Clinician Reviews

Newly discovered genes could explain body fat differences between men and women with obesity, as well as why some people gain excess weight in childhood.

Identifying specific genes adds to growing evidence that biology, in part, drives obesity. Researchers hope the findings will lead to effective treatments, and in the meantime add to the understanding that there are many types of obesity that come from a mix of genes and environmental factors.

Although the study is not the first to point to specific genes, “we were quite surprised by the proposed function of some of the genes we identified,” Lena R. Kaisinger, lead study investigator and a PhD student in the MRC Epidemiology Unit at the University of Cambridge (England), wrote in an email. For example, the genes also manage cell death and influence how cells respond to DNA damage. 

The investigators are not sure why genes involved in body size perform this kind of double duty, which opens avenues for future research.

The gene sequencing study was published online in the journal Cell Genomics.
 

Differences between women and men

The researchers found five new genes in females and two new genes in males linked to greater body mass index (BMI): DIDO1, KIAA1109, MC4R, PTPRG and SLC12A5 in women and MC4R and SLTM in men. People who recall having obesity as a child were more likely to have rare genetic changes in two other genes, OBSCN and MADD.

“The key thing is that when you see real genes with real gene names, it really makes real the notion that genetics underlie obesity,” said Lee Kaplan, MD, PhD, director of the Obesity and Metabolism Institute in Boston, who was not affiliated with the research.

Ms. Kaisinger and colleagues found these significant genetic differences by studying genomes of about 420,000 people stored in the UK Biobank, a huge biomedical database. The researchers decided to look at genes by sex and age because these are “two areas that we still know very little about,” Ms. Kaisinger said.

“We know that different types of obesity connect to different ages,” said Dr. Kaplan, who is also past president of the Obesity Society. “But what they’ve done now is find genes that are associated with particular subtypes of obesity ... some more common in one sex and some more common in different phases of life, including early onset obesity.”
 

The future is already here

Treatment for obesity based on a person’s genes already exists. For example, in June 2022, the Food and Drug Administration approved setmelanotide (Imcivree) for weight management in adults and children aged over 6 years with specific genetic markers. 

Even as encouraging as setmelanotide is to Ms. Kaisinger and colleagues, these are still early days for translating the current research findings into clinical obesity tests and potential treatment, she said.

The “holy grail,” Dr. Kaplan said, is a future where people get screened for a particular genetic profile and their provider can say something like, “You’re probably most susceptible to this type, so we’ll treat you with this particular drug that’s been developed for people with this phenotype.”

Dr. Kaplan added: “That’s exactly what we are trying to do.”

Moving forward, Ms. Kaisinger and colleagues plan to repeat the study in larger and more diverse populations. They also plan to reverse the usual road map for studies, which typically start in animals and then progress to humans.

“We plan to take the most promising gene candidates forward into mouse models to learn more about their function and how exactly their dysfunction results in obesity,” Ms. Kaisinger said. 

Three study coauthors are employees and shareholders of Adrestia Therapeutics. No other conflicts of interest were reported.

A version of this article appeared on WebMD.com.

Newly discovered genes could explain body fat differences between men and women with obesity, as well as why some people gain excess weight in childhood.

Identifying specific genes adds to growing evidence that biology, in part, drives obesity. Researchers hope the findings will lead to effective treatments, and in the meantime add to the understanding that there are many types of obesity that come from a mix of genes and environmental factors.

Although the study is not the first to point to specific genes, “we were quite surprised by the proposed function of some of the genes we identified,” Lena R. Kaisinger, lead study investigator and a PhD student in the MRC Epidemiology Unit at the University of Cambridge (England), wrote in an email. For example, the genes also manage cell death and influence how cells respond to DNA damage. 

The investigators are not sure why genes involved in body size perform this kind of double duty, which opens avenues for future research.

The gene sequencing study was published online in the journal Cell Genomics.
 

Differences between women and men

The researchers found five new genes in females and two new genes in males linked to greater body mass index (BMI): DIDO1, KIAA1109, MC4R, PTPRG and SLC12A5 in women and MC4R and SLTM in men. People who recall having obesity as a child were more likely to have rare genetic changes in two other genes, OBSCN and MADD.

“The key thing is that when you see real genes with real gene names, it really makes real the notion that genetics underlie obesity,” said Lee Kaplan, MD, PhD, director of the Obesity and Metabolism Institute in Boston, who was not affiliated with the research.

Ms. Kaisinger and colleagues found these significant genetic differences by studying genomes of about 420,000 people stored in the UK Biobank, a huge biomedical database. The researchers decided to look at genes by sex and age because these are “two areas that we still know very little about,” Ms. Kaisinger said.

“We know that different types of obesity connect to different ages,” said Dr. Kaplan, who is also past president of the Obesity Society. “But what they’ve done now is find genes that are associated with particular subtypes of obesity ... some more common in one sex and some more common in different phases of life, including early onset obesity.”
 

The future is already here

Treatment for obesity based on a person’s genes already exists. For example, in June 2022, the Food and Drug Administration approved setmelanotide (Imcivree) for weight management in adults and children aged over 6 years with specific genetic markers. 

Even as encouraging as setmelanotide is to Ms. Kaisinger and colleagues, these are still early days for translating the current research findings into clinical obesity tests and potential treatment, she said.

The “holy grail,” Dr. Kaplan said, is a future where people get screened for a particular genetic profile and their provider can say something like, “You’re probably most susceptible to this type, so we’ll treat you with this particular drug that’s been developed for people with this phenotype.”

Dr. Kaplan added: “That’s exactly what we are trying to do.”

Moving forward, Ms. Kaisinger and colleagues plan to repeat the study in larger and more diverse populations. They also plan to reverse the usual road map for studies, which typically start in animals and then progress to humans.

“We plan to take the most promising gene candidates forward into mouse models to learn more about their function and how exactly their dysfunction results in obesity,” Ms. Kaisinger said. 

Three study coauthors are employees and shareholders of Adrestia Therapeutics. No other conflicts of interest were reported.

A version of this article appeared on WebMD.com.

Newly discovered genes could explain body fat differences between men and women with obesity, as well as why some people gain excess weight in childhood.

Identifying specific genes adds to growing evidence that biology, in part, drives obesity. Researchers hope the findings will lead to effective treatments, and in the meantime add to the understanding that there are many types of obesity that come from a mix of genes and environmental factors.

Although the study is not the first to point to specific genes, “we were quite surprised by the proposed function of some of the genes we identified,” Lena R. Kaisinger, lead study investigator and a PhD student in the MRC Epidemiology Unit at the University of Cambridge (England), wrote in an email. For example, the genes also manage cell death and influence how cells respond to DNA damage. 

The investigators are not sure why genes involved in body size perform this kind of double duty, which opens avenues for future research.

The gene sequencing study was published online in the journal Cell Genomics.
 

Differences between women and men

The researchers found five new genes in females and two new genes in males linked to greater body mass index (BMI): DIDO1, KIAA1109, MC4R, PTPRG and SLC12A5 in women and MC4R and SLTM in men. People who recall having obesity as a child were more likely to have rare genetic changes in two other genes, OBSCN and MADD.

“The key thing is that when you see real genes with real gene names, it really makes real the notion that genetics underlie obesity,” said Lee Kaplan, MD, PhD, director of the Obesity and Metabolism Institute in Boston, who was not affiliated with the research.

Ms. Kaisinger and colleagues found these significant genetic differences by studying genomes of about 420,000 people stored in the UK Biobank, a huge biomedical database. The researchers decided to look at genes by sex and age because these are “two areas that we still know very little about,” Ms. Kaisinger said.

“We know that different types of obesity connect to different ages,” said Dr. Kaplan, who is also past president of the Obesity Society. “But what they’ve done now is find genes that are associated with particular subtypes of obesity ... some more common in one sex and some more common in different phases of life, including early onset obesity.”
 

The future is already here

Treatment for obesity based on a person’s genes already exists. For example, in June 2022, the Food and Drug Administration approved setmelanotide (Imcivree) for weight management in adults and children aged over 6 years with specific genetic markers. 

Even as encouraging as setmelanotide is to Ms. Kaisinger and colleagues, these are still early days for translating the current research findings into clinical obesity tests and potential treatment, she said.

The “holy grail,” Dr. Kaplan said, is a future where people get screened for a particular genetic profile and their provider can say something like, “You’re probably most susceptible to this type, so we’ll treat you with this particular drug that’s been developed for people with this phenotype.”

Dr. Kaplan added: “That’s exactly what we are trying to do.”

Moving forward, Ms. Kaisinger and colleagues plan to repeat the study in larger and more diverse populations. They also plan to reverse the usual road map for studies, which typically start in animals and then progress to humans.

“We plan to take the most promising gene candidates forward into mouse models to learn more about their function and how exactly their dysfunction results in obesity,” Ms. Kaisinger said. 

Three study coauthors are employees and shareholders of Adrestia Therapeutics. No other conflicts of interest were reported.

A version of this article appeared on WebMD.com.

As we navigate the ever-evolving landscape of diabetic foot disease management, I’d like to discuss the updated 2023 International Working Group on the Diabetic Foot guidelines and their implications for our practice. The goal is to create a common language of risk that is easily related from clinician to clinician to patient.

Whatever language we use, though, the problem we face is vast:

• Diabetic foot ulcers affect approximately 18.6 million people worldwide and 1.6 million in the United States each year.
• They are associated with high rates of premature death, with a 5-year mortality rate of 30%. This rate is greater than 70% for those with above-foot amputations, worse than all but the most aggressive cancers.
• The direct costs of treating diabetic foot ulcers in the United States is estimated at $9 billion-$13 billion annually.
• Over 550 million people worldwide have diabetes, with 18.6 million developing foot ulcers annually. Up to 34% of those with diabetes will develop a foot ulcer.
• About 20% of those with a diabetic foot ulcer will undergo amputation, a major cause of which is infection, which affects 50% of foot ulcers.
• Up to 20% of those with a foot ulcer require hospitalization, with 15%-20% undergoing amputation. Inequities exist in diabetes-related foot complications:
• –Rates of major amputation are higher in non-Hispanic Black, Hispanic, and Native American populations, compared with non-Hispanic White populations.
• –Non-Hispanic Black and Hispanic populations present with more advanced ulcers and peripheral artery disease, and are more likely to undergo amputation without revascularization attempt.

The IWGDF, a multidisciplinary team of international experts, has recently updated its guidelines. This team, comprising endocrinologists, internal medicine physicians, physiatrists, podiatrists, and vascular surgeons from across the globe, has worked tirelessly to provide us with a comprehensive guide to managing diabetes-related foot ulcers.

The updated guidelines address five critical clinical questions, each with up to 13 important outcomes. The systematic review that underpins these guidelines identified 149 eligible studies, assessing 28 different systems. This exhaustive research has led to the development of seven key recommendations that address the clinical questions and consider the existence of different clinical settings.

One of the significant updates in the 2023 guidelines is the recommendation of SINBAD – site, ischemia, neuropathy, bacterial infection, area, and depth – as the priority wound classification system for people with diabetes and a foot ulcer. This system is particularly useful for interprofessional communication, describing each composite variable, and conducting clinical audits using the full score. However, the guidelines also recommend the use of other, more specific assessment systems for infection and peripheral artery disease from the Infectious Diseases Society of America/IWGDF when resources and an appropriate level of expertise exist.

The introduction of the Wound, Ischemia and Foot Infection (WIfI) classification system in the guidelines is also a noteworthy development. This system is crucial in assessing perfusion and the likely benefit of revascularization in a person with diabetes and a foot ulcer. By assessing the level of wound ischemia and infection, we can make informed decisions about the need for vascular intervention, which can significantly affect the patient’s outcome. This can be done simply by classifying each of the three categories of wound, ischemia, or foot infection as none, mild, moderate, or severe. By simplifying the very dynamic comorbidities of tissue loss, ischemia, and infection into a usable and predictive scale, it helps us to communicate risk across disciplines. This has been found to be highly predictive of healing, amputation, and mortality.

We use WIfI every day across our system. An example might include a patient we recently treated:

A 76-year-old woman presented with a wound to her left foot. Her past medical history revealed type 2 diabetes, peripheral neuropathy, and documented peripheral artery disease with prior bilateral femoral-popliteal bypass conducted at an external facility. In addition to gangrenous changes to her fourth toe, she displayed erythema and lymphangitic streaking up her dorsal foot. While she was afebrile, her white cell count was 13,000/mcL. Radiographic examinations did not show signs of osteomyelitis. Noninvasive vascular evaluations revealed an ankle brachial index of 0.4 and a toe pressure of 10 mm Hg. An aortogram with a lower-extremity runoff arteriogram confirmed the obstruction of her left femoral-popliteal bypass.

Taking these results into account, her WIfI score was determined as: wound 2 (moderate), ischemia 3 (severe), foot infection 2 (moderate, no sepsis), translating to a clinical stage 4. This denotes a high risk for major amputation.

Following a team discussion, she was taken to the operating room for an initial debridement of her infection which consisted of a partial fourth ray resection to the level of the mid-metatarsal. Following control of the infection, she received a vascular assessment which ultimately constituted a femoral to distal anterior tibial bypass. Following both of these, she was discharged on a negative-pressure wound therapy device, receiving a split-thickness skin graft 4 weeks later.

The guidelines also emphasize the need for specific training, skills, and experience to ensure the accuracy of the recommended systems for characterizing foot ulcers. The person applying these systems should be appropriately trained and, according to their national or regional standards, should have the knowledge, expertise, and skills necessary to manage people with a diabetes-related foot ulcer.

As we continue to navigate the complexities of diabetes-related foot disease, these guidelines serve as a valuable compass, guiding our decisions and actions. They remind us of the importance of continuous learning, collaboration, and the application of evidence-based practice in our work.

I encourage you to delve into these guidelines. Let’s use them to improve our practice, enhance our communication, and, ultimately, provide better care for our patients.

Dr. Armstrong is professor of surgery, director of limb preservation, University of Southern California, Los Angeles. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

As we navigate the ever-evolving landscape of diabetic foot disease management, I’d like to discuss the updated 2023 International Working Group on the Diabetic Foot guidelines and their implications for our practice. The goal is to create a common language of risk that is easily related from clinician to clinician to patient.

Whatever language we use, though, the problem we face is vast:

• Diabetic foot ulcers affect approximately 18.6 million people worldwide and 1.6 million in the United States each year.
• They are associated with high rates of premature death, with a 5-year mortality rate of 30%. This rate is greater than 70% for those with above-foot amputations, worse than all but the most aggressive cancers.
• The direct costs of treating diabetic foot ulcers in the United States is estimated at $9 billion-$13 billion annually.
• Over 550 million people worldwide have diabetes, with 18.6 million developing foot ulcers annually. Up to 34% of those with diabetes will develop a foot ulcer.
• About 20% of those with a diabetic foot ulcer will undergo amputation, a major cause of which is infection, which affects 50% of foot ulcers.
• Up to 20% of those with a foot ulcer require hospitalization, with 15%-20% undergoing amputation. Inequities exist in diabetes-related foot complications:
• –Rates of major amputation are higher in non-Hispanic Black, Hispanic, and Native American populations, compared with non-Hispanic White populations.
• –Non-Hispanic Black and Hispanic populations present with more advanced ulcers and peripheral artery disease, and are more likely to undergo amputation without revascularization attempt.

The IWGDF, a multidisciplinary team of international experts, has recently updated its guidelines. This team, comprising endocrinologists, internal medicine physicians, physiatrists, podiatrists, and vascular surgeons from across the globe, has worked tirelessly to provide us with a comprehensive guide to managing diabetes-related foot ulcers.

The updated guidelines address five critical clinical questions, each with up to 13 important outcomes. The systematic review that underpins these guidelines identified 149 eligible studies, assessing 28 different systems. This exhaustive research has led to the development of seven key recommendations that address the clinical questions and consider the existence of different clinical settings.

One of the significant updates in the 2023 guidelines is the recommendation of SINBAD – site, ischemia, neuropathy, bacterial infection, area, and depth – as the priority wound classification system for people with diabetes and a foot ulcer. This system is particularly useful for interprofessional communication, describing each composite variable, and conducting clinical audits using the full score. However, the guidelines also recommend the use of other, more specific assessment systems for infection and peripheral artery disease from the Infectious Diseases Society of America/IWGDF when resources and an appropriate level of expertise exist.

The introduction of the Wound, Ischemia and Foot Infection (WIfI) classification system in the guidelines is also a noteworthy development. This system is crucial in assessing perfusion and the likely benefit of revascularization in a person with diabetes and a foot ulcer. By assessing the level of wound ischemia and infection, we can make informed decisions about the need for vascular intervention, which can significantly affect the patient’s outcome. This can be done simply by classifying each of the three categories of wound, ischemia, or foot infection as none, mild, moderate, or severe. By simplifying the very dynamic comorbidities of tissue loss, ischemia, and infection into a usable and predictive scale, it helps us to communicate risk across disciplines. This has been found to be highly predictive of healing, amputation, and mortality.

We use WIfI every day across our system. An example might include a patient we recently treated:

A 76-year-old woman presented with a wound to her left foot. Her past medical history revealed type 2 diabetes, peripheral neuropathy, and documented peripheral artery disease with prior bilateral femoral-popliteal bypass conducted at an external facility. In addition to gangrenous changes to her fourth toe, she displayed erythema and lymphangitic streaking up her dorsal foot. While she was afebrile, her white cell count was 13,000/mcL. Radiographic examinations did not show signs of osteomyelitis. Noninvasive vascular evaluations revealed an ankle brachial index of 0.4 and a toe pressure of 10 mm Hg. An aortogram with a lower-extremity runoff arteriogram confirmed the obstruction of her left femoral-popliteal bypass.

Taking these results into account, her WIfI score was determined as: wound 2 (moderate), ischemia 3 (severe), foot infection 2 (moderate, no sepsis), translating to a clinical stage 4. This denotes a high risk for major amputation.

Following a team discussion, she was taken to the operating room for an initial debridement of her infection which consisted of a partial fourth ray resection to the level of the mid-metatarsal. Following control of the infection, she received a vascular assessment which ultimately constituted a femoral to distal anterior tibial bypass. Following both of these, she was discharged on a negative-pressure wound therapy device, receiving a split-thickness skin graft 4 weeks later.

The guidelines also emphasize the need for specific training, skills, and experience to ensure the accuracy of the recommended systems for characterizing foot ulcers. The person applying these systems should be appropriately trained and, according to their national or regional standards, should have the knowledge, expertise, and skills necessary to manage people with a diabetes-related foot ulcer.

As we continue to navigate the complexities of diabetes-related foot disease, these guidelines serve as a valuable compass, guiding our decisions and actions. They remind us of the importance of continuous learning, collaboration, and the application of evidence-based practice in our work.

I encourage you to delve into these guidelines. Let’s use them to improve our practice, enhance our communication, and, ultimately, provide better care for our patients.

Dr. Armstrong is professor of surgery, director of limb preservation, University of Southern California, Los Angeles. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

As we navigate the ever-evolving landscape of diabetic foot disease management, I’d like to discuss the updated 2023 International Working Group on the Diabetic Foot guidelines and their implications for our practice. The goal is to create a common language of risk that is easily related from clinician to clinician to patient.

Whatever language we use, though, the problem we face is vast:

• Diabetic foot ulcers affect approximately 18.6 million people worldwide and 1.6 million in the United States each year.
• They are associated with high rates of premature death, with a 5-year mortality rate of 30%. This rate is greater than 70% for those with above-foot amputations, worse than all but the most aggressive cancers.
• The direct costs of treating diabetic foot ulcers in the United States is estimated at $9 billion-$13 billion annually.
• Over 550 million people worldwide have diabetes, with 18.6 million developing foot ulcers annually. Up to 34% of those with diabetes will develop a foot ulcer.
• About 20% of those with a diabetic foot ulcer will undergo amputation, a major cause of which is infection, which affects 50% of foot ulcers.
• Up to 20% of those with a foot ulcer require hospitalization, with 15%-20% undergoing amputation. Inequities exist in diabetes-related foot complications:
• –Rates of major amputation are higher in non-Hispanic Black, Hispanic, and Native American populations, compared with non-Hispanic White populations.
• –Non-Hispanic Black and Hispanic populations present with more advanced ulcers and peripheral artery disease, and are more likely to undergo amputation without revascularization attempt.

The IWGDF, a multidisciplinary team of international experts, has recently updated its guidelines. This team, comprising endocrinologists, internal medicine physicians, physiatrists, podiatrists, and vascular surgeons from across the globe, has worked tirelessly to provide us with a comprehensive guide to managing diabetes-related foot ulcers.

The updated guidelines address five critical clinical questions, each with up to 13 important outcomes. The systematic review that underpins these guidelines identified 149 eligible studies, assessing 28 different systems. This exhaustive research has led to the development of seven key recommendations that address the clinical questions and consider the existence of different clinical settings.

One of the significant updates in the 2023 guidelines is the recommendation of SINBAD – site, ischemia, neuropathy, bacterial infection, area, and depth – as the priority wound classification system for people with diabetes and a foot ulcer. This system is particularly useful for interprofessional communication, describing each composite variable, and conducting clinical audits using the full score. However, the guidelines also recommend the use of other, more specific assessment systems for infection and peripheral artery disease from the Infectious Diseases Society of America/IWGDF when resources and an appropriate level of expertise exist.

The introduction of the Wound, Ischemia and Foot Infection (WIfI) classification system in the guidelines is also a noteworthy development. This system is crucial in assessing perfusion and the likely benefit of revascularization in a person with diabetes and a foot ulcer. By assessing the level of wound ischemia and infection, we can make informed decisions about the need for vascular intervention, which can significantly affect the patient’s outcome. This can be done simply by classifying each of the three categories of wound, ischemia, or foot infection as none, mild, moderate, or severe. By simplifying the very dynamic comorbidities of tissue loss, ischemia, and infection into a usable and predictive scale, it helps us to communicate risk across disciplines. This has been found to be highly predictive of healing, amputation, and mortality.

We use WIfI every day across our system. An example might include a patient we recently treated:

A 76-year-old woman presented with a wound to her left foot. Her past medical history revealed type 2 diabetes, peripheral neuropathy, and documented peripheral artery disease with prior bilateral femoral-popliteal bypass conducted at an external facility. In addition to gangrenous changes to her fourth toe, she displayed erythema and lymphangitic streaking up her dorsal foot. While she was afebrile, her white cell count was 13,000/mcL. Radiographic examinations did not show signs of osteomyelitis. Noninvasive vascular evaluations revealed an ankle brachial index of 0.4 and a toe pressure of 10 mm Hg. An aortogram with a lower-extremity runoff arteriogram confirmed the obstruction of her left femoral-popliteal bypass.

Taking these results into account, her WIfI score was determined as: wound 2 (moderate), ischemia 3 (severe), foot infection 2 (moderate, no sepsis), translating to a clinical stage 4. This denotes a high risk for major amputation.

Following a team discussion, she was taken to the operating room for an initial debridement of her infection which consisted of a partial fourth ray resection to the level of the mid-metatarsal. Following control of the infection, she received a vascular assessment which ultimately constituted a femoral to distal anterior tibial bypass. Following both of these, she was discharged on a negative-pressure wound therapy device, receiving a split-thickness skin graft 4 weeks later.

The guidelines also emphasize the need for specific training, skills, and experience to ensure the accuracy of the recommended systems for characterizing foot ulcers. The person applying these systems should be appropriately trained and, according to their national or regional standards, should have the knowledge, expertise, and skills necessary to manage people with a diabetes-related foot ulcer.

As we continue to navigate the complexities of diabetes-related foot disease, these guidelines serve as a valuable compass, guiding our decisions and actions. They remind us of the importance of continuous learning, collaboration, and the application of evidence-based practice in our work.

I encourage you to delve into these guidelines. Let’s use them to improve our practice, enhance our communication, and, ultimately, provide better care for our patients.

Dr. Armstrong is professor of surgery, director of limb preservation, University of Southern California, Los Angeles. He has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

As with porridge, so with blood pressure: Just right makes all the difference.

Ill-fitting blood pressure measurement cuffs produce erroneous readings that impair hypertension treatment, according to research published in JAMA Internal Medicine.

People whose mid-upper arm circumference exceeds 32 cm require larger cuffs than the standard size, but in many cases the regular-sized cuff is used on everyone. As a result, patients with larger arms may be falsely diagnosed with high blood pressure because of a too-small cuff, leading to overprescribing of medications that could make their health worse, according to the researchers.  

“A person whose blood pressure is 120/80, which is normal – if they’re using the wrong cuff, they could get a measurement that says 140/90, let’s say,” said study author Tammy M. Brady, MD, PhD, vice chair for clinical research in the department of pediatrics at Johns Hopkins University, Baltimore. “They might think they not only have hypertension, but stage 2 hypertension. Providers might give one or even two medicines to lower this, which could lead to hypotension,” Dr. Brady said.

Conversely, someone with smaller arms whose cuff is too big may present with an artificially low blood pressure. The implications of using ill-fitting cuffs are well known. Dr. Brady, among others, has studied the topic extensively. Even so, she said the measurement errors in the latest study were larger than expected.
 

The Goldilocks test

People with an arm circumference of 20-25 cm should use a smaller cuff than the regular size, Dr. Brady and colleagues reported. Circumferences of 25.1-32 cm require a regular-sized cuff; large cuffs are for circumferences of 32.1-40 cm; and extra-large cuffs should be used at 40.1-55 cm.

The study included 195 residents of Baltimore (128 women, 67 men; 132 Black, 58 White, 5 Hispanic) with an average age of 54 years. The researchers measured every participant’s blood pressure using an automated device on four occasions, taking three measurements each time.

The first three sets of measurements used, respectively, an appropriate cuff size for each person’s arm circumference; a cuff that was too big; and a cuff that was too small. This study design ensured that a regular-sized cuff would be used during one of the three measurements – sometimes that cuff was too small, sometimes it was appropriate, and other times it was too big.

The final set of three measurements used the appropriate cuff size for a person’s arm every time. Dr. Brady and colleagues then compared people’s blood pressure measurements when using the right-sized cuff to measurements with a regular-sized cuff that was not suited for them.

They found that using a cuff that was too large for the patient’s arm (i.e., using a regular cuff when a small cuff was the right choice) led to understating systolic blood pressure by –3.6 mm Hg (95% confidence interval [CI], –5.6 to –1.7). A cuff that was one size too small – using regular instead of a large – overestimated systolic blood pressure by 4.8 (3.0-6.6) mm Hg. And a cuff that was two sizes too small – someone who should have received an extra-large cuff but received the regular size – overestimated systolic blood pressure by 19.5 (16.1-22.9) mm Hg. All differences were statistically significant, the researchers reported.

“To our knowledge, this is the first randomized cross-over trial to examine the effect of miscuffing on automated blood pressure readings,” Mathias Lalika, MD, MPH, of the Mayo Clinic in Rochester, Minn.; Stephen P. Juraschek, MD, PhD, of Beth Israel Deaconess Medical Center in Boston; and LaPrincess C. Brewer, MD, MPH, of the Mayo Clinic, wrote in an editorial accompanying the journal article.

“Interestingly, the degree of underestimation or overestimation increased as the appropriate cuff size progressed from the regular to extra-large BP cuff. More importantly, the effect of miscuffing did not vary with BP or obesity status,” they wrote.

“This was more of a pragmatic trial to see real world, all comers,” Dr. Brady said, when regular-sized cuffs are used whether or not that made sense.

“This study reaffirms findings of previous studies and highlights a major source of error in blood pressure measurement,” Raj Padwal, MD, director of the University of Alberta Hypertension Clinic, Edmonton, Alta., said in an interview. Dr. Padwal, who was not involved in the study, said the findings highlight the importance of ensuring that technicians who typically measure blood pressure understand the value of using the right-sized cuff.

Dr. Brady noted that measuring arm circumference takes about 15 seconds. He advised health organizations and clinics to carry multiple cuffs sizes to avoid a scramble to find a right-sized cuff. In the editorial, Dr. Lalika, Dr. Juraschek, and Dr. Brewer call for particular attention to providing the right-sized cuffs to facilities that work with underserved populations, such as federally qualified health centers.

Dr. Padwal added that even a perfectly measured blood pressure test at a clinic indicates pressure at a moment in time. Ten minutes later the story could be different. For this reason, he and other clinicians recommend frequent home blood pressure measurements rather than relying solely on the sparse number of readings collected in the clinic setting.

“A properly educated patient can give many readings that are separated in space and time and, when averaged, can give a much better picture of overall blood pressure and future risk,” Dr. Padwal said. 

Dr. Brady agreed with the value of home readings but said home-based readings also can be erroneous if the patient uses a cuff that is the wrong size. She cochairs a committee for the American Medical Association that recommends validated home blood pressure measurement devices on a periodically updated website called Validate BP. The details for each device listing show the cuff sizes available per device. Many devices provide only the standard cuff, Dr. Brady noted, but some offer multiple cuff sizes.

“One of the things that would be great if it came out of this paper is if patients were empowered to ask physicians to measure their arm” and then use that information to select the appropriate cuff for their home device, she said.

Dr. Brady and Dr. Padwal reported no relevant financial relationships. This study was supported by Resolve to Save Lives, which is funded by Bloomberg Philanthropies, the Bill & Melinda Gates Foundation, and Gates Philanthropy Partners, which is funded with support from the Chan Zuckerberg Foundation.

A version of this article appeared on Medscape.com.

As with porridge, so with blood pressure: Just right makes all the difference.

Ill-fitting blood pressure measurement cuffs produce erroneous readings that impair hypertension treatment, according to research published in JAMA Internal Medicine.

People whose mid-upper arm circumference exceeds 32 cm require larger cuffs than the standard size, but in many cases the regular-sized cuff is used on everyone. As a result, patients with larger arms may be falsely diagnosed with high blood pressure because of a too-small cuff, leading to overprescribing of medications that could make their health worse, according to the researchers.  

“A person whose blood pressure is 120/80, which is normal – if they’re using the wrong cuff, they could get a measurement that says 140/90, let’s say,” said study author Tammy M. Brady, MD, PhD, vice chair for clinical research in the department of pediatrics at Johns Hopkins University, Baltimore. “They might think they not only have hypertension, but stage 2 hypertension. Providers might give one or even two medicines to lower this, which could lead to hypotension,” Dr. Brady said.

Conversely, someone with smaller arms whose cuff is too big may present with an artificially low blood pressure. The implications of using ill-fitting cuffs are well known. Dr. Brady, among others, has studied the topic extensively. Even so, she said the measurement errors in the latest study were larger than expected.
 

The Goldilocks test

People with an arm circumference of 20-25 cm should use a smaller cuff than the regular size, Dr. Brady and colleagues reported. Circumferences of 25.1-32 cm require a regular-sized cuff; large cuffs are for circumferences of 32.1-40 cm; and extra-large cuffs should be used at 40.1-55 cm.

The study included 195 residents of Baltimore (128 women, 67 men; 132 Black, 58 White, 5 Hispanic) with an average age of 54 years. The researchers measured every participant’s blood pressure using an automated device on four occasions, taking three measurements each time.

The first three sets of measurements used, respectively, an appropriate cuff size for each person’s arm circumference; a cuff that was too big; and a cuff that was too small. This study design ensured that a regular-sized cuff would be used during one of the three measurements – sometimes that cuff was too small, sometimes it was appropriate, and other times it was too big.

The final set of three measurements used the appropriate cuff size for a person’s arm every time. Dr. Brady and colleagues then compared people’s blood pressure measurements when using the right-sized cuff to measurements with a regular-sized cuff that was not suited for them.

They found that using a cuff that was too large for the patient’s arm (i.e., using a regular cuff when a small cuff was the right choice) led to understating systolic blood pressure by –3.6 mm Hg (95% confidence interval [CI], –5.6 to –1.7). A cuff that was one size too small – using regular instead of a large – overestimated systolic blood pressure by 4.8 (3.0-6.6) mm Hg. And a cuff that was two sizes too small – someone who should have received an extra-large cuff but received the regular size – overestimated systolic blood pressure by 19.5 (16.1-22.9) mm Hg. All differences were statistically significant, the researchers reported.

“To our knowledge, this is the first randomized cross-over trial to examine the effect of miscuffing on automated blood pressure readings,” Mathias Lalika, MD, MPH, of the Mayo Clinic in Rochester, Minn.; Stephen P. Juraschek, MD, PhD, of Beth Israel Deaconess Medical Center in Boston; and LaPrincess C. Brewer, MD, MPH, of the Mayo Clinic, wrote in an editorial accompanying the journal article.

“Interestingly, the degree of underestimation or overestimation increased as the appropriate cuff size progressed from the regular to extra-large BP cuff. More importantly, the effect of miscuffing did not vary with BP or obesity status,” they wrote.

“This was more of a pragmatic trial to see real world, all comers,” Dr. Brady said, when regular-sized cuffs are used whether or not that made sense.

“This study reaffirms findings of previous studies and highlights a major source of error in blood pressure measurement,” Raj Padwal, MD, director of the University of Alberta Hypertension Clinic, Edmonton, Alta., said in an interview. Dr. Padwal, who was not involved in the study, said the findings highlight the importance of ensuring that technicians who typically measure blood pressure understand the value of using the right-sized cuff.

Dr. Brady noted that measuring arm circumference takes about 15 seconds. He advised health organizations and clinics to carry multiple cuffs sizes to avoid a scramble to find a right-sized cuff. In the editorial, Dr. Lalika, Dr. Juraschek, and Dr. Brewer call for particular attention to providing the right-sized cuffs to facilities that work with underserved populations, such as federally qualified health centers.

Dr. Padwal added that even a perfectly measured blood pressure test at a clinic indicates pressure at a moment in time. Ten minutes later the story could be different. For this reason, he and other clinicians recommend frequent home blood pressure measurements rather than relying solely on the sparse number of readings collected in the clinic setting.

“A properly educated patient can give many readings that are separated in space and time and, when averaged, can give a much better picture of overall blood pressure and future risk,” Dr. Padwal said. 

Dr. Brady agreed with the value of home readings but said home-based readings also can be erroneous if the patient uses a cuff that is the wrong size. She cochairs a committee for the American Medical Association that recommends validated home blood pressure measurement devices on a periodically updated website called Validate BP. The details for each device listing show the cuff sizes available per device. Many devices provide only the standard cuff, Dr. Brady noted, but some offer multiple cuff sizes.

“One of the things that would be great if it came out of this paper is if patients were empowered to ask physicians to measure their arm” and then use that information to select the appropriate cuff for their home device, she said.

Dr. Brady and Dr. Padwal reported no relevant financial relationships. This study was supported by Resolve to Save Lives, which is funded by Bloomberg Philanthropies, the Bill & Melinda Gates Foundation, and Gates Philanthropy Partners, which is funded with support from the Chan Zuckerberg Foundation.

A version of this article appeared on Medscape.com.

As with porridge, so with blood pressure: Just right makes all the difference.

Ill-fitting blood pressure measurement cuffs produce erroneous readings that impair hypertension treatment, according to research published in JAMA Internal Medicine.

People whose mid-upper arm circumference exceeds 32 cm require larger cuffs than the standard size, but in many cases the regular-sized cuff is used on everyone. As a result, patients with larger arms may be falsely diagnosed with high blood pressure because of a too-small cuff, leading to overprescribing of medications that could make their health worse, according to the researchers.  

“A person whose blood pressure is 120/80, which is normal – if they’re using the wrong cuff, they could get a measurement that says 140/90, let’s say,” said study author Tammy M. Brady, MD, PhD, vice chair for clinical research in the department of pediatrics at Johns Hopkins University, Baltimore. “They might think they not only have hypertension, but stage 2 hypertension. Providers might give one or even two medicines to lower this, which could lead to hypotension,” Dr. Brady said.

Conversely, someone with smaller arms whose cuff is too big may present with an artificially low blood pressure. The implications of using ill-fitting cuffs are well known. Dr. Brady, among others, has studied the topic extensively. Even so, she said the measurement errors in the latest study were larger than expected.
 

The Goldilocks test

People with an arm circumference of 20-25 cm should use a smaller cuff than the regular size, Dr. Brady and colleagues reported. Circumferences of 25.1-32 cm require a regular-sized cuff; large cuffs are for circumferences of 32.1-40 cm; and extra-large cuffs should be used at 40.1-55 cm.

The study included 195 residents of Baltimore (128 women, 67 men; 132 Black, 58 White, 5 Hispanic) with an average age of 54 years. The researchers measured every participant’s blood pressure using an automated device on four occasions, taking three measurements each time.

The first three sets of measurements used, respectively, an appropriate cuff size for each person’s arm circumference; a cuff that was too big; and a cuff that was too small. This study design ensured that a regular-sized cuff would be used during one of the three measurements – sometimes that cuff was too small, sometimes it was appropriate, and other times it was too big.

The final set of three measurements used the appropriate cuff size for a person’s arm every time. Dr. Brady and colleagues then compared people’s blood pressure measurements when using the right-sized cuff to measurements with a regular-sized cuff that was not suited for them.

They found that using a cuff that was too large for the patient’s arm (i.e., using a regular cuff when a small cuff was the right choice) led to understating systolic blood pressure by –3.6 mm Hg (95% confidence interval [CI], –5.6 to –1.7). A cuff that was one size too small – using regular instead of a large – overestimated systolic blood pressure by 4.8 (3.0-6.6) mm Hg. And a cuff that was two sizes too small – someone who should have received an extra-large cuff but received the regular size – overestimated systolic blood pressure by 19.5 (16.1-22.9) mm Hg. All differences were statistically significant, the researchers reported.

“To our knowledge, this is the first randomized cross-over trial to examine the effect of miscuffing on automated blood pressure readings,” Mathias Lalika, MD, MPH, of the Mayo Clinic in Rochester, Minn.; Stephen P. Juraschek, MD, PhD, of Beth Israel Deaconess Medical Center in Boston; and LaPrincess C. Brewer, MD, MPH, of the Mayo Clinic, wrote in an editorial accompanying the journal article.

“Interestingly, the degree of underestimation or overestimation increased as the appropriate cuff size progressed from the regular to extra-large BP cuff. More importantly, the effect of miscuffing did not vary with BP or obesity status,” they wrote.

“This was more of a pragmatic trial to see real world, all comers,” Dr. Brady said, when regular-sized cuffs are used whether or not that made sense.

“This study reaffirms findings of previous studies and highlights a major source of error in blood pressure measurement,” Raj Padwal, MD, director of the University of Alberta Hypertension Clinic, Edmonton, Alta., said in an interview. Dr. Padwal, who was not involved in the study, said the findings highlight the importance of ensuring that technicians who typically measure blood pressure understand the value of using the right-sized cuff.

Dr. Brady noted that measuring arm circumference takes about 15 seconds. He advised health organizations and clinics to carry multiple cuffs sizes to avoid a scramble to find a right-sized cuff. In the editorial, Dr. Lalika, Dr. Juraschek, and Dr. Brewer call for particular attention to providing the right-sized cuffs to facilities that work with underserved populations, such as federally qualified health centers.

Dr. Padwal added that even a perfectly measured blood pressure test at a clinic indicates pressure at a moment in time. Ten minutes later the story could be different. For this reason, he and other clinicians recommend frequent home blood pressure measurements rather than relying solely on the sparse number of readings collected in the clinic setting.

“A properly educated patient can give many readings that are separated in space and time and, when averaged, can give a much better picture of overall blood pressure and future risk,” Dr. Padwal said. 

Dr. Brady agreed with the value of home readings but said home-based readings also can be erroneous if the patient uses a cuff that is the wrong size. She cochairs a committee for the American Medical Association that recommends validated home blood pressure measurement devices on a periodically updated website called Validate BP. The details for each device listing show the cuff sizes available per device. Many devices provide only the standard cuff, Dr. Brady noted, but some offer multiple cuff sizes.

“One of the things that would be great if it came out of this paper is if patients were empowered to ask physicians to measure their arm” and then use that information to select the appropriate cuff for their home device, she said.

Dr. Brady and Dr. Padwal reported no relevant financial relationships. This study was supported by Resolve to Save Lives, which is funded by Bloomberg Philanthropies, the Bill & Melinda Gates Foundation, and Gates Philanthropy Partners, which is funded with support from the Chan Zuckerberg Foundation.

A version of this article appeared on Medscape.com.

I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

I’m 47 years old. Two years ago, when the U.S. Preventive Services Task Force (USPSTF) followed the American Cancer Society and lowered the starting age for colorectal cancer (CRC) screening from 50 to 45, my family physician brought up screening options at a health maintenance visit. Although I had expressed some skepticism about this change when the ACS updated its screening guideline in 2018, I generally follow the USPSTF recommendations in my own clinical practice, so I dutifully selected a test that, fortunately, came out negative.

Not everyone in the primary care community, however, is on board with screening average-risk adults in their late 40s for colorectal cancer. The American Academy of Family Physicians (AAFP) published a notable dissent, arguing that the evidence from modeling studies cited by the USPSTF to support lowering the starting age was insufficient. The AAFP also expressed concern that devoting screening resources to younger adults could come at the expense of improving screening rates in older adults who are at higher risk for CRC and increase health care costs without corresponding benefit.

Now, the American College of Physicians has joined the AAFP by releasing an updated guidance statement for CRC screening that discourages screening asymptomatic, average-risk adults between the ages of 45 and 49. In addition to the uncertainty surrounding benefits of screening adults in this age range, the ACP pointed out that starting screening at age 45, compared with age 50, would increase the number of colonoscopies and colonoscopy complications. My colleagues and I recently published a systematic review estimating that for every 10,000 screening colonoscopies performed, 8 people suffer a bowel perforation and 16 to 36 have severe bleeding requiring hospitalization. One in 3 patients undergoing colonoscopies report minor adverse events such as abdominal pain, bloating, and abdominal discomfort in the first 2 weeks following the procedure.

Other aspects of the ACP guidance differ from other colorectal cancer screening guidelines. Unlike the USPSTF, which made no distinctions between various recommended screening tests, the ACP preferentially endorsed fecal immunochemical or high-sensitivity fecal occult blood testing every 2 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years. That leaves out stool DNA testing, which my patients increasingly request because they have seen television or online advertisements, and newer blood tests that detect methylation sequences in circulating tumor DNA.

Perhaps most controversial is the ACP’s suggestion that it is probably reasonable for some adults to start screening later than age 50 or undergo screening at longer intervals than currently recommended (for example, colonoscopy every 15 years). Recent data support extending the interval to repeat screening colonoscopy in selected populations; a large cross-sectional study found a low prevalence of advanced adenomas and colorectal cancers in colonoscopies performed 10 or more years after an initial negative colonoscopy, particularly in women and younger patients without gastrointestinal symptoms. A prominent BMJ guideline suggests that patients need not be screened until their estimated 15-year CRC risk is greater than 3% (which most people do not reach until their 60s) and then only need a single sigmoidoscopy or colonoscopy.

Despite some departures from other guidelines, it’s worth emphasizing that the ACP guideline agrees that screening for CRC is generally worthwhile between the ages of 50 and 75 years. On that front, we in primary care have more work to do; the Centers for Disease Control and Prevention estimates that 28% of American adults older than 50 are not up-to-date on CRC screening. And despite some recent debate about the relative benefits and harms of screening colonoscopy, compared with less invasive fecal tests, gastroenterologists and family physicians can agree that the best screening test is the test that gets done.

A version of this article first appeared on Medscape.com.

I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

I’m 47 years old. Two years ago, when the U.S. Preventive Services Task Force (USPSTF) followed the American Cancer Society and lowered the starting age for colorectal cancer (CRC) screening from 50 to 45, my family physician brought up screening options at a health maintenance visit. Although I had expressed some skepticism about this change when the ACS updated its screening guideline in 2018, I generally follow the USPSTF recommendations in my own clinical practice, so I dutifully selected a test that, fortunately, came out negative.

Not everyone in the primary care community, however, is on board with screening average-risk adults in their late 40s for colorectal cancer. The American Academy of Family Physicians (AAFP) published a notable dissent, arguing that the evidence from modeling studies cited by the USPSTF to support lowering the starting age was insufficient. The AAFP also expressed concern that devoting screening resources to younger adults could come at the expense of improving screening rates in older adults who are at higher risk for CRC and increase health care costs without corresponding benefit.

Now, the American College of Physicians has joined the AAFP by releasing an updated guidance statement for CRC screening that discourages screening asymptomatic, average-risk adults between the ages of 45 and 49. In addition to the uncertainty surrounding benefits of screening adults in this age range, the ACP pointed out that starting screening at age 45, compared with age 50, would increase the number of colonoscopies and colonoscopy complications. My colleagues and I recently published a systematic review estimating that for every 10,000 screening colonoscopies performed, 8 people suffer a bowel perforation and 16 to 36 have severe bleeding requiring hospitalization. One in 3 patients undergoing colonoscopies report minor adverse events such as abdominal pain, bloating, and abdominal discomfort in the first 2 weeks following the procedure.

Other aspects of the ACP guidance differ from other colorectal cancer screening guidelines. Unlike the USPSTF, which made no distinctions between various recommended screening tests, the ACP preferentially endorsed fecal immunochemical or high-sensitivity fecal occult blood testing every 2 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years. That leaves out stool DNA testing, which my patients increasingly request because they have seen television or online advertisements, and newer blood tests that detect methylation sequences in circulating tumor DNA.

Perhaps most controversial is the ACP’s suggestion that it is probably reasonable for some adults to start screening later than age 50 or undergo screening at longer intervals than currently recommended (for example, colonoscopy every 15 years). Recent data support extending the interval to repeat screening colonoscopy in selected populations; a large cross-sectional study found a low prevalence of advanced adenomas and colorectal cancers in colonoscopies performed 10 or more years after an initial negative colonoscopy, particularly in women and younger patients without gastrointestinal symptoms. A prominent BMJ guideline suggests that patients need not be screened until their estimated 15-year CRC risk is greater than 3% (which most people do not reach until their 60s) and then only need a single sigmoidoscopy or colonoscopy.

Despite some departures from other guidelines, it’s worth emphasizing that the ACP guideline agrees that screening for CRC is generally worthwhile between the ages of 50 and 75 years. On that front, we in primary care have more work to do; the Centers for Disease Control and Prevention estimates that 28% of American adults older than 50 are not up-to-date on CRC screening. And despite some recent debate about the relative benefits and harms of screening colonoscopy, compared with less invasive fecal tests, gastroenterologists and family physicians can agree that the best screening test is the test that gets done.

A version of this article first appeared on Medscape.com.

I’m Dr. Kenny Lin. I am a family physician and associate director of the Lancaster General Hospital Family Medicine Residency, and I blog at Common Sense Family Doctor.

I’m 47 years old. Two years ago, when the U.S. Preventive Services Task Force (USPSTF) followed the American Cancer Society and lowered the starting age for colorectal cancer (CRC) screening from 50 to 45, my family physician brought up screening options at a health maintenance visit. Although I had expressed some skepticism about this change when the ACS updated its screening guideline in 2018, I generally follow the USPSTF recommendations in my own clinical practice, so I dutifully selected a test that, fortunately, came out negative.

Not everyone in the primary care community, however, is on board with screening average-risk adults in their late 40s for colorectal cancer. The American Academy of Family Physicians (AAFP) published a notable dissent, arguing that the evidence from modeling studies cited by the USPSTF to support lowering the starting age was insufficient. The AAFP also expressed concern that devoting screening resources to younger adults could come at the expense of improving screening rates in older adults who are at higher risk for CRC and increase health care costs without corresponding benefit.

Now, the American College of Physicians has joined the AAFP by releasing an updated guidance statement for CRC screening that discourages screening asymptomatic, average-risk adults between the ages of 45 and 49. In addition to the uncertainty surrounding benefits of screening adults in this age range, the ACP pointed out that starting screening at age 45, compared with age 50, would increase the number of colonoscopies and colonoscopy complications. My colleagues and I recently published a systematic review estimating that for every 10,000 screening colonoscopies performed, 8 people suffer a bowel perforation and 16 to 36 have severe bleeding requiring hospitalization. One in 3 patients undergoing colonoscopies report minor adverse events such as abdominal pain, bloating, and abdominal discomfort in the first 2 weeks following the procedure.

Other aspects of the ACP guidance differ from other colorectal cancer screening guidelines. Unlike the USPSTF, which made no distinctions between various recommended screening tests, the ACP preferentially endorsed fecal immunochemical or high-sensitivity fecal occult blood testing every 2 years, colonoscopy every 10 years, or flexible sigmoidoscopy every 10 years plus a fecal immunochemical test every 2 years. That leaves out stool DNA testing, which my patients increasingly request because they have seen television or online advertisements, and newer blood tests that detect methylation sequences in circulating tumor DNA.

Perhaps most controversial is the ACP’s suggestion that it is probably reasonable for some adults to start screening later than age 50 or undergo screening at longer intervals than currently recommended (for example, colonoscopy every 15 years). Recent data support extending the interval to repeat screening colonoscopy in selected populations; a large cross-sectional study found a low prevalence of advanced adenomas and colorectal cancers in colonoscopies performed 10 or more years after an initial negative colonoscopy, particularly in women and younger patients without gastrointestinal symptoms. A prominent BMJ guideline suggests that patients need not be screened until their estimated 15-year CRC risk is greater than 3% (which most people do not reach until their 60s) and then only need a single sigmoidoscopy or colonoscopy.

Despite some departures from other guidelines, it’s worth emphasizing that the ACP guideline agrees that screening for CRC is generally worthwhile between the ages of 50 and 75 years. On that front, we in primary care have more work to do; the Centers for Disease Control and Prevention estimates that 28% of American adults older than 50 are not up-to-date on CRC screening. And despite some recent debate about the relative benefits and harms of screening colonoscopy, compared with less invasive fecal tests, gastroenterologists and family physicians can agree that the best screening test is the test that gets done.

A version of this article first appeared on Medscape.com.

COVID-19 hospitalizations continue their steady summer march upward, and now a new variant has perched atop the list of the most prevalent forms of the virus.

Called “Eris” among avid COVID trackers, the strain EG.5 now accounts for 17% of all U.S. COVID infections, according to the latest Centers for Disease Control and Prevention estimates. That’s up from 12% the week prior. 

EG.5 has been rising worldwide, just weeks after the World Health Organization added the strain to its official monitoring list. In the United Kingdom, it now accounts for 1 in 10 COVID cases, The Independent reported.

EG.5 is a descendant of the XBB strains that have dominated tracking lists in recent months. It has the same makeup as XBB.1.9.2 but carries an extra spike mutation, according to a summary published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The spike protein is the part of the virus that allows it to enter human cells. But there’s no indication so far that EG.5 is more contagious or severe than other recent variants, according to the CIDRAP summary and a recent podcast from the American Medical Association. The CDC said that current vaccines protect against the variant.

U.S. hospitals saw a 12% increase in COVID admissions during the week ending on July 22, with 8,047 people being admitted because of the virus, up from an all-time low of 6,306 the week of June 24. In 17 states, the past-week increase in hospitalizations was 20% or greater. In Minnesota, the rate jumped by 50%, and in West Virginia, it jumped by 63%. Meanwhile, deaths reached their lowest weekly rate ever for the week of data ending July 29, with just 176 deaths reported by the CDC.

A version of this article first appeared on WebMD.com.

COVID-19 hospitalizations continue their steady summer march upward, and now a new variant has perched atop the list of the most prevalent forms of the virus.

Called “Eris” among avid COVID trackers, the strain EG.5 now accounts for 17% of all U.S. COVID infections, according to the latest Centers for Disease Control and Prevention estimates. That’s up from 12% the week prior. 

EG.5 has been rising worldwide, just weeks after the World Health Organization added the strain to its official monitoring list. In the United Kingdom, it now accounts for 1 in 10 COVID cases, The Independent reported.

EG.5 is a descendant of the XBB strains that have dominated tracking lists in recent months. It has the same makeup as XBB.1.9.2 but carries an extra spike mutation, according to a summary published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The spike protein is the part of the virus that allows it to enter human cells. But there’s no indication so far that EG.5 is more contagious or severe than other recent variants, according to the CIDRAP summary and a recent podcast from the American Medical Association. The CDC said that current vaccines protect against the variant.

U.S. hospitals saw a 12% increase in COVID admissions during the week ending on July 22, with 8,047 people being admitted because of the virus, up from an all-time low of 6,306 the week of June 24. In 17 states, the past-week increase in hospitalizations was 20% or greater. In Minnesota, the rate jumped by 50%, and in West Virginia, it jumped by 63%. Meanwhile, deaths reached their lowest weekly rate ever for the week of data ending July 29, with just 176 deaths reported by the CDC.

A version of this article first appeared on WebMD.com.

COVID-19 hospitalizations continue their steady summer march upward, and now a new variant has perched atop the list of the most prevalent forms of the virus.

Called “Eris” among avid COVID trackers, the strain EG.5 now accounts for 17% of all U.S. COVID infections, according to the latest Centers for Disease Control and Prevention estimates. That’s up from 12% the week prior. 

EG.5 has been rising worldwide, just weeks after the World Health Organization added the strain to its official monitoring list. In the United Kingdom, it now accounts for 1 in 10 COVID cases, The Independent reported.

EG.5 is a descendant of the XBB strains that have dominated tracking lists in recent months. It has the same makeup as XBB.1.9.2 but carries an extra spike mutation, according to a summary published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The spike protein is the part of the virus that allows it to enter human cells. But there’s no indication so far that EG.5 is more contagious or severe than other recent variants, according to the CIDRAP summary and a recent podcast from the American Medical Association. The CDC said that current vaccines protect against the variant.

U.S. hospitals saw a 12% increase in COVID admissions during the week ending on July 22, with 8,047 people being admitted because of the virus, up from an all-time low of 6,306 the week of June 24. In 17 states, the past-week increase in hospitalizations was 20% or greater. In Minnesota, the rate jumped by 50%, and in West Virginia, it jumped by 63%. Meanwhile, deaths reached their lowest weekly rate ever for the week of data ending July 29, with just 176 deaths reported by the CDC.

A version of this article first appeared on WebMD.com.

A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).

Chinese University of Hong Kong

Is there a ‘safe’ dose for glucocorticoids?

To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.

The study was published in Annals of the Rheumatic Diseases.

The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.

University of Wisconsin School of Medicine and Public Health

Long-term glucocorticoid use discouraged

Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”

Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.

“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.

Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
 

How might risk increase with dose?

While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.

University of Michigan

A version of this article first appeared on Medscape.com.

A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).

Chinese University of Hong Kong

Is there a ‘safe’ dose for glucocorticoids?

To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.

The study was published in Annals of the Rheumatic Diseases.

The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.

University of Wisconsin School of Medicine and Public Health

Long-term glucocorticoid use discouraged

Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”

Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.

“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.

Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
 

How might risk increase with dose?

While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.

University of Michigan

A version of this article first appeared on Medscape.com.

A daily prednisolone dose of 5 mg or higher is associated with increased risk for major adverse cardiovascular events (MACE) among patients with rheumatoid arthritis (RA), data suggest. Patients taking daily doses below this threshold did not appear to have an increased risk of MACE, compared with those not taking glucocorticoids (GCs).

Chinese University of Hong Kong

Is there a ‘safe’ dose for glucocorticoids?

To analyze this relationship, Dr. Lam and colleagues used the Hospital Authority Data Collaboration Laboratory, a citywide health care database. The investigators recruited patients with RA who had no history of MACE from 2006 to 2015 and followed them until the end of 2018. The primary outcome was the first occurrence of a MACE, defined as a composite of myocardial infarction (MI), unstable angina, ischemic or hemorrhagic cerebrovascular accident, transient ischemic attack, and CV death.

The study was published in Annals of the Rheumatic Diseases.

The analysis included 12,233 patients with RA and had over 105,826 person-years of follow-up. The average follow-up time was 8.7 years. During the study period, 860 patients had their first MACE. After controlling for confounding factors, a daily prednisolone dose of 5 mg or higher doubled the risk for MACE, compared with GC nonusers. MACE risk increased by 7% per month.

University of Wisconsin School of Medicine and Public Health

Long-term glucocorticoid use discouraged

Daily doses of less than 5 mg were not associated with higher MACE risk, but more research is necessary to understand whether these low doses are clinically efficacious, Dr. Tam said. “The study results suggest that a very-low-dose GC (less than 5 mg prednisolone daily) may be cardiovascular risk–neutral. However, further evaluation is needed to determine whether this dose is therapeutic. Other potential side effects, such as bone loss, increased infection risk, dyslipidemia, and hyperglycemia, should also be considered.”

Both the American College of Rheumatology and the European Alliance of Associations for Rheumatology acknowledge that short-term GCs may be necessary for some RA patients, but they emphasize using the smallest necessary dose for the shortest period possible because of the known toxicity of GCs.

“We recommend stopping GCs as soon as it is clinically feasible, in line with previous recommendations, until these issues are investigated further,” Dr. Tam added.

Dr. Bartels agreed that long-term use of GCs should be avoided if possible, even at lower doses, because although CV risk may be less of an issue, studies have shown an increased risk for infection even at GC doses of less than 5 mg a day.
 

How might risk increase with dose?

While the study showed a distinct difference in risk with doses of prednisolone higher and lower than 5 mg, more information on how risk increases with dose could be useful, said Beth Wallace, MD, an assistant professor in internal medicine at the University of Michigan, Ann Arbor, and a staff rheumatologist at the VA Ann Arbor Healthcare Center. She was also unaffiliated with the research. “If someone is on 5-10 mg ... how much better is that than being on 10-20 mg or being on 20-30 mg?” she asked. While these study findings are “very important,” she said, it would be useful to know the risk associated with 7.5 mg vs. a higher dose.

University of Michigan

A version of this article first appeared on Medscape.com.

Public perception of disease is everything. “Diabetics” are now referred to as “people living with diabetes,” and an “obese person” is now an “individual living with obesity.”

But what is the definition of obesity? Does it refer to a disease or a risk factor? And is the term so tainted in negativity, blame, and bias that the only solution is to scrap it and completely rename it? Society (and medicine) have changed significantly since the Latin word obesitas was adopted back in the 1600s.

Despite so much hinging on the word “obesity,” it’s remarkable that the label persists while the concepts underpinning it have evolved significantly. So perhaps it is more about finding the least-worst option rather than pursuing the impossibility of a solution that suits all?

This is precisely the challenge faced by a Lancet Diabetes & Endocrinology Commission on the Definition and Diagnosis of Clinical Obesity, which is due to publish its initial findings this coming fall. The global task force has 60 leaders in the clinical management of obesity, including representatives with lived experiences of obesity. Leading the project is Francesco Rubino, MD, chair of metabolic and bariatric surgery at King’s College London.

“Renaming ‘obesity’ is very important,” states Dr. Rubino. “The word is so stigmatized, with so much misunderstanding and misperception, some might say the only solution is to change the name.”

One possibility for a new name, introduced by the American Association of Clinical Endocrinologists (now –Endocrinology) and the American College of Endocrinology back in 2016, was based on framing the disease on the central characteristic of adiposity and was termed ABCD, for adiposity-based chronic disease.

Dr. Rubino welcomes “ABCD” but has some reservations. “It is good from a physiological point of view, but the problem is it speaks to scientists and medical professionals. I don’t know how much it would appeal to the general public. ‘ABCD’ still falls short of telling us what the illness is.”

He adds that the Lancet Commission’s approach is rather to call it “clinical obesity.” “ ‘Obesity’ itself doesn’t necessarily convey the message that you have a disease or an illness,” he observes. “It is similar to the difference in meaning between depression and clinical depression, which communicate two different things.”

But underpinning any renaming is greater clarification of the definition and diagnosis of obesity. In 1997, the World Health Organization recognized obesity as a chronic disease; in 2013, the American Medical Association did likewise, adding that it warranted medical attention; while it took until 2021 for the European Commission to define obesity as a “chronic relapsing disease, which in turn acts as a gateway to a range of other non-communicable diseases.”

Yet, 25 years after the initial recognition of obesity as a disease, the concept is still riddled with negativity, whether openly or unconsciously. Such stigma denigrates overweight people and those with obesity as “lazy, sloppy, unintelligent, and unattractive.”

Dr. Rubino explains that first, it’s important to establish and define the essential components and characteristics of the disease of obesity. This is key to improving access to clinical care, reducing personal blame, and nurturing a more supportive research environment to help inform both clinical and policy decision-making.

“This is the question that is at the core of our commission. We have a problem with the current definition of obesity, and the way we measure it does not allow us to accurately define a state of illness with obesity,” he explains.
 

Labels shape public perceptions of disease; ‘obesity’ epitomizes this

Another expert championing the need for a name that better reflects the definition – whatever that turns out to be – is Margaret Steele, PhD, School of Public Health, University College Cork (Ireland), who, according to her university webpage, has a special interest in “ ‘fatness’ as a cultural, social and political phenomenon.”

She believes that labels, including “obesity,” have a pivotal role in shaping public perceptions. In our digital, information-rich age, the boundaries of medicine and society overlap, with public perception shaping decisions of a medical nature as never before. But with this comes controversy and division – obesity management being a case in point.

Specifically, the word “obesity” is too widely associated with negative connotations, she says, and therefore she welcomes the dialogue around redefining and renaming it. Despite wide general support for a name and definition that reflects adiposity, due to its central physiologic role in the complications of obesity, Dr. Steele believes that the “effects on adipose tissue are downstream of brain issues and the food environment,” and she wants to see more attention brought to this.

Referring to most Westernized societies, she describes how people who grew up in times of food scarcity, before processed foods became widely available, have a different taste profile from those who grew up afterwards. “Growing up in 1940s and ‘50s Ireland, people recall how they remember getting an orange as a treat at Christmas, because the idea that you could have food all year-round – any fruit and veg that you want, when you want it – just wasn’t there.”

By comparison, societal changes leading to more financial and time pressure in later decades meant that fast, high-fat, high-sugar, and processed foods became more desirable, she points out. “Most young children now recognize the company name, and even the specific fast-food brand [they like], before they know their alphabet.”

The current environment has cultivated “a very different physical reaction to foods, maybe a different kind of emotional response,” she believes, highlighting the tightly woven relationship between obesity, society, mental health, and food options.

Dr. Steele wants to stimulate a conversation about the term used to describe individuals, conventionally described as ‘”obese” or using the word “obesity.” “We’re thinking in terms of maybe chronic appetite, chronic food intake, or dietary intake dysregulation.”

Changing medical terminology when it has become useless or harmful is not new, she argues, with co-author, Francis Finucane, MD, consultant endocrinologist at Galway University Hospitals, Ireland, in a recent paper on the subject.

“In the 20th century, the terms ‘feeble-minded’ and ‘moron’ had become used in a pejorative way in the wider culture and were dropped from medical usage,” Dr. Steele points out. She adds that changing the term “obesity” can facilitate pursuit of the strategic goals of clinical medicine “without causing needless controversy with those who, given their own goals and contexts, understand body mass index or body weight in a radically different way.”
 

Obesity: Disease, risk factor, or both?

Dr. Rubino stresses that prior to any renaming, there is a need to establish and define the essential components and characteristics of the disease of obesity. “This question is at the core of our Commission, and it is not an easy conversation to have.” He further explains that the struggle with the current definition of obesity, and the way it is conceived, is largely centered on it still being considered a risk factor for something else.

Disease is characterized by three things, says Dr. Rubino. These comprise the phenomenon of having a pathogenic cause, leading to pathophysiologic alterations (of the organs), causing clinical manifestations.

He adds that obesity is currently described by what it can cause – for example, type 2 diabetes, cancer, or hypertension. “Each of these things have their own clinical manifestations but obesity doesn’t. [As a disease], we don’t have a definition of the clinical manifestations of obesity other than excess adiposity.”

“If we use BMI, this does not predict excess adiposity, nor does it determine a disease here and now. There is no disease without an illness, which is the clinical manifestation, and the perception by the patient of it being an illness,” explains Dr. Rubino, pointing out that the Lancet Commission is filling this gap in knowledge by asking, “If obesity is an illness, then what does it look like?”

He adds that waist circumference probably provides a better measure than BMI in directly indicating the abnormal distribution of adiposity, known to be associated with poor cardiometabolic outcomes, “but it doesn’t tell you if you have an illness here and now – only that someone is at risk of developing cardiovascular disease in the future. Most people with some excess fat around the waist are perfectly functional and don’t feel ill.”

He also explains that confusion persists around whether obesity – or excess adiposity – is a risk factor for or a symptom of another disease. “The picture is blurred, and we do not know how to discriminate between these. We only have one name, and it applies to all those things, and we have one criterion – BMI – to diagnose it!”

Dr. Rubino adds, “So, what defines it? Is it diabetes? No, because that is another disease. You don’t define a disease by another. It has to stand on its own.”

Recently, the American Medical Association advised that BMI now be used in conjunction with other valid measures of risk such as, but not limited to, measurements of visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic/metabolic factors.

Aayush Visaria, MD, an internal medicine resident at Rutgers University, New Brunswick, New Jersey, agrees that a new name might help change public perception of obesity for the better. A study he presented at the 2023 Endocrine Society Meeting found that BMI “vastly underestimates” obesity.

He agrees with Dr. Rubino that the challenge lies in the lack of precise understanding of the mechanisms driving obesity: “It’s multifactorial, so not just appetite or food intake. Putting this into one phrase is difficult.”

However, if a new term can incorporate the many facets of the disease, “overall, it’ll reduce stigma because we’ll start to think about obesity as a disease process, not a personal thing with blame attached,” says Dr. Visaria.

But simultaneously, he expresses caution around possible negative connotations associated with the classification of obesity as a disease. Dr. Steele also reflects on this risk, highlighting that medicalizing body size can be counterproductive in feeding into weight stigma and fatphobia.

“Medicalizing obesity can be discouraging rather than empowering, but by specifying more clearly that we’re talking about a specific set of interrelated metabolic conditions, it would make it much clearer, and that ... this isn’t about making people skinny, it isn’t about an aesthetic thing,” Dr. Steele observes.
 

The word ‘obesity’ hinders disease explanations

Dr. Steele explains that her goal is to overcome the ambiguity around the word “obesity” that hinders explanations of the disease of obesity to the wider public.

“Much confusion and controversy might be avoided if we were to clarify that when doctors say that obesity is a disease, they do not mean that being ‘fat’ is a disease.”

Nevertheless, adipose tissue is an active endocrine organ, producing hormones that function less well in people with obesity, she notes. “This new knowledge has led to better treatments, including drugs like semaglutide and tirzepatide. These drugs, like bariatric surgery, typically lead to significant weight loss and to improvements in overall metabolic health.”

Dr. Rubino also expresses concerns around medicalization, as determined by definition and diagnosis and the availability of drug treatment that could potentially lead to overtreatment. “Currently, when everyone with a BMI of greater than 30 gets access to every obesity treatment out there, we see drugs are running out of stock. We should prioritize that treatment.”

Ultimately, the diagnosis of obesity as a disease needs an anthropometric biomarker that provides, on an individual level, the confidence that a person has a disease today, or at least close to a 100% likelihood of developing this disease and illness, asserts Dr. Rubino.

“If we use BMI, or even waist circumference, these might diagnose the disease; but if the person lives to 90 years, what’s the point of labeling somebody as having an illness?” he points out.

“As doctors, we have to be cautious. We say this is a disease, but you must think about the implications for the person on the receiving end of that diagnosis of a chronic disease that is substantially incurable. When we say it, we need to be certain.”

Dr. Steele and Dr. Visaria have disclosed no relevant financial relationships. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, Metadeq, GHP Scientific, and ViBo Health for no remuneration.

A version of this article first appeared on Medscape.com.

Public perception of disease is everything. “Diabetics” are now referred to as “people living with diabetes,” and an “obese person” is now an “individual living with obesity.”

But what is the definition of obesity? Does it refer to a disease or a risk factor? And is the term so tainted in negativity, blame, and bias that the only solution is to scrap it and completely rename it? Society (and medicine) have changed significantly since the Latin word obesitas was adopted back in the 1600s.

Despite so much hinging on the word “obesity,” it’s remarkable that the label persists while the concepts underpinning it have evolved significantly. So perhaps it is more about finding the least-worst option rather than pursuing the impossibility of a solution that suits all?

This is precisely the challenge faced by a Lancet Diabetes & Endocrinology Commission on the Definition and Diagnosis of Clinical Obesity, which is due to publish its initial findings this coming fall. The global task force has 60 leaders in the clinical management of obesity, including representatives with lived experiences of obesity. Leading the project is Francesco Rubino, MD, chair of metabolic and bariatric surgery at King’s College London.

“Renaming ‘obesity’ is very important,” states Dr. Rubino. “The word is so stigmatized, with so much misunderstanding and misperception, some might say the only solution is to change the name.”

One possibility for a new name, introduced by the American Association of Clinical Endocrinologists (now –Endocrinology) and the American College of Endocrinology back in 2016, was based on framing the disease on the central characteristic of adiposity and was termed ABCD, for adiposity-based chronic disease.

Dr. Rubino welcomes “ABCD” but has some reservations. “It is good from a physiological point of view, but the problem is it speaks to scientists and medical professionals. I don’t know how much it would appeal to the general public. ‘ABCD’ still falls short of telling us what the illness is.”

He adds that the Lancet Commission’s approach is rather to call it “clinical obesity.” “ ‘Obesity’ itself doesn’t necessarily convey the message that you have a disease or an illness,” he observes. “It is similar to the difference in meaning between depression and clinical depression, which communicate two different things.”

But underpinning any renaming is greater clarification of the definition and diagnosis of obesity. In 1997, the World Health Organization recognized obesity as a chronic disease; in 2013, the American Medical Association did likewise, adding that it warranted medical attention; while it took until 2021 for the European Commission to define obesity as a “chronic relapsing disease, which in turn acts as a gateway to a range of other non-communicable diseases.”

Yet, 25 years after the initial recognition of obesity as a disease, the concept is still riddled with negativity, whether openly or unconsciously. Such stigma denigrates overweight people and those with obesity as “lazy, sloppy, unintelligent, and unattractive.”

Dr. Rubino explains that first, it’s important to establish and define the essential components and characteristics of the disease of obesity. This is key to improving access to clinical care, reducing personal blame, and nurturing a more supportive research environment to help inform both clinical and policy decision-making.

“This is the question that is at the core of our commission. We have a problem with the current definition of obesity, and the way we measure it does not allow us to accurately define a state of illness with obesity,” he explains.
 

Labels shape public perceptions of disease; ‘obesity’ epitomizes this

Another expert championing the need for a name that better reflects the definition – whatever that turns out to be – is Margaret Steele, PhD, School of Public Health, University College Cork (Ireland), who, according to her university webpage, has a special interest in “ ‘fatness’ as a cultural, social and political phenomenon.”

She believes that labels, including “obesity,” have a pivotal role in shaping public perceptions. In our digital, information-rich age, the boundaries of medicine and society overlap, with public perception shaping decisions of a medical nature as never before. But with this comes controversy and division – obesity management being a case in point.

Specifically, the word “obesity” is too widely associated with negative connotations, she says, and therefore she welcomes the dialogue around redefining and renaming it. Despite wide general support for a name and definition that reflects adiposity, due to its central physiologic role in the complications of obesity, Dr. Steele believes that the “effects on adipose tissue are downstream of brain issues and the food environment,” and she wants to see more attention brought to this.

Referring to most Westernized societies, she describes how people who grew up in times of food scarcity, before processed foods became widely available, have a different taste profile from those who grew up afterwards. “Growing up in 1940s and ‘50s Ireland, people recall how they remember getting an orange as a treat at Christmas, because the idea that you could have food all year-round – any fruit and veg that you want, when you want it – just wasn’t there.”

By comparison, societal changes leading to more financial and time pressure in later decades meant that fast, high-fat, high-sugar, and processed foods became more desirable, she points out. “Most young children now recognize the company name, and even the specific fast-food brand [they like], before they know their alphabet.”

The current environment has cultivated “a very different physical reaction to foods, maybe a different kind of emotional response,” she believes, highlighting the tightly woven relationship between obesity, society, mental health, and food options.

Dr. Steele wants to stimulate a conversation about the term used to describe individuals, conventionally described as ‘”obese” or using the word “obesity.” “We’re thinking in terms of maybe chronic appetite, chronic food intake, or dietary intake dysregulation.”

Changing medical terminology when it has become useless or harmful is not new, she argues, with co-author, Francis Finucane, MD, consultant endocrinologist at Galway University Hospitals, Ireland, in a recent paper on the subject.

“In the 20th century, the terms ‘feeble-minded’ and ‘moron’ had become used in a pejorative way in the wider culture and were dropped from medical usage,” Dr. Steele points out. She adds that changing the term “obesity” can facilitate pursuit of the strategic goals of clinical medicine “without causing needless controversy with those who, given their own goals and contexts, understand body mass index or body weight in a radically different way.”
 

Obesity: Disease, risk factor, or both?

Dr. Rubino stresses that prior to any renaming, there is a need to establish and define the essential components and characteristics of the disease of obesity. “This question is at the core of our Commission, and it is not an easy conversation to have.” He further explains that the struggle with the current definition of obesity, and the way it is conceived, is largely centered on it still being considered a risk factor for something else.

Disease is characterized by three things, says Dr. Rubino. These comprise the phenomenon of having a pathogenic cause, leading to pathophysiologic alterations (of the organs), causing clinical manifestations.

He adds that obesity is currently described by what it can cause – for example, type 2 diabetes, cancer, or hypertension. “Each of these things have their own clinical manifestations but obesity doesn’t. [As a disease], we don’t have a definition of the clinical manifestations of obesity other than excess adiposity.”

“If we use BMI, this does not predict excess adiposity, nor does it determine a disease here and now. There is no disease without an illness, which is the clinical manifestation, and the perception by the patient of it being an illness,” explains Dr. Rubino, pointing out that the Lancet Commission is filling this gap in knowledge by asking, “If obesity is an illness, then what does it look like?”

He adds that waist circumference probably provides a better measure than BMI in directly indicating the abnormal distribution of adiposity, known to be associated with poor cardiometabolic outcomes, “but it doesn’t tell you if you have an illness here and now – only that someone is at risk of developing cardiovascular disease in the future. Most people with some excess fat around the waist are perfectly functional and don’t feel ill.”

He also explains that confusion persists around whether obesity – or excess adiposity – is a risk factor for or a symptom of another disease. “The picture is blurred, and we do not know how to discriminate between these. We only have one name, and it applies to all those things, and we have one criterion – BMI – to diagnose it!”

Dr. Rubino adds, “So, what defines it? Is it diabetes? No, because that is another disease. You don’t define a disease by another. It has to stand on its own.”

Recently, the American Medical Association advised that BMI now be used in conjunction with other valid measures of risk such as, but not limited to, measurements of visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic/metabolic factors.

Aayush Visaria, MD, an internal medicine resident at Rutgers University, New Brunswick, New Jersey, agrees that a new name might help change public perception of obesity for the better. A study he presented at the 2023 Endocrine Society Meeting found that BMI “vastly underestimates” obesity.

He agrees with Dr. Rubino that the challenge lies in the lack of precise understanding of the mechanisms driving obesity: “It’s multifactorial, so not just appetite or food intake. Putting this into one phrase is difficult.”

However, if a new term can incorporate the many facets of the disease, “overall, it’ll reduce stigma because we’ll start to think about obesity as a disease process, not a personal thing with blame attached,” says Dr. Visaria.

But simultaneously, he expresses caution around possible negative connotations associated with the classification of obesity as a disease. Dr. Steele also reflects on this risk, highlighting that medicalizing body size can be counterproductive in feeding into weight stigma and fatphobia.

“Medicalizing obesity can be discouraging rather than empowering, but by specifying more clearly that we’re talking about a specific set of interrelated metabolic conditions, it would make it much clearer, and that ... this isn’t about making people skinny, it isn’t about an aesthetic thing,” Dr. Steele observes.
 

The word ‘obesity’ hinders disease explanations

Dr. Steele explains that her goal is to overcome the ambiguity around the word “obesity” that hinders explanations of the disease of obesity to the wider public.

“Much confusion and controversy might be avoided if we were to clarify that when doctors say that obesity is a disease, they do not mean that being ‘fat’ is a disease.”

Nevertheless, adipose tissue is an active endocrine organ, producing hormones that function less well in people with obesity, she notes. “This new knowledge has led to better treatments, including drugs like semaglutide and tirzepatide. These drugs, like bariatric surgery, typically lead to significant weight loss and to improvements in overall metabolic health.”

Dr. Rubino also expresses concerns around medicalization, as determined by definition and diagnosis and the availability of drug treatment that could potentially lead to overtreatment. “Currently, when everyone with a BMI of greater than 30 gets access to every obesity treatment out there, we see drugs are running out of stock. We should prioritize that treatment.”

Ultimately, the diagnosis of obesity as a disease needs an anthropometric biomarker that provides, on an individual level, the confidence that a person has a disease today, or at least close to a 100% likelihood of developing this disease and illness, asserts Dr. Rubino.

“If we use BMI, or even waist circumference, these might diagnose the disease; but if the person lives to 90 years, what’s the point of labeling somebody as having an illness?” he points out.

“As doctors, we have to be cautious. We say this is a disease, but you must think about the implications for the person on the receiving end of that diagnosis of a chronic disease that is substantially incurable. When we say it, we need to be certain.”

Dr. Steele and Dr. Visaria have disclosed no relevant financial relationships. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, Metadeq, GHP Scientific, and ViBo Health for no remuneration.

A version of this article first appeared on Medscape.com.

Public perception of disease is everything. “Diabetics” are now referred to as “people living with diabetes,” and an “obese person” is now an “individual living with obesity.”

But what is the definition of obesity? Does it refer to a disease or a risk factor? And is the term so tainted in negativity, blame, and bias that the only solution is to scrap it and completely rename it? Society (and medicine) have changed significantly since the Latin word obesitas was adopted back in the 1600s.

Despite so much hinging on the word “obesity,” it’s remarkable that the label persists while the concepts underpinning it have evolved significantly. So perhaps it is more about finding the least-worst option rather than pursuing the impossibility of a solution that suits all?

This is precisely the challenge faced by a Lancet Diabetes & Endocrinology Commission on the Definition and Diagnosis of Clinical Obesity, which is due to publish its initial findings this coming fall. The global task force has 60 leaders in the clinical management of obesity, including representatives with lived experiences of obesity. Leading the project is Francesco Rubino, MD, chair of metabolic and bariatric surgery at King’s College London.

“Renaming ‘obesity’ is very important,” states Dr. Rubino. “The word is so stigmatized, with so much misunderstanding and misperception, some might say the only solution is to change the name.”

One possibility for a new name, introduced by the American Association of Clinical Endocrinologists (now –Endocrinology) and the American College of Endocrinology back in 2016, was based on framing the disease on the central characteristic of adiposity and was termed ABCD, for adiposity-based chronic disease.

Dr. Rubino welcomes “ABCD” but has some reservations. “It is good from a physiological point of view, but the problem is it speaks to scientists and medical professionals. I don’t know how much it would appeal to the general public. ‘ABCD’ still falls short of telling us what the illness is.”

He adds that the Lancet Commission’s approach is rather to call it “clinical obesity.” “ ‘Obesity’ itself doesn’t necessarily convey the message that you have a disease or an illness,” he observes. “It is similar to the difference in meaning between depression and clinical depression, which communicate two different things.”

But underpinning any renaming is greater clarification of the definition and diagnosis of obesity. In 1997, the World Health Organization recognized obesity as a chronic disease; in 2013, the American Medical Association did likewise, adding that it warranted medical attention; while it took until 2021 for the European Commission to define obesity as a “chronic relapsing disease, which in turn acts as a gateway to a range of other non-communicable diseases.”

Yet, 25 years after the initial recognition of obesity as a disease, the concept is still riddled with negativity, whether openly or unconsciously. Such stigma denigrates overweight people and those with obesity as “lazy, sloppy, unintelligent, and unattractive.”

Dr. Rubino explains that first, it’s important to establish and define the essential components and characteristics of the disease of obesity. This is key to improving access to clinical care, reducing personal blame, and nurturing a more supportive research environment to help inform both clinical and policy decision-making.

“This is the question that is at the core of our commission. We have a problem with the current definition of obesity, and the way we measure it does not allow us to accurately define a state of illness with obesity,” he explains.
 

Labels shape public perceptions of disease; ‘obesity’ epitomizes this

Another expert championing the need for a name that better reflects the definition – whatever that turns out to be – is Margaret Steele, PhD, School of Public Health, University College Cork (Ireland), who, according to her university webpage, has a special interest in “ ‘fatness’ as a cultural, social and political phenomenon.”

She believes that labels, including “obesity,” have a pivotal role in shaping public perceptions. In our digital, information-rich age, the boundaries of medicine and society overlap, with public perception shaping decisions of a medical nature as never before. But with this comes controversy and division – obesity management being a case in point.

Specifically, the word “obesity” is too widely associated with negative connotations, she says, and therefore she welcomes the dialogue around redefining and renaming it. Despite wide general support for a name and definition that reflects adiposity, due to its central physiologic role in the complications of obesity, Dr. Steele believes that the “effects on adipose tissue are downstream of brain issues and the food environment,” and she wants to see more attention brought to this.

Referring to most Westernized societies, she describes how people who grew up in times of food scarcity, before processed foods became widely available, have a different taste profile from those who grew up afterwards. “Growing up in 1940s and ‘50s Ireland, people recall how they remember getting an orange as a treat at Christmas, because the idea that you could have food all year-round – any fruit and veg that you want, when you want it – just wasn’t there.”

By comparison, societal changes leading to more financial and time pressure in later decades meant that fast, high-fat, high-sugar, and processed foods became more desirable, she points out. “Most young children now recognize the company name, and even the specific fast-food brand [they like], before they know their alphabet.”

The current environment has cultivated “a very different physical reaction to foods, maybe a different kind of emotional response,” she believes, highlighting the tightly woven relationship between obesity, society, mental health, and food options.

Dr. Steele wants to stimulate a conversation about the term used to describe individuals, conventionally described as ‘”obese” or using the word “obesity.” “We’re thinking in terms of maybe chronic appetite, chronic food intake, or dietary intake dysregulation.”

Changing medical terminology when it has become useless or harmful is not new, she argues, with co-author, Francis Finucane, MD, consultant endocrinologist at Galway University Hospitals, Ireland, in a recent paper on the subject.

“In the 20th century, the terms ‘feeble-minded’ and ‘moron’ had become used in a pejorative way in the wider culture and were dropped from medical usage,” Dr. Steele points out. She adds that changing the term “obesity” can facilitate pursuit of the strategic goals of clinical medicine “without causing needless controversy with those who, given their own goals and contexts, understand body mass index or body weight in a radically different way.”
 

Obesity: Disease, risk factor, or both?

Dr. Rubino stresses that prior to any renaming, there is a need to establish and define the essential components and characteristics of the disease of obesity. “This question is at the core of our Commission, and it is not an easy conversation to have.” He further explains that the struggle with the current definition of obesity, and the way it is conceived, is largely centered on it still being considered a risk factor for something else.

Disease is characterized by three things, says Dr. Rubino. These comprise the phenomenon of having a pathogenic cause, leading to pathophysiologic alterations (of the organs), causing clinical manifestations.

He adds that obesity is currently described by what it can cause – for example, type 2 diabetes, cancer, or hypertension. “Each of these things have their own clinical manifestations but obesity doesn’t. [As a disease], we don’t have a definition of the clinical manifestations of obesity other than excess adiposity.”

“If we use BMI, this does not predict excess adiposity, nor does it determine a disease here and now. There is no disease without an illness, which is the clinical manifestation, and the perception by the patient of it being an illness,” explains Dr. Rubino, pointing out that the Lancet Commission is filling this gap in knowledge by asking, “If obesity is an illness, then what does it look like?”

He adds that waist circumference probably provides a better measure than BMI in directly indicating the abnormal distribution of adiposity, known to be associated with poor cardiometabolic outcomes, “but it doesn’t tell you if you have an illness here and now – only that someone is at risk of developing cardiovascular disease in the future. Most people with some excess fat around the waist are perfectly functional and don’t feel ill.”

He also explains that confusion persists around whether obesity – or excess adiposity – is a risk factor for or a symptom of another disease. “The picture is blurred, and we do not know how to discriminate between these. We only have one name, and it applies to all those things, and we have one criterion – BMI – to diagnose it!”

Dr. Rubino adds, “So, what defines it? Is it diabetes? No, because that is another disease. You don’t define a disease by another. It has to stand on its own.”

Recently, the American Medical Association advised that BMI now be used in conjunction with other valid measures of risk such as, but not limited to, measurements of visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic/metabolic factors.

Aayush Visaria, MD, an internal medicine resident at Rutgers University, New Brunswick, New Jersey, agrees that a new name might help change public perception of obesity for the better. A study he presented at the 2023 Endocrine Society Meeting found that BMI “vastly underestimates” obesity.

He agrees with Dr. Rubino that the challenge lies in the lack of precise understanding of the mechanisms driving obesity: “It’s multifactorial, so not just appetite or food intake. Putting this into one phrase is difficult.”

However, if a new term can incorporate the many facets of the disease, “overall, it’ll reduce stigma because we’ll start to think about obesity as a disease process, not a personal thing with blame attached,” says Dr. Visaria.

But simultaneously, he expresses caution around possible negative connotations associated with the classification of obesity as a disease. Dr. Steele also reflects on this risk, highlighting that medicalizing body size can be counterproductive in feeding into weight stigma and fatphobia.

“Medicalizing obesity can be discouraging rather than empowering, but by specifying more clearly that we’re talking about a specific set of interrelated metabolic conditions, it would make it much clearer, and that ... this isn’t about making people skinny, it isn’t about an aesthetic thing,” Dr. Steele observes.
 

The word ‘obesity’ hinders disease explanations

Dr. Steele explains that her goal is to overcome the ambiguity around the word “obesity” that hinders explanations of the disease of obesity to the wider public.

“Much confusion and controversy might be avoided if we were to clarify that when doctors say that obesity is a disease, they do not mean that being ‘fat’ is a disease.”

Nevertheless, adipose tissue is an active endocrine organ, producing hormones that function less well in people with obesity, she notes. “This new knowledge has led to better treatments, including drugs like semaglutide and tirzepatide. These drugs, like bariatric surgery, typically lead to significant weight loss and to improvements in overall metabolic health.”

Dr. Rubino also expresses concerns around medicalization, as determined by definition and diagnosis and the availability of drug treatment that could potentially lead to overtreatment. “Currently, when everyone with a BMI of greater than 30 gets access to every obesity treatment out there, we see drugs are running out of stock. We should prioritize that treatment.”

Ultimately, the diagnosis of obesity as a disease needs an anthropometric biomarker that provides, on an individual level, the confidence that a person has a disease today, or at least close to a 100% likelihood of developing this disease and illness, asserts Dr. Rubino.

“If we use BMI, or even waist circumference, these might diagnose the disease; but if the person lives to 90 years, what’s the point of labeling somebody as having an illness?” he points out.

“As doctors, we have to be cautious. We say this is a disease, but you must think about the implications for the person on the receiving end of that diagnosis of a chronic disease that is substantially incurable. When we say it, we need to be certain.”

Dr. Steele and Dr. Visaria have disclosed no relevant financial relationships. Dr. Rubino disclosed that he has received research grants from Novo Nordisk, Medtronic, and Johnson & Johnson. He has undertaken paid consultancy work for GI Dynamics and received honoraria for lectures from Medtronic, Novo Nordisk, and Johnson & Johnson. He is a member of the data safety monitoring board for GT Metabolic Solutions and has provided scientific advice to Keyron, Metadeq, GHP Scientific, and ViBo Health for no remuneration.

A version of this article first appeared on Medscape.com.

The annual probability of a person with overweight or obesity losing at least 5% of their body weight is about 1 in 10, while weight loss to a healthy category is even less common, new research finds.

On the brighter side, those with higher body mass index (BMI) had greater odds of losing at least 5% of body weight than those with lower BMI, and women were more likely to do so than men. The chances of achieving a healthy weight category – defined as BMI of 18.5-24.9 kg/m² – was less likely than losing 5% in all groups, however.

Even a modest 5% weight loss at any BMI has been associated with improved health measures, including lower systolic and diastolic blood pressure, lower fasting glucose level, lower hemoglobin A1c level, and higher HDL cholesterol level, write Lyudmyla Kompaniyets, PhD, of the National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and colleagues.

The data from more than 18 million U.S. adults from a nationwide ambulatory electronic medical record database, called IQVIA, suggest that “clinicians and public health efforts can focus on messaging and referrals to interventions that support individuals with excess weight in achieving and sustaining meaningful weight loss, i.e., ≥ 5% for adults at any level of excess weight,” the authors say.

The study population was health care–seeking but not necessarily for weight loss, and their intent to lose weight was unknown. “Several studies suggest that persons who are trying to lose weight may experience greater reductions in weight,” the researchers point out in their article, which was published in JAMA Network Open.

At the initial visit, 72.5% of the participants were categorized as having either overweight (BMI, 25.0-29.9kg/m²) or obesity (BMI, ≥ 30.0 kg/m²). The median age of the patients was 54 years. A little over half (56.7%) were women, 72.3% were White, and 7.7% were Black.

During a maximum follow-up period of 14 years, the proportion with 5% or greater weight loss was 33.4% of those with initial overweight and 41.8% with initial obesity. The proportion achieving healthy weight (BMI, 18.5-24.9 kg/m²) was just 23.2% and 2.0%, respectively.

For the combined overweight/obesity groups, the adjusted annual probability of 5% or greater weight loss was 1 in 10, increasing with BMI category from 1 in 12 for those with initial overweight to 1 in 6 for those with initial BMI of 45 kg/m² or higher. The annual probability was slightly lower among Black than White women (1 in 9 vs. 1 in 8, respectively).

In contrast, the adjusted annual probability of reducing BMI to the healthy category ranged from 1 in 19 with initial overweight to 1 in 1,667 with initial BMI of 45 kg/m² or higher. This probability was higher among women than men and was highest among White women.

“These findings could, in part, be explained by barriers in availability of and access to obesity management options, including lifestyle interventions and pharmacotherapy. There is a continual need for policies and strategies that ensure community access to nutrition and physical activity opportunities,” Dr. Kompaniyets and colleague write.

Moreover, they say, “understanding patterns of weight loss could help support populations, including Hispanic or Latino and non-Hispanic Black individuals, who are disproportionately affected by obesity due to factors such as structural racism and race and ethnicity-based social and economic disadvantages.”

The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The annual probability of a person with overweight or obesity losing at least 5% of their body weight is about 1 in 10, while weight loss to a healthy category is even less common, new research finds.

On the brighter side, those with higher body mass index (BMI) had greater odds of losing at least 5% of body weight than those with lower BMI, and women were more likely to do so than men. The chances of achieving a healthy weight category – defined as BMI of 18.5-24.9 kg/m² – was less likely than losing 5% in all groups, however.

Even a modest 5% weight loss at any BMI has been associated with improved health measures, including lower systolic and diastolic blood pressure, lower fasting glucose level, lower hemoglobin A1c level, and higher HDL cholesterol level, write Lyudmyla Kompaniyets, PhD, of the National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and colleagues.

The data from more than 18 million U.S. adults from a nationwide ambulatory electronic medical record database, called IQVIA, suggest that “clinicians and public health efforts can focus on messaging and referrals to interventions that support individuals with excess weight in achieving and sustaining meaningful weight loss, i.e., ≥ 5% for adults at any level of excess weight,” the authors say.

The study population was health care–seeking but not necessarily for weight loss, and their intent to lose weight was unknown. “Several studies suggest that persons who are trying to lose weight may experience greater reductions in weight,” the researchers point out in their article, which was published in JAMA Network Open.

At the initial visit, 72.5% of the participants were categorized as having either overweight (BMI, 25.0-29.9kg/m²) or obesity (BMI, ≥ 30.0 kg/m²). The median age of the patients was 54 years. A little over half (56.7%) were women, 72.3% were White, and 7.7% were Black.

During a maximum follow-up period of 14 years, the proportion with 5% or greater weight loss was 33.4% of those with initial overweight and 41.8% with initial obesity. The proportion achieving healthy weight (BMI, 18.5-24.9 kg/m²) was just 23.2% and 2.0%, respectively.

For the combined overweight/obesity groups, the adjusted annual probability of 5% or greater weight loss was 1 in 10, increasing with BMI category from 1 in 12 for those with initial overweight to 1 in 6 for those with initial BMI of 45 kg/m² or higher. The annual probability was slightly lower among Black than White women (1 in 9 vs. 1 in 8, respectively).

In contrast, the adjusted annual probability of reducing BMI to the healthy category ranged from 1 in 19 with initial overweight to 1 in 1,667 with initial BMI of 45 kg/m² or higher. This probability was higher among women than men and was highest among White women.

“These findings could, in part, be explained by barriers in availability of and access to obesity management options, including lifestyle interventions and pharmacotherapy. There is a continual need for policies and strategies that ensure community access to nutrition and physical activity opportunities,” Dr. Kompaniyets and colleague write.

Moreover, they say, “understanding patterns of weight loss could help support populations, including Hispanic or Latino and non-Hispanic Black individuals, who are disproportionately affected by obesity due to factors such as structural racism and race and ethnicity-based social and economic disadvantages.”

The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

The annual probability of a person with overweight or obesity losing at least 5% of their body weight is about 1 in 10, while weight loss to a healthy category is even less common, new research finds.

On the brighter side, those with higher body mass index (BMI) had greater odds of losing at least 5% of body weight than those with lower BMI, and women were more likely to do so than men. The chances of achieving a healthy weight category – defined as BMI of 18.5-24.9 kg/m² – was less likely than losing 5% in all groups, however.

Even a modest 5% weight loss at any BMI has been associated with improved health measures, including lower systolic and diastolic blood pressure, lower fasting glucose level, lower hemoglobin A1c level, and higher HDL cholesterol level, write Lyudmyla Kompaniyets, PhD, of the National Center for Chronic Disease Prevention and Health Promotion, Atlanta, and colleagues.

The data from more than 18 million U.S. adults from a nationwide ambulatory electronic medical record database, called IQVIA, suggest that “clinicians and public health efforts can focus on messaging and referrals to interventions that support individuals with excess weight in achieving and sustaining meaningful weight loss, i.e., ≥ 5% for adults at any level of excess weight,” the authors say.

The study population was health care–seeking but not necessarily for weight loss, and their intent to lose weight was unknown. “Several studies suggest that persons who are trying to lose weight may experience greater reductions in weight,” the researchers point out in their article, which was published in JAMA Network Open.

At the initial visit, 72.5% of the participants were categorized as having either overweight (BMI, 25.0-29.9kg/m²) or obesity (BMI, ≥ 30.0 kg/m²). The median age of the patients was 54 years. A little over half (56.7%) were women, 72.3% were White, and 7.7% were Black.

During a maximum follow-up period of 14 years, the proportion with 5% or greater weight loss was 33.4% of those with initial overweight and 41.8% with initial obesity. The proportion achieving healthy weight (BMI, 18.5-24.9 kg/m²) was just 23.2% and 2.0%, respectively.

For the combined overweight/obesity groups, the adjusted annual probability of 5% or greater weight loss was 1 in 10, increasing with BMI category from 1 in 12 for those with initial overweight to 1 in 6 for those with initial BMI of 45 kg/m² or higher. The annual probability was slightly lower among Black than White women (1 in 9 vs. 1 in 8, respectively).

In contrast, the adjusted annual probability of reducing BMI to the healthy category ranged from 1 in 19 with initial overweight to 1 in 1,667 with initial BMI of 45 kg/m² or higher. This probability was higher among women than men and was highest among White women.

“These findings could, in part, be explained by barriers in availability of and access to obesity management options, including lifestyle interventions and pharmacotherapy. There is a continual need for policies and strategies that ensure community access to nutrition and physical activity opportunities,” Dr. Kompaniyets and colleague write.

Moreover, they say, “understanding patterns of weight loss could help support populations, including Hispanic or Latino and non-Hispanic Black individuals, who are disproportionately affected by obesity due to factors such as structural racism and race and ethnicity-based social and economic disadvantages.”

The authors have disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Brisbane, Australia – Most cases of virologic failure on dolutegravir treatment for HIV are likely due to adherence problems and more time on treatment is needed before switching to another drug, according to new data from the ADVANCE trial.
 

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.

The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.

Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.

“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.

This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
 

The guidelines

Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.

Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.

Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.

But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
 

Time to viral resuppression

At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.

Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.

We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.

“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”

And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”

Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.

“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”

A version of this article first appeared on Medscape.com.

Brisbane, Australia – Most cases of virologic failure on dolutegravir treatment for HIV are likely due to adherence problems and more time on treatment is needed before switching to another drug, according to new data from the ADVANCE trial.
 

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.

The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.

Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.

“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.

This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
 

The guidelines

Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.

Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.

Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.

But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
 

Time to viral resuppression

At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.

Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.

We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.

“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”

And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”

Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.

“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”

A version of this article first appeared on Medscape.com.

Brisbane, Australia – Most cases of virologic failure on dolutegravir treatment for HIV are likely due to adherence problems and more time on treatment is needed before switching to another drug, according to new data from the ADVANCE trial.
 

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” said Andrew Hill, MD, from the department of pharmacology and therapeutics at the University of Liverpool, England.

The new data was presented here at the International AIDS Society conference on HIV Science. The ADVANCE trial is a three-arm randomized study involving 1,053 treatment-naive individuals comparing two triple-therapy combinations — dolutegravir, emtricitabine, and one of two tenofovir prodrugs – with a standard care regimen of tenofovir disoproxil fumarate, emtricitabine, and efavirenz.

Although the usual approach for someone in a clinical trial who experiences elevations in HIV RNA levels while on a dolutegravir-based treatment is to switch them to another therapy, the ADVANCE investigators opted for a different strategy.

“We actually continued treatment despite high viral load, and we didn’t have standard discontinuation preferences,” Dr. Hill said at the meeting. They instead provided counseling about adherence, which gave an opportunity to examine viral resuppression rates in participants in both the dolutegravir and efavirenz arms.

This revealed that 95% of patients in the two dolutegravir arms of the study were able to achieve resuppression of their viral load – defined as below 50 viral RNA copies per mL – without any emergence of resistance.
 

The guidelines

Current World Health Organization guidelines recommend that anyone whose viral load goes above 1,000 copies per mL who is on a non-nucleoside reverse transcriptase inhibitor such as efavirenz should be switched to an appropriate regimen.

Those who experience viremia on an integrase inhibitor such as dolutegravir should receive adherence counseling, have a repeat viral load test done in 3 months, and – if their viral load is still elevated – be switched to another regimen.

Dr. Hill and his team were examining how this might play out in a clinical trial setting and they found that there were a similar number of episodes of initial virologic failure in both the dolutegravir and efavirenz groups.

But after adherence counseling, testing for resistance and – if no resistance was evident – continuation with treatment, they saw differences emerge between the two groups.

“What we saw was a faster time to resuppression in the people followed-up long term on dolutegravir and also a higher percentage of people becoming suppressed when they remained on dolutegravir,” he said.
 

Time to viral resuppression

At 24 weeks after restarting treatment, 88% of people in the dolutegravir group had resuppressed their viral RNA, compared with 46% of people in the efavirenz group. At 48 weeks, those figures were 95% and 66%, respectively.

Dr. Hill pointed out that a significant number of people were lost to follow-up after virologic failure, and genotyping was not performed at baseline.

We addressed the question of how much adherence counseling should be undertaken in people who experienced viremia while on dolutegravir therapy, Dr. Hill said, particularly as there were often very good reasons for lack of adherence, such as homelessness.

“If you can get through those difficult phases, people can go back on their meds,” he said in an interview. “It’s almost a sociological problem rather than a clinical issue.”

And with efavirenz and the lower rates of resuppression observed in the study, Dr. Hill said it was a more fragile drug, so viremia therefore provided the opportunity for resistance to emerge, “and then once the resistant virus is there, you can’t get virus undetectable.”

Laura Waters, MD, a genitourinary and HIV medicine consultant at the Mortimer Market Centre in London, who was not involved in the study, said the results support recommendations to give people on drugs such as dolutegravir, which have a high genetic barrier to resistance, more time to improve their adherence before switching to another therapy.

“Although it provides that reassuring proof of concept, it doesn’t negate the importance of having to continue to monitor, because nothing is infallible,” she told this news organization. “We’ve talked about high-barrier drugs in the past, and you do start seeing resistance emerge.”

A version of this article first appeared on Medscape.com.

Brisbane, Australia – Concerns about lower lymphocyte levels in HIV with the once-daily oral drug islatravir in combination with doravirine changed the trajectory of clinical trial plans that are now back on track, according to investigators.

The nucleoside reverse transcriptase translocation inhibitor hit a roadblock in December 2021 when the U.S. Food and Drug Administration put a hold on investigational new drug applications for both the oral and implant formulations of islatravir after some patients in clinical trials showed decreases in total lymphocyte and CD4+ cell counts.

A phase 3, double-blind, randomized, controlled trial was underway at the time of once-daily islatravir (0.75 mg) in combination with 100 mg doravirine, compared with bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) as initial therapy for HIV infection in treatment-naïve individuals. Recruitment was stopped, 83 participants short of the planned 680, but the trial could continue the full 48 weeks.

Jürgen Rockstroh, MD, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn, Germany, presented the latest results from that trial of 597 patients at the International AIDS Society conference on HIV Science.

At week 48 after starting therapy, 88.9% of participants in the islatravir and doravirine arm and 88.3% of patients in the B/F/TAF arm achieved the primary outcome of HIV-1 RNA levels below 50 copies/mL.

One patient treated with islatravir and doravirine and four patients taking B/F/TAF experienced virologic failure.

Dr. Rockstroh told the conference the patient who developed viremia with the new islatravir combination had very high viral load at baseline but showed a rapid response to treatment, which reduced his viral load down to around 1,200 copies/mL by week 4.

However, by week 24, his islatravir concentration had reduced below detectable levels, suggesting a problem with adherence. His viral load increased again, and three treatment-resistant mutations were detected.

While both arms of the study showed a significant increase in CD4+ T cell counts, Dr. Rockstroh pointed out that some individuals in the islatravir and doravirine arm had a lower absolute increase in lymphocyte counts at week 48.

Overall, the mean change in CD4+ T cell counts was 182 cells/mL in the islatravir and doravirine group, compared with 234 cells/mL in the B/F/TAF group.

More patients in the islatravir combination arm discontinued treatment due to a decrease in CD4+ T cell or total lymphocyte counts – 5.4%, compared with 2% in the B/F/TAF arm, however.

“These changes in lymphocyte counts did not lead to any difference in the amount of infection-related adverse events, which happened in both arms in relatively comparable percentages,” Dr. Rockstroh said at the conference.
 

New lower dose

Because of persistent concerns about the impact on CD4+ T cells and total lymphocytes, Dr. Rockstroh said another phase 3 trial is now underway using a lower 0.25 mg dose of islatravir, again combined with 100 mg doravirine, in people who are treatment-naïve and virologically suppressed.

The study also examined the impact of both treatments on weight gain and found the mean change in weight was similar between both arms – 3.45 kg gain in those on islatravir with doravirine and 3.32 kg gain in those on B/F/TAF, which was not significantly different.

There are several important reasons it is a good idea to have more treatment options available for people with HIV, Dr. Rockstroh said in an interview.

With integrase inhibitors potentially interfering with metabolic health, weight gain, hypertension, insulin resistance, and possible diabetes, “I think it’s wise that we at least have alternative strategies,” he said.

James McMahon, MD, PhD, an infectious diseases physician and head of the Infectious Diseases Clinical Research Unit at the Alfred Hospital and Monash University in Melbourne, said there is always a need for new HIV treatments, particularly ones that are more powerful.

“Whenever you get a drug that’s potent at low dose, it means you can have smaller pills, [and] you can then consider giving more of it in long-acting formulations,” Dr. McMahon said.

He pointed out that the study did not show any signal of increased infections with the lower CD4+ T cell counts in the islatravir and doravirine arm, “but that difference is enough to raise that concern that it’s not ideal, and it should be moved forward with a lower dose, which is what they’ve done.”

A version of this article first appeared on Medscape.com.

Brisbane, Australia – Concerns about lower lymphocyte levels in HIV with the once-daily oral drug islatravir in combination with doravirine changed the trajectory of clinical trial plans that are now back on track, according to investigators.

The nucleoside reverse transcriptase translocation inhibitor hit a roadblock in December 2021 when the U.S. Food and Drug Administration put a hold on investigational new drug applications for both the oral and implant formulations of islatravir after some patients in clinical trials showed decreases in total lymphocyte and CD4+ cell counts.

A phase 3, double-blind, randomized, controlled trial was underway at the time of once-daily islatravir (0.75 mg) in combination with 100 mg doravirine, compared with bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) as initial therapy for HIV infection in treatment-naïve individuals. Recruitment was stopped, 83 participants short of the planned 680, but the trial could continue the full 48 weeks.

Jürgen Rockstroh, MD, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn, Germany, presented the latest results from that trial of 597 patients at the International AIDS Society conference on HIV Science.

At week 48 after starting therapy, 88.9% of participants in the islatravir and doravirine arm and 88.3% of patients in the B/F/TAF arm achieved the primary outcome of HIV-1 RNA levels below 50 copies/mL.

One patient treated with islatravir and doravirine and four patients taking B/F/TAF experienced virologic failure.

Dr. Rockstroh told the conference the patient who developed viremia with the new islatravir combination had very high viral load at baseline but showed a rapid response to treatment, which reduced his viral load down to around 1,200 copies/mL by week 4.

However, by week 24, his islatravir concentration had reduced below detectable levels, suggesting a problem with adherence. His viral load increased again, and three treatment-resistant mutations were detected.

While both arms of the study showed a significant increase in CD4+ T cell counts, Dr. Rockstroh pointed out that some individuals in the islatravir and doravirine arm had a lower absolute increase in lymphocyte counts at week 48.

Overall, the mean change in CD4+ T cell counts was 182 cells/mL in the islatravir and doravirine group, compared with 234 cells/mL in the B/F/TAF group.

More patients in the islatravir combination arm discontinued treatment due to a decrease in CD4+ T cell or total lymphocyte counts – 5.4%, compared with 2% in the B/F/TAF arm, however.

“These changes in lymphocyte counts did not lead to any difference in the amount of infection-related adverse events, which happened in both arms in relatively comparable percentages,” Dr. Rockstroh said at the conference.
 

New lower dose

Because of persistent concerns about the impact on CD4+ T cells and total lymphocytes, Dr. Rockstroh said another phase 3 trial is now underway using a lower 0.25 mg dose of islatravir, again combined with 100 mg doravirine, in people who are treatment-naïve and virologically suppressed.

The study also examined the impact of both treatments on weight gain and found the mean change in weight was similar between both arms – 3.45 kg gain in those on islatravir with doravirine and 3.32 kg gain in those on B/F/TAF, which was not significantly different.

There are several important reasons it is a good idea to have more treatment options available for people with HIV, Dr. Rockstroh said in an interview.

With integrase inhibitors potentially interfering with metabolic health, weight gain, hypertension, insulin resistance, and possible diabetes, “I think it’s wise that we at least have alternative strategies,” he said.

James McMahon, MD, PhD, an infectious diseases physician and head of the Infectious Diseases Clinical Research Unit at the Alfred Hospital and Monash University in Melbourne, said there is always a need for new HIV treatments, particularly ones that are more powerful.

“Whenever you get a drug that’s potent at low dose, it means you can have smaller pills, [and] you can then consider giving more of it in long-acting formulations,” Dr. McMahon said.

He pointed out that the study did not show any signal of increased infections with the lower CD4+ T cell counts in the islatravir and doravirine arm, “but that difference is enough to raise that concern that it’s not ideal, and it should be moved forward with a lower dose, which is what they’ve done.”

A version of this article first appeared on Medscape.com.

Brisbane, Australia – Concerns about lower lymphocyte levels in HIV with the once-daily oral drug islatravir in combination with doravirine changed the trajectory of clinical trial plans that are now back on track, according to investigators.

The nucleoside reverse transcriptase translocation inhibitor hit a roadblock in December 2021 when the U.S. Food and Drug Administration put a hold on investigational new drug applications for both the oral and implant formulations of islatravir after some patients in clinical trials showed decreases in total lymphocyte and CD4+ cell counts.

A phase 3, double-blind, randomized, controlled trial was underway at the time of once-daily islatravir (0.75 mg) in combination with 100 mg doravirine, compared with bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) as initial therapy for HIV infection in treatment-naïve individuals. Recruitment was stopped, 83 participants short of the planned 680, but the trial could continue the full 48 weeks.

Jürgen Rockstroh, MD, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn, Germany, presented the latest results from that trial of 597 patients at the International AIDS Society conference on HIV Science.

At week 48 after starting therapy, 88.9% of participants in the islatravir and doravirine arm and 88.3% of patients in the B/F/TAF arm achieved the primary outcome of HIV-1 RNA levels below 50 copies/mL.

One patient treated with islatravir and doravirine and four patients taking B/F/TAF experienced virologic failure.

Dr. Rockstroh told the conference the patient who developed viremia with the new islatravir combination had very high viral load at baseline but showed a rapid response to treatment, which reduced his viral load down to around 1,200 copies/mL by week 4.

However, by week 24, his islatravir concentration had reduced below detectable levels, suggesting a problem with adherence. His viral load increased again, and three treatment-resistant mutations were detected.

While both arms of the study showed a significant increase in CD4+ T cell counts, Dr. Rockstroh pointed out that some individuals in the islatravir and doravirine arm had a lower absolute increase in lymphocyte counts at week 48.

Overall, the mean change in CD4+ T cell counts was 182 cells/mL in the islatravir and doravirine group, compared with 234 cells/mL in the B/F/TAF group.

More patients in the islatravir combination arm discontinued treatment due to a decrease in CD4+ T cell or total lymphocyte counts – 5.4%, compared with 2% in the B/F/TAF arm, however.

“These changes in lymphocyte counts did not lead to any difference in the amount of infection-related adverse events, which happened in both arms in relatively comparable percentages,” Dr. Rockstroh said at the conference.
 

New lower dose

Because of persistent concerns about the impact on CD4+ T cells and total lymphocytes, Dr. Rockstroh said another phase 3 trial is now underway using a lower 0.25 mg dose of islatravir, again combined with 100 mg doravirine, in people who are treatment-naïve and virologically suppressed.

The study also examined the impact of both treatments on weight gain and found the mean change in weight was similar between both arms – 3.45 kg gain in those on islatravir with doravirine and 3.32 kg gain in those on B/F/TAF, which was not significantly different.

There are several important reasons it is a good idea to have more treatment options available for people with HIV, Dr. Rockstroh said in an interview.

With integrase inhibitors potentially interfering with metabolic health, weight gain, hypertension, insulin resistance, and possible diabetes, “I think it’s wise that we at least have alternative strategies,” he said.

James McMahon, MD, PhD, an infectious diseases physician and head of the Infectious Diseases Clinical Research Unit at the Alfred Hospital and Monash University in Melbourne, said there is always a need for new HIV treatments, particularly ones that are more powerful.

“Whenever you get a drug that’s potent at low dose, it means you can have smaller pills, [and] you can then consider giving more of it in long-acting formulations,” Dr. McMahon said.

He pointed out that the study did not show any signal of increased infections with the lower CD4+ T cell counts in the islatravir and doravirine arm, “but that difference is enough to raise that concern that it’s not ideal, and it should be moved forward with a lower dose, which is what they’ve done.”

A version of this article first appeared on Medscape.com.