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The principle of resilience and survival is crucial for medically significant fungi. These microorganisms are far from creating the postapocalyptic scenario depicted in TV series like The Last of Us, and much work is necessary to learn more about them. Accurate statistics on fungal infections, accompanied by clinical histories, simple laboratory tests, new antifungals, and a necessary One Health approach are lacking. 

The entomopathogenic fungus Ophiocordyceps unilateralis was made notorious by the TV series, but for now, it only manages to control the brains of some ants at will. Luckily, there are no signs that fungi affecting humans are inclined to create zombies.

What is clear is that the world belongs to the kingdom of fungi and that fungi are everywhere. There are already close to 150,000 described species, but millions remain to be discovered. They abound in decomposing organic matter, soil, or animal excrement, including that of bats and pigeons. Some fungi have even managed to find a home in hospitals. Lastly, we must not forget those that establish themselves in the human microbiome.

Given such diversity, it is legitimate to ask whether any of them could be capable of generating new pandemics. Could the forgotten Cryptococcus neoformans, Aspergillus fumigatus, or Histoplasma species, among others, trigger new health emergencies on the scale of the one generated by SARS-CoV-2?

We cannot forget that a coronavirus has already confirmed that reality can surpass fiction. However, Edith Sánchez Paredes, a biologist, doctor in biomedical sciences, and specialist in medical mycology, provided a reassuring response to Medscape Spanish Edition on this point.

“That would be very difficult to see because the way fungal infections are acquired is not from person to person, in most cases,” said Dr. Sánchez Paredes, from the Mycology Unit of the Faculty of Medicine at the National Autonomous University of Mexico.

Close to 300 species have already been classified as pathogenic in humans. Although the numbers are not precise and are increasing, it is estimated that around 1,500,000 people worldwide die each year of systemic fungal infections.

“However, it is important to emphasize that establishment of an infection depends not only on the causal agent. A crucial factor is the host, in this case, the human. Generally, these types of infections will develop in individuals with some deficiency in their immune system. The more deficient the immune response, the more likely a fungal infection may occur,” stated Dr. Sánchez Paredes.

The possibility of a pandemic like the one experienced with SARS-CoV-2 in the short term is remote, but the threat posed by fungal infections persists.

In 2022, the World Health Organization (WHO) defined a priority list of pathogenic fungi, with the aim of guiding actions to control them. It is mentioned there that invasive fungal diseases are on the rise worldwide, particularly in immunocompromised populations.

“Despite the growing concern, fungal infections receive very little attention and resources, leading to a paucity of quality data on fungal disease distribution and antifungal resistance patterns. Consequently, it is impossible to estimate their exact burden,” as stated in the document.

In line with this, an article published in Mycoses in 2022 concluded that fungal infections are neglected diseases in Latin America. Among other difficulties, deficiencies in access to tests such as polymerase chain reaction or serum detection of beta-1,3-D-glucan have been reported there.

In terms of treatments, most countries encounter problems with access to liposomal amphotericin B and new azoles, such as posaconazole and isavuconazole.

“Unfortunately, in Latin America, we suffer from a poor infrastructure for diagnosing fungal infections; likewise, we have limited access to antifungals available in the global market. What’s more, we lack reliable data on the epidemiology of fungal infections in the region, so many times governments are unaware of the true extent of the problem,” said Rogelio de Jesús Treviño Rangel, PhD, a medical microbiologist and expert in clinical mycology, professor, and researcher at the Faculty of Medicine of the Autonomous University of Nuevo León in Mexico.
 

Need for More Medical Mycology Training

Dr. Fernando Messina is a medical mycologist with the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital in Buenos Aires, Argentina. He has noted an increase in the number of cases of cryptococcosis, histoplasmosis, and aspergillosis in his daily practice.

“Particularly, pulmonary aspergillosis is steadily increasing. This is because many patients have structural lung alterations that favor the appearance of this mycosis. This is related to the increase in cases of tuberculosis and the rise in life expectancy of patients with chronic obstructive pulmonary disease or other pulmonary or systemic diseases,” Dr. Messina stated.

For Dr. Messina, the main obstacle in current clinical practice is the low level of awareness among nonspecialist physicians regarding the presence of systemic fungal infections, and because these infections are more common than realized, it is vital to consider fungal etiology before starting empirical antibiotic therapy.

“Health professionals usually do not think about mycoses because mycology occupies a very small space in medical education at universities. As the Venezuelan mycologist Gioconda Cunto de San Blas once said, ‘Mycology is the Cinderella of microbiology.’ To change this, we need to give more space to mycoses in undergraduate and postgraduate studies,” Dr. Messina asserted.

He added, “The main challenge is to train professionals with an emphasis on the clinical interpretation of cases. Current medicine has a strong trend toward molecular biology and the use of rapid diagnostic methods, without considering the clinical symptoms or the patient’s history. Determinations are very useful, but it is necessary to interpret the results.”

Dr. Messina sees it as unlikely in the short term for a pandemic to be caused by fungi, but if it were to occur, he believes it would happen in healthcare systems in regions that are not prepared in terms of infrastructure. However, as seen in the health emergency resulting from SARS-CoV-2, he thinks the impact would be mitigated by the performance of healthcare professionals.

“In general, we have the ability to adapt to any adverse situation or change — although it is clear that we need more doctors, biochemists, and microbiologists trained in mycology,” emphasized Dr. Messina.

More than 40 interns pass through Muñiz Hospital each year. They are doctors and biochemists from Argentina, other countries in the region, or even Europe, seeking to enhance their training in mycology. Regarding fungal infection laboratory work, the interest lies in learning to use traditional techniques and innovative molecular methods.

“Rapid diagnostic methods, especially the detection of circulating antigens, have marked a change in the prognosis of deep mycosis in immunocompromised hosts. The possibility of screening and monitoring in this group of patients is very important and has a great benefit,” said Gabriela Santiso, PhD, a biochemist and head of the Mycology Unit of the Francisco Javier Muñiz Infectious Diseases Hospital.

According to Dr. Santiso, the current landscape includes the ability to identify genus and species, which can help in understanding resistance to antifungals. Furthermore, conducting sensitivity tests to these drugs, using standardized commercial methods, also provides timely information for treatment.

But Dr. Santiso warns that Latin America is a vast region with great disparity in human and technological resources. Although most countries in the region have networks facilitating access to timely diagnosis, resources are generally more available in major urban centers.

This often clashes with the epidemiology of most fungal infections. “Let’s not forget that many fungal pathologies affect low-income people who have difficulties accessing health centers, which sometimes turns them into chronic diseases that are hard to treat,” Dr. Santiso pointed out.

In mycology laboratories, the biggest cost is incurred by new diagnostic tests, such as those allowing molecular identification. Conventional methods are not usually expensive, but they require time and effort to train human resources to handle them.

Because new methodologies are not always available or easily accessible throughout the region, Dr. Santiso recommended not neglecting traditional mycological techniques. “Molecular methods, rapid diagnostic methods, and conventional mycology techniques are complementary and not mutually exclusive tests. Continuous training and updating are needed in this area,” she emphasized.
 

Why Are Resistant Fungal Infections Becoming Increasingly Common?

The first barrier for fungi to cause infection in humans is body temperature; most of them cannot withstand 37 °C. However, they also struggle to evade the immune response that is activated when they try to enter the body. 

“We are normally exposed to many of these fungi, almost all the time, but if our immune system is adequate, it may not go beyond a mild infection, in most cases subclinical, which will resolve quickly,” Dr. Sánchez Paredes stated.

However, according to Dr. Sánchez Paredes, if the immune response is weak, “the fungus will have no trouble establishing itself in our organs. Some are even part of our microbiota, such as Candida albicans, which in the face of an imbalance or immunocompromise, can lead to serious infections.”

It is clear that the population at risk for immunosuppression has increased. According to the WHO, this is due to the high prevalence of such diseases as tuberculosis, cancer, and HIV infection, among others.

But the WHO also believes that the increase in fungal infections is related to greater population access to critical care units, invasive procedures, chemotherapy, or immunotherapy treatments.

Furthermore, factors related to the fungus itself and the environment play a role. “These organisms have enzymes, proteins, and other molecules that allow them to survive in the environment in which they normally inhabit. When they face a new and stressful one, they must express other molecules that will allow them to survive. All of this helps them evade elements of the immune system, antifungals, and, of course, body temperature,” according to Dr. Sánchez Paredes.

It is possible that climate change is also behind the noticeable increase in fungal infections and that this crisis may have an even greater impact in the future. The temperature of the environment has increased, and fungi will have to adapt to the planet’s temperature, to the point where body temperature may no longer be a significant barrier for them.

Environmental changes would also be responsible for modifications in the distribution of endemic mycoses, and it is believed that fungi will more frequently find new ecological niches, be able to survive in other environments, and alter distribution zones.

This is what is happening between Mexico and the United States with coccidioidomycosis, or valley fever. “We will begin to see cases of some mycoses where they were not normally seen, so we will have to conduct more studies to confirm that the fungus is inhabiting these new areas or is simply appearing in new sites owing to migration and the great mobility of populations,” Dr. Sánchez Paredes said.

Finally, exposure to environmental factors would partly be responsible for the increasing resistance to first-line antifungals observed in these microorganisms. This seems to be the case with A. fumigatus when exposed to azoles used as fungicides in agriculture.
 

One Health in Fungal Infections

The increasing resistance to antifungals is a clear testament that human, animal, and environmental health are interconnected. This is why a multidisciplinary approach that adopts the perspective of One Health is necessary for its management.

“The use of fungicides in agriculture, structurally similar to the azoles used in clinics, generates resistance in Aspergillus fumigatus found in the environment. These fungi in humans can be associated with infections that do not respond to first-line treatment,” explained Carlos Arturo Álvarez, an infectious diseases physician and professor at the Faculty of Medicine at the National University of Colombia.

According to Dr. Álvarez, the approach to control them should not only focus on the search for diagnostic methods that allow early detection of antifungal resistance or research on new antifungal treatments. He believes that progress must also be made with strategies that allow for the proper use of antifungals in agriculture.

“Unfortunately, the One Health approach is not yet well implemented in the region, and in my view, there is a lack of articulation in the different sectors. That is, there is a need for true coordination between government offices of agriculture, animal and human health, academia, and international organizations. This is not happening yet, and I believe we are in the initial stage of visibility,” Dr. Álvarez opined.

Veterinary public health is another pillar of the aforementioned approach. For various reasons, animals experience a higher frequency of fungal infections. A few carry and transmit true zoonoses that affect human health, but most often, animals act only as sentinels indicating a potential source of transmission.

Carolina Segundo Zaragoza, PhD, has worked in veterinary mycology for 30 years. She currently heads the veterinary mycology laboratory at the Animal Production Teaching, Research, and Extension Center in Altiplano, under the Faculty of Veterinary Medicine and Animal Husbandry at the National Autonomous University of Mexico. Because she has frequent contact with specialists in human mycology, during her professional career she has received several patient consultations, most of which were for cutaneous mycoses.

“They detect some dermatomycosis and realize that the common factor is owning a companion animal or a production animal with which the patient has contact. Both animals and humans present the same type of lesions, and then comes the question: Who infected whom? I remind them that the main source of infection is the soil and that animals should not be blamed in the first instance,” Dr. Segundo Zaragoza clarified.

She is currently collaborating on a research project analyzing the presence of Coccidioides immitis in the soil. This pathogen is responsible for coccidioidomycosis in dogs and humans, and she sees with satisfaction how these types of initiatives, which include some components of the One Health vision, are becoming more common in Mexico.

“Fortunately, human mycologists are increasingly providing more space for the dissemination of veterinary mycology. So I have had the opportunity to be invited to different forums on medical mycology to present the clinical cases we can have in animals and talk about the research projects we carry out. I have more and more opportunities to conduct joint research with human mycologists and veterinary doctors,” she said.

Dr. Segundo Zaragoza believes that to better implement the One Health vision, standardizing the criteria for detecting, diagnosing, and treating mycoses is necessary. She considers that teamwork will be key to achieving the common goal of safeguarding the well-being and health of humans and animals.
 

Alarms Sound for Candida auris

The WHO included the yeast Candida auris in its group of pathogens with critical priority, and since 2009, it has raised alarm owing to the ease with which it grows in hospitals. In that setting, C auris is known for its high transmissibility, its ability to cause outbreaks, and the high mortality rate from disseminated infections.

“It has been a concern for the mycological community because it shows resistance to most antifungals used clinically, mainly azoles, but also for causing epidemic outbreaks,” emphasized Dr. Sánchez Paredes.

Its mode of transmission is not very clear, but it has been documented to be present on the skin and persist in hospital materials and furniture. It causes nosocomial infections in critically ill patients, such as those in intensive care, and those with cancer or who have received a transplant.

Risk factors for its development include renal insufficiency, hospital stays of more than 15 days, mechanical ventilation, central lines, use of parenteral nutrition, and presence of sepsis.

As for other mycoses, there are no precise studies reporting global incidence rates, but the trend indicates an increase in the detection of outbreaks in various countries lately — something that began to be visible during the COVID-19 pandemic.

In Mexico, Dr. Treviño Rangel and colleagues from Nuevo León reported the first case of candidemia caused by this agent. It occurred in May 2020 and involved a 58-year-old woman with a history of severe endometriosis and multiple complications in the gastrointestinal tract. The patient’s condition improved favorably thanks to antifungal therapy with caspofungin and liposomal amphotericin B.

However, 3 months after that episode, the group reported an outbreak of C. auris at the same hospital in 12 critically ill patients co-infected with SARS-CoV-2. All were on mechanical ventilation, had peripherally inserted central catheters and urinary catheters, and had a prolonged hospital stay (20-70 days). The mortality in patients with candidemia in this cohort was 83.3%.
 

Open Ending

As seen in some science fiction series, fungal infections in the region still have an open ending, and Global Action For Fungal Infections (GAFFI) has estimated that with better diagnostics and treatments, deaths caused by fungi could decrease to less than 750,000 per year worldwide.

But if everything continues as is, some aspects of what is to come may resemble the dystopia depicted in The Last of Us. No zombies, but emerging and reemerging fungi in a chaotic distribution, and resistant to all established treatments.

“The risk factors of patients and their immune status, combined with the behavior of mycoses, bring a complicated scenario. But therapeutic failure resulting from multidrug resistance to antifungals could make it catastrophic,” Dr. Sánchez Paredes summarized.

At the moment, there are only four families of drugs capable of counteracting fungal infections — and as mentioned, some are already scarce in Latin America’s hospital pharmacies.

“Historically, fungal infections have been given less importance than those caused by viruses or bacteria. Even in some developed countries, the true extent of morbidity and mortality they present is unknown. This results in less investment in the development of new antifungal molecules because knowledge is lacking about the incidence and prevalence of these diseases,” Dr. Treviño Rangel pointed out.

He added that the main limitation for the development of new drugs is economic. “Unfortunately, not many pharmaceutical companies are willing to invest in the development of new antifungals, and there are no government programs specifically promoting and supporting research into new therapeutic options against these neglected diseases,” he asserted.

Development of vaccines to prevent fungal infections faces the same barriers. Although, according to Dr. Treviño Rangel, the difficulties are compounded by the great similarity between fungal cells and human cells. This makes it possible for harmful cross-reactivity to occur. In addition, because most severe fungal infections occur in individuals with immunosuppression, a vaccine would need to trigger an adequate immune response despite this issue.

Meanwhile, fungi quietly continue to do what they do best: resist and survive. For millions of years, they have mutated and adapted to new environments. Some theories even blame them for the extinction of dinosaurs and the subsequent rise of mammals. They exist on the edge of life and death, decomposing and creating. There is consensus that at the moment, it does not seem feasible for them to generate a pandemic like the one due to SARS-CoV-2, given their transmission mechanism. But who is willing to rule out that this may not happen in the long or medium term?

Dr. Sánchez Paredes, Dr. Treviño Rangel, Dr. Messina, Dr. Santiso, Dr. Álvarez, and Dr. Segundo Zaragoza have declared no relevant financial conflicts of interest. 
 

This story was translated from Medscape Spanish Edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with both type 2 diabetes (T2D) and obesity who have a lower diabetes severity, as characterized by the individualized metabolic surgery (IMS) scoring system, achieve better weight loss outcomes with semaglutide.

METHODOLOGY:

• Prior studies indicate that semaglutide leads to inferior weight loss outcomes in patients with obesity who have T2D vs those without T2D; however, no study has assessed semaglutide’s weight loss effects as a function of T2D severity.
• The IMS score, which includes four parameters (A1c, < 7%; insulin use; number of T2D medications; and T2D duration), is a validated tool that can categorize T2D severity as mild (0-24.9 points), moderate (25-94.9 points), or severe (95-180 points).
• This retrospective cohort study of patients with obesity and T2D taking ≥ 1 mg of semaglutide investigated weight loss outcomes over 12 months based on IMS scores at baseline as well as changes in glycemic parameters.
• The primary endpoint was weight loss outcomes based on four IMS score quartiles (quartile 1, 12-78 points; quartile 2, 79-107 points; quartile 3, 108-129 points; and quartile 4, 130-172 points) at 12 months after starting semaglutide.

TAKEAWAY:

• Investigators included 297 patients (42% women; mean age, 61.5 years).
• At 12 months, the weight loss outcomes decreased in a stepwise manner as the IMS score quartiles increased from 1 to 4 (total body weight loss %; quartile 1, 8.8; quartile 2, 6.9; quartile 3, 5.7; and quartile 4, 5.0).
• Similarly, patients in the mild to moderate IMS category achieved significantly superior weight loss outcomes than those in the severe category (−8.3% vs −5.5%; P = .006) at 12 months.
• All four individual IMS parameters (ie, being on insulin, having a higher baseline level of A1c, having a longer duration of T2D, and using a greater number of diabetes medications) were independently associated with significantly inferior weight loss outcomes.
• Glycemic parameters, such as fasting blood glucose and A1c levels, did not improve regardless of the IMS severity at baseline.

IN PRACTICE:

“Our findings could help clinicians set informed expectations for weight loss outcomes in patients with severe T2D taking semaglutide; however, it is likely that the cardiometabolic benefits associated with semaglutide treatment in this population far exceed the effect on weight loss,” the authors commented.

SOURCE:

Wissam Ghusn, MD, from the Department of Medicine, Mayo Clinic, Rochester, Minnesota, led this study, which was published online in eClinicalMedicine.

LIMITATIONS:

Due to the retrospective nature of this study, the authors had limited ability to abstract data on all IMS parameters. The presence of predominantly White and male patients in this cohort limited the generalizability of this study’s findings to other external populations. The number of patients in the mild IMS category was extremely low.

DISCLOSURES:

This study did not receive any specific grants, but the involved research staff received payments from the Mayo Clinic. One of the authors declared serving as a consultant, having contracts, and holding equity in various companies.

A version of this article appeared on Medscape.com.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development. 

Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.

Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.

Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test. 

If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.

Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.

There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development. 

One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.

Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.

Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
 

A version of this article appeared on Medscape.com.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development. 

Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.

Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.

Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test. 

If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.

Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.

There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development. 

One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.

Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.

Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
 

A version of this article appeared on Medscape.com.

A blood test that measures lipoprotein(a) [Lp(a)] has received breakthrough device designation from the US Food and Drug Administration (FDA).

The Tina-quant Lp(a) RxDx assay, developed by Roche in partnership with Amgen, is designed to identify adults with elevated Lp(a) levels who may benefit from lipid-lowering therapies currently in development. 

Lp(a) is a type of lipoprotein that is genetically inherited. Elevated levels have been associated with an increased risk for heart disease, stroke, and other blood vessel diseases.

Worldwide, about 1 in 5 people have high Lp(a) levels that are not significantly affected by lifestyle changes, such as diet and exercise. Elevated Lp(a) is particularly prevalent among women and people of African descent.

Lp(a) testing is “an important tool for clinicians, enabling them to make a more accurate assessment of [cardiovascular] risk, and it is expected to become a part of regular diagnostic testing in the coming years,” Roche said in a news release announcing the breakthrough designation for the Lp(a) blood test. 

If approved, the Tina-quant Lp(a) RxDx assay will be available on select Roche cobas platforms, the company reported.

Although low-density-lipoprotein (LDL) cholesterol particles are much more abundant than Lp(a) particles and carry the greatest overall risk for heart disease, on a per-particle basis, atherogenic risk associated with Lp(a) is about six times higher than that associated with LDL cholesterol, a recent study showed.

There currently are no approved pharmacologic therapies to lower Lp(a) levels in the United States, but several hopefuls are in development. 

One is zerlasiran (Silence Therapeutics), a short interfering RNA (siRNA) agent, or “gene silencing” therapy, which binds to and temporarily blocks the action of the LPA gene, which encodes for apolipoprotein A, a dominant and rate-limiting component in the hepatic synthesis of the Lp(a) particle.

Treatment with zerlasiran produced significant and sustained reductions in Lp(a) concentrations in adults with elevated Lp(a) in the phase 1 APOLLO trial and the phase 2 ALPACAR-360 trial.

Other siRNA agents in development to lower Lp(a) levels include pelacarsen, lepodisiran, olpasiran, and muvalaplin.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Onyda XR (clonidine hydrochloride) for the treatment of attention-deficit/hyperactivity disorder (ADHD), drug manufacturer Tris Pharma announced in a statement.

The drug is the first approved liquid nonstimulant ADHD medication. The once-daily extended-release oral suspension, with nighttime dosing, can be used alone or as an adjunctive therapy to FDA-approved stimulant medications in pediatric patients 6 years of age or older.

“People with ADHD require a range of therapeutic options that are designed for their individual needs, because not every medication or type of therapy works for every patient,” Ann Childress, MD, a psychiatrist and president of the Las Vegas–based Center for Psychiatry and Behavioral Medicine, said in the release. 

“The approval of Onyda XR, the only liquid non-stimulant ADHD medication, with nighttime dosing that shifts the release profile, is a convenient option for patients needing better ADHD control,” she added.

The approval was based on “adequate and well-controlled studies” of the company’s extended-release tablets.

Onyda XR is contraindicated in patients with a history of a hypersensitivity reaction to clonidine. 

The medication can cause dose-related decreases in blood pressure and heart rate. Vital signs should be monitored frequently in at-risk patients. In studies with the extended-release tablets, somnolence and sedation were commonly reported adverse reactions. The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular block, especially in patients taking other sympatholytic drugs, the company noted.

Onyda XR should be available in pharmacies in the second half of 2024.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Onyda XR (clonidine hydrochloride) for the treatment of attention-deficit/hyperactivity disorder (ADHD), drug manufacturer Tris Pharma announced in a statement.

The drug is the first approved liquid nonstimulant ADHD medication. The once-daily extended-release oral suspension, with nighttime dosing, can be used alone or as an adjunctive therapy to FDA-approved stimulant medications in pediatric patients 6 years of age or older.

“People with ADHD require a range of therapeutic options that are designed for their individual needs, because not every medication or type of therapy works for every patient,” Ann Childress, MD, a psychiatrist and president of the Las Vegas–based Center for Psychiatry and Behavioral Medicine, said in the release. 

“The approval of Onyda XR, the only liquid non-stimulant ADHD medication, with nighttime dosing that shifts the release profile, is a convenient option for patients needing better ADHD control,” she added.

The approval was based on “adequate and well-controlled studies” of the company’s extended-release tablets.

Onyda XR is contraindicated in patients with a history of a hypersensitivity reaction to clonidine. 

The medication can cause dose-related decreases in blood pressure and heart rate. Vital signs should be monitored frequently in at-risk patients. In studies with the extended-release tablets, somnolence and sedation were commonly reported adverse reactions. The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular block, especially in patients taking other sympatholytic drugs, the company noted.

Onyda XR should be available in pharmacies in the second half of 2024.
 

A version of this article appeared on Medscape.com.

The US Food and Drug Administration (FDA) has approved Onyda XR (clonidine hydrochloride) for the treatment of attention-deficit/hyperactivity disorder (ADHD), drug manufacturer Tris Pharma announced in a statement.

The drug is the first approved liquid nonstimulant ADHD medication. The once-daily extended-release oral suspension, with nighttime dosing, can be used alone or as an adjunctive therapy to FDA-approved stimulant medications in pediatric patients 6 years of age or older.

“People with ADHD require a range of therapeutic options that are designed for their individual needs, because not every medication or type of therapy works for every patient,” Ann Childress, MD, a psychiatrist and president of the Las Vegas–based Center for Psychiatry and Behavioral Medicine, said in the release. 

“The approval of Onyda XR, the only liquid non-stimulant ADHD medication, with nighttime dosing that shifts the release profile, is a convenient option for patients needing better ADHD control,” she added.

The approval was based on “adequate and well-controlled studies” of the company’s extended-release tablets.

Onyda XR is contraindicated in patients with a history of a hypersensitivity reaction to clonidine. 

The medication can cause dose-related decreases in blood pressure and heart rate. Vital signs should be monitored frequently in at-risk patients. In studies with the extended-release tablets, somnolence and sedation were commonly reported adverse reactions. The sympatholytic action of clonidine may worsen sinus node dysfunction and atrioventricular block, especially in patients taking other sympatholytic drugs, the company noted.

Onyda XR should be available in pharmacies in the second half of 2024.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A structured exercise program leads to improvements in sexual health and sexual symptoms caused by endocrine therapy, as well as fatigue and overall quality of life in women with metastatic breast cancer, a randomized controlled trial found.

METHODOLOGY:

• Patients with metastatic breast cancer often experience issues with sexual health. Data on the effectiveness of interventions such as exercise are lacking.
• The PREFERABLE-EFFECT trial enrolled 355 women (mean age, 55.4 years) with metastatic breast cancer; 75% had received first- or second-line treatment at enrollment, and 68% had bone metastases.
• Trial participants were randomly allocated to either usual care or a 9-month (twice weekly) supervised exercise program combining aerobic, resistance, and balance exercises. All participants received general exercise advice and an activity tracker.
• Patients were assessed at baseline and 3, 6, and 9 months. Exercise intervention effects were analyzed on an intent-to-treat basis with mixed models.

TAKEAWAY:

• At baseline, most women showed no interest in sexual activity, and 60% were not sexually active. Nearly half (46%) of sexually active women reported no or little sexual enjoyment. Low sexual function was associated with depression and older age.
• Among patients receiving endocrine therapy, 27% reported vaginal pain and 40% reported vaginal dryness during sexual activity.
• The exercise intervention significantly improved sexual functioning (effect size = 0.28; P = .003) and endocrine sexual symptoms (effect size = 0.25; P = .003) at 6 months, and these effects were sustained at 9 months. Sexual enjoyment also appeared to improve in the exercise group, but due to the small sample size, this was not a statistically significant effect.
• Prior results from the trial showed that the exercise program had significant benefits for fatigue and overall quality of life (primary outcomes).

IN PRACTICE:

Patients with metastatic breast cancer “often suffer from sexual health issues and this topic should be addressed by clinicians,” said study presenter Martina Schmidt, PhD, with the German Cancer Research Center, Heidelberg.

“Physical exercise should be a crucial component of the prescription we offer to our patients,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

SOURCE:

The research (abstract 269MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress.

LIMITATIONS:

Further research needs to be done to determine the optimal role of exercise in addressing symptom burden.

DISCLOSURES:

This research was funded by the European Union’s Horizon 2020 research and innovation program and the National Health and Medical Research Council of Australia. Dr. Schmidt has no relevant conflicts of interest. Dr. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

A version of this article appeared on Medscape.com.

TOPLINE:

A structured exercise program leads to improvements in sexual health and sexual symptoms caused by endocrine therapy, as well as fatigue and overall quality of life in women with metastatic breast cancer, a randomized controlled trial found.

METHODOLOGY:

• Patients with metastatic breast cancer often experience issues with sexual health. Data on the effectiveness of interventions such as exercise are lacking.
• The PREFERABLE-EFFECT trial enrolled 355 women (mean age, 55.4 years) with metastatic breast cancer; 75% had received first- or second-line treatment at enrollment, and 68% had bone metastases.
• Trial participants were randomly allocated to either usual care or a 9-month (twice weekly) supervised exercise program combining aerobic, resistance, and balance exercises. All participants received general exercise advice and an activity tracker.
• Patients were assessed at baseline and 3, 6, and 9 months. Exercise intervention effects were analyzed on an intent-to-treat basis with mixed models.

TAKEAWAY:

• At baseline, most women showed no interest in sexual activity, and 60% were not sexually active. Nearly half (46%) of sexually active women reported no or little sexual enjoyment. Low sexual function was associated with depression and older age.
• Among patients receiving endocrine therapy, 27% reported vaginal pain and 40% reported vaginal dryness during sexual activity.
• The exercise intervention significantly improved sexual functioning (effect size = 0.28; P = .003) and endocrine sexual symptoms (effect size = 0.25; P = .003) at 6 months, and these effects were sustained at 9 months. Sexual enjoyment also appeared to improve in the exercise group, but due to the small sample size, this was not a statistically significant effect.
• Prior results from the trial showed that the exercise program had significant benefits for fatigue and overall quality of life (primary outcomes).

IN PRACTICE:

Patients with metastatic breast cancer “often suffer from sexual health issues and this topic should be addressed by clinicians,” said study presenter Martina Schmidt, PhD, with the German Cancer Research Center, Heidelberg.

“Physical exercise should be a crucial component of the prescription we offer to our patients,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

SOURCE:

The research (abstract 269MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress.

LIMITATIONS:

Further research needs to be done to determine the optimal role of exercise in addressing symptom burden.

DISCLOSURES:

This research was funded by the European Union’s Horizon 2020 research and innovation program and the National Health and Medical Research Council of Australia. Dr. Schmidt has no relevant conflicts of interest. Dr. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

A version of this article appeared on Medscape.com.

TOPLINE:

A structured exercise program leads to improvements in sexual health and sexual symptoms caused by endocrine therapy, as well as fatigue and overall quality of life in women with metastatic breast cancer, a randomized controlled trial found.

METHODOLOGY:

• Patients with metastatic breast cancer often experience issues with sexual health. Data on the effectiveness of interventions such as exercise are lacking.
• The PREFERABLE-EFFECT trial enrolled 355 women (mean age, 55.4 years) with metastatic breast cancer; 75% had received first- or second-line treatment at enrollment, and 68% had bone metastases.
• Trial participants were randomly allocated to either usual care or a 9-month (twice weekly) supervised exercise program combining aerobic, resistance, and balance exercises. All participants received general exercise advice and an activity tracker.
• Patients were assessed at baseline and 3, 6, and 9 months. Exercise intervention effects were analyzed on an intent-to-treat basis with mixed models.

TAKEAWAY:

• At baseline, most women showed no interest in sexual activity, and 60% were not sexually active. Nearly half (46%) of sexually active women reported no or little sexual enjoyment. Low sexual function was associated with depression and older age.
• Among patients receiving endocrine therapy, 27% reported vaginal pain and 40% reported vaginal dryness during sexual activity.
• The exercise intervention significantly improved sexual functioning (effect size = 0.28; P = .003) and endocrine sexual symptoms (effect size = 0.25; P = .003) at 6 months, and these effects were sustained at 9 months. Sexual enjoyment also appeared to improve in the exercise group, but due to the small sample size, this was not a statistically significant effect.
• Prior results from the trial showed that the exercise program had significant benefits for fatigue and overall quality of life (primary outcomes).

IN PRACTICE:

Patients with metastatic breast cancer “often suffer from sexual health issues and this topic should be addressed by clinicians,” said study presenter Martina Schmidt, PhD, with the German Cancer Research Center, Heidelberg.

“Physical exercise should be a crucial component of the prescription we offer to our patients,” said study discussant Matteo Lambertini, MD, PhD, with University of Genova, Genova, Italy.

SOURCE:

The research (abstract 269MO) was presented at the European Society for Medical Oncology Breast Cancer 2024 Annual Congress.

LIMITATIONS:

Further research needs to be done to determine the optimal role of exercise in addressing symptom burden.

DISCLOSURES:

This research was funded by the European Union’s Horizon 2020 research and innovation program and the National Health and Medical Research Council of Australia. Dr. Schmidt has no relevant conflicts of interest. Dr. Lambertini has financial relationships with various pharmaceutical companies including Roche, Novartis, AstraZeneca, Lilly, Exact Sciences, Pfizer, and others.

A version of this article appeared on Medscape.com.

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

NASHVILLE, TENNESSEE — Individuals with multiple sclerosis are living longer, healthier lives. More than half of patients with MS are 55 years or older, and the incidence of late-onset MS is rising.

This can lead to complex treatment decisions, according to Amy Perrin Ross, APN, MSN, CNRN, MSCN, who is the neuroscience program coordinator at Loyola Medical Center in Maywood, Illinois.

“Age was ranked as the second most important factor affecting treatment decisions in a recent survey of MS specialists,” said Ms. Ross, during a presentation at the annual meeting of the Consortium of Multiple Sclerosis Centers. But there is little evidence to support treatment decisions, since there are few older patients enrolled in clinical trials. The average age is around 30-34 years.
 

MS in Older Patients

Aging is associated with immune system changes. There is a decline in inflammatory activity and an accompanying 17% reduction in the relapse rate with every 5 years of advancing age, and the majority of relapses occur within 30 years of onset. The bad news is that patients have reduced capacity to recover from relapses as they age.

“When I’m talking to patients about pros and cons [of treatment], I do mention that, yes, your relapse rate might be less, but as we age, we have less of an ability to completely recover,” said Ms. Ross.

The efficacy of disease-modifying therapies (DMTs) goes down with advancing age. One meta-analyis of 38 randomized trials and 13 therapies found that benefit with respect to disease progression generally disappeared by the age of 53. “Age is an essential modifier of drug efficacy,” said Ms. Ross.

On the other hand, another meta-analysis found that success in treating relapses was similar across age groups. “So it seems that we can successfully treat our patients’ relapses: There was no significant association between age and reductions in annualized relapse rate,” she said, though she noted that clinical trial populations are likely to be dissimilar to aging patients, many of whom have gone years without experiencing a relapse.

Aging can also lead to differences in potential adverse effects of DMTs. Patients with MS experience faster immunosenescence, in which normal changes to the innate and adaptive immune system are accelerated. This can lead to greater risk of infection, and other adverse events can include post-administration reactions and changes to serum IgG levels.

Other conditions that should be monitored for include progressive multifocal leukoencephalopathy, and malignancies are more prevalent among people with MS than the general population, although it is unclear if this is due to the use of DMTs or other factors, or even just coincidence, said Ms. Ross. “Those are all things to keep in mind as we’re pushing forward with therapy for patients,” she said.

Comorbidities that occur with aging can also affect treatment outcomes, and could tip the balance against use of DMTs in some situations.
 

What Does the Literature Say?

There has been a range of retrospective studies looking at the results of discontinuation of DMTs with advancing age, and the results have been mixed. Some factors are associated with greater likelihood of disease reactivation, including younger age, female sex, shorter duration without a relapse, MRI activity, and degree of disability.

A study of a French registry including patients aged 50 years and older who went off DMTs found that 100% of patients who discontinued therapy were on older injectable DMTs, and 34.9% of that group restarted therapy over a mean follow-up of 7 years. The risk of relapse or disability progression was similar between the groups, but discontinuers who started with Expanded Disability Status Scale (EDSS) scores lower than 6.0 were more likely to reach an EDSS score of 6.0.

The DISCOMS study compared 259 patients randomized to continue DMTs versus discontinuation of DMTs. “What they found was that noninferiority was not shown. Disease activity, such as relapses and new lesions, [occurred in] 12% of the discontinuers and 5% of the continuers,” said Ms. Ross.

One option to balance risk and benefit is DMT de-escalation, with the aim to match disease therapy with disease activity over time. A 2023 survey of 224 neurologists to identify characteristics in older patients that would prompt de-escalation. The most common reasons were overall safety or comorbidity concerns (62% endorsed), high risk of infection (59%), low disease activity or stable disease (50%), concerns about efficacy (41%), high disability (37%), and patient choice (36%). About 7% reported that they generally do not de-escalate.

The preferred de-escalation therapies included glatiramer acetate (29%), fumarates (27%), teriflunomide (23%), and interferon betas (21%).

Ms. Ross noted that the study was likely conducted around the height of the COVID-19 pandemic. “So I wonder if some of these results might be a little bit different [than if it was conducted at a different time],” she said.
 

Other Concerns and Options

During the Q&A session, one audience member asked if physicians should consider low-efficacy medications in older patients with the idea that they at least get a little bit of protection.

Patricia Coyle, MD, who also presented during the session, framed her response around whether the patient had relapsing or progressive MS. “If somebody has had relapsing MS and has never transitioned to progressive MS, and they’re 70, maybe they don’t need to be on any DMT. If there’s no longer a focal inflammatory relapsing phase, if we could feel confident on that possibility, then maybe they don’t need to be on a relapsing DMT,” said Dr. Coyle, who is director of the MS Comprehensive Care Center at Stony Brook University Medical Center in Stony Brook, New York.

Alternatively, if a patient has progressive MS, she said she would recommend discontinuing treatment if she believes the patient is being harmed by it, to focus instead on health and wellness.

Another questioner wondered what to do with a 70-year-old patient who has had no infections, has normal IgG, but insists on continuing high-efficacy B-cell therapy. Dr. Coyle responded that she would tell the patient that she believes it isn’t offering any benefit, but if the patient insisted, she would continue: “I’m not living with MS the way they are. If they tell me, ‘I believe it’s helping me and I want to stay on it,’ then so long as I don’t think I’m overtly harming them, I’m going to treat them.”

Ms. Ross agreed, and suggested that ceding to the patient’s will is an important consideration. “I think sometimes what we’re doing, if we’re not causing harm, what we’re doing is bolstering these people’s ability to continue to have hope, and that in my mind is a big part of managing their disease,” she said.

Ms. Ross has financial relationships with Alexion Pharmaceuticals, Amgen/Horizon, ArgenX, Banner, Bristol Myers Squibb, EMD Serono, Roche, Sandoz, TG Therapeutics, UCB, and Viatris. Dr. Coyle has consulted for Accordant, Amgen, Bristol Myers Squibb, EMD Serono, Genentech, GlaxoSmithKline, Horizon Therapeutics, LabCorp, Eli Lilly, Mylan, Novartis, and Sanofi Genzyme. She has received research funding from Celgene, CorEvitas, Genentech/Roche, NINDS, and Sanofi Genzyme.
 

PULMONARY VASCULAR AND CARDIOVASCULAR NETWORK

Pulmonary Vascular Disease Section

In the right clinical scenario, three key hemodynamic components obtained by right heart catheterization (RHC) define precapillary pulmonary hypertension (PH) warranting vasodilator treatment: mean pulmonary arterial pressure >20 mm Hg, pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg, and pulmonary vascular resistance (PVR) >2 Wood units.¹ While these cutoffs are straightforward, a gap in practical application is evidenced by considerable variability in how PH providers perform and interpret RHC hemodynamic information.

CHEST

A recent survey of 145 PH providers conducted by CHEST’s Pulmonary Vascular Disease Section shed light on the current RHC practices in the US.² Regarding the respondents’ characteristics, 85% were in the 30-60 age range, 68% were males, and 71% were pulmonologists.

CHEST

About half of the providers perform the RHC themselves. Most review the hemodynamic tracings, but up to 21% rely on the final report alone. Regarding PCWP, most (86%) obtain it during end-expiration, but only 42% routinely measure a PCWP saturation for confirmation. When faced with PVR discrepancies between thermodilution and indirect Fick (IFick), up to 30% chose either IFick or didn’t know which one to trust. Nearly 20% repeat the RHC at least annually, and 80% whenever the patient declines.

CHEST

References

1. Simonneau et al. Eur Resp J. 2019;53(1):1801913

2. Soto et al. CHEST. 2023;164(4):Supplement A5832-A5834

PULMONARY VASCULAR AND CARDIOVASCULAR NETWORK

Pulmonary Vascular Disease Section

In the right clinical scenario, three key hemodynamic components obtained by right heart catheterization (RHC) define precapillary pulmonary hypertension (PH) warranting vasodilator treatment: mean pulmonary arterial pressure >20 mm Hg, pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg, and pulmonary vascular resistance (PVR) >2 Wood units.¹ While these cutoffs are straightforward, a gap in practical application is evidenced by considerable variability in how PH providers perform and interpret RHC hemodynamic information.

CHEST

A recent survey of 145 PH providers conducted by CHEST’s Pulmonary Vascular Disease Section shed light on the current RHC practices in the US.² Regarding the respondents’ characteristics, 85% were in the 30-60 age range, 68% were males, and 71% were pulmonologists.

CHEST

About half of the providers perform the RHC themselves. Most review the hemodynamic tracings, but up to 21% rely on the final report alone. Regarding PCWP, most (86%) obtain it during end-expiration, but only 42% routinely measure a PCWP saturation for confirmation. When faced with PVR discrepancies between thermodilution and indirect Fick (IFick), up to 30% chose either IFick or didn’t know which one to trust. Nearly 20% repeat the RHC at least annually, and 80% whenever the patient declines.

CHEST

References

1. Simonneau et al. Eur Resp J. 2019;53(1):1801913

2. Soto et al. CHEST. 2023;164(4):Supplement A5832-A5834

PULMONARY VASCULAR AND CARDIOVASCULAR NETWORK

Pulmonary Vascular Disease Section

In the right clinical scenario, three key hemodynamic components obtained by right heart catheterization (RHC) define precapillary pulmonary hypertension (PH) warranting vasodilator treatment: mean pulmonary arterial pressure >20 mm Hg, pulmonary capillary wedge pressure (PCWP) ≤15 mm Hg, and pulmonary vascular resistance (PVR) >2 Wood units.¹ While these cutoffs are straightforward, a gap in practical application is evidenced by considerable variability in how PH providers perform and interpret RHC hemodynamic information.

CHEST

A recent survey of 145 PH providers conducted by CHEST’s Pulmonary Vascular Disease Section shed light on the current RHC practices in the US.² Regarding the respondents’ characteristics, 85% were in the 30-60 age range, 68% were males, and 71% were pulmonologists.

CHEST

About half of the providers perform the RHC themselves. Most review the hemodynamic tracings, but up to 21% rely on the final report alone. Regarding PCWP, most (86%) obtain it during end-expiration, but only 42% routinely measure a PCWP saturation for confirmation. When faced with PVR discrepancies between thermodilution and indirect Fick (IFick), up to 30% chose either IFick or didn’t know which one to trust. Nearly 20% repeat the RHC at least annually, and 80% whenever the patient declines.

CHEST

References

1. Simonneau et al. Eur Resp J. 2019;53(1):1801913

2. Soto et al. CHEST. 2023;164(4):Supplement A5832-A5834

DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK

Pulmonary Physiology and Rehabilitation Section

Cardiopulmonary exercise testing (CPET) is a clinically useful modality to discriminate between cardiac, pulmonary, and musculoskeletal limitations to physical exertion. However, it is relatively underutilized due to the lack of local expertise necessary for accurate interpretation. Several studies have explored automation of CPET interpretation, the most notable of which utilized machine learning.¹

Recently, Schwendinger et al. investigated the ability of machine learning algorithms to not only categorize (pulmonary-vascular, mechanical-ventilatory, cardiocirculatory, and muscular), but also assign severity scores (0-6) to exercise limitations found in a group of 200 CPETs performed on adult patients referred to a lung clinic in Germany.² Decision trees were constructed for each of the limitation categories by identifying variables with the lowest Root Mean Square Error (RMSE), which were comparable to agreement within expert interpretations. Combining decision trees allowed for a more comprehensive analysis with identification of multiple abnormalities in the same test.

CHEST

A major limitation to the study is limited applicability to general patient populations without suspected lung disease. This bias is reflected in the decision tree for cardiovascular limitation that relied on VO₂ peak and FEV₁ alone. The authors were unable to construct a decision tree for muscular limitations due to a lack of identified cases.

CHEST

DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK

Pulmonary Physiology and Rehabilitation Section

Cardiopulmonary exercise testing (CPET) is a clinically useful modality to discriminate between cardiac, pulmonary, and musculoskeletal limitations to physical exertion. However, it is relatively underutilized due to the lack of local expertise necessary for accurate interpretation. Several studies have explored automation of CPET interpretation, the most notable of which utilized machine learning.¹

Recently, Schwendinger et al. investigated the ability of machine learning algorithms to not only categorize (pulmonary-vascular, mechanical-ventilatory, cardiocirculatory, and muscular), but also assign severity scores (0-6) to exercise limitations found in a group of 200 CPETs performed on adult patients referred to a lung clinic in Germany.² Decision trees were constructed for each of the limitation categories by identifying variables with the lowest Root Mean Square Error (RMSE), which were comparable to agreement within expert interpretations. Combining decision trees allowed for a more comprehensive analysis with identification of multiple abnormalities in the same test.

CHEST

A major limitation to the study is limited applicability to general patient populations without suspected lung disease. This bias is reflected in the decision tree for cardiovascular limitation that relied on VO₂ peak and FEV₁ alone. The authors were unable to construct a decision tree for muscular limitations due to a lack of identified cases.

CHEST

DIFFUSE LUNG DISEASE AND LUNG TRANSPLANT NETWORK

Pulmonary Physiology and Rehabilitation Section

Cardiopulmonary exercise testing (CPET) is a clinically useful modality to discriminate between cardiac, pulmonary, and musculoskeletal limitations to physical exertion. However, it is relatively underutilized due to the lack of local expertise necessary for accurate interpretation. Several studies have explored automation of CPET interpretation, the most notable of which utilized machine learning.¹

Recently, Schwendinger et al. investigated the ability of machine learning algorithms to not only categorize (pulmonary-vascular, mechanical-ventilatory, cardiocirculatory, and muscular), but also assign severity scores (0-6) to exercise limitations found in a group of 200 CPETs performed on adult patients referred to a lung clinic in Germany.² Decision trees were constructed for each of the limitation categories by identifying variables with the lowest Root Mean Square Error (RMSE), which were comparable to agreement within expert interpretations. Combining decision trees allowed for a more comprehensive analysis with identification of multiple abnormalities in the same test.

CHEST

A major limitation to the study is limited applicability to general patient populations without suspected lung disease. This bias is reflected in the decision tree for cardiovascular limitation that relied on VO₂ peak and FEV₁ alone. The authors were unable to construct a decision tree for muscular limitations due to a lack of identified cases.

CHEST

THORACIC ONCOLOGY AND CHEST PROCEDURES NETWORK

Pleural Disease Section

Optimal management of primary spontaneous (PSP) and secondary spontaneous pneumothorax (SSP) remains an area of ongoing debate, with both CHEST and the British Thoracic Society (BTS) offering guidelines to address management decisions.

The consensus for treatment of PSP depends on the size of the pneumothorax; if smaller than 2-3 cm, the patient can be observed for 3-6 hours and if radiographically stable, can discharge home with close (within 48 hours) follow-up and repeat chest radiograph (CXR).^1,2 If symptomatic or large, an intervention is recommended or home discharge with a Heimlich valve and close follow up (48 hours) with interval CXR.¹ For the management of SSP, it is recommended that the patient remain hospitalized, with a lower threshold to intervene with chest tube placement.^1,2

Both the 2001 CHEST guidelines and 2010 BTS guidelines recommend the use of a small bore pigtail catheter (<14 Fr) for management of PSP.^1,2 Expert consensus and retrospective studies recommend the use of a large bore chest tube (>28 French) in patients with secondary spontaneous pneumothorax and concomitant hemothorax, empyema, large air leaks, or mechanical ventilation.^3,4

For patients requiring pleurodesis, talc slurry is frequently used due to it being widely available and inexpensive.⁵ However, talc is associated with impurities and has been associated with severe pain, fever, dyspnea, and pneumonitis.^6,7 Other agents such as doxycycline have been studied but overall data is lacking. One study comparing doxycycline solution with talc slurry showed less recurrence of pneumothorax with talc as compared with doxycycline with no difference in side effects.⁸

– Praneet Iyer, MD

Member-at-Large

– Cristina Salmon, MD

Fellow-in-Training

– John N. Shumar, DO

Member-at-Large

References

1. Baumann MH, AACP Pneumothorax Consensus Group, et al. Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement. CHEST. 2001;119:590-602. doi: 10.1378/chest.119.2.590

2. Roberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ; BTS Pleural Disease Guideline Group Management of a malignant pleural effusion: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65:ii32-ii40. doi: 10.1136/thx.2010.136994

3. Lin YC, Tu CY, Liang SJ, et al. Pigtail catheter for the management of pneumothorax in mechanically ventilated patients. Am J Emerg Med. 2010;28(4):466-471. doi: 10.1016/j.ajem.2009.01.033. Epub 2010 Jan 28. PMID: 20466227.4. Baumann MH. Pleural Disease: An International Textbook. London: Arnold Publishers; 2003.

5. How CH, Hsu HH, Chen JS. Chemical pleurodesis for spontaneous pneumothorax. J Formos Med Assoc. 2013;112:749-755. 10.1016/j.jfma.2013.10.016

6. Rehse DH, Aye RW, Florence MG. Respiratory failure following talc pleurodesis. Am J Surg. 1999;177:437-440. Doi: 10.1016/S0002-9610(99)00075-6

7. Ferrer J, Villarino MA, Tura JM, et al. Talc preparations used for pleurodesis vary markedly from one preparation to another. CHEST. 2001;119:1901-1905. doi: 10.1378/chest.119.6.1901

8. Park EH, Kim JH, Yee J, et al. Comparisons of doxycycline solution with talc slurry for chemical pleurodesis and risk factors for recurrence in South Korean patients with spontaneous pneumothorax. Eur J Hosp Pharm. 2019;26(5):275-279. doi: 10.1136/ejhpharm-2017-001465. Epub 2018 Apr 18. PMID: 31656615; PMCID: PMC6788261.

THORACIC ONCOLOGY AND CHEST PROCEDURES NETWORK

Pleural Disease Section

Optimal management of primary spontaneous (PSP) and secondary spontaneous pneumothorax (SSP) remains an area of ongoing debate, with both CHEST and the British Thoracic Society (BTS) offering guidelines to address management decisions.

The consensus for treatment of PSP depends on the size of the pneumothorax; if smaller than 2-3 cm, the patient can be observed for 3-6 hours and if radiographically stable, can discharge home with close (within 48 hours) follow-up and repeat chest radiograph (CXR).^1,2 If symptomatic or large, an intervention is recommended or home discharge with a Heimlich valve and close follow up (48 hours) with interval CXR.¹ For the management of SSP, it is recommended that the patient remain hospitalized, with a lower threshold to intervene with chest tube placement.^1,2

Both the 2001 CHEST guidelines and 2010 BTS guidelines recommend the use of a small bore pigtail catheter (<14 Fr) for management of PSP.^1,2 Expert consensus and retrospective studies recommend the use of a large bore chest tube (>28 French) in patients with secondary spontaneous pneumothorax and concomitant hemothorax, empyema, large air leaks, or mechanical ventilation.^3,4

For patients requiring pleurodesis, talc slurry is frequently used due to it being widely available and inexpensive.⁵ However, talc is associated with impurities and has been associated with severe pain, fever, dyspnea, and pneumonitis.^6,7 Other agents such as doxycycline have been studied but overall data is lacking. One study comparing doxycycline solution with talc slurry showed less recurrence of pneumothorax with talc as compared with doxycycline with no difference in side effects.⁸

– Praneet Iyer, MD

Member-at-Large

– Cristina Salmon, MD

Fellow-in-Training

– John N. Shumar, DO

Member-at-Large

References

1. Baumann MH, AACP Pneumothorax Consensus Group, et al. Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement. CHEST. 2001;119:590-602. doi: 10.1378/chest.119.2.590

2. Roberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ; BTS Pleural Disease Guideline Group Management of a malignant pleural effusion: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65:ii32-ii40. doi: 10.1136/thx.2010.136994

3. Lin YC, Tu CY, Liang SJ, et al. Pigtail catheter for the management of pneumothorax in mechanically ventilated patients. Am J Emerg Med. 2010;28(4):466-471. doi: 10.1016/j.ajem.2009.01.033. Epub 2010 Jan 28. PMID: 20466227.4. Baumann MH. Pleural Disease: An International Textbook. London: Arnold Publishers; 2003.

5. How CH, Hsu HH, Chen JS. Chemical pleurodesis for spontaneous pneumothorax. J Formos Med Assoc. 2013;112:749-755. 10.1016/j.jfma.2013.10.016

6. Rehse DH, Aye RW, Florence MG. Respiratory failure following talc pleurodesis. Am J Surg. 1999;177:437-440. Doi: 10.1016/S0002-9610(99)00075-6

7. Ferrer J, Villarino MA, Tura JM, et al. Talc preparations used for pleurodesis vary markedly from one preparation to another. CHEST. 2001;119:1901-1905. doi: 10.1378/chest.119.6.1901

8. Park EH, Kim JH, Yee J, et al. Comparisons of doxycycline solution with talc slurry for chemical pleurodesis and risk factors for recurrence in South Korean patients with spontaneous pneumothorax. Eur J Hosp Pharm. 2019;26(5):275-279. doi: 10.1136/ejhpharm-2017-001465. Epub 2018 Apr 18. PMID: 31656615; PMCID: PMC6788261.

THORACIC ONCOLOGY AND CHEST PROCEDURES NETWORK

Pleural Disease Section

Optimal management of primary spontaneous (PSP) and secondary spontaneous pneumothorax (SSP) remains an area of ongoing debate, with both CHEST and the British Thoracic Society (BTS) offering guidelines to address management decisions.

The consensus for treatment of PSP depends on the size of the pneumothorax; if smaller than 2-3 cm, the patient can be observed for 3-6 hours and if radiographically stable, can discharge home with close (within 48 hours) follow-up and repeat chest radiograph (CXR).^1,2 If symptomatic or large, an intervention is recommended or home discharge with a Heimlich valve and close follow up (48 hours) with interval CXR.¹ For the management of SSP, it is recommended that the patient remain hospitalized, with a lower threshold to intervene with chest tube placement.^1,2

Both the 2001 CHEST guidelines and 2010 BTS guidelines recommend the use of a small bore pigtail catheter (<14 Fr) for management of PSP.^1,2 Expert consensus and retrospective studies recommend the use of a large bore chest tube (>28 French) in patients with secondary spontaneous pneumothorax and concomitant hemothorax, empyema, large air leaks, or mechanical ventilation.^3,4

For patients requiring pleurodesis, talc slurry is frequently used due to it being widely available and inexpensive.⁵ However, talc is associated with impurities and has been associated with severe pain, fever, dyspnea, and pneumonitis.^6,7 Other agents such as doxycycline have been studied but overall data is lacking. One study comparing doxycycline solution with talc slurry showed less recurrence of pneumothorax with talc as compared with doxycycline with no difference in side effects.⁸

– Praneet Iyer, MD

Member-at-Large

– Cristina Salmon, MD

Fellow-in-Training

– John N. Shumar, DO

Member-at-Large

References

1. Baumann MH, AACP Pneumothorax Consensus Group, et al. Management of spontaneous pneumothorax: an American College of Chest Physicians Delphi consensus statement. CHEST. 2001;119:590-602. doi: 10.1378/chest.119.2.590

2. Roberts ME, Neville E, Berrisford RG, Antunes G, Ali NJ; BTS Pleural Disease Guideline Group Management of a malignant pleural effusion: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65:ii32-ii40. doi: 10.1136/thx.2010.136994

3. Lin YC, Tu CY, Liang SJ, et al. Pigtail catheter for the management of pneumothorax in mechanically ventilated patients. Am J Emerg Med. 2010;28(4):466-471. doi: 10.1016/j.ajem.2009.01.033. Epub 2010 Jan 28. PMID: 20466227.4. Baumann MH. Pleural Disease: An International Textbook. London: Arnold Publishers; 2003.

5. How CH, Hsu HH, Chen JS. Chemical pleurodesis for spontaneous pneumothorax. J Formos Med Assoc. 2013;112:749-755. 10.1016/j.jfma.2013.10.016

6. Rehse DH, Aye RW, Florence MG. Respiratory failure following talc pleurodesis. Am J Surg. 1999;177:437-440. Doi: 10.1016/S0002-9610(99)00075-6

7. Ferrer J, Villarino MA, Tura JM, et al. Talc preparations used for pleurodesis vary markedly from one preparation to another. CHEST. 2001;119:1901-1905. doi: 10.1378/chest.119.6.1901

8. Park EH, Kim JH, Yee J, et al. Comparisons of doxycycline solution with talc slurry for chemical pleurodesis and risk factors for recurrence in South Korean patients with spontaneous pneumothorax. Eur J Hosp Pharm. 2019;26(5):275-279. doi: 10.1136/ejhpharm-2017-001465. Epub 2018 Apr 18. PMID: 31656615; PMCID: PMC6788261.