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Gut microbiome dysregulation implicated in OCD
SAN FRANCISCO – Patients with obsessive-compulsive disorder have a gut bacterial microbiome marked by diminished species diversity and abundance, compared with that of healthy controls, according to the first study to examine the issue.
Results of this pilot study also suggest that OCD patients with tic disorder have a distinctly different gut microbiome, compared with other OCD patients, Jasmine Turna said at the annual conference of the Anxiety and Depression Association of America.
She reported on 11 OCD patients and 12 healthy controls who underwent gut microbiome analysis using DNA extracted from their morning stool samples. Results from another nine OCD patients and 10 controls remained pending at the time of the conference but will be completed shortly.
In addition to the decreased abundance and diversity of bacteria present in the microbiomes of the OCD patients, compared with controls, another key finding was that the OCD patients had increased levels of systemic inflammation. Their mean level of high-sensitivity C-reactive protein was 3.03 mg/L, compared with 1.1 mg/L in the controls. In addition, the microbiome in those OCD patients who had elevated systemic inflammation as defined by a CRP level greater than 2.0 mg/L was more restricted than was that of OCD patients with a normal-range CRP.
In an interview, Ms. Turna noted that a cross-sectional study such as this is hypothesis generating and not definitive. Even if these findings are replicated, that will not answer the key question of whether the altered microbiome present in OCD patients is a contributing cause or a consequence of the psychiatric disorder. But she and her coinvestigators already have launched a prospective randomized controlled trial that attempts to address this question by having a group of OCD patients regularly consume a probiotic in an effort to diversify their gut microbiome.
“Maybe getting more fermented foods into the diet – kimchi, miso, yogurt, kefir – could be an adjunctive therapy,” she said. “Right now, OCD research is kind of at a standstill. Our treatments work in a lot of people, but they also don’t work in a lot of people. Our research opens up a new place to explore.”
Ms. Turna reported having no financial conflicts.
SAN FRANCISCO – Patients with obsessive-compulsive disorder have a gut bacterial microbiome marked by diminished species diversity and abundance, compared with that of healthy controls, according to the first study to examine the issue.
Results of this pilot study also suggest that OCD patients with tic disorder have a distinctly different gut microbiome, compared with other OCD patients, Jasmine Turna said at the annual conference of the Anxiety and Depression Association of America.
She reported on 11 OCD patients and 12 healthy controls who underwent gut microbiome analysis using DNA extracted from their morning stool samples. Results from another nine OCD patients and 10 controls remained pending at the time of the conference but will be completed shortly.
In addition to the decreased abundance and diversity of bacteria present in the microbiomes of the OCD patients, compared with controls, another key finding was that the OCD patients had increased levels of systemic inflammation. Their mean level of high-sensitivity C-reactive protein was 3.03 mg/L, compared with 1.1 mg/L in the controls. In addition, the microbiome in those OCD patients who had elevated systemic inflammation as defined by a CRP level greater than 2.0 mg/L was more restricted than was that of OCD patients with a normal-range CRP.
In an interview, Ms. Turna noted that a cross-sectional study such as this is hypothesis generating and not definitive. Even if these findings are replicated, that will not answer the key question of whether the altered microbiome present in OCD patients is a contributing cause or a consequence of the psychiatric disorder. But she and her coinvestigators already have launched a prospective randomized controlled trial that attempts to address this question by having a group of OCD patients regularly consume a probiotic in an effort to diversify their gut microbiome.
“Maybe getting more fermented foods into the diet – kimchi, miso, yogurt, kefir – could be an adjunctive therapy,” she said. “Right now, OCD research is kind of at a standstill. Our treatments work in a lot of people, but they also don’t work in a lot of people. Our research opens up a new place to explore.”
Ms. Turna reported having no financial conflicts.
SAN FRANCISCO – Patients with obsessive-compulsive disorder have a gut bacterial microbiome marked by diminished species diversity and abundance, compared with that of healthy controls, according to the first study to examine the issue.
Results of this pilot study also suggest that OCD patients with tic disorder have a distinctly different gut microbiome, compared with other OCD patients, Jasmine Turna said at the annual conference of the Anxiety and Depression Association of America.
She reported on 11 OCD patients and 12 healthy controls who underwent gut microbiome analysis using DNA extracted from their morning stool samples. Results from another nine OCD patients and 10 controls remained pending at the time of the conference but will be completed shortly.
In addition to the decreased abundance and diversity of bacteria present in the microbiomes of the OCD patients, compared with controls, another key finding was that the OCD patients had increased levels of systemic inflammation. Their mean level of high-sensitivity C-reactive protein was 3.03 mg/L, compared with 1.1 mg/L in the controls. In addition, the microbiome in those OCD patients who had elevated systemic inflammation as defined by a CRP level greater than 2.0 mg/L was more restricted than was that of OCD patients with a normal-range CRP.
In an interview, Ms. Turna noted that a cross-sectional study such as this is hypothesis generating and not definitive. Even if these findings are replicated, that will not answer the key question of whether the altered microbiome present in OCD patients is a contributing cause or a consequence of the psychiatric disorder. But she and her coinvestigators already have launched a prospective randomized controlled trial that attempts to address this question by having a group of OCD patients regularly consume a probiotic in an effort to diversify their gut microbiome.
“Maybe getting more fermented foods into the diet – kimchi, miso, yogurt, kefir – could be an adjunctive therapy,” she said. “Right now, OCD research is kind of at a standstill. Our treatments work in a lot of people, but they also don’t work in a lot of people. Our research opens up a new place to explore.”
Ms. Turna reported having no financial conflicts.
AT ANXIETY AND DEPRESSION CONFERENCE 2017
Key clinical point:
Major finding: Patients with obsessive-compulsive disorder have a gut bacterial microbiome that is distinctly different from healthy controls, with less abundance and species diversity.
Data source: This study analyzed DNA extracted from morning stool samples to map the gut microbiomes of 11 patients with obsessive-compulsive disorder and 12 healthy controls.
Disclosures: The study presenter reported having no financial conflicts.
Know your new hyaluronic acid–based fillers
WAILEA, HAWAII – American dermatologists are now gaining access to a lot of new hyaluronic acid-based fillers, designed to address limitations in the older, tried-and-true product lines, according to Nowell Solish, MD.
These products have been available in Canada for years. Dr. Solish, a dermatologist at the University of Toronto, shared insights regarding their optimal use, based on his extensive experience with them.
Allergan’s earlier Juvéderm Ultra range of dermal fillers is based on Hylacross, which utilizes crosslinked high–molecular weight HA.
“These products have been around a long time and have lots of benefits, but there were definitely some things missing in the product line,” he explained. “We wanted more control of gel swelling – that is, how much water the hyaluronic acid takes up.”
The Vycross technology employs a proprietary mix of low– and high–molecular weight HA, which results in a highly crosslinked gel that’s moldable immediately after injection, displays minimal gel swelling, and is designed to last longer than earlier-generation fillers.
The main difference between the three products lies in their HA concentrations: Juvéderm Voluma XC has the highest concentration of HA and Juvéderm Volbella XC the lowest, with Volift in between.
The company claims that outcomes with Volbella and Volift last up to 12 months, while Voluma outcomes lasts for up to 24 months. Dr. Solish suggested that his American colleagues take that with a grain of salt.
“I would say I always underpromise and overdeliver with my patients,” he noted. “I think you can probably detect Voluma at 2 years, but, the question is, how good is the effect? How happy is the patient? I think 2 years is a little bit of a stretch. I think it lasts for about 9 months to a year before reinjection.”
Voluma has been available in the United States for several years, while Dr. Solish has been using it far longer. His impression is that Voluma is great for creating volume, especially in the cheeks, midface, and submalar area. He finds that he gets his best results by implanting the product in a series of small, 0.2-mL, tent-like boluses. The reinjection volume is typically substantially less than that employed in initial treatment.
Volbella received approval from the FDA in autumn 2016 for perioral injection and is just now reaching the U.S. marketplace.
“In my humble opinion, I don’t think Volbella is really good for volume,” he explained. “I think it’s great for what I call lip hydration, to give that lip a lipstick look. Where I find that I use this product the most is for the perioral rhytids – the vertical lip lines people sometimes call smokers’ lines. I implant it in the lip mucosa to straighten out the folds.”
Dr. Solish cautioned that Volbella is a fast-flowing product.
“The thing you have to be careful about with Volbella is it has a very low extrusion force,” he noted. “That means it’s very easy to unload the syringe and get too much product out. And there’s no question that there’s a direct correlation between speed of injection and adverse events, mainly edema. So, just remember to slow your hand down, or off-label to add a 31- or even 32-gauge needle to the syringe.”
Volift is not yet approved in the United States, but it’s coming. Dr. Solish called it “a good workhorse product” for mild-to-moderate lines around the face.
“Sales will be much higher than for Volbella, because Volift is great for the in-between things,” the dermatologist continued. “You have Voluma for volume on the midface and cheeks, but Volift is great for nasolabial folds and, especially, for marionette lines and smile lines, where you don’t want a lot of bulk.”
The main adverse event encountered with any of the three products is delayed-onset development of nonpainful inflammatory nodules arising 3-6 months post injection. In one Canadian study, the incidence was less than 0.5% (Dermatol Surg. 2015 Sep;41[9]:1060-7).
Dr. Solish recommended treating the nodules with weekly or biweekly intralesional injections of hyaluronidase, followed by intralesional injections of 0.1 mL/cm2 of triamcinolone (Kenalog) at 2.5 mg/mL to 5.0 mg/mL.
Turning to Galderma’s NASHA technology, Dr. Solish explained that it relies on naturally occurring entanglement of HA chains to create gel particles formulated at 20 mg/dL. By varying the gel particle size and the amount of crosslinking, the company has created a series of products with different properties.
Restylane Refyne features smaller-size particles and less crosslinking, which makes for a softer gel. It’s an excellent option for marionette lines, mild nasolabial folds, and small perioral lines, and “it’s my absolute go-to for tear troughs,” Dr. Solish said.
In contrast, Restylane Defyne has bigger gel particles and more extensive HA crosslinking. It is firmer than Refyne and is best suited for achieving lift and volume. He implants it in the cheeks, forehead, temples, and deeper nasolabial folds.
In addition to these two products, which are new to the United States, Galderma has rebranded Perlane as Restylane Lyft, approved for midfacial augmentation. Another product, Restylane Silk, is similar to Volbella in that it is fast-flowing and not a big volumizer. Dr. Solish called it “lipstick in a syringe,” best suited for improving definition of the lips and for addressing perioral fine lines.
Dr. Solish reported serving as an investigator and/or consultant for Allergan, Galderma, Indeed, Merz, Revance Therapeutics, and Valeant. The SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – American dermatologists are now gaining access to a lot of new hyaluronic acid-based fillers, designed to address limitations in the older, tried-and-true product lines, according to Nowell Solish, MD.
These products have been available in Canada for years. Dr. Solish, a dermatologist at the University of Toronto, shared insights regarding their optimal use, based on his extensive experience with them.
Allergan’s earlier Juvéderm Ultra range of dermal fillers is based on Hylacross, which utilizes crosslinked high–molecular weight HA.
“These products have been around a long time and have lots of benefits, but there were definitely some things missing in the product line,” he explained. “We wanted more control of gel swelling – that is, how much water the hyaluronic acid takes up.”
The Vycross technology employs a proprietary mix of low– and high–molecular weight HA, which results in a highly crosslinked gel that’s moldable immediately after injection, displays minimal gel swelling, and is designed to last longer than earlier-generation fillers.
The main difference between the three products lies in their HA concentrations: Juvéderm Voluma XC has the highest concentration of HA and Juvéderm Volbella XC the lowest, with Volift in between.
The company claims that outcomes with Volbella and Volift last up to 12 months, while Voluma outcomes lasts for up to 24 months. Dr. Solish suggested that his American colleagues take that with a grain of salt.
“I would say I always underpromise and overdeliver with my patients,” he noted. “I think you can probably detect Voluma at 2 years, but, the question is, how good is the effect? How happy is the patient? I think 2 years is a little bit of a stretch. I think it lasts for about 9 months to a year before reinjection.”
Voluma has been available in the United States for several years, while Dr. Solish has been using it far longer. His impression is that Voluma is great for creating volume, especially in the cheeks, midface, and submalar area. He finds that he gets his best results by implanting the product in a series of small, 0.2-mL, tent-like boluses. The reinjection volume is typically substantially less than that employed in initial treatment.
Volbella received approval from the FDA in autumn 2016 for perioral injection and is just now reaching the U.S. marketplace.
“In my humble opinion, I don’t think Volbella is really good for volume,” he explained. “I think it’s great for what I call lip hydration, to give that lip a lipstick look. Where I find that I use this product the most is for the perioral rhytids – the vertical lip lines people sometimes call smokers’ lines. I implant it in the lip mucosa to straighten out the folds.”
Dr. Solish cautioned that Volbella is a fast-flowing product.
“The thing you have to be careful about with Volbella is it has a very low extrusion force,” he noted. “That means it’s very easy to unload the syringe and get too much product out. And there’s no question that there’s a direct correlation between speed of injection and adverse events, mainly edema. So, just remember to slow your hand down, or off-label to add a 31- or even 32-gauge needle to the syringe.”
Volift is not yet approved in the United States, but it’s coming. Dr. Solish called it “a good workhorse product” for mild-to-moderate lines around the face.
“Sales will be much higher than for Volbella, because Volift is great for the in-between things,” the dermatologist continued. “You have Voluma for volume on the midface and cheeks, but Volift is great for nasolabial folds and, especially, for marionette lines and smile lines, where you don’t want a lot of bulk.”
The main adverse event encountered with any of the three products is delayed-onset development of nonpainful inflammatory nodules arising 3-6 months post injection. In one Canadian study, the incidence was less than 0.5% (Dermatol Surg. 2015 Sep;41[9]:1060-7).
Dr. Solish recommended treating the nodules with weekly or biweekly intralesional injections of hyaluronidase, followed by intralesional injections of 0.1 mL/cm2 of triamcinolone (Kenalog) at 2.5 mg/mL to 5.0 mg/mL.
Turning to Galderma’s NASHA technology, Dr. Solish explained that it relies on naturally occurring entanglement of HA chains to create gel particles formulated at 20 mg/dL. By varying the gel particle size and the amount of crosslinking, the company has created a series of products with different properties.
Restylane Refyne features smaller-size particles and less crosslinking, which makes for a softer gel. It’s an excellent option for marionette lines, mild nasolabial folds, and small perioral lines, and “it’s my absolute go-to for tear troughs,” Dr. Solish said.
In contrast, Restylane Defyne has bigger gel particles and more extensive HA crosslinking. It is firmer than Refyne and is best suited for achieving lift and volume. He implants it in the cheeks, forehead, temples, and deeper nasolabial folds.
In addition to these two products, which are new to the United States, Galderma has rebranded Perlane as Restylane Lyft, approved for midfacial augmentation. Another product, Restylane Silk, is similar to Volbella in that it is fast-flowing and not a big volumizer. Dr. Solish called it “lipstick in a syringe,” best suited for improving definition of the lips and for addressing perioral fine lines.
Dr. Solish reported serving as an investigator and/or consultant for Allergan, Galderma, Indeed, Merz, Revance Therapeutics, and Valeant. The SDEF and this news organization are owned by the same parent company.
WAILEA, HAWAII – American dermatologists are now gaining access to a lot of new hyaluronic acid-based fillers, designed to address limitations in the older, tried-and-true product lines, according to Nowell Solish, MD.
These products have been available in Canada for years. Dr. Solish, a dermatologist at the University of Toronto, shared insights regarding their optimal use, based on his extensive experience with them.
Allergan’s earlier Juvéderm Ultra range of dermal fillers is based on Hylacross, which utilizes crosslinked high–molecular weight HA.
“These products have been around a long time and have lots of benefits, but there were definitely some things missing in the product line,” he explained. “We wanted more control of gel swelling – that is, how much water the hyaluronic acid takes up.”
The Vycross technology employs a proprietary mix of low– and high–molecular weight HA, which results in a highly crosslinked gel that’s moldable immediately after injection, displays minimal gel swelling, and is designed to last longer than earlier-generation fillers.
The main difference between the three products lies in their HA concentrations: Juvéderm Voluma XC has the highest concentration of HA and Juvéderm Volbella XC the lowest, with Volift in between.
The company claims that outcomes with Volbella and Volift last up to 12 months, while Voluma outcomes lasts for up to 24 months. Dr. Solish suggested that his American colleagues take that with a grain of salt.
“I would say I always underpromise and overdeliver with my patients,” he noted. “I think you can probably detect Voluma at 2 years, but, the question is, how good is the effect? How happy is the patient? I think 2 years is a little bit of a stretch. I think it lasts for about 9 months to a year before reinjection.”
Voluma has been available in the United States for several years, while Dr. Solish has been using it far longer. His impression is that Voluma is great for creating volume, especially in the cheeks, midface, and submalar area. He finds that he gets his best results by implanting the product in a series of small, 0.2-mL, tent-like boluses. The reinjection volume is typically substantially less than that employed in initial treatment.
Volbella received approval from the FDA in autumn 2016 for perioral injection and is just now reaching the U.S. marketplace.
“In my humble opinion, I don’t think Volbella is really good for volume,” he explained. “I think it’s great for what I call lip hydration, to give that lip a lipstick look. Where I find that I use this product the most is for the perioral rhytids – the vertical lip lines people sometimes call smokers’ lines. I implant it in the lip mucosa to straighten out the folds.”
Dr. Solish cautioned that Volbella is a fast-flowing product.
“The thing you have to be careful about with Volbella is it has a very low extrusion force,” he noted. “That means it’s very easy to unload the syringe and get too much product out. And there’s no question that there’s a direct correlation between speed of injection and adverse events, mainly edema. So, just remember to slow your hand down, or off-label to add a 31- or even 32-gauge needle to the syringe.”
Volift is not yet approved in the United States, but it’s coming. Dr. Solish called it “a good workhorse product” for mild-to-moderate lines around the face.
“Sales will be much higher than for Volbella, because Volift is great for the in-between things,” the dermatologist continued. “You have Voluma for volume on the midface and cheeks, but Volift is great for nasolabial folds and, especially, for marionette lines and smile lines, where you don’t want a lot of bulk.”
The main adverse event encountered with any of the three products is delayed-onset development of nonpainful inflammatory nodules arising 3-6 months post injection. In one Canadian study, the incidence was less than 0.5% (Dermatol Surg. 2015 Sep;41[9]:1060-7).
Dr. Solish recommended treating the nodules with weekly or biweekly intralesional injections of hyaluronidase, followed by intralesional injections of 0.1 mL/cm2 of triamcinolone (Kenalog) at 2.5 mg/mL to 5.0 mg/mL.
Turning to Galderma’s NASHA technology, Dr. Solish explained that it relies on naturally occurring entanglement of HA chains to create gel particles formulated at 20 mg/dL. By varying the gel particle size and the amount of crosslinking, the company has created a series of products with different properties.
Restylane Refyne features smaller-size particles and less crosslinking, which makes for a softer gel. It’s an excellent option for marionette lines, mild nasolabial folds, and small perioral lines, and “it’s my absolute go-to for tear troughs,” Dr. Solish said.
In contrast, Restylane Defyne has bigger gel particles and more extensive HA crosslinking. It is firmer than Refyne and is best suited for achieving lift and volume. He implants it in the cheeks, forehead, temples, and deeper nasolabial folds.
In addition to these two products, which are new to the United States, Galderma has rebranded Perlane as Restylane Lyft, approved for midfacial augmentation. Another product, Restylane Silk, is similar to Volbella in that it is fast-flowing and not a big volumizer. Dr. Solish called it “lipstick in a syringe,” best suited for improving definition of the lips and for addressing perioral fine lines.
Dr. Solish reported serving as an investigator and/or consultant for Allergan, Galderma, Indeed, Merz, Revance Therapeutics, and Valeant. The SDEF and this news organization are owned by the same parent company.
EXPERT ANALYSIS FROM THE SDEF HAWAII DERMATOLOGY SEMINAR
Hoarding disorder patients deem few treatments as acceptable
SAN FRANCISCO – Patients with hoarding disorder are notoriously difficult to engage in treatment. They are embarrassed by their behavior and reluctant to seek help. And Carolyn I. Rodriguez, MD, PhD, has a good idea why: Her first-of-its-kind survey of individuals with hoarding disorder showed they find the currently available array of treatments and services by and large unacceptable.
The online survey included 203 individuals with clinically significant hoarding symptoms as defined by a Saving Inventory–Revised score of at least 40. The survey contained written and audio thumbnail descriptions of 11 current treatments and services, some evidence based, others not. Participants were asked to rate the acceptability of each of the 11 interventions on a 0-10 scale, with 0 being not at all acceptable.
The results? “Nobody wanted anything!” Dr. Rodriguez said at the annual conference of the Anxiety and Depression Association of America.
Acceptability of a given intervention was defined a priori as an average score of 6 or more on the Likert Scale. She had hoped to see some 7s and 8s, strong endorsements that might have helped guide her efforts to develop attractive and engaging new therapies for this common disorder. But in fact, only 3 of the 11 items squeaked by the acceptability threshold with tepid endorsements hovering around 6: individual cognitive-behavioral therapy (CBT), with an average rating of 6.2; use of a professional organizing service, at 6.1; and use of a self-help book, at 6.0.
The least acceptable of the 11 options, not surprisingly, was a court-appointed guardian, with an average score of less than 1. Next most unpopular was use of a cleaning and removal service, followed by pharmacotherapy with a serotonin reuptake inhibitor, drug therapy with a stimulant, and group CBT.
Rounding out the list of 11 treatments and services were an online support group, a facilitated support group based upon the model described in the book “Buried in Treasures” (Oxford University Press, 2013), by David F. Tolin, PhD; Randy O. Frost, PhD; and Gail Steketee, PhD; and involvement of a case manager.
Participants were asked to describe what they liked and disliked about the 11 options. What they liked about the three that were acceptable – albeit barely – was the prospect of personalized care, being held accountable, and their belief that those three strategies really work. What they disliked about the least acceptable interventions was the feeling that they would have no control over the process, anticipation that these treatments and services would cause them distress, and skepticism about their efficacy.
Actually, while the evidence regarding pharmacotherapy is limited to a few open-label, uncontrolled, prospective case series involving hoarding disorder patients not concurrently in psychotherapy, the medication data look quite promising, according to Dr. Rodriguez, who is affiliated with the department of psychiatry and behavioral sciences at Stanford (Calif.) University.
Investigators at the University of California, San Diego, treated 24 patients meeting DSM-5 criteria for hoarding disorder with extended-release venlafaxine (Effexor XR) for 12 weeks. Twenty-three of the 24 completed the study, achieving a mean 32% reduction in Saving Inventory–Revised scores and a 36% reduction in UCLA Hoarding Severity Scale scores (Int Clin Psychopharmacol. 2014 Sep;29[5]:266-73).
Sixteen of the 23 completers were categorized as treatment responders. The investigators noted that this 70% efficacy rate for venlafaxine extended-release was markedly better than published CBT success rates, which hover around 28% for individual CBT and range from 10% to 30% for group CBT.
Also, Dr. Rodriguez has published her experience in prescribing extended-release methylphenidate for four patients with hoarding disorder without comorbid attention-deficit/hyperactivity disorder, all of whom previously had failed to respond to at least one serotonin reuptake inhibitor. The therapeutic rationale for stimulant therapy was that patients with hoarding disorder have problems with attention and decision making that may contribute to accumulation of clutter.
In this 4-week study, patients were started on methylphenidate extended-release at 18 mg/day, with the dosing increased by 18 mg/day each week to a maximum of 72 mg/day. Three of the four patients achieved at least a 50% reduction in measures of inattention, and two patients showed decreases in hoarding symptoms of 25% and 32% on the Saving Inventory–Revised. But at the end of 4 weeks, all four patients opted not to continue on the medication because they didn’t like the side effects, mainly insomnia and palpitations (J Clin Psychopharmacol. 2013 Jun;33[3]:444-7).
Pharmacotherapy has a couple of other potentially appealing features: It works much faster than does psychotherapy, and it also is effective therapy for some of the other psychiatric conditions commonly comorbid with hoarding disorder.
Several audience members observed that even though survey participants did not rate group CBT or facilitated support groups as acceptable treatments, in their own experience as therapists, they’ve found these interventions to be among the most successful. Dr. Rodriguez agreed. Based in part upon her survey findings, her new research initiatives emphasize offering choice, since there’s clearly no one-size-fits-all intervention. She’s also stressing accountability, incorporation of tools aimed at reducing shame and stigma, and providing more information about evidence-based therapies to strengthen patients’ beliefs that treatment actually works.
Toward that end, she recently has trained individuals from the community in how to run a 3-month, skills-based, group therapy program using the Buried in Treasures approach with group in-home visits and decluttering sessions. These group therapy modules will be evaluated formally as to acceptability and efficacy.
Hoarding disorder has a prevalence of 2%-6%. It’s a condition that poses significant public health risks, including fire hazard and pest infestation. Hoarding disorder typically starts in childhood or the teen years and follows a chronic, progressive course. Affected individuals do not initiate treatment until age 50, on average. The condition is more common in men than women. They are often single, highly educated, and live alone. Insight is often poor. A family history of hoarding is common. Psychiatric comorbidity also is common, with depression topping the list.
Dr. Rodriguez’s survey was funded by the National Institute of Mental Health and foundation grants. She reported serving as a consultant to Allergan, Rugen Therapeutics, and BlackThorn Therapeutics.
SAN FRANCISCO – Patients with hoarding disorder are notoriously difficult to engage in treatment. They are embarrassed by their behavior and reluctant to seek help. And Carolyn I. Rodriguez, MD, PhD, has a good idea why: Her first-of-its-kind survey of individuals with hoarding disorder showed they find the currently available array of treatments and services by and large unacceptable.
The online survey included 203 individuals with clinically significant hoarding symptoms as defined by a Saving Inventory–Revised score of at least 40. The survey contained written and audio thumbnail descriptions of 11 current treatments and services, some evidence based, others not. Participants were asked to rate the acceptability of each of the 11 interventions on a 0-10 scale, with 0 being not at all acceptable.
The results? “Nobody wanted anything!” Dr. Rodriguez said at the annual conference of the Anxiety and Depression Association of America.
Acceptability of a given intervention was defined a priori as an average score of 6 or more on the Likert Scale. She had hoped to see some 7s and 8s, strong endorsements that might have helped guide her efforts to develop attractive and engaging new therapies for this common disorder. But in fact, only 3 of the 11 items squeaked by the acceptability threshold with tepid endorsements hovering around 6: individual cognitive-behavioral therapy (CBT), with an average rating of 6.2; use of a professional organizing service, at 6.1; and use of a self-help book, at 6.0.
The least acceptable of the 11 options, not surprisingly, was a court-appointed guardian, with an average score of less than 1. Next most unpopular was use of a cleaning and removal service, followed by pharmacotherapy with a serotonin reuptake inhibitor, drug therapy with a stimulant, and group CBT.
Rounding out the list of 11 treatments and services were an online support group, a facilitated support group based upon the model described in the book “Buried in Treasures” (Oxford University Press, 2013), by David F. Tolin, PhD; Randy O. Frost, PhD; and Gail Steketee, PhD; and involvement of a case manager.
Participants were asked to describe what they liked and disliked about the 11 options. What they liked about the three that were acceptable – albeit barely – was the prospect of personalized care, being held accountable, and their belief that those three strategies really work. What they disliked about the least acceptable interventions was the feeling that they would have no control over the process, anticipation that these treatments and services would cause them distress, and skepticism about their efficacy.
Actually, while the evidence regarding pharmacotherapy is limited to a few open-label, uncontrolled, prospective case series involving hoarding disorder patients not concurrently in psychotherapy, the medication data look quite promising, according to Dr. Rodriguez, who is affiliated with the department of psychiatry and behavioral sciences at Stanford (Calif.) University.
Investigators at the University of California, San Diego, treated 24 patients meeting DSM-5 criteria for hoarding disorder with extended-release venlafaxine (Effexor XR) for 12 weeks. Twenty-three of the 24 completed the study, achieving a mean 32% reduction in Saving Inventory–Revised scores and a 36% reduction in UCLA Hoarding Severity Scale scores (Int Clin Psychopharmacol. 2014 Sep;29[5]:266-73).
Sixteen of the 23 completers were categorized as treatment responders. The investigators noted that this 70% efficacy rate for venlafaxine extended-release was markedly better than published CBT success rates, which hover around 28% for individual CBT and range from 10% to 30% for group CBT.
Also, Dr. Rodriguez has published her experience in prescribing extended-release methylphenidate for four patients with hoarding disorder without comorbid attention-deficit/hyperactivity disorder, all of whom previously had failed to respond to at least one serotonin reuptake inhibitor. The therapeutic rationale for stimulant therapy was that patients with hoarding disorder have problems with attention and decision making that may contribute to accumulation of clutter.
In this 4-week study, patients were started on methylphenidate extended-release at 18 mg/day, with the dosing increased by 18 mg/day each week to a maximum of 72 mg/day. Three of the four patients achieved at least a 50% reduction in measures of inattention, and two patients showed decreases in hoarding symptoms of 25% and 32% on the Saving Inventory–Revised. But at the end of 4 weeks, all four patients opted not to continue on the medication because they didn’t like the side effects, mainly insomnia and palpitations (J Clin Psychopharmacol. 2013 Jun;33[3]:444-7).
Pharmacotherapy has a couple of other potentially appealing features: It works much faster than does psychotherapy, and it also is effective therapy for some of the other psychiatric conditions commonly comorbid with hoarding disorder.
Several audience members observed that even though survey participants did not rate group CBT or facilitated support groups as acceptable treatments, in their own experience as therapists, they’ve found these interventions to be among the most successful. Dr. Rodriguez agreed. Based in part upon her survey findings, her new research initiatives emphasize offering choice, since there’s clearly no one-size-fits-all intervention. She’s also stressing accountability, incorporation of tools aimed at reducing shame and stigma, and providing more information about evidence-based therapies to strengthen patients’ beliefs that treatment actually works.
Toward that end, she recently has trained individuals from the community in how to run a 3-month, skills-based, group therapy program using the Buried in Treasures approach with group in-home visits and decluttering sessions. These group therapy modules will be evaluated formally as to acceptability and efficacy.
Hoarding disorder has a prevalence of 2%-6%. It’s a condition that poses significant public health risks, including fire hazard and pest infestation. Hoarding disorder typically starts in childhood or the teen years and follows a chronic, progressive course. Affected individuals do not initiate treatment until age 50, on average. The condition is more common in men than women. They are often single, highly educated, and live alone. Insight is often poor. A family history of hoarding is common. Psychiatric comorbidity also is common, with depression topping the list.
Dr. Rodriguez’s survey was funded by the National Institute of Mental Health and foundation grants. She reported serving as a consultant to Allergan, Rugen Therapeutics, and BlackThorn Therapeutics.
SAN FRANCISCO – Patients with hoarding disorder are notoriously difficult to engage in treatment. They are embarrassed by their behavior and reluctant to seek help. And Carolyn I. Rodriguez, MD, PhD, has a good idea why: Her first-of-its-kind survey of individuals with hoarding disorder showed they find the currently available array of treatments and services by and large unacceptable.
The online survey included 203 individuals with clinically significant hoarding symptoms as defined by a Saving Inventory–Revised score of at least 40. The survey contained written and audio thumbnail descriptions of 11 current treatments and services, some evidence based, others not. Participants were asked to rate the acceptability of each of the 11 interventions on a 0-10 scale, with 0 being not at all acceptable.
The results? “Nobody wanted anything!” Dr. Rodriguez said at the annual conference of the Anxiety and Depression Association of America.
Acceptability of a given intervention was defined a priori as an average score of 6 or more on the Likert Scale. She had hoped to see some 7s and 8s, strong endorsements that might have helped guide her efforts to develop attractive and engaging new therapies for this common disorder. But in fact, only 3 of the 11 items squeaked by the acceptability threshold with tepid endorsements hovering around 6: individual cognitive-behavioral therapy (CBT), with an average rating of 6.2; use of a professional organizing service, at 6.1; and use of a self-help book, at 6.0.
The least acceptable of the 11 options, not surprisingly, was a court-appointed guardian, with an average score of less than 1. Next most unpopular was use of a cleaning and removal service, followed by pharmacotherapy with a serotonin reuptake inhibitor, drug therapy with a stimulant, and group CBT.
Rounding out the list of 11 treatments and services were an online support group, a facilitated support group based upon the model described in the book “Buried in Treasures” (Oxford University Press, 2013), by David F. Tolin, PhD; Randy O. Frost, PhD; and Gail Steketee, PhD; and involvement of a case manager.
Participants were asked to describe what they liked and disliked about the 11 options. What they liked about the three that were acceptable – albeit barely – was the prospect of personalized care, being held accountable, and their belief that those three strategies really work. What they disliked about the least acceptable interventions was the feeling that they would have no control over the process, anticipation that these treatments and services would cause them distress, and skepticism about their efficacy.
Actually, while the evidence regarding pharmacotherapy is limited to a few open-label, uncontrolled, prospective case series involving hoarding disorder patients not concurrently in psychotherapy, the medication data look quite promising, according to Dr. Rodriguez, who is affiliated with the department of psychiatry and behavioral sciences at Stanford (Calif.) University.
Investigators at the University of California, San Diego, treated 24 patients meeting DSM-5 criteria for hoarding disorder with extended-release venlafaxine (Effexor XR) for 12 weeks. Twenty-three of the 24 completed the study, achieving a mean 32% reduction in Saving Inventory–Revised scores and a 36% reduction in UCLA Hoarding Severity Scale scores (Int Clin Psychopharmacol. 2014 Sep;29[5]:266-73).
Sixteen of the 23 completers were categorized as treatment responders. The investigators noted that this 70% efficacy rate for venlafaxine extended-release was markedly better than published CBT success rates, which hover around 28% for individual CBT and range from 10% to 30% for group CBT.
Also, Dr. Rodriguez has published her experience in prescribing extended-release methylphenidate for four patients with hoarding disorder without comorbid attention-deficit/hyperactivity disorder, all of whom previously had failed to respond to at least one serotonin reuptake inhibitor. The therapeutic rationale for stimulant therapy was that patients with hoarding disorder have problems with attention and decision making that may contribute to accumulation of clutter.
In this 4-week study, patients were started on methylphenidate extended-release at 18 mg/day, with the dosing increased by 18 mg/day each week to a maximum of 72 mg/day. Three of the four patients achieved at least a 50% reduction in measures of inattention, and two patients showed decreases in hoarding symptoms of 25% and 32% on the Saving Inventory–Revised. But at the end of 4 weeks, all four patients opted not to continue on the medication because they didn’t like the side effects, mainly insomnia and palpitations (J Clin Psychopharmacol. 2013 Jun;33[3]:444-7).
Pharmacotherapy has a couple of other potentially appealing features: It works much faster than does psychotherapy, and it also is effective therapy for some of the other psychiatric conditions commonly comorbid with hoarding disorder.
Several audience members observed that even though survey participants did not rate group CBT or facilitated support groups as acceptable treatments, in their own experience as therapists, they’ve found these interventions to be among the most successful. Dr. Rodriguez agreed. Based in part upon her survey findings, her new research initiatives emphasize offering choice, since there’s clearly no one-size-fits-all intervention. She’s also stressing accountability, incorporation of tools aimed at reducing shame and stigma, and providing more information about evidence-based therapies to strengthen patients’ beliefs that treatment actually works.
Toward that end, she recently has trained individuals from the community in how to run a 3-month, skills-based, group therapy program using the Buried in Treasures approach with group in-home visits and decluttering sessions. These group therapy modules will be evaluated formally as to acceptability and efficacy.
Hoarding disorder has a prevalence of 2%-6%. It’s a condition that poses significant public health risks, including fire hazard and pest infestation. Hoarding disorder typically starts in childhood or the teen years and follows a chronic, progressive course. Affected individuals do not initiate treatment until age 50, on average. The condition is more common in men than women. They are often single, highly educated, and live alone. Insight is often poor. A family history of hoarding is common. Psychiatric comorbidity also is common, with depression topping the list.
Dr. Rodriguez’s survey was funded by the National Institute of Mental Health and foundation grants. She reported serving as a consultant to Allergan, Rugen Therapeutics, and BlackThorn Therapeutics.
AT ANXIETY AND DEPRESSION CONFERENCE 2017
Key clinical point:
Major finding: Only three interventions received even lukewarm endorsement: individual cognitive-behavioral therapy, a professional organizing service, and self-help books.
Data source: In an online survey, 203 individuals with clinically significant hoarding disorder symptoms rated the acceptability of 11 different therapies and services.
Disclosures: This work was funded by the National Institute of Mental Health and foundation grants. The study presenter reported serving as a consultant to Allergan, Rugen Therapeutics, and BlackThorn Therapeutics.
Low-calorie sweeteners may allow more glucose to enter fat cells
ORLANDO – Consumption of low-calorie sweeteners was associated with upregulation of gene expression for glucose transporters in experiments using human mesenchymal stromal cells and adipose tissue, according to new research.
The effect was strongest in individuals with obesity.
Using human subcutaneous fat tissue taken from individuals who consumed low-calorie sweeteners, Sabyasachi Sen, MD, of George Washington University, Washington, and his colleagues showed that these cells had at least a twofold overexpression of glucose transporters. Also overexpressed were sweet taste receptors and adipogenic genes.
Dr. Sen and his colleagues first tested the effects of both physiologic and supraphysiologic doses of sucralose on human adipose-derived mesenchymal stromal cells (MSCs). In the presence of adipogenic media, sucralose was added to the MSCs for a period of 12 days.
When sucralose was added at a concentration of 0.2 millimoles (mM), the investigators detected “small but reproducible” increases in expression of adiponectin, as well as genes that encode for the production of fatty acid binding proteins (FABP4) and proteins implicated in body weight homeostasis (CEBPA). Increases ranged from 1.04- to 1.32-fold.
Dr. Sen explained that the 0.2 mM concentration approximates the amount of sucralose in the tissues of individuals with high low-calorie sweetener consumption.
These effects were more pronounced when the sucralose concentration was raised to a supraphysiologic 1 mM. Then, CEBPA expression increased by a factor of 3.45, adiponectin by 4.39, and FABP4 by 4.06. More intracellular fat droplets were seen with higher sucralose concentrations in a “dose dependent fashion,” said Dr. Sen and his colleagues.
The researchers also took subcutaneous fat biopsies from four individuals of healthy weight (body mass index [BMI] less than 24.9 kg/m2) and from four individuals with obesity (BMI greater than 24.9). Participants ranged in age from 36 years to 60 years.
Individuals in both groups had kept a 7-day food diary before the biopsies were taken, so Dr. Sen and his coinvestigators knew whether or not they had consumed low-calorie sweeteners and in what quantity. Reported sweeteners were sucralose, acesulfame-potassium, and aspartame.
The adipose tissue biopsies were examined for mRNA expression of adipogenic genes, as well as for glucose transporters and inflammatory markers.
In individuals with low-calorie sweetener exposure, the glucose transporter GLUT1 was overexpressed by 2- to 2.2-fold, while the glucose transporter GLUT4 was overexpressed by a factor of 2.7-4.3.
In addition, low-calorie sweetener consumption was associated with up to 2.5-fold overexpression of the sweet taste receptor TAS1R3. Sweet taste receptors are G protein–coupled receptors that are present in taste buds and in other tissues, serving as carbohydrate sensors.
Adipogenic genes were also overexpressed; a 1.5- to 2.4-fold increase was seen in PPARG, for example.
“This expression pattern was most apparent in obese individuals,” the investigators wrote in the abstract accompanying the study, which was presented at the annual meeting of the Endocrine Society.
Further and larger studies are called for, especially in individuals with diabetes and obesity, Dr. Sen said. “However, from our study, we believe that low-calorie sweeteners promote additional fat formation by allowing more glucose to enter the cells, and promote inflammation, which may be more detrimental to obese individuals.”
Dr. Sen and his collaborators reported no relevant disclosures.
[email protected]
On Twitter @karioakes
ORLANDO – Consumption of low-calorie sweeteners was associated with upregulation of gene expression for glucose transporters in experiments using human mesenchymal stromal cells and adipose tissue, according to new research.
The effect was strongest in individuals with obesity.
Using human subcutaneous fat tissue taken from individuals who consumed low-calorie sweeteners, Sabyasachi Sen, MD, of George Washington University, Washington, and his colleagues showed that these cells had at least a twofold overexpression of glucose transporters. Also overexpressed were sweet taste receptors and adipogenic genes.
Dr. Sen and his colleagues first tested the effects of both physiologic and supraphysiologic doses of sucralose on human adipose-derived mesenchymal stromal cells (MSCs). In the presence of adipogenic media, sucralose was added to the MSCs for a period of 12 days.
When sucralose was added at a concentration of 0.2 millimoles (mM), the investigators detected “small but reproducible” increases in expression of adiponectin, as well as genes that encode for the production of fatty acid binding proteins (FABP4) and proteins implicated in body weight homeostasis (CEBPA). Increases ranged from 1.04- to 1.32-fold.
Dr. Sen explained that the 0.2 mM concentration approximates the amount of sucralose in the tissues of individuals with high low-calorie sweetener consumption.
These effects were more pronounced when the sucralose concentration was raised to a supraphysiologic 1 mM. Then, CEBPA expression increased by a factor of 3.45, adiponectin by 4.39, and FABP4 by 4.06. More intracellular fat droplets were seen with higher sucralose concentrations in a “dose dependent fashion,” said Dr. Sen and his colleagues.
The researchers also took subcutaneous fat biopsies from four individuals of healthy weight (body mass index [BMI] less than 24.9 kg/m2) and from four individuals with obesity (BMI greater than 24.9). Participants ranged in age from 36 years to 60 years.
Individuals in both groups had kept a 7-day food diary before the biopsies were taken, so Dr. Sen and his coinvestigators knew whether or not they had consumed low-calorie sweeteners and in what quantity. Reported sweeteners were sucralose, acesulfame-potassium, and aspartame.
The adipose tissue biopsies were examined for mRNA expression of adipogenic genes, as well as for glucose transporters and inflammatory markers.
In individuals with low-calorie sweetener exposure, the glucose transporter GLUT1 was overexpressed by 2- to 2.2-fold, while the glucose transporter GLUT4 was overexpressed by a factor of 2.7-4.3.
In addition, low-calorie sweetener consumption was associated with up to 2.5-fold overexpression of the sweet taste receptor TAS1R3. Sweet taste receptors are G protein–coupled receptors that are present in taste buds and in other tissues, serving as carbohydrate sensors.
Adipogenic genes were also overexpressed; a 1.5- to 2.4-fold increase was seen in PPARG, for example.
“This expression pattern was most apparent in obese individuals,” the investigators wrote in the abstract accompanying the study, which was presented at the annual meeting of the Endocrine Society.
Further and larger studies are called for, especially in individuals with diabetes and obesity, Dr. Sen said. “However, from our study, we believe that low-calorie sweeteners promote additional fat formation by allowing more glucose to enter the cells, and promote inflammation, which may be more detrimental to obese individuals.”
Dr. Sen and his collaborators reported no relevant disclosures.
[email protected]
On Twitter @karioakes
ORLANDO – Consumption of low-calorie sweeteners was associated with upregulation of gene expression for glucose transporters in experiments using human mesenchymal stromal cells and adipose tissue, according to new research.
The effect was strongest in individuals with obesity.
Using human subcutaneous fat tissue taken from individuals who consumed low-calorie sweeteners, Sabyasachi Sen, MD, of George Washington University, Washington, and his colleagues showed that these cells had at least a twofold overexpression of glucose transporters. Also overexpressed were sweet taste receptors and adipogenic genes.
Dr. Sen and his colleagues first tested the effects of both physiologic and supraphysiologic doses of sucralose on human adipose-derived mesenchymal stromal cells (MSCs). In the presence of adipogenic media, sucralose was added to the MSCs for a period of 12 days.
When sucralose was added at a concentration of 0.2 millimoles (mM), the investigators detected “small but reproducible” increases in expression of adiponectin, as well as genes that encode for the production of fatty acid binding proteins (FABP4) and proteins implicated in body weight homeostasis (CEBPA). Increases ranged from 1.04- to 1.32-fold.
Dr. Sen explained that the 0.2 mM concentration approximates the amount of sucralose in the tissues of individuals with high low-calorie sweetener consumption.
These effects were more pronounced when the sucralose concentration was raised to a supraphysiologic 1 mM. Then, CEBPA expression increased by a factor of 3.45, adiponectin by 4.39, and FABP4 by 4.06. More intracellular fat droplets were seen with higher sucralose concentrations in a “dose dependent fashion,” said Dr. Sen and his colleagues.
The researchers also took subcutaneous fat biopsies from four individuals of healthy weight (body mass index [BMI] less than 24.9 kg/m2) and from four individuals with obesity (BMI greater than 24.9). Participants ranged in age from 36 years to 60 years.
Individuals in both groups had kept a 7-day food diary before the biopsies were taken, so Dr. Sen and his coinvestigators knew whether or not they had consumed low-calorie sweeteners and in what quantity. Reported sweeteners were sucralose, acesulfame-potassium, and aspartame.
The adipose tissue biopsies were examined for mRNA expression of adipogenic genes, as well as for glucose transporters and inflammatory markers.
In individuals with low-calorie sweetener exposure, the glucose transporter GLUT1 was overexpressed by 2- to 2.2-fold, while the glucose transporter GLUT4 was overexpressed by a factor of 2.7-4.3.
In addition, low-calorie sweetener consumption was associated with up to 2.5-fold overexpression of the sweet taste receptor TAS1R3. Sweet taste receptors are G protein–coupled receptors that are present in taste buds and in other tissues, serving as carbohydrate sensors.
Adipogenic genes were also overexpressed; a 1.5- to 2.4-fold increase was seen in PPARG, for example.
“This expression pattern was most apparent in obese individuals,” the investigators wrote in the abstract accompanying the study, which was presented at the annual meeting of the Endocrine Society.
Further and larger studies are called for, especially in individuals with diabetes and obesity, Dr. Sen said. “However, from our study, we believe that low-calorie sweeteners promote additional fat formation by allowing more glucose to enter the cells, and promote inflammation, which may be more detrimental to obese individuals.”
Dr. Sen and his collaborators reported no relevant disclosures.
[email protected]
On Twitter @karioakes
Key clinical point:
Major finding: Glucose transporters and sweet taste receptors were upregulated by 2.0- to 4.3-fold in participants who used low-calorie sweeteners.
Data source: In vitro examination of human adipose tissue-derived mesenchymal stromal cells, and examination of biopsied adipose tissue from eight individuals with varying low-calorie sweetener intake.
Disclosures: None of the study authors reported relevant disclosures, and no external source of funding was reported.
Dupilumab approval marks the first targeted treatment for AD
The approval of dupilumab, the first targeted biologic therapy approved in the United States for treatment of atopic dermatitis, provides a welcome, long-awaited alternative to currently available therapies for moderate to severe disease, according to two of the pivotal trial investigators.
In late March, the Food and Drug Administration approved dupilumab, a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, for the treatment of moderate to severe AD in adults “whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.” It is administered subcutaneously, with an initial 600-mg dose, followed by 300 mg every other week, according to the prescribing information.
Dupilumab (Dupixent) was the second novel treatment approved for AD in less than 4 months – after years of no approvals of new therapies for this indication. In December, crisaborole ointment (Eucrisa) was approved for treatment of mild to moderate AD in patients aged 2 years and older. Crisaborole is a topical phosphodiesterase-4 inhibitor.
Dupilumab’s approval was based on three phase III studies of adults with moderate to severe AD: SOLO-1 and SOLO-2, which evaluated dupilumab as monotherapy, and the CHRONOS study, which compared dupilumab with topical corticosteroids to treatment with topical corticosteroids alone.
At 16 weeks in the SOLO trials, those treated with dupilumab had improvements in signs and symptoms of AD, including pruritus, anxiety and depression, and quality of life, compared with placebo. Almost 40% of those treated with dupilumab met the primary outcome – a score of clear or almost clear on the Investigator’s Global Assessment and a reduction of 2 points or more in that score from baseline – compared with 8%-10% of those on placebo (P less than .001). Injection-site reactions and conjunctivitis were more common among those treated with dupilumab (N Engl J Med. 2016;375:2335-48).
Emma Guttman-Yassky, MD, PhD, also an investigator in the SOLO 1 and SOLO 2 trials, said that prior to the approval, “we had nothing to treat our patients safely long term.”
“With dupilumab, because it’s specific, it provides the safety that we need,” while providing efficacy that is similar to or better than that of cyclosporine, with the caveat that dupilumab and cyclosporine have not been evaluated in a head-to-head study, Dr. Guttman-Yassky, professor and vice-chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.
About 5%-10% of those treated at her site had allergic conjunctivitis; most cases resolved with eye drops. So far, “it looks very safe but we need to have long-term data,” she added.
Dr. Simpson said that he was pleased to see the maintenance of therapeutic effects with no emergence of new side effects with the report of 52-week CHRONOS data in March at the American Academy of Dermatology annual meeting.
“We’re entering the era and the decade of atopic dermatitis,” he said. “Dermatologists should look out for many new topical and systemic therapies now that we’re uncovering and figuring out the pathophysiology of atopic dermatitis.”
Dupilumab, which costs $37,000 per year, is marketed by Regeneron and Sanofi. Studies in children and adolescents with AD are underway.
Dr. Guttman-Yassky has received funding from Regeneron for mechanistic studies and is working with most companies developing AD treatments. Dr. Simpson has received research grants from and serves as a consultant to Regeneron, as well as other pharmaceutical companies.
The approval of dupilumab, the first targeted biologic therapy approved in the United States for treatment of atopic dermatitis, provides a welcome, long-awaited alternative to currently available therapies for moderate to severe disease, according to two of the pivotal trial investigators.
In late March, the Food and Drug Administration approved dupilumab, a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, for the treatment of moderate to severe AD in adults “whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.” It is administered subcutaneously, with an initial 600-mg dose, followed by 300 mg every other week, according to the prescribing information.
Dupilumab (Dupixent) was the second novel treatment approved for AD in less than 4 months – after years of no approvals of new therapies for this indication. In December, crisaborole ointment (Eucrisa) was approved for treatment of mild to moderate AD in patients aged 2 years and older. Crisaborole is a topical phosphodiesterase-4 inhibitor.
Dupilumab’s approval was based on three phase III studies of adults with moderate to severe AD: SOLO-1 and SOLO-2, which evaluated dupilumab as monotherapy, and the CHRONOS study, which compared dupilumab with topical corticosteroids to treatment with topical corticosteroids alone.
At 16 weeks in the SOLO trials, those treated with dupilumab had improvements in signs and symptoms of AD, including pruritus, anxiety and depression, and quality of life, compared with placebo. Almost 40% of those treated with dupilumab met the primary outcome – a score of clear or almost clear on the Investigator’s Global Assessment and a reduction of 2 points or more in that score from baseline – compared with 8%-10% of those on placebo (P less than .001). Injection-site reactions and conjunctivitis were more common among those treated with dupilumab (N Engl J Med. 2016;375:2335-48).
Emma Guttman-Yassky, MD, PhD, also an investigator in the SOLO 1 and SOLO 2 trials, said that prior to the approval, “we had nothing to treat our patients safely long term.”
“With dupilumab, because it’s specific, it provides the safety that we need,” while providing efficacy that is similar to or better than that of cyclosporine, with the caveat that dupilumab and cyclosporine have not been evaluated in a head-to-head study, Dr. Guttman-Yassky, professor and vice-chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.
About 5%-10% of those treated at her site had allergic conjunctivitis; most cases resolved with eye drops. So far, “it looks very safe but we need to have long-term data,” she added.
Dr. Simpson said that he was pleased to see the maintenance of therapeutic effects with no emergence of new side effects with the report of 52-week CHRONOS data in March at the American Academy of Dermatology annual meeting.
“We’re entering the era and the decade of atopic dermatitis,” he said. “Dermatologists should look out for many new topical and systemic therapies now that we’re uncovering and figuring out the pathophysiology of atopic dermatitis.”
Dupilumab, which costs $37,000 per year, is marketed by Regeneron and Sanofi. Studies in children and adolescents with AD are underway.
Dr. Guttman-Yassky has received funding from Regeneron for mechanistic studies and is working with most companies developing AD treatments. Dr. Simpson has received research grants from and serves as a consultant to Regeneron, as well as other pharmaceutical companies.
The approval of dupilumab, the first targeted biologic therapy approved in the United States for treatment of atopic dermatitis, provides a welcome, long-awaited alternative to currently available therapies for moderate to severe disease, according to two of the pivotal trial investigators.
In late March, the Food and Drug Administration approved dupilumab, a monoclonal antibody that inhibits signaling of both interleukin-4 and interleukin-13, for the treatment of moderate to severe AD in adults “whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable.” It is administered subcutaneously, with an initial 600-mg dose, followed by 300 mg every other week, according to the prescribing information.
Dupilumab (Dupixent) was the second novel treatment approved for AD in less than 4 months – after years of no approvals of new therapies for this indication. In December, crisaborole ointment (Eucrisa) was approved for treatment of mild to moderate AD in patients aged 2 years and older. Crisaborole is a topical phosphodiesterase-4 inhibitor.
Dupilumab’s approval was based on three phase III studies of adults with moderate to severe AD: SOLO-1 and SOLO-2, which evaluated dupilumab as monotherapy, and the CHRONOS study, which compared dupilumab with topical corticosteroids to treatment with topical corticosteroids alone.
At 16 weeks in the SOLO trials, those treated with dupilumab had improvements in signs and symptoms of AD, including pruritus, anxiety and depression, and quality of life, compared with placebo. Almost 40% of those treated with dupilumab met the primary outcome – a score of clear or almost clear on the Investigator’s Global Assessment and a reduction of 2 points or more in that score from baseline – compared with 8%-10% of those on placebo (P less than .001). Injection-site reactions and conjunctivitis were more common among those treated with dupilumab (N Engl J Med. 2016;375:2335-48).
Emma Guttman-Yassky, MD, PhD, also an investigator in the SOLO 1 and SOLO 2 trials, said that prior to the approval, “we had nothing to treat our patients safely long term.”
“With dupilumab, because it’s specific, it provides the safety that we need,” while providing efficacy that is similar to or better than that of cyclosporine, with the caveat that dupilumab and cyclosporine have not been evaluated in a head-to-head study, Dr. Guttman-Yassky, professor and vice-chair of dermatology at the Icahn School of Medicine at Mount Sinai, New York, said in an interview.
About 5%-10% of those treated at her site had allergic conjunctivitis; most cases resolved with eye drops. So far, “it looks very safe but we need to have long-term data,” she added.
Dr. Simpson said that he was pleased to see the maintenance of therapeutic effects with no emergence of new side effects with the report of 52-week CHRONOS data in March at the American Academy of Dermatology annual meeting.
“We’re entering the era and the decade of atopic dermatitis,” he said. “Dermatologists should look out for many new topical and systemic therapies now that we’re uncovering and figuring out the pathophysiology of atopic dermatitis.”
Dupilumab, which costs $37,000 per year, is marketed by Regeneron and Sanofi. Studies in children and adolescents with AD are underway.
Dr. Guttman-Yassky has received funding from Regeneron for mechanistic studies and is working with most companies developing AD treatments. Dr. Simpson has received research grants from and serves as a consultant to Regeneron, as well as other pharmaceutical companies.
Avoid hysterectomy in POP repairs
SAN ANTONIO – The Systematic Review Group of the Society of Gynecologic Surgeons is suggesting uterine preservation, when not contraindicated, for most pelvic organ prolapse repairs to decrease mesh erosion, operating room time, and blood loss.
The advice is based on a review of 94 original studies, including 12 randomized controlled trials (RCTs) and 41 nonrandomized comparative studies, winnowed down to the strongest work from an original review of 7,324 abstracts through January 2017.
Short-term prolapse outcomes – 12-30 months in most of the studies – “are usually not clinically significant due to uterine preservation,” with the one exception of vaginal hysterectomy with native tissue reconstruction, which the group recommended over laparoscopic sacrohysteropexy, Kate Meriwether, MD, a gynecologic surgeon at the University of Louisville, Ky., said at the annual scientific meeting of the Society of Gynecologic Surgeons.
Hysterectomy for prolapse surgery is common: More than 74,000 hysterectomies are done in the United States each year with prolapse as the main indication. Even so, it’s not always necessary to take out the uterus, and perhaps more than a third of women would prefer to keep theirs, Dr. Meriwether said, speaking on behalf of the SGS Systematic Review Group.
The recommendations from the Systematic Review Group must be sent to the SGS board and the full membership before they can be approved as guidelines.*
The Review Group made a grade A recommendation for vaginal hysterectomy with native tissue reconstruction over laparoscopic sacrohysteropexy, meaning it was based on high-quality evidence. The rest of the advice came in the form of suggestions, based on moderate grade B evidence, often nonrandomized comparative studies and case reviews.
The Review Group suggested uterine preservation during laparoscopic native tissue prolapse repair to reduce operating room (OR) time and blood loss, and preserve vaginal length, based on four nonrandomized comparison studies using various approaches, with a total of 446 women and up to 3 years’ follow-up. There might be a higher risk of apical recurrence without hysterectomy, but without worsening of prolapse symptoms.
The Review Group also suggested uterine preservation in transvaginal mesh reconstruction for prolapse, based on four RCTs and nine comparison studies with 1,381 women and up to 30 months’ follow-up. The studies found a decreased risk of mesh erosion, reoperating for mesh erosion, blood loss, and postop bleeding, and improved posterior and apical Pelvic Organ Prolapse Quantification scores when women keep their uterus.
However, “the patient should be counseled that there may be increased de novo stress incontinence, overactive bladder,” postop constipation, and shorter vaginal length, Dr. Meriwether said.
Also, “we suggest preservation of the uterus in transvaginal apical native tissue repair of prolapse, as it does not worsen any outcomes and slightly reduces OR time and estimated blood loss,” based on 13 studies, including four RCTs, and a total of 1,449 women followed for up to 26 months, she said.
The Review Group also came out in favor of the Manchester procedure, when available, over vaginal hysterectomy with native tissue suspension, based on one RCT and five nonrandomized studies involving 1,126 women and up to 61 months’ follow-up. The Manchester procedure pushed back the time to prolapse reoperation 9 months in one study, and also decreased transfusions, OR time, and blood loss. It also better preserved perineal length.
The group suggested uterine preservation when considering mesh sacrocolpopexy versus mesh sacrohysteropexy, to reduce mesh erosion, OR time, blood loss, hospital stay, and surgery costs, although there might be a slight worsening of Pelvic Floor Distress Inventory and Pelvic Floor Impact scores. The advice was based on nine nonrandomized comparison studies involving 745 women followed for up to 39 months. There was no difference in prolapse resolution between the two techniques.
The one grade A recommendation, for vaginal hysterectomy with native tissue reconstruction over laparoscopic sacrohysteropexy, was based on two RCTs with 182 women followed for up to 12 months.
Hysterectomy in those studies significantly reduced the risk of repeat surgery for prolapse and urinary symptoms, shortened OR time, and improved quality of life scores. However, the benefits came at the cost of slightly shorter vaginal length, worse Pelvic Organ Prolapse Quantification point C scores, greater blood loss, and up to a day longer spent in the hospital.
Dr. Meriwether reported having no relevant financial disclosures.
*Correction, 6/8/2017: An earlier version of this story misstated the status of the Systematic Review Group's recommendations. The recommendations have not been approved as official SGS guidelines. Also, the meeting sponsor information was updated.
SAN ANTONIO – The Systematic Review Group of the Society of Gynecologic Surgeons is suggesting uterine preservation, when not contraindicated, for most pelvic organ prolapse repairs to decrease mesh erosion, operating room time, and blood loss.
The advice is based on a review of 94 original studies, including 12 randomized controlled trials (RCTs) and 41 nonrandomized comparative studies, winnowed down to the strongest work from an original review of 7,324 abstracts through January 2017.
Short-term prolapse outcomes – 12-30 months in most of the studies – “are usually not clinically significant due to uterine preservation,” with the one exception of vaginal hysterectomy with native tissue reconstruction, which the group recommended over laparoscopic sacrohysteropexy, Kate Meriwether, MD, a gynecologic surgeon at the University of Louisville, Ky., said at the annual scientific meeting of the Society of Gynecologic Surgeons.
Hysterectomy for prolapse surgery is common: More than 74,000 hysterectomies are done in the United States each year with prolapse as the main indication. Even so, it’s not always necessary to take out the uterus, and perhaps more than a third of women would prefer to keep theirs, Dr. Meriwether said, speaking on behalf of the SGS Systematic Review Group.
The recommendations from the Systematic Review Group must be sent to the SGS board and the full membership before they can be approved as guidelines.*
The Review Group made a grade A recommendation for vaginal hysterectomy with native tissue reconstruction over laparoscopic sacrohysteropexy, meaning it was based on high-quality evidence. The rest of the advice came in the form of suggestions, based on moderate grade B evidence, often nonrandomized comparative studies and case reviews.
The Review Group suggested uterine preservation during laparoscopic native tissue prolapse repair to reduce operating room (OR) time and blood loss, and preserve vaginal length, based on four nonrandomized comparison studies using various approaches, with a total of 446 women and up to 3 years’ follow-up. There might be a higher risk of apical recurrence without hysterectomy, but without worsening of prolapse symptoms.
The Review Group also suggested uterine preservation in transvaginal mesh reconstruction for prolapse, based on four RCTs and nine comparison studies with 1,381 women and up to 30 months’ follow-up. The studies found a decreased risk of mesh erosion, reoperating for mesh erosion, blood loss, and postop bleeding, and improved posterior and apical Pelvic Organ Prolapse Quantification scores when women keep their uterus.
However, “the patient should be counseled that there may be increased de novo stress incontinence, overactive bladder,” postop constipation, and shorter vaginal length, Dr. Meriwether said.
Also, “we suggest preservation of the uterus in transvaginal apical native tissue repair of prolapse, as it does not worsen any outcomes and slightly reduces OR time and estimated blood loss,” based on 13 studies, including four RCTs, and a total of 1,449 women followed for up to 26 months, she said.
The Review Group also came out in favor of the Manchester procedure, when available, over vaginal hysterectomy with native tissue suspension, based on one RCT and five nonrandomized studies involving 1,126 women and up to 61 months’ follow-up. The Manchester procedure pushed back the time to prolapse reoperation 9 months in one study, and also decreased transfusions, OR time, and blood loss. It also better preserved perineal length.
The group suggested uterine preservation when considering mesh sacrocolpopexy versus mesh sacrohysteropexy, to reduce mesh erosion, OR time, blood loss, hospital stay, and surgery costs, although there might be a slight worsening of Pelvic Floor Distress Inventory and Pelvic Floor Impact scores. The advice was based on nine nonrandomized comparison studies involving 745 women followed for up to 39 months. There was no difference in prolapse resolution between the two techniques.
The one grade A recommendation, for vaginal hysterectomy with native tissue reconstruction over laparoscopic sacrohysteropexy, was based on two RCTs with 182 women followed for up to 12 months.
Hysterectomy in those studies significantly reduced the risk of repeat surgery for prolapse and urinary symptoms, shortened OR time, and improved quality of life scores. However, the benefits came at the cost of slightly shorter vaginal length, worse Pelvic Organ Prolapse Quantification point C scores, greater blood loss, and up to a day longer spent in the hospital.
Dr. Meriwether reported having no relevant financial disclosures.
*Correction, 6/8/2017: An earlier version of this story misstated the status of the Systematic Review Group's recommendations. The recommendations have not been approved as official SGS guidelines. Also, the meeting sponsor information was updated.
SAN ANTONIO – The Systematic Review Group of the Society of Gynecologic Surgeons is suggesting uterine preservation, when not contraindicated, for most pelvic organ prolapse repairs to decrease mesh erosion, operating room time, and blood loss.
The advice is based on a review of 94 original studies, including 12 randomized controlled trials (RCTs) and 41 nonrandomized comparative studies, winnowed down to the strongest work from an original review of 7,324 abstracts through January 2017.
Short-term prolapse outcomes – 12-30 months in most of the studies – “are usually not clinically significant due to uterine preservation,” with the one exception of vaginal hysterectomy with native tissue reconstruction, which the group recommended over laparoscopic sacrohysteropexy, Kate Meriwether, MD, a gynecologic surgeon at the University of Louisville, Ky., said at the annual scientific meeting of the Society of Gynecologic Surgeons.
Hysterectomy for prolapse surgery is common: More than 74,000 hysterectomies are done in the United States each year with prolapse as the main indication. Even so, it’s not always necessary to take out the uterus, and perhaps more than a third of women would prefer to keep theirs, Dr. Meriwether said, speaking on behalf of the SGS Systematic Review Group.
The recommendations from the Systematic Review Group must be sent to the SGS board and the full membership before they can be approved as guidelines.*
The Review Group made a grade A recommendation for vaginal hysterectomy with native tissue reconstruction over laparoscopic sacrohysteropexy, meaning it was based on high-quality evidence. The rest of the advice came in the form of suggestions, based on moderate grade B evidence, often nonrandomized comparative studies and case reviews.
The Review Group suggested uterine preservation during laparoscopic native tissue prolapse repair to reduce operating room (OR) time and blood loss, and preserve vaginal length, based on four nonrandomized comparison studies using various approaches, with a total of 446 women and up to 3 years’ follow-up. There might be a higher risk of apical recurrence without hysterectomy, but without worsening of prolapse symptoms.
The Review Group also suggested uterine preservation in transvaginal mesh reconstruction for prolapse, based on four RCTs and nine comparison studies with 1,381 women and up to 30 months’ follow-up. The studies found a decreased risk of mesh erosion, reoperating for mesh erosion, blood loss, and postop bleeding, and improved posterior and apical Pelvic Organ Prolapse Quantification scores when women keep their uterus.
However, “the patient should be counseled that there may be increased de novo stress incontinence, overactive bladder,” postop constipation, and shorter vaginal length, Dr. Meriwether said.
Also, “we suggest preservation of the uterus in transvaginal apical native tissue repair of prolapse, as it does not worsen any outcomes and slightly reduces OR time and estimated blood loss,” based on 13 studies, including four RCTs, and a total of 1,449 women followed for up to 26 months, she said.
The Review Group also came out in favor of the Manchester procedure, when available, over vaginal hysterectomy with native tissue suspension, based on one RCT and five nonrandomized studies involving 1,126 women and up to 61 months’ follow-up. The Manchester procedure pushed back the time to prolapse reoperation 9 months in one study, and also decreased transfusions, OR time, and blood loss. It also better preserved perineal length.
The group suggested uterine preservation when considering mesh sacrocolpopexy versus mesh sacrohysteropexy, to reduce mesh erosion, OR time, blood loss, hospital stay, and surgery costs, although there might be a slight worsening of Pelvic Floor Distress Inventory and Pelvic Floor Impact scores. The advice was based on nine nonrandomized comparison studies involving 745 women followed for up to 39 months. There was no difference in prolapse resolution between the two techniques.
The one grade A recommendation, for vaginal hysterectomy with native tissue reconstruction over laparoscopic sacrohysteropexy, was based on two RCTs with 182 women followed for up to 12 months.
Hysterectomy in those studies significantly reduced the risk of repeat surgery for prolapse and urinary symptoms, shortened OR time, and improved quality of life scores. However, the benefits came at the cost of slightly shorter vaginal length, worse Pelvic Organ Prolapse Quantification point C scores, greater blood loss, and up to a day longer spent in the hospital.
Dr. Meriwether reported having no relevant financial disclosures.
*Correction, 6/8/2017: An earlier version of this story misstated the status of the Systematic Review Group's recommendations. The recommendations have not been approved as official SGS guidelines. Also, the meeting sponsor information was updated.
Ultrasound, cystoscopy combo tops CT for asymptomatic microscopic hematuria
Combining renal ultrasound and bladder cystoscopy is the most cost-effective approach for the initial evaluation of asymptomatic microscopic hematuria, even among patients at risk for genitourinary malignancy, according to a report published online April 17 in JAMA Internal Medicine.
“The superiority of this approach over the use of CT plus cystoscopy is driven primarily by higher costs of CT and the associated complications, albeit rare,” said Joshua A. Halpern, MD, of the department of urology, CornellUniversity, New York, and his associates. “Given the low prevalence of upper-tract malignant abnormalities in patients with asymptomatic microscopic hematuria, the small advantage in the sensitivity of CT imaging does not compensate for the significant additional costs.”
Every year, hundreds of thousands of patients undergo urinalysis for a variety of indications, and an estimated 40% are found to have microscopic hematuria in the absence of any urinary symptoms. This finding requires further evaluation because of one particular possible cause: a genitourinary malignancy. An estimated 11% of people with asymptomatic microscopic hematuria are found to have malignant abnormalities, the investigators said.
They assessed the cost-effectiveness of four common follow-up evaluations by creating a decision-analysis model to simulate the rates of cancer detection in adults with no history of cancer and with negative urine cultures that ruled out UTI as the cause of the hematuria.
The model was based on data from real-world experience in the medical literature and incorporated information on cancer incidence, diagnostic test accuracy, and complications.
The four approaches they examined were CT plus cystoscopy, which is considered the preferred method of diagnostic work-up by the American Urological Association; renal ultrasound plus cystoscopy, which many clinicians in the United States and other countries use instead; cystoscopy alone; and CT alone.
Compared with no follow-up evaluation, CT alone detected the fewest cancers (221 per 10,000 patients) at the highest cost ($9,300,000 per 10,000 patients). Cystoscopy alone detected 222 cancers per 10,000 at a cost of $10,287 per 10,000. Ultrasound plus cystoscopy detected 23 additional cancers per 10,000 patients at a relatively low cost of $53,810 per 10,000. Replacing ultrasound with CT detected just one additional cancer but cost an additional $6,480,484 per 10,000 patients.
The findings were similar in several sensitivity analyses, as well as in a subgroup analysis involving only higher-risk patients – men, smokers, and patients aged 50 years and older, the investigators noted (JAMA Intern Med. 2017 Apr 17. doi: 10.1001/jamaintenmed.2017.0739).
Dr. Halpern and his associates also applied their results to nationwide 2012 statistics for 485,222 patient visits to urologists to assess microscopic hematuria. If all urologists complied with AUA guidelines and used CT instead of ultrasound plus cystoscopy to assess these patients, they would have detected only 60 additional cancers, at an additional cost of $389,914,648.
Given these findings, renal ultrasound plus bladder cystoscopy should be considered the first-line assessment for these patients, Dr. Halpern and his associates said. Rewriting practice guidelines accordingly “will substantially reduce national expenditures associated with asymptomatic microscopic hematuria evaluation by up to $390 million.”
Moreover, recommending ultrasound rather than CT might have the unintended but beneficial consequence of improving compliance with further evaluation, because many primary care physicians are reluctant to refer these patients for radiocontrast CT studies, the researchers noted.
No sponsor was cited for this study. Dr. Halpern and his associates reported having no relevant financial disclosures.
The substantial differences between ultrasound and CT in cost per cancer detected, combined with the harm from CT-related contrast reactions and radiation exposure, strongly support renal ultrasound plus cystoscopy as the preferred first-line approach to assessing asymptomatic microscopic hematuria.
According to Halpern et al., this approach would cost approximately $54,000 per cancer detected. Replacing ultrasound with CT would detect just 1 additional cancer per 10,000 assessments, at an incremental cost of $6.5 million.
Leslee L. Subak, MD, and Deborah Grady, MD, are in the departments of obstetrics, gynecology, and reproductive sciences; urology; and epidemiology and biostatistics at the University of California, San Francisco. Dr. Subak reported receiving funding from Astellas to research urinary incontinence. Dr. Subak and Dr. Grady made these remarks in an invited commentary accompanying Dr. Halpern’s report (JAMA Intern Med. 2017 Apr 17. doi: 10.1001/jamainternmed.2017.0758).
The substantial differences between ultrasound and CT in cost per cancer detected, combined with the harm from CT-related contrast reactions and radiation exposure, strongly support renal ultrasound plus cystoscopy as the preferred first-line approach to assessing asymptomatic microscopic hematuria.
According to Halpern et al., this approach would cost approximately $54,000 per cancer detected. Replacing ultrasound with CT would detect just 1 additional cancer per 10,000 assessments, at an incremental cost of $6.5 million.
Leslee L. Subak, MD, and Deborah Grady, MD, are in the departments of obstetrics, gynecology, and reproductive sciences; urology; and epidemiology and biostatistics at the University of California, San Francisco. Dr. Subak reported receiving funding from Astellas to research urinary incontinence. Dr. Subak and Dr. Grady made these remarks in an invited commentary accompanying Dr. Halpern’s report (JAMA Intern Med. 2017 Apr 17. doi: 10.1001/jamainternmed.2017.0758).
The substantial differences between ultrasound and CT in cost per cancer detected, combined with the harm from CT-related contrast reactions and radiation exposure, strongly support renal ultrasound plus cystoscopy as the preferred first-line approach to assessing asymptomatic microscopic hematuria.
According to Halpern et al., this approach would cost approximately $54,000 per cancer detected. Replacing ultrasound with CT would detect just 1 additional cancer per 10,000 assessments, at an incremental cost of $6.5 million.
Leslee L. Subak, MD, and Deborah Grady, MD, are in the departments of obstetrics, gynecology, and reproductive sciences; urology; and epidemiology and biostatistics at the University of California, San Francisco. Dr. Subak reported receiving funding from Astellas to research urinary incontinence. Dr. Subak and Dr. Grady made these remarks in an invited commentary accompanying Dr. Halpern’s report (JAMA Intern Med. 2017 Apr 17. doi: 10.1001/jamainternmed.2017.0758).
Combining renal ultrasound and bladder cystoscopy is the most cost-effective approach for the initial evaluation of asymptomatic microscopic hematuria, even among patients at risk for genitourinary malignancy, according to a report published online April 17 in JAMA Internal Medicine.
“The superiority of this approach over the use of CT plus cystoscopy is driven primarily by higher costs of CT and the associated complications, albeit rare,” said Joshua A. Halpern, MD, of the department of urology, CornellUniversity, New York, and his associates. “Given the low prevalence of upper-tract malignant abnormalities in patients with asymptomatic microscopic hematuria, the small advantage in the sensitivity of CT imaging does not compensate for the significant additional costs.”
Every year, hundreds of thousands of patients undergo urinalysis for a variety of indications, and an estimated 40% are found to have microscopic hematuria in the absence of any urinary symptoms. This finding requires further evaluation because of one particular possible cause: a genitourinary malignancy. An estimated 11% of people with asymptomatic microscopic hematuria are found to have malignant abnormalities, the investigators said.
They assessed the cost-effectiveness of four common follow-up evaluations by creating a decision-analysis model to simulate the rates of cancer detection in adults with no history of cancer and with negative urine cultures that ruled out UTI as the cause of the hematuria.
The model was based on data from real-world experience in the medical literature and incorporated information on cancer incidence, diagnostic test accuracy, and complications.
The four approaches they examined were CT plus cystoscopy, which is considered the preferred method of diagnostic work-up by the American Urological Association; renal ultrasound plus cystoscopy, which many clinicians in the United States and other countries use instead; cystoscopy alone; and CT alone.
Compared with no follow-up evaluation, CT alone detected the fewest cancers (221 per 10,000 patients) at the highest cost ($9,300,000 per 10,000 patients). Cystoscopy alone detected 222 cancers per 10,000 at a cost of $10,287 per 10,000. Ultrasound plus cystoscopy detected 23 additional cancers per 10,000 patients at a relatively low cost of $53,810 per 10,000. Replacing ultrasound with CT detected just one additional cancer but cost an additional $6,480,484 per 10,000 patients.
The findings were similar in several sensitivity analyses, as well as in a subgroup analysis involving only higher-risk patients – men, smokers, and patients aged 50 years and older, the investigators noted (JAMA Intern Med. 2017 Apr 17. doi: 10.1001/jamaintenmed.2017.0739).
Dr. Halpern and his associates also applied their results to nationwide 2012 statistics for 485,222 patient visits to urologists to assess microscopic hematuria. If all urologists complied with AUA guidelines and used CT instead of ultrasound plus cystoscopy to assess these patients, they would have detected only 60 additional cancers, at an additional cost of $389,914,648.
Given these findings, renal ultrasound plus bladder cystoscopy should be considered the first-line assessment for these patients, Dr. Halpern and his associates said. Rewriting practice guidelines accordingly “will substantially reduce national expenditures associated with asymptomatic microscopic hematuria evaluation by up to $390 million.”
Moreover, recommending ultrasound rather than CT might have the unintended but beneficial consequence of improving compliance with further evaluation, because many primary care physicians are reluctant to refer these patients for radiocontrast CT studies, the researchers noted.
No sponsor was cited for this study. Dr. Halpern and his associates reported having no relevant financial disclosures.
Combining renal ultrasound and bladder cystoscopy is the most cost-effective approach for the initial evaluation of asymptomatic microscopic hematuria, even among patients at risk for genitourinary malignancy, according to a report published online April 17 in JAMA Internal Medicine.
“The superiority of this approach over the use of CT plus cystoscopy is driven primarily by higher costs of CT and the associated complications, albeit rare,” said Joshua A. Halpern, MD, of the department of urology, CornellUniversity, New York, and his associates. “Given the low prevalence of upper-tract malignant abnormalities in patients with asymptomatic microscopic hematuria, the small advantage in the sensitivity of CT imaging does not compensate for the significant additional costs.”
Every year, hundreds of thousands of patients undergo urinalysis for a variety of indications, and an estimated 40% are found to have microscopic hematuria in the absence of any urinary symptoms. This finding requires further evaluation because of one particular possible cause: a genitourinary malignancy. An estimated 11% of people with asymptomatic microscopic hematuria are found to have malignant abnormalities, the investigators said.
They assessed the cost-effectiveness of four common follow-up evaluations by creating a decision-analysis model to simulate the rates of cancer detection in adults with no history of cancer and with negative urine cultures that ruled out UTI as the cause of the hematuria.
The model was based on data from real-world experience in the medical literature and incorporated information on cancer incidence, diagnostic test accuracy, and complications.
The four approaches they examined were CT plus cystoscopy, which is considered the preferred method of diagnostic work-up by the American Urological Association; renal ultrasound plus cystoscopy, which many clinicians in the United States and other countries use instead; cystoscopy alone; and CT alone.
Compared with no follow-up evaluation, CT alone detected the fewest cancers (221 per 10,000 patients) at the highest cost ($9,300,000 per 10,000 patients). Cystoscopy alone detected 222 cancers per 10,000 at a cost of $10,287 per 10,000. Ultrasound plus cystoscopy detected 23 additional cancers per 10,000 patients at a relatively low cost of $53,810 per 10,000. Replacing ultrasound with CT detected just one additional cancer but cost an additional $6,480,484 per 10,000 patients.
The findings were similar in several sensitivity analyses, as well as in a subgroup analysis involving only higher-risk patients – men, smokers, and patients aged 50 years and older, the investigators noted (JAMA Intern Med. 2017 Apr 17. doi: 10.1001/jamaintenmed.2017.0739).
Dr. Halpern and his associates also applied their results to nationwide 2012 statistics for 485,222 patient visits to urologists to assess microscopic hematuria. If all urologists complied with AUA guidelines and used CT instead of ultrasound plus cystoscopy to assess these patients, they would have detected only 60 additional cancers, at an additional cost of $389,914,648.
Given these findings, renal ultrasound plus bladder cystoscopy should be considered the first-line assessment for these patients, Dr. Halpern and his associates said. Rewriting practice guidelines accordingly “will substantially reduce national expenditures associated with asymptomatic microscopic hematuria evaluation by up to $390 million.”
Moreover, recommending ultrasound rather than CT might have the unintended but beneficial consequence of improving compliance with further evaluation, because many primary care physicians are reluctant to refer these patients for radiocontrast CT studies, the researchers noted.
No sponsor was cited for this study. Dr. Halpern and his associates reported having no relevant financial disclosures.
FROM JAMA INTERNAL MEDICINE
Key clinical point: Combining renal ultrasound and bladder cystoscopy is the most cost-effective approach for the initial evaluation of asymptomatic microscopic hematuria.
Major finding: If all urologists complied with AUA guidelines and used CT instead of ultrasound plus cystoscopy to assess the 485,222 patients who were seen for asymptomatic microscopic hematuria in 2012, they would have detected only 60 additional cancers, at an additional cost of $389,914,648.
Data source: Decision-analysis modeling of four common approaches to assessing asymptomatic microscopic hematuria.
Disclosures: No sponsor was cited for this study. Dr. Halpern and his associates reported having no relevant financial disclosures.
Lupus low disease activity definition gains momentum
MELBOURNE – A metric for low disease activity in lupus is nearly ready for prime-time in both clinical practice and clinical trials, according to speakers at a recent international conference on systemic lupus erythematosus.
The Lupus Low Disease Activity State definition, developed by the Asia Pacific Lupus Collaboration, represents a state which, if sustained, is associated with a low likelihood of adverse outcome, said Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne.
“On the other hand, patients that are overall doing relatively well have less active disease and tend to look a little more homogeneous and potentially are easier to define,” Dr. Nikpour said. “If we’re able to define this group of patients who are doing well, that definition could potentially serve as a therapeutic target.”
The consensus definition of a Lupus Low Disease Activity State (LLDAS), contains five items. The first is that the patient must have a SLEDAI-2K score of less than or equal to 4, with no activity in major organs. Secondly, patients must show no new features of lupus activity, compared with the previous assessment. The third LLDAS item is a Physician Global Assessment score of 1 or less on a scale of 0 to 3. The fourth item is a current prednisolone or equivalent dose of 7.5 mg/day or less, and the fifth is that patients are on well-tolerated standard doses of immunosuppressants and approved biologic agents.
While the definition has been retrospectively validated, Dr. Nikpour presented data from a prospective study that examined the agreement between LLDAS and the clinical judgment of 50 lupus experts on 50 cases.
These data showed overall agreement between experts and LLDAS rating of remission or low, moderate, or high disease activity in 78% of cases.
“Where there were disagreements, when we looked at the cases in more detail, it really boiled down to whether the expert felt that serologic activity [such as] low complement/raised anti-dsDNA was important, and some experts also accepted prednisone doses up to 10 mg per day in what they thought would be a low disease activity state,” Dr. Nikpour said.
In the same session, Chak-Sing Lau, MBChB, MD, chair of rheumatology and clinical immunology at the University of Hong Kong, presented data from another prospective, cross-sectional validation study of the LLDAS measure in 339 lupus patients who were followed for 30 months.
This study showed that 92.6% of patients had ever achieved LLDAS during the study period, and 62.1% of patient days were spent in LLDAS. Researchers also found that patients who spent a higher percentage of time in LLDAS had a significantly lower incidence of flare, even after adjustment for gender and age.
Commenting on the study, Dr. Nikpour said LLDAS could be a feasible target for lupus – or at least part of one – and a therapeutic endpoint or outcome measure in clinical trials.
“We now have a prospective validation of LLDAS in the Asia Pacific cohort, again looking at protection against future flares, damage accrual, and perhaps even mortality, and a state which confers better health-related quality of life,” she said in an interview.
The study involved 305 patients with active disease who were randomized to standard of care plus 300 mg or 1,000 mg anifrolumab every 4 weeks, or placebo, with follow-up at 28 and 52 weeks.
The analysis showed that LLDAS was strongly associated with the trial’s primary endpoint of SRI-4 response plus a sustained reduction of oral corticosteroid dose to below 10 mg/day, although LLDAS also proved itself more stringent than the SRI-4 response criteria.
Similarly, LLDAS attainment was strongly associated with BILAG (British Isles Lupus Assessment Group)–Based Composite Lupus Assessment response but again, was more stringent. However LLDAS was less stringent than the major clinical response definition used in the study, which was BILAG ‘C’ or less across all systems for a minimum of 6 months.
Patients who achieved a low disease activity state at week 52 also showed significantly greater improvements in patient global score, and in seven of the eight lupus quality of life domains, compared with patients who did not achieve LLDAS.
“The purpose of this analysis is not to evaluate the efficacy of anifrolumab but rather to evaluate the utility of this measure, and we believe that this has been attained,” Dr. Morand told the audience.
In an interview, Dr. Morand said the accumulating evidence for the validity of LLDAS both in clinical trials and clinical practice was approaching a tipping point, with numerous presentations at the conference addressing the question of LLDAS.
“Of course those findings have to be peer reviewed and published, and probably it needs to be tested in another clinical trial or two and still hold water, but I think it’s got momentum now.”
Dr. Nikpour declared research support, honoraria, and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
MELBOURNE – A metric for low disease activity in lupus is nearly ready for prime-time in both clinical practice and clinical trials, according to speakers at a recent international conference on systemic lupus erythematosus.
The Lupus Low Disease Activity State definition, developed by the Asia Pacific Lupus Collaboration, represents a state which, if sustained, is associated with a low likelihood of adverse outcome, said Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne.
“On the other hand, patients that are overall doing relatively well have less active disease and tend to look a little more homogeneous and potentially are easier to define,” Dr. Nikpour said. “If we’re able to define this group of patients who are doing well, that definition could potentially serve as a therapeutic target.”
The consensus definition of a Lupus Low Disease Activity State (LLDAS), contains five items. The first is that the patient must have a SLEDAI-2K score of less than or equal to 4, with no activity in major organs. Secondly, patients must show no new features of lupus activity, compared with the previous assessment. The third LLDAS item is a Physician Global Assessment score of 1 or less on a scale of 0 to 3. The fourth item is a current prednisolone or equivalent dose of 7.5 mg/day or less, and the fifth is that patients are on well-tolerated standard doses of immunosuppressants and approved biologic agents.
While the definition has been retrospectively validated, Dr. Nikpour presented data from a prospective study that examined the agreement between LLDAS and the clinical judgment of 50 lupus experts on 50 cases.
These data showed overall agreement between experts and LLDAS rating of remission or low, moderate, or high disease activity in 78% of cases.
“Where there were disagreements, when we looked at the cases in more detail, it really boiled down to whether the expert felt that serologic activity [such as] low complement/raised anti-dsDNA was important, and some experts also accepted prednisone doses up to 10 mg per day in what they thought would be a low disease activity state,” Dr. Nikpour said.
In the same session, Chak-Sing Lau, MBChB, MD, chair of rheumatology and clinical immunology at the University of Hong Kong, presented data from another prospective, cross-sectional validation study of the LLDAS measure in 339 lupus patients who were followed for 30 months.
This study showed that 92.6% of patients had ever achieved LLDAS during the study period, and 62.1% of patient days were spent in LLDAS. Researchers also found that patients who spent a higher percentage of time in LLDAS had a significantly lower incidence of flare, even after adjustment for gender and age.
Commenting on the study, Dr. Nikpour said LLDAS could be a feasible target for lupus – or at least part of one – and a therapeutic endpoint or outcome measure in clinical trials.
“We now have a prospective validation of LLDAS in the Asia Pacific cohort, again looking at protection against future flares, damage accrual, and perhaps even mortality, and a state which confers better health-related quality of life,” she said in an interview.
The study involved 305 patients with active disease who were randomized to standard of care plus 300 mg or 1,000 mg anifrolumab every 4 weeks, or placebo, with follow-up at 28 and 52 weeks.
The analysis showed that LLDAS was strongly associated with the trial’s primary endpoint of SRI-4 response plus a sustained reduction of oral corticosteroid dose to below 10 mg/day, although LLDAS also proved itself more stringent than the SRI-4 response criteria.
Similarly, LLDAS attainment was strongly associated with BILAG (British Isles Lupus Assessment Group)–Based Composite Lupus Assessment response but again, was more stringent. However LLDAS was less stringent than the major clinical response definition used in the study, which was BILAG ‘C’ or less across all systems for a minimum of 6 months.
Patients who achieved a low disease activity state at week 52 also showed significantly greater improvements in patient global score, and in seven of the eight lupus quality of life domains, compared with patients who did not achieve LLDAS.
“The purpose of this analysis is not to evaluate the efficacy of anifrolumab but rather to evaluate the utility of this measure, and we believe that this has been attained,” Dr. Morand told the audience.
In an interview, Dr. Morand said the accumulating evidence for the validity of LLDAS both in clinical trials and clinical practice was approaching a tipping point, with numerous presentations at the conference addressing the question of LLDAS.
“Of course those findings have to be peer reviewed and published, and probably it needs to be tested in another clinical trial or two and still hold water, but I think it’s got momentum now.”
Dr. Nikpour declared research support, honoraria, and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
MELBOURNE – A metric for low disease activity in lupus is nearly ready for prime-time in both clinical practice and clinical trials, according to speakers at a recent international conference on systemic lupus erythematosus.
The Lupus Low Disease Activity State definition, developed by the Asia Pacific Lupus Collaboration, represents a state which, if sustained, is associated with a low likelihood of adverse outcome, said Mandana Nikpour, MBBS, PhD, of St. Vincent’s Hospital and the University of Melbourne.
“On the other hand, patients that are overall doing relatively well have less active disease and tend to look a little more homogeneous and potentially are easier to define,” Dr. Nikpour said. “If we’re able to define this group of patients who are doing well, that definition could potentially serve as a therapeutic target.”
The consensus definition of a Lupus Low Disease Activity State (LLDAS), contains five items. The first is that the patient must have a SLEDAI-2K score of less than or equal to 4, with no activity in major organs. Secondly, patients must show no new features of lupus activity, compared with the previous assessment. The third LLDAS item is a Physician Global Assessment score of 1 or less on a scale of 0 to 3. The fourth item is a current prednisolone or equivalent dose of 7.5 mg/day or less, and the fifth is that patients are on well-tolerated standard doses of immunosuppressants and approved biologic agents.
While the definition has been retrospectively validated, Dr. Nikpour presented data from a prospective study that examined the agreement between LLDAS and the clinical judgment of 50 lupus experts on 50 cases.
These data showed overall agreement between experts and LLDAS rating of remission or low, moderate, or high disease activity in 78% of cases.
“Where there were disagreements, when we looked at the cases in more detail, it really boiled down to whether the expert felt that serologic activity [such as] low complement/raised anti-dsDNA was important, and some experts also accepted prednisone doses up to 10 mg per day in what they thought would be a low disease activity state,” Dr. Nikpour said.
In the same session, Chak-Sing Lau, MBChB, MD, chair of rheumatology and clinical immunology at the University of Hong Kong, presented data from another prospective, cross-sectional validation study of the LLDAS measure in 339 lupus patients who were followed for 30 months.
This study showed that 92.6% of patients had ever achieved LLDAS during the study period, and 62.1% of patient days were spent in LLDAS. Researchers also found that patients who spent a higher percentage of time in LLDAS had a significantly lower incidence of flare, even after adjustment for gender and age.
Commenting on the study, Dr. Nikpour said LLDAS could be a feasible target for lupus – or at least part of one – and a therapeutic endpoint or outcome measure in clinical trials.
“We now have a prospective validation of LLDAS in the Asia Pacific cohort, again looking at protection against future flares, damage accrual, and perhaps even mortality, and a state which confers better health-related quality of life,” she said in an interview.
The study involved 305 patients with active disease who were randomized to standard of care plus 300 mg or 1,000 mg anifrolumab every 4 weeks, or placebo, with follow-up at 28 and 52 weeks.
The analysis showed that LLDAS was strongly associated with the trial’s primary endpoint of SRI-4 response plus a sustained reduction of oral corticosteroid dose to below 10 mg/day, although LLDAS also proved itself more stringent than the SRI-4 response criteria.
Similarly, LLDAS attainment was strongly associated with BILAG (British Isles Lupus Assessment Group)–Based Composite Lupus Assessment response but again, was more stringent. However LLDAS was less stringent than the major clinical response definition used in the study, which was BILAG ‘C’ or less across all systems for a minimum of 6 months.
Patients who achieved a low disease activity state at week 52 also showed significantly greater improvements in patient global score, and in seven of the eight lupus quality of life domains, compared with patients who did not achieve LLDAS.
“The purpose of this analysis is not to evaluate the efficacy of anifrolumab but rather to evaluate the utility of this measure, and we believe that this has been attained,” Dr. Morand told the audience.
In an interview, Dr. Morand said the accumulating evidence for the validity of LLDAS both in clinical trials and clinical practice was approaching a tipping point, with numerous presentations at the conference addressing the question of LLDAS.
“Of course those findings have to be peer reviewed and published, and probably it needs to be tested in another clinical trial or two and still hold water, but I think it’s got momentum now.”
Dr. Nikpour declared research support, honoraria, and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
Key clinical point:
Major finding: The Lupus Low Disease Activity State definition shows significant agreement with clinical judgment and with other endpoints of treatment response, and is associated with a reduced risk of disease flare.
Data source: Three prospective validation studies, two cohort studies, and one clinical trial.
Disclosures: Dr. Nikpour declared research support, honoraria and consultancies with several pharmaceutical companies. The MUSE trial was funded by MedImmune, and Dr. Morand declared research support, consultancies, and travel funding from several pharmaceutical companies. Dr. Lau declared advisory board and consultancy roles with several pharmaceutical companies.
Neoadjuvant therapy timing may impact pancreatic cancer outcomes
SEATTLE – In patients with pancreatic cancer, an interval of 8 weeks between receiving neoadjuvant chemoradiation and surgical resection may improve resection margins, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.
The delay in resection did not negatively impact outcomes, and there was a modest improvement in overall survival among patients who had an 8-10 week interval between treatments.
“Attention should be focused on the treatment interval to time of resection in prospective studies,” said lead study author Raphael J. Louie, MD, of Dartmouth (N.H.) Hitchcock Norris Cotton Cancer Center.
Dr. Louie explained that for patients with pancreatic adenocarcinoma who receive neoadjuvant chemoradiation, it is unclear how long the optimal interval should be between therapy completion and surgical resection.
For this study, Dr. Louie and his colleagues sought to determine the optimal interval between neoadjuvant therapy and surgery to maximize response and oncologic outcomes.
“We hypothesized that there may be benefit to a delay,” he said.
The retrospective analysis included 637 patients who had been diagnosed with pancreatic adenocarcinoma at the Norris Cotton Cancer Center, and who had completed neoadjuvant chemoradiation and underwent R0 surgical resection between Jan. 1, 2004, and Dec. 31, 2015.
Of this group, 195 patients had metastatic disease, 28 underwent upfront surgical exploration, and 94 were lost to follow-up or had a poor performance status and were not included in the final analysis.
The cohort was grouped according to time from chemoradiation completion to surgery: 6-8 weeks, 8-10 weeks, and more than 10 weeks.
A total of 320 patients received neoadjuvant chemoradiation and 288 completed the full course. Of this group, 128 were evaluable by pathologic review.
Among patients with a 6- to 8-week interval, 61% had an R0 resection margin. This percentage rose to 72% for those who had an 8- to 10-week interval, and in similar fashion, 70% for those who had a 10- to 13-week interval (P = .6)
However, there was no statistical difference when the three groups were compared collectively.
Of 26 patients who were resected within 6-8 weeks of chemoradiation, 11% achieved a complete response (CR), 27% had a partial response (PR), and 61% had recurrence for an average disease-free survival of 20 months.
In the group (n = 58) of patients who were resected within 8-10 weeks, 7% had CR, 71% had PR, and 62% had recurrence, for an average disease-free survival of 17 months. Finally, the 44 patients who were resected within 10-13 weeks had similar outcomes; 5% had CR, 61% had PR, and 61% of patients had recurrence for an average disease-free survival of 14 months.
Dr. Louie noted that even though they observed improved PR in the 8- to 10-week group, there was no statistical significance in disease-free survival (P = .71) or overall survival (P = .19).
“Allowing more time from neoadjuvant therapy completion to surgical resection may improve the pathologic response,” said Dr. Louie. “Larger studies are needed to determine if the time interval to surgical resection has oncologic benefit for these patients.”
Dr. Louie has no disclosures.
SEATTLE – In patients with pancreatic cancer, an interval of 8 weeks between receiving neoadjuvant chemoradiation and surgical resection may improve resection margins, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.
The delay in resection did not negatively impact outcomes, and there was a modest improvement in overall survival among patients who had an 8-10 week interval between treatments.
“Attention should be focused on the treatment interval to time of resection in prospective studies,” said lead study author Raphael J. Louie, MD, of Dartmouth (N.H.) Hitchcock Norris Cotton Cancer Center.
Dr. Louie explained that for patients with pancreatic adenocarcinoma who receive neoadjuvant chemoradiation, it is unclear how long the optimal interval should be between therapy completion and surgical resection.
For this study, Dr. Louie and his colleagues sought to determine the optimal interval between neoadjuvant therapy and surgery to maximize response and oncologic outcomes.
“We hypothesized that there may be benefit to a delay,” he said.
The retrospective analysis included 637 patients who had been diagnosed with pancreatic adenocarcinoma at the Norris Cotton Cancer Center, and who had completed neoadjuvant chemoradiation and underwent R0 surgical resection between Jan. 1, 2004, and Dec. 31, 2015.
Of this group, 195 patients had metastatic disease, 28 underwent upfront surgical exploration, and 94 were lost to follow-up or had a poor performance status and were not included in the final analysis.
The cohort was grouped according to time from chemoradiation completion to surgery: 6-8 weeks, 8-10 weeks, and more than 10 weeks.
A total of 320 patients received neoadjuvant chemoradiation and 288 completed the full course. Of this group, 128 were evaluable by pathologic review.
Among patients with a 6- to 8-week interval, 61% had an R0 resection margin. This percentage rose to 72% for those who had an 8- to 10-week interval, and in similar fashion, 70% for those who had a 10- to 13-week interval (P = .6)
However, there was no statistical difference when the three groups were compared collectively.
Of 26 patients who were resected within 6-8 weeks of chemoradiation, 11% achieved a complete response (CR), 27% had a partial response (PR), and 61% had recurrence for an average disease-free survival of 20 months.
In the group (n = 58) of patients who were resected within 8-10 weeks, 7% had CR, 71% had PR, and 62% had recurrence, for an average disease-free survival of 17 months. Finally, the 44 patients who were resected within 10-13 weeks had similar outcomes; 5% had CR, 61% had PR, and 61% of patients had recurrence for an average disease-free survival of 14 months.
Dr. Louie noted that even though they observed improved PR in the 8- to 10-week group, there was no statistical significance in disease-free survival (P = .71) or overall survival (P = .19).
“Allowing more time from neoadjuvant therapy completion to surgical resection may improve the pathologic response,” said Dr. Louie. “Larger studies are needed to determine if the time interval to surgical resection has oncologic benefit for these patients.”
Dr. Louie has no disclosures.
SEATTLE – In patients with pancreatic cancer, an interval of 8 weeks between receiving neoadjuvant chemoradiation and surgical resection may improve resection margins, according to findings presented at the annual Society of Surgical Oncology Cancer Symposium.
The delay in resection did not negatively impact outcomes, and there was a modest improvement in overall survival among patients who had an 8-10 week interval between treatments.
“Attention should be focused on the treatment interval to time of resection in prospective studies,” said lead study author Raphael J. Louie, MD, of Dartmouth (N.H.) Hitchcock Norris Cotton Cancer Center.
Dr. Louie explained that for patients with pancreatic adenocarcinoma who receive neoadjuvant chemoradiation, it is unclear how long the optimal interval should be between therapy completion and surgical resection.
For this study, Dr. Louie and his colleagues sought to determine the optimal interval between neoadjuvant therapy and surgery to maximize response and oncologic outcomes.
“We hypothesized that there may be benefit to a delay,” he said.
The retrospective analysis included 637 patients who had been diagnosed with pancreatic adenocarcinoma at the Norris Cotton Cancer Center, and who had completed neoadjuvant chemoradiation and underwent R0 surgical resection between Jan. 1, 2004, and Dec. 31, 2015.
Of this group, 195 patients had metastatic disease, 28 underwent upfront surgical exploration, and 94 were lost to follow-up or had a poor performance status and were not included in the final analysis.
The cohort was grouped according to time from chemoradiation completion to surgery: 6-8 weeks, 8-10 weeks, and more than 10 weeks.
A total of 320 patients received neoadjuvant chemoradiation and 288 completed the full course. Of this group, 128 were evaluable by pathologic review.
Among patients with a 6- to 8-week interval, 61% had an R0 resection margin. This percentage rose to 72% for those who had an 8- to 10-week interval, and in similar fashion, 70% for those who had a 10- to 13-week interval (P = .6)
However, there was no statistical difference when the three groups were compared collectively.
Of 26 patients who were resected within 6-8 weeks of chemoradiation, 11% achieved a complete response (CR), 27% had a partial response (PR), and 61% had recurrence for an average disease-free survival of 20 months.
In the group (n = 58) of patients who were resected within 8-10 weeks, 7% had CR, 71% had PR, and 62% had recurrence, for an average disease-free survival of 17 months. Finally, the 44 patients who were resected within 10-13 weeks had similar outcomes; 5% had CR, 61% had PR, and 61% of patients had recurrence for an average disease-free survival of 14 months.
Dr. Louie noted that even though they observed improved PR in the 8- to 10-week group, there was no statistical significance in disease-free survival (P = .71) or overall survival (P = .19).
“Allowing more time from neoadjuvant therapy completion to surgical resection may improve the pathologic response,” said Dr. Louie. “Larger studies are needed to determine if the time interval to surgical resection has oncologic benefit for these patients.”
Dr. Louie has no disclosures.
AT SSO 2017
Key clinical point: A longer interval between neoadjuvant therapy and surgical resection could improve some outcomes in pancreatic cancer.
Major finding: Resection after 8 weeks may improve resection margins and may provide a modest improvement in survival for some patients.
Data source: Retrospective cohort study of 128 evaluable patients with biopsy-proven pancreatic adenocarcinoma who received neoadjuvant chemoradiation.
Disclosures: Dr. Louie has no disclosures.
Guideline endorses doublet therapy after pancreatic cancer surgery in chemo-naive patients
A recommendation on postop adjuvant chemotherapy has been updated in the Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline, according to an article published online on April 11 in the Journal of Clinical Oncology.
In the absence of medical or surgical contraindications, all patients who have resected pancreatic cancer and did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy, according to the new recommendation. “The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance; alternatively, monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered. Adjuvant treatment should be initiated within 8 weeks of surgical resection, assuming complete recovery,” Alok A. Khorana, MD, of the Cleveland Clinic, and members of the guideline committee wrote.
The recommendation was based on results of the ESPAC-4 study, a multicenter, international, open-label randomized controlled phase III trial (Lancet. 2017;389:1011-24). ESPAC-4 compared adjuvant combination chemotherapy of gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma.
Median overall survival was 28 months (95% confidence interval, 23.5-31.5 months) in the doublet arm and 25.5 months (95% CI, 22.7 to 27.9 months) for gemcitabine alone (hazard ratio, 0.82; 95% CI, 0.68-0.98; P = .032). Grade 3 and 4 adverse events were similar in both arms, although higher rates of hand-foot syndrome and diarrhea occurred in patients randomly assigned to the doublet arm.
The remaining recommendations from the original 2016 ASCO guideline are unchanged.
The revised guideline is available at this link.
[email protected]
On Twitter @maryjodales
A recommendation on postop adjuvant chemotherapy has been updated in the Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline, according to an article published online on April 11 in the Journal of Clinical Oncology.
In the absence of medical or surgical contraindications, all patients who have resected pancreatic cancer and did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy, according to the new recommendation. “The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance; alternatively, monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered. Adjuvant treatment should be initiated within 8 weeks of surgical resection, assuming complete recovery,” Alok A. Khorana, MD, of the Cleveland Clinic, and members of the guideline committee wrote.
The recommendation was based on results of the ESPAC-4 study, a multicenter, international, open-label randomized controlled phase III trial (Lancet. 2017;389:1011-24). ESPAC-4 compared adjuvant combination chemotherapy of gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma.
Median overall survival was 28 months (95% confidence interval, 23.5-31.5 months) in the doublet arm and 25.5 months (95% CI, 22.7 to 27.9 months) for gemcitabine alone (hazard ratio, 0.82; 95% CI, 0.68-0.98; P = .032). Grade 3 and 4 adverse events were similar in both arms, although higher rates of hand-foot syndrome and diarrhea occurred in patients randomly assigned to the doublet arm.
The remaining recommendations from the original 2016 ASCO guideline are unchanged.
The revised guideline is available at this link.
[email protected]
On Twitter @maryjodales
A recommendation on postop adjuvant chemotherapy has been updated in the Potentially Curable Pancreatic Cancer: American Society of Clinical Oncology Clinical Practice Guideline, according to an article published online on April 11 in the Journal of Clinical Oncology.
In the absence of medical or surgical contraindications, all patients who have resected pancreatic cancer and did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy, according to the new recommendation. “The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance; alternatively, monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered. Adjuvant treatment should be initiated within 8 weeks of surgical resection, assuming complete recovery,” Alok A. Khorana, MD, of the Cleveland Clinic, and members of the guideline committee wrote.
The recommendation was based on results of the ESPAC-4 study, a multicenter, international, open-label randomized controlled phase III trial (Lancet. 2017;389:1011-24). ESPAC-4 compared adjuvant combination chemotherapy of gemcitabine and capecitabine with gemcitabine monotherapy in 730 evaluable patients with resected pancreatic ductal adenocarcinoma.
Median overall survival was 28 months (95% confidence interval, 23.5-31.5 months) in the doublet arm and 25.5 months (95% CI, 22.7 to 27.9 months) for gemcitabine alone (hazard ratio, 0.82; 95% CI, 0.68-0.98; P = .032). Grade 3 and 4 adverse events were similar in both arms, although higher rates of hand-foot syndrome and diarrhea occurred in patients randomly assigned to the doublet arm.
The remaining recommendations from the original 2016 ASCO guideline are unchanged.
The revised guideline is available at this link.
[email protected]
On Twitter @maryjodales
FROM THE JOURNAL OF CLINICAL ONCOLOGY