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Could boosting fat taste receptors help cut calories?
Desire for dietary lipids has been traced to the taste receptors CD36 and GPR120, and these have been found to be malfunctioning in both obese animals and humans, leading to low perception of fat levels in food.
The study was published online in Cellular and Molecular Gastroenterology and Hepatology. “Ours is the first study on targeting fat taste receptors, leading to [the] activation of tongue-gut loop as a therapeutic approach, and it opens new vistas to synthesize more potent chemical compounds to decrease progressive weight gain under [high-fat diet] consumption,” the authors wrote.
The perception of fat has recently been identified as a potential sixth basic taste quality, joining sweet, sour, bitter, salt, and umami. CD36 is expressed by taste cells, where it senses dietary long-chain fatty acids (LCFAs), and its deletion led mice to ignore LCFAs and oily solutions that they would otherwise prefer. GPR120 has also been proposed as a lipid sensor.
Previous researchers had suggested that CD36 may play a role in the preference for eating fats, while GPR120 could have a role in lipid satiation following consumption. “Our team also supported these conclusions and proposed that CD36 might be involved in immediate early detection [of fat in foods], whereas GPR120 will be responsible for post-ingestive regulation of lipid food intake,” the authors wrote.
The researchers showed that lipids bind to CD36 when they are present in low concentrations, but at high concentrations they bind to GPR120, suggesting that the two receptors are nonoverlapping but nevertheless complement one another during fatty acid–mediated signaling with taste bud cells (TBC). They are also coexpressed within the same type of TBC.
Experiments in rodents suggest that obese animals have reduced capacity to sense dietary fatty acids, which drives consumption of greater amounts. Fat-rich diets can also reduce fat taste perception, and this has been shown cross-sectionally in obese human subjects, and a single nucleotide polymorphism in CD36 that leads to a reduction in expression is linked to reduced perception of dietary fatty acids.
To test the idea that altering the receptors could change behavior, the researchers synthesized two novel fat taste receptor agonists (FTAs) that are derived from the LCFA linoleic acid, which is abundant in Western diets.
Using nerve recordings, the researchers confirmed that a message from TBCs is sent to the brain via the chorda tympani nerve, and the two FTAs increased the nerve signal. The signals from LCFAs alone were boosted with the addition of the FTAs, suggesting that these molecules can be effective even in the presence of dietary lipids. They also confirmed that FTAs activate the tongue-brain-gut loop by increasing pancreato-bile secretion more than linoleic acid alone.
Given the choice between two bottles, mice preferred the one containing FTAs, and the experiments indicated that FTAs are 95-142 times more potent than natural LCFA as food attractants.
It is well known that diet and lifestyle interventions rarely result in long-term weight loss, and products designed to mimic ‘fat-like’ texture – such as maltodextrin, inulin, and plant fibers – have had limited success because they do not have a fat-like taste and can lead to gastrointestinal side effects. Agonists of CD36 and GPR120 added to low- or noncaloric foods could boost their appeal and lead to earlier satiation.
Importantly, in obese mice, both TFAs led to decreased food intake as well as reduced weight gain and fat mass, without affecting lean mass. One of the agents also promoted a higher metabolic rate through increased energy expenditure.
The researchers also examined the agents’ effects on the microbiota of the obese mice, which contain high concentrations of bacteria belonging to the Lachnospiraceae family. Both inhibitors reduced the numbers of Lachnospiraceae bacteria, and promoted other bacterial families that may contribute to an anti-inflammatory effect. Obese animals exposed to TFAs also showed improvements in dyslipidemia, and there was evidence that they could reduce liver lipid concentrations.
There was no evidence of any mutagenicity, genotoxicity, or endocrine disruption. In sum, these new agonists might enable the development of novel treatments of obesity, which would have a major impact on human health.
The authors stated that they have no financial conflicts of interest. The study received financial support from institutions including the Société d'Accélération du Transfert de Technologies and the University of Burgundy.
This article was updated 2/15/23.
The obesity epidemic represents a significant public health crisis that has spread to most countries on the planet. In addition to being a major risk factor for diabetes and cardiovascular disease, obesity also impacts the incidence of gastrointestinal cancers. Despite major efforts of health professionals and public health messaging, it remains very difficult for patients to achieve sustained weight loss by changing diet and increasing physical activity alone. Novel approaches to regulate food intake and thus obesity are urgently needed.
While these are preclinical studies, it will now be fascinating to determine if these or similar compounds can be developed into drugs or food additives to impact human food intake and thus become an additional tool in the fight against the obesity epidemic.
Klaus H. Kaestner, PhD, MS, is with the department of genetics and Center for Molecular Studies in Digestive and Liver Diseases, University of Pennsylvania, Philadelphia. He has no financial conflicts of interest.
The obesity epidemic represents a significant public health crisis that has spread to most countries on the planet. In addition to being a major risk factor for diabetes and cardiovascular disease, obesity also impacts the incidence of gastrointestinal cancers. Despite major efforts of health professionals and public health messaging, it remains very difficult for patients to achieve sustained weight loss by changing diet and increasing physical activity alone. Novel approaches to regulate food intake and thus obesity are urgently needed.
While these are preclinical studies, it will now be fascinating to determine if these or similar compounds can be developed into drugs or food additives to impact human food intake and thus become an additional tool in the fight against the obesity epidemic.
Klaus H. Kaestner, PhD, MS, is with the department of genetics and Center for Molecular Studies in Digestive and Liver Diseases, University of Pennsylvania, Philadelphia. He has no financial conflicts of interest.
The obesity epidemic represents a significant public health crisis that has spread to most countries on the planet. In addition to being a major risk factor for diabetes and cardiovascular disease, obesity also impacts the incidence of gastrointestinal cancers. Despite major efforts of health professionals and public health messaging, it remains very difficult for patients to achieve sustained weight loss by changing diet and increasing physical activity alone. Novel approaches to regulate food intake and thus obesity are urgently needed.
While these are preclinical studies, it will now be fascinating to determine if these or similar compounds can be developed into drugs or food additives to impact human food intake and thus become an additional tool in the fight against the obesity epidemic.
Klaus H. Kaestner, PhD, MS, is with the department of genetics and Center for Molecular Studies in Digestive and Liver Diseases, University of Pennsylvania, Philadelphia. He has no financial conflicts of interest.
Desire for dietary lipids has been traced to the taste receptors CD36 and GPR120, and these have been found to be malfunctioning in both obese animals and humans, leading to low perception of fat levels in food.
The study was published online in Cellular and Molecular Gastroenterology and Hepatology. “Ours is the first study on targeting fat taste receptors, leading to [the] activation of tongue-gut loop as a therapeutic approach, and it opens new vistas to synthesize more potent chemical compounds to decrease progressive weight gain under [high-fat diet] consumption,” the authors wrote.
The perception of fat has recently been identified as a potential sixth basic taste quality, joining sweet, sour, bitter, salt, and umami. CD36 is expressed by taste cells, where it senses dietary long-chain fatty acids (LCFAs), and its deletion led mice to ignore LCFAs and oily solutions that they would otherwise prefer. GPR120 has also been proposed as a lipid sensor.
Previous researchers had suggested that CD36 may play a role in the preference for eating fats, while GPR120 could have a role in lipid satiation following consumption. “Our team also supported these conclusions and proposed that CD36 might be involved in immediate early detection [of fat in foods], whereas GPR120 will be responsible for post-ingestive regulation of lipid food intake,” the authors wrote.
The researchers showed that lipids bind to CD36 when they are present in low concentrations, but at high concentrations they bind to GPR120, suggesting that the two receptors are nonoverlapping but nevertheless complement one another during fatty acid–mediated signaling with taste bud cells (TBC). They are also coexpressed within the same type of TBC.
Experiments in rodents suggest that obese animals have reduced capacity to sense dietary fatty acids, which drives consumption of greater amounts. Fat-rich diets can also reduce fat taste perception, and this has been shown cross-sectionally in obese human subjects, and a single nucleotide polymorphism in CD36 that leads to a reduction in expression is linked to reduced perception of dietary fatty acids.
To test the idea that altering the receptors could change behavior, the researchers synthesized two novel fat taste receptor agonists (FTAs) that are derived from the LCFA linoleic acid, which is abundant in Western diets.
Using nerve recordings, the researchers confirmed that a message from TBCs is sent to the brain via the chorda tympani nerve, and the two FTAs increased the nerve signal. The signals from LCFAs alone were boosted with the addition of the FTAs, suggesting that these molecules can be effective even in the presence of dietary lipids. They also confirmed that FTAs activate the tongue-brain-gut loop by increasing pancreato-bile secretion more than linoleic acid alone.
Given the choice between two bottles, mice preferred the one containing FTAs, and the experiments indicated that FTAs are 95-142 times more potent than natural LCFA as food attractants.
It is well known that diet and lifestyle interventions rarely result in long-term weight loss, and products designed to mimic ‘fat-like’ texture – such as maltodextrin, inulin, and plant fibers – have had limited success because they do not have a fat-like taste and can lead to gastrointestinal side effects. Agonists of CD36 and GPR120 added to low- or noncaloric foods could boost their appeal and lead to earlier satiation.
Importantly, in obese mice, both TFAs led to decreased food intake as well as reduced weight gain and fat mass, without affecting lean mass. One of the agents also promoted a higher metabolic rate through increased energy expenditure.
The researchers also examined the agents’ effects on the microbiota of the obese mice, which contain high concentrations of bacteria belonging to the Lachnospiraceae family. Both inhibitors reduced the numbers of Lachnospiraceae bacteria, and promoted other bacterial families that may contribute to an anti-inflammatory effect. Obese animals exposed to TFAs also showed improvements in dyslipidemia, and there was evidence that they could reduce liver lipid concentrations.
There was no evidence of any mutagenicity, genotoxicity, or endocrine disruption. In sum, these new agonists might enable the development of novel treatments of obesity, which would have a major impact on human health.
The authors stated that they have no financial conflicts of interest. The study received financial support from institutions including the Société d'Accélération du Transfert de Technologies and the University of Burgundy.
This article was updated 2/15/23.
Desire for dietary lipids has been traced to the taste receptors CD36 and GPR120, and these have been found to be malfunctioning in both obese animals and humans, leading to low perception of fat levels in food.
The study was published online in Cellular and Molecular Gastroenterology and Hepatology. “Ours is the first study on targeting fat taste receptors, leading to [the] activation of tongue-gut loop as a therapeutic approach, and it opens new vistas to synthesize more potent chemical compounds to decrease progressive weight gain under [high-fat diet] consumption,” the authors wrote.
The perception of fat has recently been identified as a potential sixth basic taste quality, joining sweet, sour, bitter, salt, and umami. CD36 is expressed by taste cells, where it senses dietary long-chain fatty acids (LCFAs), and its deletion led mice to ignore LCFAs and oily solutions that they would otherwise prefer. GPR120 has also been proposed as a lipid sensor.
Previous researchers had suggested that CD36 may play a role in the preference for eating fats, while GPR120 could have a role in lipid satiation following consumption. “Our team also supported these conclusions and proposed that CD36 might be involved in immediate early detection [of fat in foods], whereas GPR120 will be responsible for post-ingestive regulation of lipid food intake,” the authors wrote.
The researchers showed that lipids bind to CD36 when they are present in low concentrations, but at high concentrations they bind to GPR120, suggesting that the two receptors are nonoverlapping but nevertheless complement one another during fatty acid–mediated signaling with taste bud cells (TBC). They are also coexpressed within the same type of TBC.
Experiments in rodents suggest that obese animals have reduced capacity to sense dietary fatty acids, which drives consumption of greater amounts. Fat-rich diets can also reduce fat taste perception, and this has been shown cross-sectionally in obese human subjects, and a single nucleotide polymorphism in CD36 that leads to a reduction in expression is linked to reduced perception of dietary fatty acids.
To test the idea that altering the receptors could change behavior, the researchers synthesized two novel fat taste receptor agonists (FTAs) that are derived from the LCFA linoleic acid, which is abundant in Western diets.
Using nerve recordings, the researchers confirmed that a message from TBCs is sent to the brain via the chorda tympani nerve, and the two FTAs increased the nerve signal. The signals from LCFAs alone were boosted with the addition of the FTAs, suggesting that these molecules can be effective even in the presence of dietary lipids. They also confirmed that FTAs activate the tongue-brain-gut loop by increasing pancreato-bile secretion more than linoleic acid alone.
Given the choice between two bottles, mice preferred the one containing FTAs, and the experiments indicated that FTAs are 95-142 times more potent than natural LCFA as food attractants.
It is well known that diet and lifestyle interventions rarely result in long-term weight loss, and products designed to mimic ‘fat-like’ texture – such as maltodextrin, inulin, and plant fibers – have had limited success because they do not have a fat-like taste and can lead to gastrointestinal side effects. Agonists of CD36 and GPR120 added to low- or noncaloric foods could boost their appeal and lead to earlier satiation.
Importantly, in obese mice, both TFAs led to decreased food intake as well as reduced weight gain and fat mass, without affecting lean mass. One of the agents also promoted a higher metabolic rate through increased energy expenditure.
The researchers also examined the agents’ effects on the microbiota of the obese mice, which contain high concentrations of bacteria belonging to the Lachnospiraceae family. Both inhibitors reduced the numbers of Lachnospiraceae bacteria, and promoted other bacterial families that may contribute to an anti-inflammatory effect. Obese animals exposed to TFAs also showed improvements in dyslipidemia, and there was evidence that they could reduce liver lipid concentrations.
There was no evidence of any mutagenicity, genotoxicity, or endocrine disruption. In sum, these new agonists might enable the development of novel treatments of obesity, which would have a major impact on human health.
The authors stated that they have no financial conflicts of interest. The study received financial support from institutions including the Société d'Accélération du Transfert de Technologies and the University of Burgundy.
This article was updated 2/15/23.
FROM CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
Pruritic rash on arms and legs
Atopic dermatitis (AD) is one of the most common chronic, inflammatory skin diseases encountered by dermatologists. AD is characterized by pruritus and a chronic course of exacerbations and remissions. AD is thought to involve the interplay of genetic predisposition, immune dysregulation, and environmental factors. It is also associated with other allergic conditions, including asthma.
Although AD typically presents with pruritus as the hallmark symptom in all patients, the appearance of skin lesions may vary among different skin types. In individuals with light-colored skin, AD often appears as erythematous patches and plaques. It also more commonly affects the flexor surfaces of the skin. In individuals with darker skin tones, AD may more often result in follicularly centered papules, lichenification, and pigmentary changes. Lesions may also present on extensor surfaces rather than the typical flexure surfaces. Erythema in darker skin types may appear reddish-brown, have a violaceous hue, or be an ashen gray or darker brown color rather than bright red. Because erythema is more difficult to detect in darker skin types, clinicians may mistakenly minimize the severity of AD.
Clinical severity may also differ between ethnicities. Black patients have an increased tendency toward hyperlinearity of the palms, periorbital dark circles, Dennie-Morgan lines, and diffuse xerosis. Compared with White patients, Black patients with AD are also more likely to develop prurigo nodularis and lichenification. In contrast, Asian patients with AD often experience psoriasiform features, with lesions having more well-defined borders and increased scaling and lichenification.
Beyond differences in clinical appearance, AD may appear molecularly and histologically distinct in ethnic skin. One study suggests that Black patients with AD may have decreased Th1 and Th17 but share similar upregulation of Th2 and Th22 as seen in White patients. Another study showed that Asian patients may have higher Th17 and Th22 and lower Th1/interferon compared with White patients.
Regardless of skin type, treatment goals remain the same. Treatment goals aim to repair and improve the function of the skin barrier while preventing and managing flares. Clinical studies have shown that skincare regimens incorporating ceramide-containing moisturizers may improve AD by increasing the lipid content in the skin. This may offer clinical benefit in patients with skin of color. However, some treatments often used for AD may lead to other skin issues in skin in color. For example, long-term use of topical steroids may worsen hypopigmentation in darker skin types. Management strategies should take into account the unique clinical and genetic features of AD among different patient demographic groups.
William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.
Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
Atopic dermatitis (AD) is one of the most common chronic, inflammatory skin diseases encountered by dermatologists. AD is characterized by pruritus and a chronic course of exacerbations and remissions. AD is thought to involve the interplay of genetic predisposition, immune dysregulation, and environmental factors. It is also associated with other allergic conditions, including asthma.
Although AD typically presents with pruritus as the hallmark symptom in all patients, the appearance of skin lesions may vary among different skin types. In individuals with light-colored skin, AD often appears as erythematous patches and plaques. It also more commonly affects the flexor surfaces of the skin. In individuals with darker skin tones, AD may more often result in follicularly centered papules, lichenification, and pigmentary changes. Lesions may also present on extensor surfaces rather than the typical flexure surfaces. Erythema in darker skin types may appear reddish-brown, have a violaceous hue, or be an ashen gray or darker brown color rather than bright red. Because erythema is more difficult to detect in darker skin types, clinicians may mistakenly minimize the severity of AD.
Clinical severity may also differ between ethnicities. Black patients have an increased tendency toward hyperlinearity of the palms, periorbital dark circles, Dennie-Morgan lines, and diffuse xerosis. Compared with White patients, Black patients with AD are also more likely to develop prurigo nodularis and lichenification. In contrast, Asian patients with AD often experience psoriasiform features, with lesions having more well-defined borders and increased scaling and lichenification.
Beyond differences in clinical appearance, AD may appear molecularly and histologically distinct in ethnic skin. One study suggests that Black patients with AD may have decreased Th1 and Th17 but share similar upregulation of Th2 and Th22 as seen in White patients. Another study showed that Asian patients may have higher Th17 and Th22 and lower Th1/interferon compared with White patients.
Regardless of skin type, treatment goals remain the same. Treatment goals aim to repair and improve the function of the skin barrier while preventing and managing flares. Clinical studies have shown that skincare regimens incorporating ceramide-containing moisturizers may improve AD by increasing the lipid content in the skin. This may offer clinical benefit in patients with skin of color. However, some treatments often used for AD may lead to other skin issues in skin in color. For example, long-term use of topical steroids may worsen hypopigmentation in darker skin types. Management strategies should take into account the unique clinical and genetic features of AD among different patient demographic groups.
William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.
Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
Atopic dermatitis (AD) is one of the most common chronic, inflammatory skin diseases encountered by dermatologists. AD is characterized by pruritus and a chronic course of exacerbations and remissions. AD is thought to involve the interplay of genetic predisposition, immune dysregulation, and environmental factors. It is also associated with other allergic conditions, including asthma.
Although AD typically presents with pruritus as the hallmark symptom in all patients, the appearance of skin lesions may vary among different skin types. In individuals with light-colored skin, AD often appears as erythematous patches and plaques. It also more commonly affects the flexor surfaces of the skin. In individuals with darker skin tones, AD may more often result in follicularly centered papules, lichenification, and pigmentary changes. Lesions may also present on extensor surfaces rather than the typical flexure surfaces. Erythema in darker skin types may appear reddish-brown, have a violaceous hue, or be an ashen gray or darker brown color rather than bright red. Because erythema is more difficult to detect in darker skin types, clinicians may mistakenly minimize the severity of AD.
Clinical severity may also differ between ethnicities. Black patients have an increased tendency toward hyperlinearity of the palms, periorbital dark circles, Dennie-Morgan lines, and diffuse xerosis. Compared with White patients, Black patients with AD are also more likely to develop prurigo nodularis and lichenification. In contrast, Asian patients with AD often experience psoriasiform features, with lesions having more well-defined borders and increased scaling and lichenification.
Beyond differences in clinical appearance, AD may appear molecularly and histologically distinct in ethnic skin. One study suggests that Black patients with AD may have decreased Th1 and Th17 but share similar upregulation of Th2 and Th22 as seen in White patients. Another study showed that Asian patients may have higher Th17 and Th22 and lower Th1/interferon compared with White patients.
Regardless of skin type, treatment goals remain the same. Treatment goals aim to repair and improve the function of the skin barrier while preventing and managing flares. Clinical studies have shown that skincare regimens incorporating ceramide-containing moisturizers may improve AD by increasing the lipid content in the skin. This may offer clinical benefit in patients with skin of color. However, some treatments often used for AD may lead to other skin issues in skin in color. For example, long-term use of topical steroids may worsen hypopigmentation in darker skin types. Management strategies should take into account the unique clinical and genetic features of AD among different patient demographic groups.
William D. James, MD, Professor, Department of Dermatology, University of Pennsylvania, Philadelphia.
Disclosure: William D. James, MD, has disclosed the following relevant financial relationships:
Received income in an amount equal to or greater than $250 from: Elsevier.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 27-year-old student presents with a pruritic rash on his hands and in the bends of his arms and legs. He recently started clinical rotations in a nursing facility and has been using hand sanitizer multiple times per day, which has exacerbated the rash on his hands, causing them to ooze and sting. He describes the rash as itchy, especially at night. At times he reports that the itching causes difficulty sleeping. In addition, his skin has little cracks that frequently bleed. He notes that he has experienced similar symptoms in the past, which resolved with moisturizers and topical cream from the drugstore. He has tried over-the-counter hydrocortisone during this episode, with minimal improvement in symptoms. He denies any change in laundry detergents or use of new household products.
Physical examination reveals large erythematous plaques on the hands and flexure surfaces of his neck, antecubital fossa, and behind the knees with scattered excoriations. Erythematous, slightly lichenified coalescing papules are noted on the proximal arms. His face is clear. General skin pigmentation is brown and free of masses and lumps.
Product updates and reviews
HEGENBERGER RETRACTOR: IS IT HELPFUL FOR PERINEAL REPAIR?
The Hegenberger Retractor, manufactured by Hegenberger Medical (Abingdon, United Kingdom) is available for purchase in the United States through Rocket Medical. A video that I find particularly useful for explaining its use is available here: https://www.youtube.com /watch?v=p-jilXgXZLY
Background. About 85% of women having a vaginal birth experience some form of perineal trauma, and 60% to 70% receive stitches for those spontaneous tears or intentional incisions. As such, repairing perineal lacerations is a requisite skill for all obstetricians and midwives, and every provider has developed exposure techniques to perform their suturing with the goals of good tissue re-approximation, efficiency, minimized patient discomfort, reduced blood loss, and safety from needle sticks. For several millennia, the most commonly used tissue retractor for these repairs has been one’s own fingers, or those of a colleague. While cost-effective and readily available, fingers do have drawbacks as a vaginal retractor. First, their use as a retractor precludes their use for other tasks. Second, their frequent need to be inserted and replaced (see drawback #1) can be uncomfortable for patients. Third, their limited surface area is often insufficient to appropriately provide adequate tissue retraction for optimal surgical site visualization. Finally, they get tired and typically do not appreciate being stuck with needles. Given all this, it is surprising that so many centuries have passed with so little innovation for this ubiquitous procedure. Fortunately, Danish midwife Malene Hegenberger thought now was a good time to change the status quo.
Design/Functionality. The Hegenberger Retractor is brilliant in its simplicity. Its unique molded plastic design is smooth, ergonomic, nonconductive, and packaged as a single-use sterile device. Amazingly, it has a near-perfect pliability balance, making it simultaneously easy to compress for insertion while providing enough retraction tension for good visualization once it has been reexpanded. The subtle ridges on the compression points are just enough to allow for a good grip, and the notches on the sides are a convenient addition for holding extra suture if needed. The device has been cleared by the US Food and Drug Administration (FDA) as a Class 1 device and is approved for sale in the United States. In my experience with its use, I thought it was easy to place and provided excellent exposure for the repairs I was doing. In fact, I thought it provided as good if not better exposure than what I would expect from a Gelpi retractor without any of the trauma the Gelpi adds with its pointed ends. Smile emoji!
Innovation. In the early 1800s, French midwifery pioneer Marie Boivin introduced a novel pelvimeter and a revolutionary 2-part speculum to the technology of the day. Why it took more than 200 years for the ideas of another cutting-edge midwife to breach the walls of the obstetric technological establishment remains a mystery, but fortunately it has been done. While seemingly obvious, the Hegenberger Retractor is the culmination of years of work and 88 prototypes. It looks simple, but the secret to its functionality is the precision with which each dimension and every curve was designed. The device has been cleared by the FDA as a Class 1 device and is approved for sale in the United States.
Summary. There are a lot of reasons to like the Hegenberger Retractor. I like it for its simplicity; I like it for its functionality; I like it for its ability to fill a real need. On the downside, I do not like that it is a single-use plastic device, and I am not happy about adding cost to obstetric care. Most of all, I hate that I did not invent it.
Is the Hegenberger Retractor going to be needed to repair every obstetric laceration? No. Will it provide perfect exposure to repair every obstetric laceration? Of course not. But it is an incredibly clever device that will be very helpful in many situations, and I suspect it will soon become a mainstay on most maternity units as it gains recognition.
FOR MORE INFORMATION, VISIT www.rocketmedical.com
- McCandlish R, Bowler U, van Asten H, et al. A randomised controlled trial of care of the perineum during second stage of normal labour. Br J Obstet Gynaecol. 1998;105:1262-1272.
- Ferry G. Marie Boivin: from midwife to gynaecologist. Lancet. 2019;393:2192-2193. doi: 10.1016/S0140-6736(19)31188-2.
HEGENBERGER RETRACTOR: IS IT HELPFUL FOR PERINEAL REPAIR?
The Hegenberger Retractor, manufactured by Hegenberger Medical (Abingdon, United Kingdom) is available for purchase in the United States through Rocket Medical. A video that I find particularly useful for explaining its use is available here: https://www.youtube.com /watch?v=p-jilXgXZLY
Background. About 85% of women having a vaginal birth experience some form of perineal trauma, and 60% to 70% receive stitches for those spontaneous tears or intentional incisions. As such, repairing perineal lacerations is a requisite skill for all obstetricians and midwives, and every provider has developed exposure techniques to perform their suturing with the goals of good tissue re-approximation, efficiency, minimized patient discomfort, reduced blood loss, and safety from needle sticks. For several millennia, the most commonly used tissue retractor for these repairs has been one’s own fingers, or those of a colleague. While cost-effective and readily available, fingers do have drawbacks as a vaginal retractor. First, their use as a retractor precludes their use for other tasks. Second, their frequent need to be inserted and replaced (see drawback #1) can be uncomfortable for patients. Third, their limited surface area is often insufficient to appropriately provide adequate tissue retraction for optimal surgical site visualization. Finally, they get tired and typically do not appreciate being stuck with needles. Given all this, it is surprising that so many centuries have passed with so little innovation for this ubiquitous procedure. Fortunately, Danish midwife Malene Hegenberger thought now was a good time to change the status quo.
Design/Functionality. The Hegenberger Retractor is brilliant in its simplicity. Its unique molded plastic design is smooth, ergonomic, nonconductive, and packaged as a single-use sterile device. Amazingly, it has a near-perfect pliability balance, making it simultaneously easy to compress for insertion while providing enough retraction tension for good visualization once it has been reexpanded. The subtle ridges on the compression points are just enough to allow for a good grip, and the notches on the sides are a convenient addition for holding extra suture if needed. The device has been cleared by the US Food and Drug Administration (FDA) as a Class 1 device and is approved for sale in the United States. In my experience with its use, I thought it was easy to place and provided excellent exposure for the repairs I was doing. In fact, I thought it provided as good if not better exposure than what I would expect from a Gelpi retractor without any of the trauma the Gelpi adds with its pointed ends. Smile emoji!
Innovation. In the early 1800s, French midwifery pioneer Marie Boivin introduced a novel pelvimeter and a revolutionary 2-part speculum to the technology of the day. Why it took more than 200 years for the ideas of another cutting-edge midwife to breach the walls of the obstetric technological establishment remains a mystery, but fortunately it has been done. While seemingly obvious, the Hegenberger Retractor is the culmination of years of work and 88 prototypes. It looks simple, but the secret to its functionality is the precision with which each dimension and every curve was designed. The device has been cleared by the FDA as a Class 1 device and is approved for sale in the United States.
Summary. There are a lot of reasons to like the Hegenberger Retractor. I like it for its simplicity; I like it for its functionality; I like it for its ability to fill a real need. On the downside, I do not like that it is a single-use plastic device, and I am not happy about adding cost to obstetric care. Most of all, I hate that I did not invent it.
Is the Hegenberger Retractor going to be needed to repair every obstetric laceration? No. Will it provide perfect exposure to repair every obstetric laceration? Of course not. But it is an incredibly clever device that will be very helpful in many situations, and I suspect it will soon become a mainstay on most maternity units as it gains recognition.
FOR MORE INFORMATION, VISIT www.rocketmedical.com
HEGENBERGER RETRACTOR: IS IT HELPFUL FOR PERINEAL REPAIR?
The Hegenberger Retractor, manufactured by Hegenberger Medical (Abingdon, United Kingdom) is available for purchase in the United States through Rocket Medical. A video that I find particularly useful for explaining its use is available here: https://www.youtube.com /watch?v=p-jilXgXZLY
Background. About 85% of women having a vaginal birth experience some form of perineal trauma, and 60% to 70% receive stitches for those spontaneous tears or intentional incisions. As such, repairing perineal lacerations is a requisite skill for all obstetricians and midwives, and every provider has developed exposure techniques to perform their suturing with the goals of good tissue re-approximation, efficiency, minimized patient discomfort, reduced blood loss, and safety from needle sticks. For several millennia, the most commonly used tissue retractor for these repairs has been one’s own fingers, or those of a colleague. While cost-effective and readily available, fingers do have drawbacks as a vaginal retractor. First, their use as a retractor precludes their use for other tasks. Second, their frequent need to be inserted and replaced (see drawback #1) can be uncomfortable for patients. Third, their limited surface area is often insufficient to appropriately provide adequate tissue retraction for optimal surgical site visualization. Finally, they get tired and typically do not appreciate being stuck with needles. Given all this, it is surprising that so many centuries have passed with so little innovation for this ubiquitous procedure. Fortunately, Danish midwife Malene Hegenberger thought now was a good time to change the status quo.
Design/Functionality. The Hegenberger Retractor is brilliant in its simplicity. Its unique molded plastic design is smooth, ergonomic, nonconductive, and packaged as a single-use sterile device. Amazingly, it has a near-perfect pliability balance, making it simultaneously easy to compress for insertion while providing enough retraction tension for good visualization once it has been reexpanded. The subtle ridges on the compression points are just enough to allow for a good grip, and the notches on the sides are a convenient addition for holding extra suture if needed. The device has been cleared by the US Food and Drug Administration (FDA) as a Class 1 device and is approved for sale in the United States. In my experience with its use, I thought it was easy to place and provided excellent exposure for the repairs I was doing. In fact, I thought it provided as good if not better exposure than what I would expect from a Gelpi retractor without any of the trauma the Gelpi adds with its pointed ends. Smile emoji!
Innovation. In the early 1800s, French midwifery pioneer Marie Boivin introduced a novel pelvimeter and a revolutionary 2-part speculum to the technology of the day. Why it took more than 200 years for the ideas of another cutting-edge midwife to breach the walls of the obstetric technological establishment remains a mystery, but fortunately it has been done. While seemingly obvious, the Hegenberger Retractor is the culmination of years of work and 88 prototypes. It looks simple, but the secret to its functionality is the precision with which each dimension and every curve was designed. The device has been cleared by the FDA as a Class 1 device and is approved for sale in the United States.
Summary. There are a lot of reasons to like the Hegenberger Retractor. I like it for its simplicity; I like it for its functionality; I like it for its ability to fill a real need. On the downside, I do not like that it is a single-use plastic device, and I am not happy about adding cost to obstetric care. Most of all, I hate that I did not invent it.
Is the Hegenberger Retractor going to be needed to repair every obstetric laceration? No. Will it provide perfect exposure to repair every obstetric laceration? Of course not. But it is an incredibly clever device that will be very helpful in many situations, and I suspect it will soon become a mainstay on most maternity units as it gains recognition.
FOR MORE INFORMATION, VISIT www.rocketmedical.com
- McCandlish R, Bowler U, van Asten H, et al. A randomised controlled trial of care of the perineum during second stage of normal labour. Br J Obstet Gynaecol. 1998;105:1262-1272.
- Ferry G. Marie Boivin: from midwife to gynaecologist. Lancet. 2019;393:2192-2193. doi: 10.1016/S0140-6736(19)31188-2.
- McCandlish R, Bowler U, van Asten H, et al. A randomised controlled trial of care of the perineum during second stage of normal labour. Br J Obstet Gynaecol. 1998;105:1262-1272.
- Ferry G. Marie Boivin: from midwife to gynaecologist. Lancet. 2019;393:2192-2193. doi: 10.1016/S0140-6736(19)31188-2.
COMMENT & CONTROVERSY
Should treatment be initiated for mild chronic hypertension in pregnancy to improve outcomes?
JAIMEY M. PAULI, MD (JUNE 2022)
Consider this, when it comes to treating chronic hypertension
I welcome the article by Dr. Jaimey Pauli, which focuses on initiating treatment for mild chronic hypertension in pregnancy to reach a goal blood pressure (BP) of <140/90 mm Hg to prevent adverse maternal and fetal outcomes.1 I would like to offer 3 additional thoughts for your consideration. First, it is known that there is a physiological decrease in BP during the second trimester, which results in a normotensive presentation. Thus, it would be beneficial to see if pregnant women with high-normal BP levels before the third trimester be administered a lower dose of antihypertensives. However, there is also a concern that decreased maternal BP may compromise uteroplacental perfusion and fetal circulation, which also could be evaluated.2
Second, I would like to see how comorbidities affect the initiation of antihypertensives for mild chronic hypertension in pregnancy. Research incorporating pregnant women with borderline hypertension and comorbidities such as obesity, hyperlipidemia, and diabetes mellitus type 2 (DM) is likely to yield informative results. This is especially beneficial since, for example, chronic hypertension and DM are independent risk factors for adverse maternal and fetal outcomes; therefore, a mother with both these conditions may have additive effects on obstetric outcomes.3
Lastly, I would suggest you include a brief conversation about prepregnancy ways to manage women with chronic hypertension. Because many women who enter pregnancy with chronic hypertension have hypertension of unknown origin, it would be beneficial to optimize antihypertensive regimens before conception.4 Also, it should be further evaluated whether initiation of lifestyle modifications, such as weight reduction and the DASH diet before pregnancy, for women with chronic hypertension improves pregnancy outcomes.
Cassandra Maafoh, MD
Macon, Georgia
References
- Pauli JM. Should treatment be initiated for mild chronic hypertension in pregnancy to improve outcomes? OBG Manag. 2022;34:14-15.
- Brown CM, Garovic VD. Drug treatment of hypertension in pregnancy. Drugs. 2014;74:283-296. https://doi.org/10.1007/s40265-014-0187-7.
- Yanit KE, Snowden JM, Cheng YW, et al. The impact of chronic hypertension and pregestational diabetes on pregnancy outcomes. Am J Obstet Gynecol. 2012;207. https://doi. org/10.1016/j.ajog.2012.06.066.
- Seely EW, Ecker J. Chronic hypertension in pregnancy. Circulation. 2014;129:1254-1261. https:// doi.org/10.1161/circulationaha.113.003904.
BARBARA LEVY, MD (AUGUST 2022)
Are these new and rare syndromes’ pathophysiological mechanisms related?
I read with great interest Dr. Barbara Levy’s UPDATE in the August 2022 issue on testosterone therapy for women with hypoactive sexual desire disorder (HSDD), as well as her comments on persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD) that was recently so coined by the International Society for the Study of Women’s Sexual Health (ISSWSH) as a 2-component syndrome.1 The new syndrome, explains Dr. Levy, presents with “the perception of genital arousal that is involuntary, unrelated to sexual desire, without any identified cause, not relieved with orgasm, and distressing to the patient (the PGAD component),” combined with “itching, burning, tingling, or pain” (the GPD component).
Although agreeing with ISSWSH that diagnosis and management require a multidisciplinary biopsychosocial approach, in her practical advice, Dr. Levy mentioned: “neuropathic signaling” with “aberrant sensory processing” as the syndrome’s possible main pathophysiology. Interestingly, there are 2 other rare, chronic, and “poorly recognized source(s) of major distress to a small but significant group of patients.” Persistent idiopathic oro-facial pain (PIFP) disorder2 after dental interventions and burning mouth syndrome (BMS),3 defined by the absence of any local or systemic contributing etiology, also present with continuous local burning and pain (as in GPD). Consequently, PGAD/GPD may indeed have the same pathophysiological explanation—as Dr. Levy suggested—of being a (genital) peripheral chronic neuropathic pain condition.
A potentially promising new therapeutic approach for PGAD/GPD would then be to use the same, or similar, antineuropathic medications (Clonazepam, Nortriptyline, Pregabalin, etc.) in the form of topical vaginal swishing solutions similar to the presently recommended antiepileptic and/or antidepressant oral swishing treatment for PIFP and BMS. As the topical approach works well for oral neuropathic pain, vaginal swishing could potentially be the answer for PGAD/GPD peripheral neuropathic pain. Moreover, such a novel topical approach would significantly increase patient motivation for treatment by avoiding the adverse effects of ingested antiepileptic or antidepressant drugs.
This is the first time that anticonvulsant and/or antidepressant vaginal swishing is proposed as topical therapy for GPD peripheral neuropathic pain, still pending scientific/clinical validation. ●
Zwi Hoch, MD
Newton, Massachusetts
- Goldstein I, Komisaruk BR, Pukall CF, et al. International Society for the Study of Women’s Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD). J Sex Med. 2021;18:665-697.
- Baad-Hansen L, Benoliel R. Neuropathic orofacial pain: facts and fiction. Cephalgia. 2017;37:670-679.
- Kuten-Shorer M, Treister NS, Stock S, et al. Safety and tolerability of topical clonazepam solution for management of oral dysesthesia. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;124: 146-151.
Should treatment be initiated for mild chronic hypertension in pregnancy to improve outcomes?
JAIMEY M. PAULI, MD (JUNE 2022)
Consider this, when it comes to treating chronic hypertension
I welcome the article by Dr. Jaimey Pauli, which focuses on initiating treatment for mild chronic hypertension in pregnancy to reach a goal blood pressure (BP) of <140/90 mm Hg to prevent adverse maternal and fetal outcomes.1 I would like to offer 3 additional thoughts for your consideration. First, it is known that there is a physiological decrease in BP during the second trimester, which results in a normotensive presentation. Thus, it would be beneficial to see if pregnant women with high-normal BP levels before the third trimester be administered a lower dose of antihypertensives. However, there is also a concern that decreased maternal BP may compromise uteroplacental perfusion and fetal circulation, which also could be evaluated.2
Second, I would like to see how comorbidities affect the initiation of antihypertensives for mild chronic hypertension in pregnancy. Research incorporating pregnant women with borderline hypertension and comorbidities such as obesity, hyperlipidemia, and diabetes mellitus type 2 (DM) is likely to yield informative results. This is especially beneficial since, for example, chronic hypertension and DM are independent risk factors for adverse maternal and fetal outcomes; therefore, a mother with both these conditions may have additive effects on obstetric outcomes.3
Lastly, I would suggest you include a brief conversation about prepregnancy ways to manage women with chronic hypertension. Because many women who enter pregnancy with chronic hypertension have hypertension of unknown origin, it would be beneficial to optimize antihypertensive regimens before conception.4 Also, it should be further evaluated whether initiation of lifestyle modifications, such as weight reduction and the DASH diet before pregnancy, for women with chronic hypertension improves pregnancy outcomes.
Cassandra Maafoh, MD
Macon, Georgia
References
- Pauli JM. Should treatment be initiated for mild chronic hypertension in pregnancy to improve outcomes? OBG Manag. 2022;34:14-15.
- Brown CM, Garovic VD. Drug treatment of hypertension in pregnancy. Drugs. 2014;74:283-296. https://doi.org/10.1007/s40265-014-0187-7.
- Yanit KE, Snowden JM, Cheng YW, et al. The impact of chronic hypertension and pregestational diabetes on pregnancy outcomes. Am J Obstet Gynecol. 2012;207. https://doi. org/10.1016/j.ajog.2012.06.066.
- Seely EW, Ecker J. Chronic hypertension in pregnancy. Circulation. 2014;129:1254-1261. https:// doi.org/10.1161/circulationaha.113.003904.
BARBARA LEVY, MD (AUGUST 2022)
Are these new and rare syndromes’ pathophysiological mechanisms related?
I read with great interest Dr. Barbara Levy’s UPDATE in the August 2022 issue on testosterone therapy for women with hypoactive sexual desire disorder (HSDD), as well as her comments on persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD) that was recently so coined by the International Society for the Study of Women’s Sexual Health (ISSWSH) as a 2-component syndrome.1 The new syndrome, explains Dr. Levy, presents with “the perception of genital arousal that is involuntary, unrelated to sexual desire, without any identified cause, not relieved with orgasm, and distressing to the patient (the PGAD component),” combined with “itching, burning, tingling, or pain” (the GPD component).
Although agreeing with ISSWSH that diagnosis and management require a multidisciplinary biopsychosocial approach, in her practical advice, Dr. Levy mentioned: “neuropathic signaling” with “aberrant sensory processing” as the syndrome’s possible main pathophysiology. Interestingly, there are 2 other rare, chronic, and “poorly recognized source(s) of major distress to a small but significant group of patients.” Persistent idiopathic oro-facial pain (PIFP) disorder2 after dental interventions and burning mouth syndrome (BMS),3 defined by the absence of any local or systemic contributing etiology, also present with continuous local burning and pain (as in GPD). Consequently, PGAD/GPD may indeed have the same pathophysiological explanation—as Dr. Levy suggested—of being a (genital) peripheral chronic neuropathic pain condition.
A potentially promising new therapeutic approach for PGAD/GPD would then be to use the same, or similar, antineuropathic medications (Clonazepam, Nortriptyline, Pregabalin, etc.) in the form of topical vaginal swishing solutions similar to the presently recommended antiepileptic and/or antidepressant oral swishing treatment for PIFP and BMS. As the topical approach works well for oral neuropathic pain, vaginal swishing could potentially be the answer for PGAD/GPD peripheral neuropathic pain. Moreover, such a novel topical approach would significantly increase patient motivation for treatment by avoiding the adverse effects of ingested antiepileptic or antidepressant drugs.
This is the first time that anticonvulsant and/or antidepressant vaginal swishing is proposed as topical therapy for GPD peripheral neuropathic pain, still pending scientific/clinical validation. ●
Zwi Hoch, MD
Newton, Massachusetts
- Goldstein I, Komisaruk BR, Pukall CF, et al. International Society for the Study of Women’s Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD). J Sex Med. 2021;18:665-697.
- Baad-Hansen L, Benoliel R. Neuropathic orofacial pain: facts and fiction. Cephalgia. 2017;37:670-679.
- Kuten-Shorer M, Treister NS, Stock S, et al. Safety and tolerability of topical clonazepam solution for management of oral dysesthesia. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;124: 146-151.
Should treatment be initiated for mild chronic hypertension in pregnancy to improve outcomes?
JAIMEY M. PAULI, MD (JUNE 2022)
Consider this, when it comes to treating chronic hypertension
I welcome the article by Dr. Jaimey Pauli, which focuses on initiating treatment for mild chronic hypertension in pregnancy to reach a goal blood pressure (BP) of <140/90 mm Hg to prevent adverse maternal and fetal outcomes.1 I would like to offer 3 additional thoughts for your consideration. First, it is known that there is a physiological decrease in BP during the second trimester, which results in a normotensive presentation. Thus, it would be beneficial to see if pregnant women with high-normal BP levels before the third trimester be administered a lower dose of antihypertensives. However, there is also a concern that decreased maternal BP may compromise uteroplacental perfusion and fetal circulation, which also could be evaluated.2
Second, I would like to see how comorbidities affect the initiation of antihypertensives for mild chronic hypertension in pregnancy. Research incorporating pregnant women with borderline hypertension and comorbidities such as obesity, hyperlipidemia, and diabetes mellitus type 2 (DM) is likely to yield informative results. This is especially beneficial since, for example, chronic hypertension and DM are independent risk factors for adverse maternal and fetal outcomes; therefore, a mother with both these conditions may have additive effects on obstetric outcomes.3
Lastly, I would suggest you include a brief conversation about prepregnancy ways to manage women with chronic hypertension. Because many women who enter pregnancy with chronic hypertension have hypertension of unknown origin, it would be beneficial to optimize antihypertensive regimens before conception.4 Also, it should be further evaluated whether initiation of lifestyle modifications, such as weight reduction and the DASH diet before pregnancy, for women with chronic hypertension improves pregnancy outcomes.
Cassandra Maafoh, MD
Macon, Georgia
References
- Pauli JM. Should treatment be initiated for mild chronic hypertension in pregnancy to improve outcomes? OBG Manag. 2022;34:14-15.
- Brown CM, Garovic VD. Drug treatment of hypertension in pregnancy. Drugs. 2014;74:283-296. https://doi.org/10.1007/s40265-014-0187-7.
- Yanit KE, Snowden JM, Cheng YW, et al. The impact of chronic hypertension and pregestational diabetes on pregnancy outcomes. Am J Obstet Gynecol. 2012;207. https://doi. org/10.1016/j.ajog.2012.06.066.
- Seely EW, Ecker J. Chronic hypertension in pregnancy. Circulation. 2014;129:1254-1261. https:// doi.org/10.1161/circulationaha.113.003904.
BARBARA LEVY, MD (AUGUST 2022)
Are these new and rare syndromes’ pathophysiological mechanisms related?
I read with great interest Dr. Barbara Levy’s UPDATE in the August 2022 issue on testosterone therapy for women with hypoactive sexual desire disorder (HSDD), as well as her comments on persistent genital arousal disorder/genito-pelvic dysesthesia (PGAD/GPD) that was recently so coined by the International Society for the Study of Women’s Sexual Health (ISSWSH) as a 2-component syndrome.1 The new syndrome, explains Dr. Levy, presents with “the perception of genital arousal that is involuntary, unrelated to sexual desire, without any identified cause, not relieved with orgasm, and distressing to the patient (the PGAD component),” combined with “itching, burning, tingling, or pain” (the GPD component).
Although agreeing with ISSWSH that diagnosis and management require a multidisciplinary biopsychosocial approach, in her practical advice, Dr. Levy mentioned: “neuropathic signaling” with “aberrant sensory processing” as the syndrome’s possible main pathophysiology. Interestingly, there are 2 other rare, chronic, and “poorly recognized source(s) of major distress to a small but significant group of patients.” Persistent idiopathic oro-facial pain (PIFP) disorder2 after dental interventions and burning mouth syndrome (BMS),3 defined by the absence of any local or systemic contributing etiology, also present with continuous local burning and pain (as in GPD). Consequently, PGAD/GPD may indeed have the same pathophysiological explanation—as Dr. Levy suggested—of being a (genital) peripheral chronic neuropathic pain condition.
A potentially promising new therapeutic approach for PGAD/GPD would then be to use the same, or similar, antineuropathic medications (Clonazepam, Nortriptyline, Pregabalin, etc.) in the form of topical vaginal swishing solutions similar to the presently recommended antiepileptic and/or antidepressant oral swishing treatment for PIFP and BMS. As the topical approach works well for oral neuropathic pain, vaginal swishing could potentially be the answer for PGAD/GPD peripheral neuropathic pain. Moreover, such a novel topical approach would significantly increase patient motivation for treatment by avoiding the adverse effects of ingested antiepileptic or antidepressant drugs.
This is the first time that anticonvulsant and/or antidepressant vaginal swishing is proposed as topical therapy for GPD peripheral neuropathic pain, still pending scientific/clinical validation. ●
Zwi Hoch, MD
Newton, Massachusetts
- Goldstein I, Komisaruk BR, Pukall CF, et al. International Society for the Study of Women’s Sexual Health (ISSWSH) Review of Epidemiology and Pathophysiology, and a Consensus Nomenclature and Process of Care for the Management of Persistent Genital Arousal Disorder/Genito-Pelvic Dysesthesia (PGAD/GPD). J Sex Med. 2021;18:665-697.
- Baad-Hansen L, Benoliel R. Neuropathic orofacial pain: facts and fiction. Cephalgia. 2017;37:670-679.
- Kuten-Shorer M, Treister NS, Stock S, et al. Safety and tolerability of topical clonazepam solution for management of oral dysesthesia. Oral Surg Oral Med Oral Pathol Oral Radiol. 2017;124: 146-151.
New developments and barriers to palliative care
As we enter into this new year, it is a good time to review the past few years of living through a pandemic and the impact this has had on the field of palliative care.
According to the World Health Organization, “Palliative care is an approach that improves the quality of life of patients and their families who are facing the problems associated with life-threatening illness, by the prevention and relief of suffering through early identification, assessment and treatment of pain and other problems whether physical, psychosocial and spiritual.”1 They identify a global need and recognize palliative care as a “human right to health and as a standard of care particularly for individuals living with a serious illness.1 However, the WHO goes further to recognize palliative care as an essential part of the response team during crises and health emergencies like a pandemic, noting that a response team without palliative care is “medically deficient and ethically indefensible.”2
The need for palliative care in the United States is projected to grow significantly in the next decades.3 However, there has been insufficient staffing to meet these needs, even prior to the pandemic.4 The demand for palliative care reached further unprecedented levels during the pandemic as palliative care teams played an integral role and were well situated to support not only patients and families with COVID-19,5 but to also support the well-being of health care teams caring for COVID-19 patients.6,7
A recent survey that was conducted by the Center to Advance Palliative Care among palliative care leadership captured the experiences of leading their teams through a pandemic. Below are the results of this survey, which highlighted important issues and developments to palliative care during the pandemic.6
Increasing need for palliative care
One of the main findings from the national survey of palliative care leaders corroborated that the demands for palliative care have increased significantly from 2020 through the pandemic.
As with many areas in the health care system, the pandemic has emphasized the strain and short staffing of the palliative care teams. In the survey, 61% of leaders reported that palliative care consults significantly increased from prepandemic levels. But only 26% of these leaders said they had the staffing support to meet these needs.
Value of palliative care
The value of palliative care along with understanding of the role of palliative care has been better recognized during the pandemic and has been evidenced by the increase in palliative care referrals from clinical providers, compared with prepandemic levels. In addition, data collected showed that earlier palliative care consultations reduced length of hospital stay, decreased ICU admissions, and improved patient, family, and provider satisfaction.
Well-being of the workforce
The pandemic has been a tremendously stressful time for the health care workforce that has undoubtedly led to burnout. A nationwide study of physicians,8 found that 61% of physicians experienced burnout. This is a significant increase from prepandemic levels with impacts on mental health (that is, anxiety, depression). This study did not include palliative care specialists, but the CAPC survey indicates a similar feeling of burnout. Because of this, some palliative care specialists have left the field altogether, or are leaving leadership positions because of burnout and exhaustion from the pandemic. This was featured as a concern among palliative care leaders, where 93% reported concern for the emotional well-being of the palliative care team.
Telehealth
A permanent operational change that has been well-utilized and implemented across multiple health care settings has been providing palliative care through telehealth. Prior to the pandemic, the baseline use of telehealth was less than 5% with the use now greater than 75% – a modality that is favored by both patients and clinicians. This has offered a broader scope of practice, reaching individuals who may have no other means, have limitations to accessing palliative care, or were in circumstances where patients required isolation during the pandemic. However, there are limitations to this platform, including in equity of access to devices and ease of use for those with limited exposure to technology.9
Barriers to implementation
Although the important role and value of palliative care has been well recognized, there have been barriers identified in a qualitative study of the integration of palliative care into COVID-19 action plans that are mentioned below.5
- Patients and families were identified as barriers to integration of palliative care if they were not open to palliative care referral, mainly because of misperceptions of palliative care as end-of-life care.
- Palliative care knowledge among providers was identified as another barrier to integration of palliative care. There are still misperceptions among providers that palliative care is end-of-life care and palliative care involvement is stigmatized as hastening death. In addition, some felt that COVID-19 was not a traditional “palliative diagnosis” thus were less likely to integrate palliative care into care plans.
- Lack of availability of a primary provider to conduct primary palliative care and lack of motivation “not to give up” were identified as other barriers. On the other hand, palliative care provider availability and accessibility to care teams affected the integration into COVID-19 care plans.
- COVID-19 itself was identified to be a barrier because of the uncertainty of illness trajectory and outcomes, which made it difficult for doctors to ascertain when to involve palliative care.
- Leadership and institution were important factors to consider in integration of palliative care into long-term care plans, which depended on leadership engagement and institutional culture.
Takeaways
The past few years have taught us a lot, but there is still much to learn. The COVID-19 pandemic has called attention to the challenges and barriers of health care delivery and has magnified the needs of the health care system including its infrastructure, preparedness, and staffing, including the field of palliative care. More work needs to be done, but leaders have taken steps to initiate national and international preparedness plans including the integration of palliative care, which has been identified as a vital role in any humanitarian crises.10,11
Dr. Kang is a geriatrician and palliative care provider at the University of Washington, Seattle, in the division of geriatrics and gerontology. She has no conflicts related to the content of this article.
References
1. Palliative care. World Health Organization. Aug 5, 2020. https://www.who.int/news-room/fact-sheets/detail/palliative-care
2. World Health Organization. Integrating palliative care and symptom relief into the response to humanitarian emergencies and crises: A WHO guide. Geneva: World Health Organization, 2018. https://apps.who.int/iris/handle/10665/274565.
3. Hughes MT, Smith TJ. The growth of palliative care in the United States. Annual Review Public Health. 2014;35:459-75.
4. Pastrana T et al. The impact of COVID-19 on palliative care workers across the world: A qualitative analysis of responses to open-ended questions. Palliative and Supportive Care. 2021:1-6.
5. Wentlandt K et al. Identifying barriers and facilitators to palliative care integration in the management of hospitalized patients with COVID-19: A qualitative study. Palliat Med. 2022;36(6):945-54.
6. Rogers M et al. Palliative care leadership during the pandemic: Results from a recent survey. Center to Advance Palliative Care. 2022 Sept 8. https://www.capc.org/blog/palliative-care-leadership-during-the-pandemic-results-from-a-recent-survey
7. Fogelman P. Reflections form a palliative care program leader two years into the pandemic. Center to Advance Palliative Care. 2023 Jan 15. https://www.capc.org/blog/reflections-from-a-palliative-care-program-leader-two-years-into-the-pandemic
8. 2021 survey of America’s physicians Covid-19 impact edition: A year later. The Physicians Foundation. 2021.
9. Caraceni A et al. Telemedicine for outpatient palliative care during Covid-19 pandemics: A longitudinal study. BMJ Supportive & Palliative Care. 2022;0:1-7.
10. Bausewein C et al. National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany – study protocol of a mixed-methods project. BMC Palliative Care. 2022;21(10).
11. Powell RA et al. Palliative care in humanitarian crises: Always something to offer. The Lancet. 2017;389(10078):1498-9.
As we enter into this new year, it is a good time to review the past few years of living through a pandemic and the impact this has had on the field of palliative care.
According to the World Health Organization, “Palliative care is an approach that improves the quality of life of patients and their families who are facing the problems associated with life-threatening illness, by the prevention and relief of suffering through early identification, assessment and treatment of pain and other problems whether physical, psychosocial and spiritual.”1 They identify a global need and recognize palliative care as a “human right to health and as a standard of care particularly for individuals living with a serious illness.1 However, the WHO goes further to recognize palliative care as an essential part of the response team during crises and health emergencies like a pandemic, noting that a response team without palliative care is “medically deficient and ethically indefensible.”2
The need for palliative care in the United States is projected to grow significantly in the next decades.3 However, there has been insufficient staffing to meet these needs, even prior to the pandemic.4 The demand for palliative care reached further unprecedented levels during the pandemic as palliative care teams played an integral role and were well situated to support not only patients and families with COVID-19,5 but to also support the well-being of health care teams caring for COVID-19 patients.6,7
A recent survey that was conducted by the Center to Advance Palliative Care among palliative care leadership captured the experiences of leading their teams through a pandemic. Below are the results of this survey, which highlighted important issues and developments to palliative care during the pandemic.6
Increasing need for palliative care
One of the main findings from the national survey of palliative care leaders corroborated that the demands for palliative care have increased significantly from 2020 through the pandemic.
As with many areas in the health care system, the pandemic has emphasized the strain and short staffing of the palliative care teams. In the survey, 61% of leaders reported that palliative care consults significantly increased from prepandemic levels. But only 26% of these leaders said they had the staffing support to meet these needs.
Value of palliative care
The value of palliative care along with understanding of the role of palliative care has been better recognized during the pandemic and has been evidenced by the increase in palliative care referrals from clinical providers, compared with prepandemic levels. In addition, data collected showed that earlier palliative care consultations reduced length of hospital stay, decreased ICU admissions, and improved patient, family, and provider satisfaction.
Well-being of the workforce
The pandemic has been a tremendously stressful time for the health care workforce that has undoubtedly led to burnout. A nationwide study of physicians,8 found that 61% of physicians experienced burnout. This is a significant increase from prepandemic levels with impacts on mental health (that is, anxiety, depression). This study did not include palliative care specialists, but the CAPC survey indicates a similar feeling of burnout. Because of this, some palliative care specialists have left the field altogether, or are leaving leadership positions because of burnout and exhaustion from the pandemic. This was featured as a concern among palliative care leaders, where 93% reported concern for the emotional well-being of the palliative care team.
Telehealth
A permanent operational change that has been well-utilized and implemented across multiple health care settings has been providing palliative care through telehealth. Prior to the pandemic, the baseline use of telehealth was less than 5% with the use now greater than 75% – a modality that is favored by both patients and clinicians. This has offered a broader scope of practice, reaching individuals who may have no other means, have limitations to accessing palliative care, or were in circumstances where patients required isolation during the pandemic. However, there are limitations to this platform, including in equity of access to devices and ease of use for those with limited exposure to technology.9
Barriers to implementation
Although the important role and value of palliative care has been well recognized, there have been barriers identified in a qualitative study of the integration of palliative care into COVID-19 action plans that are mentioned below.5
- Patients and families were identified as barriers to integration of palliative care if they were not open to palliative care referral, mainly because of misperceptions of palliative care as end-of-life care.
- Palliative care knowledge among providers was identified as another barrier to integration of palliative care. There are still misperceptions among providers that palliative care is end-of-life care and palliative care involvement is stigmatized as hastening death. In addition, some felt that COVID-19 was not a traditional “palliative diagnosis” thus were less likely to integrate palliative care into care plans.
- Lack of availability of a primary provider to conduct primary palliative care and lack of motivation “not to give up” were identified as other barriers. On the other hand, palliative care provider availability and accessibility to care teams affected the integration into COVID-19 care plans.
- COVID-19 itself was identified to be a barrier because of the uncertainty of illness trajectory and outcomes, which made it difficult for doctors to ascertain when to involve palliative care.
- Leadership and institution were important factors to consider in integration of palliative care into long-term care plans, which depended on leadership engagement and institutional culture.
Takeaways
The past few years have taught us a lot, but there is still much to learn. The COVID-19 pandemic has called attention to the challenges and barriers of health care delivery and has magnified the needs of the health care system including its infrastructure, preparedness, and staffing, including the field of palliative care. More work needs to be done, but leaders have taken steps to initiate national and international preparedness plans including the integration of palliative care, which has been identified as a vital role in any humanitarian crises.10,11
Dr. Kang is a geriatrician and palliative care provider at the University of Washington, Seattle, in the division of geriatrics and gerontology. She has no conflicts related to the content of this article.
References
1. Palliative care. World Health Organization. Aug 5, 2020. https://www.who.int/news-room/fact-sheets/detail/palliative-care
2. World Health Organization. Integrating palliative care and symptom relief into the response to humanitarian emergencies and crises: A WHO guide. Geneva: World Health Organization, 2018. https://apps.who.int/iris/handle/10665/274565.
3. Hughes MT, Smith TJ. The growth of palliative care in the United States. Annual Review Public Health. 2014;35:459-75.
4. Pastrana T et al. The impact of COVID-19 on palliative care workers across the world: A qualitative analysis of responses to open-ended questions. Palliative and Supportive Care. 2021:1-6.
5. Wentlandt K et al. Identifying barriers and facilitators to palliative care integration in the management of hospitalized patients with COVID-19: A qualitative study. Palliat Med. 2022;36(6):945-54.
6. Rogers M et al. Palliative care leadership during the pandemic: Results from a recent survey. Center to Advance Palliative Care. 2022 Sept 8. https://www.capc.org/blog/palliative-care-leadership-during-the-pandemic-results-from-a-recent-survey
7. Fogelman P. Reflections form a palliative care program leader two years into the pandemic. Center to Advance Palliative Care. 2023 Jan 15. https://www.capc.org/blog/reflections-from-a-palliative-care-program-leader-two-years-into-the-pandemic
8. 2021 survey of America’s physicians Covid-19 impact edition: A year later. The Physicians Foundation. 2021.
9. Caraceni A et al. Telemedicine for outpatient palliative care during Covid-19 pandemics: A longitudinal study. BMJ Supportive & Palliative Care. 2022;0:1-7.
10. Bausewein C et al. National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany – study protocol of a mixed-methods project. BMC Palliative Care. 2022;21(10).
11. Powell RA et al. Palliative care in humanitarian crises: Always something to offer. The Lancet. 2017;389(10078):1498-9.
As we enter into this new year, it is a good time to review the past few years of living through a pandemic and the impact this has had on the field of palliative care.
According to the World Health Organization, “Palliative care is an approach that improves the quality of life of patients and their families who are facing the problems associated with life-threatening illness, by the prevention and relief of suffering through early identification, assessment and treatment of pain and other problems whether physical, psychosocial and spiritual.”1 They identify a global need and recognize palliative care as a “human right to health and as a standard of care particularly for individuals living with a serious illness.1 However, the WHO goes further to recognize palliative care as an essential part of the response team during crises and health emergencies like a pandemic, noting that a response team without palliative care is “medically deficient and ethically indefensible.”2
The need for palliative care in the United States is projected to grow significantly in the next decades.3 However, there has been insufficient staffing to meet these needs, even prior to the pandemic.4 The demand for palliative care reached further unprecedented levels during the pandemic as palliative care teams played an integral role and were well situated to support not only patients and families with COVID-19,5 but to also support the well-being of health care teams caring for COVID-19 patients.6,7
A recent survey that was conducted by the Center to Advance Palliative Care among palliative care leadership captured the experiences of leading their teams through a pandemic. Below are the results of this survey, which highlighted important issues and developments to palliative care during the pandemic.6
Increasing need for palliative care
One of the main findings from the national survey of palliative care leaders corroborated that the demands for palliative care have increased significantly from 2020 through the pandemic.
As with many areas in the health care system, the pandemic has emphasized the strain and short staffing of the palliative care teams. In the survey, 61% of leaders reported that palliative care consults significantly increased from prepandemic levels. But only 26% of these leaders said they had the staffing support to meet these needs.
Value of palliative care
The value of palliative care along with understanding of the role of palliative care has been better recognized during the pandemic and has been evidenced by the increase in palliative care referrals from clinical providers, compared with prepandemic levels. In addition, data collected showed that earlier palliative care consultations reduced length of hospital stay, decreased ICU admissions, and improved patient, family, and provider satisfaction.
Well-being of the workforce
The pandemic has been a tremendously stressful time for the health care workforce that has undoubtedly led to burnout. A nationwide study of physicians,8 found that 61% of physicians experienced burnout. This is a significant increase from prepandemic levels with impacts on mental health (that is, anxiety, depression). This study did not include palliative care specialists, but the CAPC survey indicates a similar feeling of burnout. Because of this, some palliative care specialists have left the field altogether, or are leaving leadership positions because of burnout and exhaustion from the pandemic. This was featured as a concern among palliative care leaders, where 93% reported concern for the emotional well-being of the palliative care team.
Telehealth
A permanent operational change that has been well-utilized and implemented across multiple health care settings has been providing palliative care through telehealth. Prior to the pandemic, the baseline use of telehealth was less than 5% with the use now greater than 75% – a modality that is favored by both patients and clinicians. This has offered a broader scope of practice, reaching individuals who may have no other means, have limitations to accessing palliative care, or were in circumstances where patients required isolation during the pandemic. However, there are limitations to this platform, including in equity of access to devices and ease of use for those with limited exposure to technology.9
Barriers to implementation
Although the important role and value of palliative care has been well recognized, there have been barriers identified in a qualitative study of the integration of palliative care into COVID-19 action plans that are mentioned below.5
- Patients and families were identified as barriers to integration of palliative care if they were not open to palliative care referral, mainly because of misperceptions of palliative care as end-of-life care.
- Palliative care knowledge among providers was identified as another barrier to integration of palliative care. There are still misperceptions among providers that palliative care is end-of-life care and palliative care involvement is stigmatized as hastening death. In addition, some felt that COVID-19 was not a traditional “palliative diagnosis” thus were less likely to integrate palliative care into care plans.
- Lack of availability of a primary provider to conduct primary palliative care and lack of motivation “not to give up” were identified as other barriers. On the other hand, palliative care provider availability and accessibility to care teams affected the integration into COVID-19 care plans.
- COVID-19 itself was identified to be a barrier because of the uncertainty of illness trajectory and outcomes, which made it difficult for doctors to ascertain when to involve palliative care.
- Leadership and institution were important factors to consider in integration of palliative care into long-term care plans, which depended on leadership engagement and institutional culture.
Takeaways
The past few years have taught us a lot, but there is still much to learn. The COVID-19 pandemic has called attention to the challenges and barriers of health care delivery and has magnified the needs of the health care system including its infrastructure, preparedness, and staffing, including the field of palliative care. More work needs to be done, but leaders have taken steps to initiate national and international preparedness plans including the integration of palliative care, which has been identified as a vital role in any humanitarian crises.10,11
Dr. Kang is a geriatrician and palliative care provider at the University of Washington, Seattle, in the division of geriatrics and gerontology. She has no conflicts related to the content of this article.
References
1. Palliative care. World Health Organization. Aug 5, 2020. https://www.who.int/news-room/fact-sheets/detail/palliative-care
2. World Health Organization. Integrating palliative care and symptom relief into the response to humanitarian emergencies and crises: A WHO guide. Geneva: World Health Organization, 2018. https://apps.who.int/iris/handle/10665/274565.
3. Hughes MT, Smith TJ. The growth of palliative care in the United States. Annual Review Public Health. 2014;35:459-75.
4. Pastrana T et al. The impact of COVID-19 on palliative care workers across the world: A qualitative analysis of responses to open-ended questions. Palliative and Supportive Care. 2021:1-6.
5. Wentlandt K et al. Identifying barriers and facilitators to palliative care integration in the management of hospitalized patients with COVID-19: A qualitative study. Palliat Med. 2022;36(6):945-54.
6. Rogers M et al. Palliative care leadership during the pandemic: Results from a recent survey. Center to Advance Palliative Care. 2022 Sept 8. https://www.capc.org/blog/palliative-care-leadership-during-the-pandemic-results-from-a-recent-survey
7. Fogelman P. Reflections form a palliative care program leader two years into the pandemic. Center to Advance Palliative Care. 2023 Jan 15. https://www.capc.org/blog/reflections-from-a-palliative-care-program-leader-two-years-into-the-pandemic
8. 2021 survey of America’s physicians Covid-19 impact edition: A year later. The Physicians Foundation. 2021.
9. Caraceni A et al. Telemedicine for outpatient palliative care during Covid-19 pandemics: A longitudinal study. BMJ Supportive & Palliative Care. 2022;0:1-7.
10. Bausewein C et al. National strategy for palliative care of severely ill and dying people and their relatives in pandemics (PallPan) in Germany – study protocol of a mixed-methods project. BMC Palliative Care. 2022;21(10).
11. Powell RA et al. Palliative care in humanitarian crises: Always something to offer. The Lancet. 2017;389(10078):1498-9.
‘Exciting’: Post-SCT, antiviral T-cell therapy shows promise
Of 58 adult and pediatric patients with a total of 70 viral infections at the time of enrollment in the open-label trial, 55 (95%) had a treatment response within 6 weeks of infusion with posoleucel, and the amount of circulating virus was reduced by an average of 97%, Thomas Pfeiffer, MD, and colleagues reported.
In 12 patients who had more than one viral infection, 10 (83%) had a response against each of the viruses, researchers noted.
The responses were defined as a reduction of viral load to normal range with complete response, or as a viral load reduction of at least 50 percent or a partial response.
The findings were published online in Clinical Cancer Research.
Specifically, the treatment evoked responses to adenovirus in 83% of 12 affected patients, BK virus in all 27 affected patients, CMV in 96% of 24 affected patients, Epstein-Barr virus in both affected patients, and human herpes virus in 75% of 4 patients. Additionally, one patient with JC virus experienced initial stabilization of viral symptoms, although the symptoms ultimately progressed, and the patient died.
“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of GvHD [graft-versus-host disease],” Dr. Pfeiffer, a pediatric cancer specialist at Washington University in St. Louis, explained in a prepared statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”
“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital and Baylor College of Medicine, Houston. “It was quite impressive how quickly patients could be treated.”
Dr. Omer explained that currently available treatments for patients who develop viral infections after allo-SCT have numerous limitations, including toxicities such as myelosuppression or kidney injury and limited efficacy.
In this study, 13 patients (22% percent) reported acute GvHD, but only 4 of the cases were considered de novo cases; 9 patients had been diagnosed with GvHD prior to posoleucel treatment. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases, Dr. Omer explained.
No patients experienced cytokine release syndrome.
“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” he said, adding that posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections.
Posoleucel utilizes healthy donor T cells rather than the patient’s or transplant donor’s T cells, which circumvents the lengthy development process of more customized therapies and allows for earlier treatment of viral infections, he noted.
The investigators are currently evaluating posoleucel in randomized phase 3 clinical trials to confirm these findings.
This study was supported by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/American Society for Clinical Oncology; the Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health.
Dr. Omer disclosed pending patent applications for engineered T-cell therapies unrelated to this study, and he has received research funding from AlloVir, which manufactures posoleucel. Dr. Pfeiffer declared no conflicts of interest.
Of 58 adult and pediatric patients with a total of 70 viral infections at the time of enrollment in the open-label trial, 55 (95%) had a treatment response within 6 weeks of infusion with posoleucel, and the amount of circulating virus was reduced by an average of 97%, Thomas Pfeiffer, MD, and colleagues reported.
In 12 patients who had more than one viral infection, 10 (83%) had a response against each of the viruses, researchers noted.
The responses were defined as a reduction of viral load to normal range with complete response, or as a viral load reduction of at least 50 percent or a partial response.
The findings were published online in Clinical Cancer Research.
Specifically, the treatment evoked responses to adenovirus in 83% of 12 affected patients, BK virus in all 27 affected patients, CMV in 96% of 24 affected patients, Epstein-Barr virus in both affected patients, and human herpes virus in 75% of 4 patients. Additionally, one patient with JC virus experienced initial stabilization of viral symptoms, although the symptoms ultimately progressed, and the patient died.
“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of GvHD [graft-versus-host disease],” Dr. Pfeiffer, a pediatric cancer specialist at Washington University in St. Louis, explained in a prepared statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”
“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital and Baylor College of Medicine, Houston. “It was quite impressive how quickly patients could be treated.”
Dr. Omer explained that currently available treatments for patients who develop viral infections after allo-SCT have numerous limitations, including toxicities such as myelosuppression or kidney injury and limited efficacy.
In this study, 13 patients (22% percent) reported acute GvHD, but only 4 of the cases were considered de novo cases; 9 patients had been diagnosed with GvHD prior to posoleucel treatment. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases, Dr. Omer explained.
No patients experienced cytokine release syndrome.
“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” he said, adding that posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections.
Posoleucel utilizes healthy donor T cells rather than the patient’s or transplant donor’s T cells, which circumvents the lengthy development process of more customized therapies and allows for earlier treatment of viral infections, he noted.
The investigators are currently evaluating posoleucel in randomized phase 3 clinical trials to confirm these findings.
This study was supported by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/American Society for Clinical Oncology; the Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health.
Dr. Omer disclosed pending patent applications for engineered T-cell therapies unrelated to this study, and he has received research funding from AlloVir, which manufactures posoleucel. Dr. Pfeiffer declared no conflicts of interest.
Of 58 adult and pediatric patients with a total of 70 viral infections at the time of enrollment in the open-label trial, 55 (95%) had a treatment response within 6 weeks of infusion with posoleucel, and the amount of circulating virus was reduced by an average of 97%, Thomas Pfeiffer, MD, and colleagues reported.
In 12 patients who had more than one viral infection, 10 (83%) had a response against each of the viruses, researchers noted.
The responses were defined as a reduction of viral load to normal range with complete response, or as a viral load reduction of at least 50 percent or a partial response.
The findings were published online in Clinical Cancer Research.
Specifically, the treatment evoked responses to adenovirus in 83% of 12 affected patients, BK virus in all 27 affected patients, CMV in 96% of 24 affected patients, Epstein-Barr virus in both affected patients, and human herpes virus in 75% of 4 patients. Additionally, one patient with JC virus experienced initial stabilization of viral symptoms, although the symptoms ultimately progressed, and the patient died.
“The key finding is that 95% of patients whose infections had been refractory to conventional therapies responded to posoleucel with corresponding reductions in viral load and with limited rates of GvHD [graft-versus-host disease],” Dr. Pfeiffer, a pediatric cancer specialist at Washington University in St. Louis, explained in a prepared statement. “Overall, posoleucel was found to be very effective and had a favorable safety profile in a highly vulnerable patient population.”
“Another exciting observation from this study was that posoleucel could be administered within 24 hours in some cases, with symptom resolution in a matter of days in some patients,” added senior author Bilal Omer, MD, a pediatric hematologist-oncologist at Texas Children’s Hospital and Baylor College of Medicine, Houston. “It was quite impressive how quickly patients could be treated.”
Dr. Omer explained that currently available treatments for patients who develop viral infections after allo-SCT have numerous limitations, including toxicities such as myelosuppression or kidney injury and limited efficacy.
In this study, 13 patients (22% percent) reported acute GvHD, but only 4 of the cases were considered de novo cases; 9 patients had been diagnosed with GvHD prior to posoleucel treatment. The most common GvHD symptoms were skin flares, which were successfully treated in the majority of cases, Dr. Omer explained.
No patients experienced cytokine release syndrome.
“The ability to target six viruses with a single therapy would be beneficial for patients with multiple viral infections,” he said, adding that posoleucel is the first T-cell therapy in development for BK virus, which can cause severe bladder infections.
Posoleucel utilizes healthy donor T cells rather than the patient’s or transplant donor’s T cells, which circumvents the lengthy development process of more customized therapies and allows for earlier treatment of viral infections, he noted.
The investigators are currently evaluating posoleucel in randomized phase 3 clinical trials to confirm these findings.
This study was supported by the National Heart, Lung, and Blood Institute Production Assistance for Cellular Therapies; Conquer Cancer Foundation/American Society for Clinical Oncology; the Dan L. Duncan Comprehensive Cancer Center; and the National Institutes of Health.
Dr. Omer disclosed pending patent applications for engineered T-cell therapies unrelated to this study, and he has received research funding from AlloVir, which manufactures posoleucel. Dr. Pfeiffer declared no conflicts of interest.
FROM CLINICAL CANCER RESEARCH
Frequent visits to green spaces linked to lower use of some meds
Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.
In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.
Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.
The growing scientific evidence supporting the health benefits of nature exposure is likely to increase the availability of high-quality green spaces in urban environments and promote the use of these spaces, lead author Anu W. Turunen, PhD, from the Finnish Institute for Health and Welfare, Kuopio, Finland, told this news organization.
This might be one way to improve health and well-being among city dwellers, Dr. Turunen added.
The findings were published online in Occupational and Environmental Medicine.
Nature exposure a timely topic
Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.
“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.
In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.
Of this number, 43% responded, resulting in 7,321 participants.
In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers.
Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.
They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”
They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.
In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.
Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.
Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.
However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.
For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.
For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.
For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.
The observed associations were attenuated by body mass index.
“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.
“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
Evidence mounts on the benefits of nature
There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.
Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.
In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.
Commenting on the current study, Dr. Klompmaker noted its strengths.
“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.
“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”
The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.
In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.
Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.
The growing scientific evidence supporting the health benefits of nature exposure is likely to increase the availability of high-quality green spaces in urban environments and promote the use of these spaces, lead author Anu W. Turunen, PhD, from the Finnish Institute for Health and Welfare, Kuopio, Finland, told this news organization.
This might be one way to improve health and well-being among city dwellers, Dr. Turunen added.
The findings were published online in Occupational and Environmental Medicine.
Nature exposure a timely topic
Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.
“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.
In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.
Of this number, 43% responded, resulting in 7,321 participants.
In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers.
Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.
They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”
They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.
In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.
Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.
Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.
However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.
For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.
For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.
For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.
The observed associations were attenuated by body mass index.
“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.
“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
Evidence mounts on the benefits of nature
There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.
Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.
In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.
Commenting on the current study, Dr. Klompmaker noted its strengths.
“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.
“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”
The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Frequent visits to green spaces such as parks and community gardens are associated with a reduced use of certain prescription medications among city dwellers, a new analysis suggests.
In a cross-sectional cohort study, frequent green space visits were associated with less frequent use of psychotropic, antihypertensive, and asthma medications in urban environments.
Viewing green or so called “blue” spaces (views of lakes, rivers, or other water views) from the home was not associated with reduced medication use.
The growing scientific evidence supporting the health benefits of nature exposure is likely to increase the availability of high-quality green spaces in urban environments and promote the use of these spaces, lead author Anu W. Turunen, PhD, from the Finnish Institute for Health and Welfare, Kuopio, Finland, told this news organization.
This might be one way to improve health and well-being among city dwellers, Dr. Turunen added.
The findings were published online in Occupational and Environmental Medicine.
Nature exposure a timely topic
Exposure to natural environments is thought to be beneficial for human health, but the evidence is inconsistent, Dr. Turunen said.
“The potential health benefits of nature exposure is a very timely topic in environmental epidemiology. Scientific evidence indicates that residential exposure to greenery and water bodies might be beneficial, especially for mental, cardiovascular, and respiratory health, but the findings are partly inconsistent and thus, more detailed information is needed,” she said.
In the current cross-sectional study, the investigators surveyed 16,000 residents of three urban areas in Finland – Helsinki, Espoo, and Vantaa – over the period of 12 months from 2015 to 2016, about their exposure to green and blue spaces.
Of this number, 43% responded, resulting in 7,321 participants.
In the questionnaire, green areas were defined as forests, parks, fields, meadows, boglands, and rocks, as well as any playgrounds or playing fields within those areas, and blue areas were defined as sea, lakes, and rivers.
Residents were asked about their use of anxiolytics, hypnotics, antidepressants, antihypertensives, and asthma medication within the past 7 to 52 weeks.
They were also asked if they had any green and blue views from any of the windows of their home, and if so, how often did they look out of those windows, selecting “seldom” to “often.”
They were also asked about how much time they spent outdoors in green spaces during the months of May and September. If so, did they spend any of that time exercising? Options ranged from never to five or more times a week.
In addition, amounts of residential green and blue spaces located within a 1 km radius of the respondents’ homes were assessed from land use and land cover data.
Covariates included health behaviors, outdoor air pollution and noise, and socioeconomic status, including household income and educational attainment.
Results showed that the presence of green and blue spaces at home, and the amount of time spent viewing them, had no association with the use of the prescribed medicines.
However, greater frequency of green space visits was associated with lower odds of using the medications surveyed.
For psychotropic medications, the odds ratios were 0.67 (95% confidence interval, 0.55-0.82) for 3-4 times per week and 0.78 (95% CI, 0.63-0.96) for 5 or more times per week.
For antihypertensive meds, the ORs were 0.64 (95% CI, 0.52-0.78) for 3-4 times per week and 0.59 (95% CI, 0.48-0.74) for 5 or more times per week.
For asthma medications, the ORs were 0.74 (95% CI, 0.58-0.94) for 3-4 times per week and 0.76 (95% CI, 0.59-0.99) for 5 or more times per week.
The observed associations were attenuated by body mass index.
“We observed that those who reported visiting green spaces often had a slightly lower BMI than those who visited green spaces less often,” Dr. Turunen said. However, no consistent interactions with socioeconomic status indicators were observed.
“We are hoping to see new results from different countries and different settings,” she noted. “Longitudinal studies, especially, are needed. In epidemiology, a large body of consistent evidence is needed to draw strong conclusions and to make recommendations.”
Evidence mounts on the benefits of nature
There is growing evidence that exposure to nature could benefit human health, especially mental and cardiovascular health, says Jochem Klompmaker, PhD, a postdoctoral researcher in the department of environmental health at the Harvard T.H. Chan School of Public Health, Boston.
Dr. Klompmaker has researched the association between exposure to green spaces and health outcomes related to neurological diseases.
In a study recently published in JAMA Network Open, and reported by this news organization, Dr. Klompmaker and his team found that among a large cohort of about 6.7 million fee-for-service Medicare beneficiaries in the United States aged 65 or older, living in areas rich with greenery, parks, and waterways was associated with fewer hospitalizations for certain neurological disorders, including Parkinson’s disease, Alzheimer’s disease, and related dementias.
Commenting on the current study, Dr. Klompmaker noted its strengths.
“A particular strength of this study is that they used data about the amount of green and blue spaces around the residential addresses of the participants, data about green space visit frequency, and data about green and blue views from home. Most other studies only have data about the amount of green and blue spaces in general,” he said.
“The strong protective associations of frequency of green space visits make sense to me and indicate the importance of one’s actual nature exposure,” he added. “Like the results of our study, these results provide clinicians with more evidence of the importance of being close to nature and of encouraging patients to take more walks. If they live near a park, that could be a good place to be more physically active and reduce stress levels.”
The study was supported by the Academy of Finland and the Ministry of the Environment. Dr. Turunen and Dr. Klompmaker report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Legacy ICDs exposed to MRI still shock, pace as needed
Functions like sensing and pacing in implantable cardioverter defibrillators (ICDs) tend to resist interference from the energy fields generated by MRI, as long as device programming is properly adjusted before the scan.
That applies even to patients with older “legacy” devices implanted before the 2015 advent of MRI-conditional ICDs despite, in practice, prevalent but misguided resistance to obtaining MRI scans in such cases.
Less is known whether such non–MRI-conditional devices, once exposed to MRI, will then reliably deliver antiarrhythmic shocks or antitachycardia pacing (ATP) when needed.
A new cohort study has tried to fill in some of that knowledge gap. It showed no evidence of an excess risk for death or ICD failure to deliver therapy within about 2 years of clinically indicated MRI scans in 629 patients with non–MRI-conditional devices.
The findings, published online in the Annals of Internal Medicine, come with caveats. For example, they’re based on the experience of one, albeit major, center and on MRIs that were for varied indications using 1.5-tesla equipment only.
Despite such safety evidence for appropriately adjusted non–MRI-conditional ICDs, many patients with the devices don›t receive clinically indicated MRI scans due to “perceived risk” that the ICDs won’t then reliably deliver appropriate therapy, observe the authors, led by Joshua Ra, MD, University of California, San Francisco.
Any such risks are “largely theoretical,” but may still explain “why some institutions are shying away from offering MRI exams” to patients with non–MRI-conditional ICDs, Dr. Ra told this news organization.
Many such hospitals refer such patients to more experienced centers, creating “significant logistical barriers in terms of patient access to these MRIs,” he said. “That seems to still be prevalent, unfortunately.”
The current findings “provide another layer of reassurance” that MRI scans in patients with non–MRI-conditional ICDs don’t impair a device’s ability to deliver shocks or ATP, Dr. Ra said.
The cohort consisted of 629 patients with non–MRI-conditional ICDs who underwent 813 clinically indicated MRI exams from 2003 to early 2015 at Johns Hopkins University, Baltimore.
Scans performed within 4 weeks of device implantation were excluded because, the report notes, that’s when spontaneous lead dislodgements or changes to device parameters are most likely to occur. Also excluded were patients with permanent epicardial leads, abandoned leads, or subcutaneous ICD lead systems, the report states.
Still, Dr. Ra said, the cohort is fairly representative of “the modern patient population” of non–MRI-conditional ICD recipients.
A total of 4,177 arrhythmia episodes were documented during a median 2.2 years between scans and last device interrogation prior to pulse-generator change-out or lead exchange.
Of note, Dr. Ra observed, the arrhythmias were confirmed in only 85% of the cohort. Most of the remainder were referral patients who were lost to follow-up whose devices were unavailable for interrogation.
Device therapy terminated “nearly all” documented spontaneous arrhythmias in that 85% of patients, the report states. They included 757 episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF), including 130 that were shocked and the remainder that were managed with ATP. There were also 105 supraventricular tachycardias, all successfully terminated with shocks.
There were no cases of VT or VF detection delay from undersensing or instances of syncope because of “abnormalities” in device detection of arrhythmias, the report states.
Of the 210 known deaths, which occurred a median 1.7 years after the scan, about half were noncardiac and more than a third were cardiac but nonarrhythmic.
Ten patients died from arrhythmia-related cardiac causes, representing 5% of deaths; but 7% of deaths were of undetermined cause.
“No direct relationship of deaths attributable to prior MRI exposure was found or reported,” the report states.
The researchers informally compared outcomes between older and more recently implanted non–MRI-conditional ICDs, the latter presumably with more modern design features. Their data, based on device interrogations, Dr. Ra said, “seem to suggest there were no differences.”
The study was supported by Johns Hopkins University and the National Institutes of Health. Author disclosures are available at apconline.org.
A version of this article first appeared on Medscape.com.
Functions like sensing and pacing in implantable cardioverter defibrillators (ICDs) tend to resist interference from the energy fields generated by MRI, as long as device programming is properly adjusted before the scan.
That applies even to patients with older “legacy” devices implanted before the 2015 advent of MRI-conditional ICDs despite, in practice, prevalent but misguided resistance to obtaining MRI scans in such cases.
Less is known whether such non–MRI-conditional devices, once exposed to MRI, will then reliably deliver antiarrhythmic shocks or antitachycardia pacing (ATP) when needed.
A new cohort study has tried to fill in some of that knowledge gap. It showed no evidence of an excess risk for death or ICD failure to deliver therapy within about 2 years of clinically indicated MRI scans in 629 patients with non–MRI-conditional devices.
The findings, published online in the Annals of Internal Medicine, come with caveats. For example, they’re based on the experience of one, albeit major, center and on MRIs that were for varied indications using 1.5-tesla equipment only.
Despite such safety evidence for appropriately adjusted non–MRI-conditional ICDs, many patients with the devices don›t receive clinically indicated MRI scans due to “perceived risk” that the ICDs won’t then reliably deliver appropriate therapy, observe the authors, led by Joshua Ra, MD, University of California, San Francisco.
Any such risks are “largely theoretical,” but may still explain “why some institutions are shying away from offering MRI exams” to patients with non–MRI-conditional ICDs, Dr. Ra told this news organization.
Many such hospitals refer such patients to more experienced centers, creating “significant logistical barriers in terms of patient access to these MRIs,” he said. “That seems to still be prevalent, unfortunately.”
The current findings “provide another layer of reassurance” that MRI scans in patients with non–MRI-conditional ICDs don’t impair a device’s ability to deliver shocks or ATP, Dr. Ra said.
The cohort consisted of 629 patients with non–MRI-conditional ICDs who underwent 813 clinically indicated MRI exams from 2003 to early 2015 at Johns Hopkins University, Baltimore.
Scans performed within 4 weeks of device implantation were excluded because, the report notes, that’s when spontaneous lead dislodgements or changes to device parameters are most likely to occur. Also excluded were patients with permanent epicardial leads, abandoned leads, or subcutaneous ICD lead systems, the report states.
Still, Dr. Ra said, the cohort is fairly representative of “the modern patient population” of non–MRI-conditional ICD recipients.
A total of 4,177 arrhythmia episodes were documented during a median 2.2 years between scans and last device interrogation prior to pulse-generator change-out or lead exchange.
Of note, Dr. Ra observed, the arrhythmias were confirmed in only 85% of the cohort. Most of the remainder were referral patients who were lost to follow-up whose devices were unavailable for interrogation.
Device therapy terminated “nearly all” documented spontaneous arrhythmias in that 85% of patients, the report states. They included 757 episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF), including 130 that were shocked and the remainder that were managed with ATP. There were also 105 supraventricular tachycardias, all successfully terminated with shocks.
There were no cases of VT or VF detection delay from undersensing or instances of syncope because of “abnormalities” in device detection of arrhythmias, the report states.
Of the 210 known deaths, which occurred a median 1.7 years after the scan, about half were noncardiac and more than a third were cardiac but nonarrhythmic.
Ten patients died from arrhythmia-related cardiac causes, representing 5% of deaths; but 7% of deaths were of undetermined cause.
“No direct relationship of deaths attributable to prior MRI exposure was found or reported,” the report states.
The researchers informally compared outcomes between older and more recently implanted non–MRI-conditional ICDs, the latter presumably with more modern design features. Their data, based on device interrogations, Dr. Ra said, “seem to suggest there were no differences.”
The study was supported by Johns Hopkins University and the National Institutes of Health. Author disclosures are available at apconline.org.
A version of this article first appeared on Medscape.com.
Functions like sensing and pacing in implantable cardioverter defibrillators (ICDs) tend to resist interference from the energy fields generated by MRI, as long as device programming is properly adjusted before the scan.
That applies even to patients with older “legacy” devices implanted before the 2015 advent of MRI-conditional ICDs despite, in practice, prevalent but misguided resistance to obtaining MRI scans in such cases.
Less is known whether such non–MRI-conditional devices, once exposed to MRI, will then reliably deliver antiarrhythmic shocks or antitachycardia pacing (ATP) when needed.
A new cohort study has tried to fill in some of that knowledge gap. It showed no evidence of an excess risk for death or ICD failure to deliver therapy within about 2 years of clinically indicated MRI scans in 629 patients with non–MRI-conditional devices.
The findings, published online in the Annals of Internal Medicine, come with caveats. For example, they’re based on the experience of one, albeit major, center and on MRIs that were for varied indications using 1.5-tesla equipment only.
Despite such safety evidence for appropriately adjusted non–MRI-conditional ICDs, many patients with the devices don›t receive clinically indicated MRI scans due to “perceived risk” that the ICDs won’t then reliably deliver appropriate therapy, observe the authors, led by Joshua Ra, MD, University of California, San Francisco.
Any such risks are “largely theoretical,” but may still explain “why some institutions are shying away from offering MRI exams” to patients with non–MRI-conditional ICDs, Dr. Ra told this news organization.
Many such hospitals refer such patients to more experienced centers, creating “significant logistical barriers in terms of patient access to these MRIs,” he said. “That seems to still be prevalent, unfortunately.”
The current findings “provide another layer of reassurance” that MRI scans in patients with non–MRI-conditional ICDs don’t impair a device’s ability to deliver shocks or ATP, Dr. Ra said.
The cohort consisted of 629 patients with non–MRI-conditional ICDs who underwent 813 clinically indicated MRI exams from 2003 to early 2015 at Johns Hopkins University, Baltimore.
Scans performed within 4 weeks of device implantation were excluded because, the report notes, that’s when spontaneous lead dislodgements or changes to device parameters are most likely to occur. Also excluded were patients with permanent epicardial leads, abandoned leads, or subcutaneous ICD lead systems, the report states.
Still, Dr. Ra said, the cohort is fairly representative of “the modern patient population” of non–MRI-conditional ICD recipients.
A total of 4,177 arrhythmia episodes were documented during a median 2.2 years between scans and last device interrogation prior to pulse-generator change-out or lead exchange.
Of note, Dr. Ra observed, the arrhythmias were confirmed in only 85% of the cohort. Most of the remainder were referral patients who were lost to follow-up whose devices were unavailable for interrogation.
Device therapy terminated “nearly all” documented spontaneous arrhythmias in that 85% of patients, the report states. They included 757 episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF), including 130 that were shocked and the remainder that were managed with ATP. There were also 105 supraventricular tachycardias, all successfully terminated with shocks.
There were no cases of VT or VF detection delay from undersensing or instances of syncope because of “abnormalities” in device detection of arrhythmias, the report states.
Of the 210 known deaths, which occurred a median 1.7 years after the scan, about half were noncardiac and more than a third were cardiac but nonarrhythmic.
Ten patients died from arrhythmia-related cardiac causes, representing 5% of deaths; but 7% of deaths were of undetermined cause.
“No direct relationship of deaths attributable to prior MRI exposure was found or reported,” the report states.
The researchers informally compared outcomes between older and more recently implanted non–MRI-conditional ICDs, the latter presumably with more modern design features. Their data, based on device interrogations, Dr. Ra said, “seem to suggest there were no differences.”
The study was supported by Johns Hopkins University and the National Institutes of Health. Author disclosures are available at apconline.org.
A version of this article first appeared on Medscape.com.
AGA’s GI Opportunity Fund invests in EndoSound®
EndoSound is an Oregon-based medical device innovator developing technology that enhances access, reduces costs, and increases the safety of endoscopic ultrasound (EUS) procedures.
The EndoSound Vision System® (EVS®) is a disruptive EUS platform. Its attachable transducer and supportive components transform a conventional upper endoscope into a fully functional endoscopic ultrasound device. The cost of existing EUS systems has limited the availability of this crucial modality in the United States and around the world.
By reducing this cost, the EVS will provide physicians with a technological option that can enable care for their patients in a greater number of locations and settings. This brings the potential for enormous benefits to patients, payers, and providers by reducing costs in the healthcare system.
EndoSound is an Oregon-based medical device innovator developing technology that enhances access, reduces costs, and increases the safety of endoscopic ultrasound (EUS) procedures.
The EndoSound Vision System® (EVS®) is a disruptive EUS platform. Its attachable transducer and supportive components transform a conventional upper endoscope into a fully functional endoscopic ultrasound device. The cost of existing EUS systems has limited the availability of this crucial modality in the United States and around the world.
By reducing this cost, the EVS will provide physicians with a technological option that can enable care for their patients in a greater number of locations and settings. This brings the potential for enormous benefits to patients, payers, and providers by reducing costs in the healthcare system.
EndoSound is an Oregon-based medical device innovator developing technology that enhances access, reduces costs, and increases the safety of endoscopic ultrasound (EUS) procedures.
The EndoSound Vision System® (EVS®) is a disruptive EUS platform. Its attachable transducer and supportive components transform a conventional upper endoscope into a fully functional endoscopic ultrasound device. The cost of existing EUS systems has limited the availability of this crucial modality in the United States and around the world.
By reducing this cost, the EVS will provide physicians with a technological option that can enable care for their patients in a greater number of locations and settings. This brings the potential for enormous benefits to patients, payers, and providers by reducing costs in the healthcare system.
The new blood pressure target in primary care
This transcript has been edited for clarity.
I’m Dr. Neil Skolnik. There are very few things that we treat more often than hypertension, so you’d think the guidelines would have been clear a long time ago. Less than 10 years ago, in 2014, JNC 8 (Eighth Joint National Committee) recommended target blood pressure for individuals under 60 to be less than 140/90, and for those older than 60, less than 150/90.
Then, based primarily on the SPRINT trial (which included only people with or at significantly elevated risk for atherosclerotic cardiovascular disease), in 2017 the American Heart Association’s hypertension guidelines lowered the target BP to less than 130/80 for most individuals. It’s a little more nuanced than that, but most of us don’t remember the nuance. I’ve written about my reservations with that statement in the AHA’s journal, Circulation.
Now the American Academy of Family Physicians has updated its recommendations, and they recommend a BP less than 140/90. This is not a small change, as it often takes additional medication to achieve lower BP targets, and additional medicines lead to additional adverse effects. I’m going share with you some details from the new guideline, and then I’m going share my opinion about it.
The AAFP guideline applies to adults with hypertension, with or without cardiovascular disease. In the comprehensive literature review, the trials ran for an average of 3.7 years, and about 75% of the patients in the trials did not have preexisting cardiovascular disease.
The key to their recommendations is that target BPs lower than 140/90 did not show a statistically significant decrease in total mortality. In regard to serious adverse events, though, lower targets led to a nominal increase that didn’t reach statistical significance. Serious adverse events were defined as death or events that required hospitalization or resulted in significant disability. In regard to all other adverse events, including syncope and hypotension, there was a significant increase, with a relative risk of 1.44 (a 44% increase in adverse events). This reflected an absolute risk increase of 3%, compared with the standard target group (specifically 9.8% vs. 6.8%), with a number needed to harm of 33 over 3.7 years.
Another potential harm of low BP targets was the need for an average of one additional medicine to reach lower BP targets. One systematic review cited an eightfold higher withdrawal rate because of adverse events in the lower-target BP groups.
The AAFP guidelines said that, in the comprehensive review of the literature, while there was no difference in mortality or stroke with lower BP targets, a small additional benefit was observed in myocardial infarction – a 16% lower incidence, with a number needed to treat of 137 over 3.7 years.
So that’s the background. Let me now go over the specifics of the AAFP recommendations.
AAFP gives a strong recommendation for a standard BP target of less than 140/90. They go on to say – and grade this next statement as a weak recommendation – that, while treating to a lower BP target does not provide additional mortality benefit, a target BP of less than 135/85 can be considered to lower the risk for MI, noting that lower BP may increase harms. They state that the lower BP target could be considered based on patient preferences and values.
The AAFP guideline is incredibly helpful. The difference in the recommendations of two large societies – American Heart Association and AAFP — stems from two things. I believe that AHA focused on the composite endpoints in trials such as SPRINT, which included only high-risk patients, and the AAFP uses mortality as the driving endpoint in a broader group of patients that included both high- and lower-risk patients.
In addition, it appears that the two organizations weigh adverse events differently in coming to their conclusions. Clearly, we see more adverse events when aiming for a lower BP level, and in my experience, patients care a lot about adverse events.
Interestingly, the International Society of Hypertension recommends an “essential” BP target of less than 140/90 for most individuals, and for those under 65, they provide the option of an “optimal” BP of less than 130/80. Remember that for certain comorbidities there are also other guidelines out there. The American Diabetes Association this year revised its target BP to less than 130/80 for people with diabetes; for prevention of recurrent stroke, guidelines from the AHA/American Stroke Association in 2021 recommend BP less than 130/80, and the International Society for Hypertension as well as the AHA recommends a BP of less than 130/80 for those with established atherosclerotic cardiovascular disease.
To repeat, though, the main topic for today is that as a general target, the AAFP guidelines recommend a BP less than 140/90.
Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He disclosed conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article first appeared on Medscape.com.
*This article was updated on 2/7/2023.
This transcript has been edited for clarity.
I’m Dr. Neil Skolnik. There are very few things that we treat more often than hypertension, so you’d think the guidelines would have been clear a long time ago. Less than 10 years ago, in 2014, JNC 8 (Eighth Joint National Committee) recommended target blood pressure for individuals under 60 to be less than 140/90, and for those older than 60, less than 150/90.
Then, based primarily on the SPRINT trial (which included only people with or at significantly elevated risk for atherosclerotic cardiovascular disease), in 2017 the American Heart Association’s hypertension guidelines lowered the target BP to less than 130/80 for most individuals. It’s a little more nuanced than that, but most of us don’t remember the nuance. I’ve written about my reservations with that statement in the AHA’s journal, Circulation.
Now the American Academy of Family Physicians has updated its recommendations, and they recommend a BP less than 140/90. This is not a small change, as it often takes additional medication to achieve lower BP targets, and additional medicines lead to additional adverse effects. I’m going share with you some details from the new guideline, and then I’m going share my opinion about it.
The AAFP guideline applies to adults with hypertension, with or without cardiovascular disease. In the comprehensive literature review, the trials ran for an average of 3.7 years, and about 75% of the patients in the trials did not have preexisting cardiovascular disease.
The key to their recommendations is that target BPs lower than 140/90 did not show a statistically significant decrease in total mortality. In regard to serious adverse events, though, lower targets led to a nominal increase that didn’t reach statistical significance. Serious adverse events were defined as death or events that required hospitalization or resulted in significant disability. In regard to all other adverse events, including syncope and hypotension, there was a significant increase, with a relative risk of 1.44 (a 44% increase in adverse events). This reflected an absolute risk increase of 3%, compared with the standard target group (specifically 9.8% vs. 6.8%), with a number needed to harm of 33 over 3.7 years.
Another potential harm of low BP targets was the need for an average of one additional medicine to reach lower BP targets. One systematic review cited an eightfold higher withdrawal rate because of adverse events in the lower-target BP groups.
The AAFP guidelines said that, in the comprehensive review of the literature, while there was no difference in mortality or stroke with lower BP targets, a small additional benefit was observed in myocardial infarction – a 16% lower incidence, with a number needed to treat of 137 over 3.7 years.
So that’s the background. Let me now go over the specifics of the AAFP recommendations.
AAFP gives a strong recommendation for a standard BP target of less than 140/90. They go on to say – and grade this next statement as a weak recommendation – that, while treating to a lower BP target does not provide additional mortality benefit, a target BP of less than 135/85 can be considered to lower the risk for MI, noting that lower BP may increase harms. They state that the lower BP target could be considered based on patient preferences and values.
The AAFP guideline is incredibly helpful. The difference in the recommendations of two large societies – American Heart Association and AAFP — stems from two things. I believe that AHA focused on the composite endpoints in trials such as SPRINT, which included only high-risk patients, and the AAFP uses mortality as the driving endpoint in a broader group of patients that included both high- and lower-risk patients.
In addition, it appears that the two organizations weigh adverse events differently in coming to their conclusions. Clearly, we see more adverse events when aiming for a lower BP level, and in my experience, patients care a lot about adverse events.
Interestingly, the International Society of Hypertension recommends an “essential” BP target of less than 140/90 for most individuals, and for those under 65, they provide the option of an “optimal” BP of less than 130/80. Remember that for certain comorbidities there are also other guidelines out there. The American Diabetes Association this year revised its target BP to less than 130/80 for people with diabetes; for prevention of recurrent stroke, guidelines from the AHA/American Stroke Association in 2021 recommend BP less than 130/80, and the International Society for Hypertension as well as the AHA recommends a BP of less than 130/80 for those with established atherosclerotic cardiovascular disease.
To repeat, though, the main topic for today is that as a general target, the AAFP guidelines recommend a BP less than 140/90.
Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He disclosed conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article first appeared on Medscape.com.
*This article was updated on 2/7/2023.
This transcript has been edited for clarity.
I’m Dr. Neil Skolnik. There are very few things that we treat more often than hypertension, so you’d think the guidelines would have been clear a long time ago. Less than 10 years ago, in 2014, JNC 8 (Eighth Joint National Committee) recommended target blood pressure for individuals under 60 to be less than 140/90, and for those older than 60, less than 150/90.
Then, based primarily on the SPRINT trial (which included only people with or at significantly elevated risk for atherosclerotic cardiovascular disease), in 2017 the American Heart Association’s hypertension guidelines lowered the target BP to less than 130/80 for most individuals. It’s a little more nuanced than that, but most of us don’t remember the nuance. I’ve written about my reservations with that statement in the AHA’s journal, Circulation.
Now the American Academy of Family Physicians has updated its recommendations, and they recommend a BP less than 140/90. This is not a small change, as it often takes additional medication to achieve lower BP targets, and additional medicines lead to additional adverse effects. I’m going share with you some details from the new guideline, and then I’m going share my opinion about it.
The AAFP guideline applies to adults with hypertension, with or without cardiovascular disease. In the comprehensive literature review, the trials ran for an average of 3.7 years, and about 75% of the patients in the trials did not have preexisting cardiovascular disease.
The key to their recommendations is that target BPs lower than 140/90 did not show a statistically significant decrease in total mortality. In regard to serious adverse events, though, lower targets led to a nominal increase that didn’t reach statistical significance. Serious adverse events were defined as death or events that required hospitalization or resulted in significant disability. In regard to all other adverse events, including syncope and hypotension, there was a significant increase, with a relative risk of 1.44 (a 44% increase in adverse events). This reflected an absolute risk increase of 3%, compared with the standard target group (specifically 9.8% vs. 6.8%), with a number needed to harm of 33 over 3.7 years.
Another potential harm of low BP targets was the need for an average of one additional medicine to reach lower BP targets. One systematic review cited an eightfold higher withdrawal rate because of adverse events in the lower-target BP groups.
The AAFP guidelines said that, in the comprehensive review of the literature, while there was no difference in mortality or stroke with lower BP targets, a small additional benefit was observed in myocardial infarction – a 16% lower incidence, with a number needed to treat of 137 over 3.7 years.
So that’s the background. Let me now go over the specifics of the AAFP recommendations.
AAFP gives a strong recommendation for a standard BP target of less than 140/90. They go on to say – and grade this next statement as a weak recommendation – that, while treating to a lower BP target does not provide additional mortality benefit, a target BP of less than 135/85 can be considered to lower the risk for MI, noting that lower BP may increase harms. They state that the lower BP target could be considered based on patient preferences and values.
The AAFP guideline is incredibly helpful. The difference in the recommendations of two large societies – American Heart Association and AAFP — stems from two things. I believe that AHA focused on the composite endpoints in trials such as SPRINT, which included only high-risk patients, and the AAFP uses mortality as the driving endpoint in a broader group of patients that included both high- and lower-risk patients.
In addition, it appears that the two organizations weigh adverse events differently in coming to their conclusions. Clearly, we see more adverse events when aiming for a lower BP level, and in my experience, patients care a lot about adverse events.
Interestingly, the International Society of Hypertension recommends an “essential” BP target of less than 140/90 for most individuals, and for those under 65, they provide the option of an “optimal” BP of less than 130/80. Remember that for certain comorbidities there are also other guidelines out there. The American Diabetes Association this year revised its target BP to less than 130/80 for people with diabetes; for prevention of recurrent stroke, guidelines from the AHA/American Stroke Association in 2021 recommend BP less than 130/80, and the International Society for Hypertension as well as the AHA recommends a BP of less than 130/80 for those with established atherosclerotic cardiovascular disease.
To repeat, though, the main topic for today is that as a general target, the AAFP guidelines recommend a BP less than 140/90.
Dr. Skolnik is professor, department of family medicine, Sidney Kimmel Medical College, Philadelphia, and associate director, department of family medicine, Abington (Pa.) Jefferson Health. He disclosed conflicts of interest with AstraZeneca, Teva, Eli Lilly, Boehringer Ingelheim, Sanofi, Sanofi Pasteur, GlaxoSmithKline, Merck, and Bayer.
A version of this article first appeared on Medscape.com.
*This article was updated on 2/7/2023.