On Feb. 17, 2022, the updated Recommended Childhood and Adolescent Immunization Schedule was released by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention. Pediatric providers across the country eagerly await this annual update to learn what changes lie in store for recommended immunization practices. During the week that has gone by since the 2022 release, I’ve had a chance to reflect on some of the highlights that are worth noting.

The SARS-CoV-2 (COVID-19) vaccines are not on the schedule yet, undoubtedly because of the preliminary nature of the vaccine data for children and the emergency use authorization vaccine status. We currently have interim recommendations for childhood COVID-19 vaccines.
 

Brand new in 2022

Two new items in the 2022 schedules are worth reviewing. The first is an entirely new recommendation to administer dengue vaccine to children aged 9-16 years living in endemic areas, but only if they already have laboratory-confirmed past dengue infection. For U.S. practitioners, the endemic areas to remember are Puerto Rico and the U.S. Virgin islands in the Caribbean, as well as Pacific island areas, such as the Marshall Islands, Palau, and the Federated States of Micronesia. There is a link in the document to additional recommendations.

The second totally new item is the combination preparation, Vaxelis, which contains DTaP, inactivated poliovirus, Haemophilus influenzae b conjugate, and hepatitis B vaccines. There are extensive recommendations for how to work it into the vaccine schedule, including some situations when it should not be used.
 

Selected reminders in childhood immunization

I’ll start with some key reminders about what not to do. Remember that the live inactivated influenza virus vaccine (LAIV) is recommended to begin only at age 2 years and older, compared with the inactivated influenza vaccine, which begins at 6 months. In addition, LAIV is contraindicated in patients aged 2-4 years who have a history of asthma or wheezing. Remember to avoid live virus vaccines, such as LAIV, MMR, and varicella, during pregnancy but be ready to administer those vaccines right after delivery. Similarly, HPV vaccine should be delayed until after pregnancy.

There are many special situation recommendations; I’ll highlight only a few here. One reminder is that although MMR and hepatitis A are both recommended to begin at 12 months, infants aged 6-11 months who are undergoing international travel to high-risk areas can begin with one dose before departure and then receive a two-dose series after turning 12 months of age.

Pneumococcal vaccination. Some children should receive both the pneumococcal conjugate vaccine (PCV13) and the pneumococcal polysaccharide vaccine (PPSV23). Those groups include children with chronic heart disease, chronic lung disease, diabetes, cerebral spinal fluid leaks or cochlear implants, and sickle cell disease, as well as many other immunocompromising conditions. Kids who need both preparations should receive the conjugate vaccine first, but they should never receive the conjugate vaccine and the polysaccharide vaccine at the same visit.

Meningococcal vaccination. Meningococcal vaccine special situations can be quite complicated. For meningococcus A,C,W,Y (MenACWY) vaccination, children with immunocompromising conditions should receive different schedules from those of typical children, but the recommendations vary by preparation.

For adolescents aged 16-23 years, the decision whether to administer the meningococcal serogroup B (MenB) vaccine is based on shared clinical decision-making, a recommendation that began in 2020. Patients with certain immunocompromising conditions are considered at higher risk and should more routinely receive MenB vaccination, with recommendations varying depending on the preparation utilized. The MenB preparations are not interchangeable. In addition, patients may receive both MenACWY and MenB vaccines on the same day, but they should be given at different body sites.
 

A few final reminders

In certain cases, you might avoid administering what would otherwise be routine vaccinations. For example, the rotavirus series should not begin if the infant is aged 15 weeks or older. Only one dose of Haemophilus influenzae b vaccine is indicated after age 15 months and none at 60 months or older if the child does not have high-risk conditions.

Finally, the total number of doses for some vaccines, such as pneumococcus and polio, vary depending on how old the child is if not already fully vaccinated. For example, for pneumococcal conjugate vaccine catch-up in a healthy child, one dose after age 24 months would bring the child up to date. For inactivated poliovirus in children aged 4 years or older, a third dose given at least 6 months after the second dose would bring that child up to date.

The tables can be a challenge to interpret, but fortunately simpler tables for parents are available. These make excellent handouts to have available in the office!
 

Dr. Basco is professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

On Feb. 17, 2022, the updated Recommended Childhood and Adolescent Immunization Schedule was released by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention. Pediatric providers across the country eagerly await this annual update to learn what changes lie in store for recommended immunization practices. During the week that has gone by since the 2022 release, I’ve had a chance to reflect on some of the highlights that are worth noting.

The SARS-CoV-2 (COVID-19) vaccines are not on the schedule yet, undoubtedly because of the preliminary nature of the vaccine data for children and the emergency use authorization vaccine status. We currently have interim recommendations for childhood COVID-19 vaccines.
 

Brand new in 2022

Two new items in the 2022 schedules are worth reviewing. The first is an entirely new recommendation to administer dengue vaccine to children aged 9-16 years living in endemic areas, but only if they already have laboratory-confirmed past dengue infection. For U.S. practitioners, the endemic areas to remember are Puerto Rico and the U.S. Virgin islands in the Caribbean, as well as Pacific island areas, such as the Marshall Islands, Palau, and the Federated States of Micronesia. There is a link in the document to additional recommendations.

The second totally new item is the combination preparation, Vaxelis, which contains DTaP, inactivated poliovirus, Haemophilus influenzae b conjugate, and hepatitis B vaccines. There are extensive recommendations for how to work it into the vaccine schedule, including some situations when it should not be used.
 

Selected reminders in childhood immunization

I’ll start with some key reminders about what not to do. Remember that the live inactivated influenza virus vaccine (LAIV) is recommended to begin only at age 2 years and older, compared with the inactivated influenza vaccine, which begins at 6 months. In addition, LAIV is contraindicated in patients aged 2-4 years who have a history of asthma or wheezing. Remember to avoid live virus vaccines, such as LAIV, MMR, and varicella, during pregnancy but be ready to administer those vaccines right after delivery. Similarly, HPV vaccine should be delayed until after pregnancy.

There are many special situation recommendations; I’ll highlight only a few here. One reminder is that although MMR and hepatitis A are both recommended to begin at 12 months, infants aged 6-11 months who are undergoing international travel to high-risk areas can begin with one dose before departure and then receive a two-dose series after turning 12 months of age.

Pneumococcal vaccination. Some children should receive both the pneumococcal conjugate vaccine (PCV13) and the pneumococcal polysaccharide vaccine (PPSV23). Those groups include children with chronic heart disease, chronic lung disease, diabetes, cerebral spinal fluid leaks or cochlear implants, and sickle cell disease, as well as many other immunocompromising conditions. Kids who need both preparations should receive the conjugate vaccine first, but they should never receive the conjugate vaccine and the polysaccharide vaccine at the same visit.

Meningococcal vaccination. Meningococcal vaccine special situations can be quite complicated. For meningococcus A,C,W,Y (MenACWY) vaccination, children with immunocompromising conditions should receive different schedules from those of typical children, but the recommendations vary by preparation.

For adolescents aged 16-23 years, the decision whether to administer the meningococcal serogroup B (MenB) vaccine is based on shared clinical decision-making, a recommendation that began in 2020. Patients with certain immunocompromising conditions are considered at higher risk and should more routinely receive MenB vaccination, with recommendations varying depending on the preparation utilized. The MenB preparations are not interchangeable. In addition, patients may receive both MenACWY and MenB vaccines on the same day, but they should be given at different body sites.
 

A few final reminders

In certain cases, you might avoid administering what would otherwise be routine vaccinations. For example, the rotavirus series should not begin if the infant is aged 15 weeks or older. Only one dose of Haemophilus influenzae b vaccine is indicated after age 15 months and none at 60 months or older if the child does not have high-risk conditions.

Finally, the total number of doses for some vaccines, such as pneumococcus and polio, vary depending on how old the child is if not already fully vaccinated. For example, for pneumococcal conjugate vaccine catch-up in a healthy child, one dose after age 24 months would bring the child up to date. For inactivated poliovirus in children aged 4 years or older, a third dose given at least 6 months after the second dose would bring that child up to date.

The tables can be a challenge to interpret, but fortunately simpler tables for parents are available. These make excellent handouts to have available in the office!
 

Dr. Basco is professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

On Feb. 17, 2022, the updated Recommended Childhood and Adolescent Immunization Schedule was released by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention. Pediatric providers across the country eagerly await this annual update to learn what changes lie in store for recommended immunization practices. During the week that has gone by since the 2022 release, I’ve had a chance to reflect on some of the highlights that are worth noting.

The SARS-CoV-2 (COVID-19) vaccines are not on the schedule yet, undoubtedly because of the preliminary nature of the vaccine data for children and the emergency use authorization vaccine status. We currently have interim recommendations for childhood COVID-19 vaccines.
 

Brand new in 2022

Two new items in the 2022 schedules are worth reviewing. The first is an entirely new recommendation to administer dengue vaccine to children aged 9-16 years living in endemic areas, but only if they already have laboratory-confirmed past dengue infection. For U.S. practitioners, the endemic areas to remember are Puerto Rico and the U.S. Virgin islands in the Caribbean, as well as Pacific island areas, such as the Marshall Islands, Palau, and the Federated States of Micronesia. There is a link in the document to additional recommendations.

The second totally new item is the combination preparation, Vaxelis, which contains DTaP, inactivated poliovirus, Haemophilus influenzae b conjugate, and hepatitis B vaccines. There are extensive recommendations for how to work it into the vaccine schedule, including some situations when it should not be used.
 

Selected reminders in childhood immunization

I’ll start with some key reminders about what not to do. Remember that the live inactivated influenza virus vaccine (LAIV) is recommended to begin only at age 2 years and older, compared with the inactivated influenza vaccine, which begins at 6 months. In addition, LAIV is contraindicated in patients aged 2-4 years who have a history of asthma or wheezing. Remember to avoid live virus vaccines, such as LAIV, MMR, and varicella, during pregnancy but be ready to administer those vaccines right after delivery. Similarly, HPV vaccine should be delayed until after pregnancy.

There are many special situation recommendations; I’ll highlight only a few here. One reminder is that although MMR and hepatitis A are both recommended to begin at 12 months, infants aged 6-11 months who are undergoing international travel to high-risk areas can begin with one dose before departure and then receive a two-dose series after turning 12 months of age.

Pneumococcal vaccination. Some children should receive both the pneumococcal conjugate vaccine (PCV13) and the pneumococcal polysaccharide vaccine (PPSV23). Those groups include children with chronic heart disease, chronic lung disease, diabetes, cerebral spinal fluid leaks or cochlear implants, and sickle cell disease, as well as many other immunocompromising conditions. Kids who need both preparations should receive the conjugate vaccine first, but they should never receive the conjugate vaccine and the polysaccharide vaccine at the same visit.

Meningococcal vaccination. Meningococcal vaccine special situations can be quite complicated. For meningococcus A,C,W,Y (MenACWY) vaccination, children with immunocompromising conditions should receive different schedules from those of typical children, but the recommendations vary by preparation.

For adolescents aged 16-23 years, the decision whether to administer the meningococcal serogroup B (MenB) vaccine is based on shared clinical decision-making, a recommendation that began in 2020. Patients with certain immunocompromising conditions are considered at higher risk and should more routinely receive MenB vaccination, with recommendations varying depending on the preparation utilized. The MenB preparations are not interchangeable. In addition, patients may receive both MenACWY and MenB vaccines on the same day, but they should be given at different body sites.
 

A few final reminders

In certain cases, you might avoid administering what would otherwise be routine vaccinations. For example, the rotavirus series should not begin if the infant is aged 15 weeks or older. Only one dose of Haemophilus influenzae b vaccine is indicated after age 15 months and none at 60 months or older if the child does not have high-risk conditions.

Finally, the total number of doses for some vaccines, such as pneumococcus and polio, vary depending on how old the child is if not already fully vaccinated. For example, for pneumococcal conjugate vaccine catch-up in a healthy child, one dose after age 24 months would bring the child up to date. For inactivated poliovirus in children aged 4 years or older, a third dose given at least 6 months after the second dose would bring that child up to date.

The tables can be a challenge to interpret, but fortunately simpler tables for parents are available. These make excellent handouts to have available in the office!
 

Dr. Basco is professor of pediatrics at the Medical University of South Carolina, Charleston, and director of the division of general pediatrics. He disclosed no relevant financial relationships. A version of this article first appeared on Medscape.com.

Catholic Medical Center has agreed to pay $3.8 million to settle claims it provided free call coverage to a cardiologist in exchange for patient referrals to the Manchester, N.H., hospital, according to federal officials.

“The cardiologist who received the free call coverage referred millions of dollars in medical procedures and services to CMC over the decade in which the free services were provided,” the Department of Justice said in a news release.

Because the hospital submitted claims for payment to Medicare, Medicaid, and other federal health care programs for the services referred by the cardiologist, the government alleged the claims were the result of unlawful kickbacks.

The settlement resolves allegations brought in a whistleblower lawsuit filed in 2018 by cardiologist David Goldberg, MD, who previously worked at Catholic Medical Center (CMC) and is represented by Douglas, Leonard & Garvey.

The news release did not name the cardiologist involved in the alleged kickback scheme but the recently unsealed lawsuit says CMC paid its cardiologists above market rates ($10,000 per weekend, $3,000 per night) to provide free coverage services for Mary-Claire Paicopolis, MD.

The lawsuit also claims Dr. Paicopolis insisted the hospital implant only Boston Scientific devices in her patients and that her preferred electrophysiologist use only its Rhythmia mapping system during ablation procedures. To keep CMC from objecting, the suit alleges Boston Scientific offered CMC early access to its Watchman left atrial appendage occluder and provided “unprecedented” support to a nonacademic community hospital site.

“It went back several years, and that and the other issues in the suit were strong motivators for Dr. Goldberg to try to rectify the situation and he deserves a lot of credit for having done so,” attorney Charles G. Douglas III told this news organization.

Dr. Goldberg will receive $570,000 of the $3.8 million settlement as well as $145,361 in expenses, attorney fees, and costs.

Although not addressed in the federal news release, the lawsuit also alleges that CMC staff manipulated mortality data by discharging patients from the ICU and then readmitting them to hospice with a new patient number, “thereby avoiding the need to claim a surgical mortality.”

The lawsuit also says CMC “created a practice of covering up medical errors” and detailed 12 patient deaths between 2012 and 2018, alleging that these deaths were the result of substandard care.

CMC spokesperson Lauren Collins-Cline said in an email that the call coverage arrangement is no longer in place and originated almost 15 years ago with the input of legal counsel in order to provide high-quality care for patients.

“While CMC vigorously disagrees with the government’s allegations that this arrangement violated federal law, we have agreed to settle in order to avoid long costly civil litigation,” she said.

As to the other claims in the complaint, Ms. Collins-Cline said they were investigated by the government and dismissed per the settlement agreement. “CMC holds itself to the highest ethical standards in patient care and business conduct. That’s embedded in our mission and will always remain our highest priority.”

Mr. Douglas, however, said the government retains the right to pursue other claims in the lawsuit in the future. “So, [the hospital] is a little more optimistic than the reality of what the government agrees is the situation.”

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

Catholic Medical Center has agreed to pay $3.8 million to settle claims it provided free call coverage to a cardiologist in exchange for patient referrals to the Manchester, N.H., hospital, according to federal officials.

“The cardiologist who received the free call coverage referred millions of dollars in medical procedures and services to CMC over the decade in which the free services were provided,” the Department of Justice said in a news release.

Because the hospital submitted claims for payment to Medicare, Medicaid, and other federal health care programs for the services referred by the cardiologist, the government alleged the claims were the result of unlawful kickbacks.

The settlement resolves allegations brought in a whistleblower lawsuit filed in 2018 by cardiologist David Goldberg, MD, who previously worked at Catholic Medical Center (CMC) and is represented by Douglas, Leonard & Garvey.

The news release did not name the cardiologist involved in the alleged kickback scheme but the recently unsealed lawsuit says CMC paid its cardiologists above market rates ($10,000 per weekend, $3,000 per night) to provide free coverage services for Mary-Claire Paicopolis, MD.

The lawsuit also claims Dr. Paicopolis insisted the hospital implant only Boston Scientific devices in her patients and that her preferred electrophysiologist use only its Rhythmia mapping system during ablation procedures. To keep CMC from objecting, the suit alleges Boston Scientific offered CMC early access to its Watchman left atrial appendage occluder and provided “unprecedented” support to a nonacademic community hospital site.

“It went back several years, and that and the other issues in the suit were strong motivators for Dr. Goldberg to try to rectify the situation and he deserves a lot of credit for having done so,” attorney Charles G. Douglas III told this news organization.

Dr. Goldberg will receive $570,000 of the $3.8 million settlement as well as $145,361 in expenses, attorney fees, and costs.

Although not addressed in the federal news release, the lawsuit also alleges that CMC staff manipulated mortality data by discharging patients from the ICU and then readmitting them to hospice with a new patient number, “thereby avoiding the need to claim a surgical mortality.”

The lawsuit also says CMC “created a practice of covering up medical errors” and detailed 12 patient deaths between 2012 and 2018, alleging that these deaths were the result of substandard care.

CMC spokesperson Lauren Collins-Cline said in an email that the call coverage arrangement is no longer in place and originated almost 15 years ago with the input of legal counsel in order to provide high-quality care for patients.

“While CMC vigorously disagrees with the government’s allegations that this arrangement violated federal law, we have agreed to settle in order to avoid long costly civil litigation,” she said.

As to the other claims in the complaint, Ms. Collins-Cline said they were investigated by the government and dismissed per the settlement agreement. “CMC holds itself to the highest ethical standards in patient care and business conduct. That’s embedded in our mission and will always remain our highest priority.”

Mr. Douglas, however, said the government retains the right to pursue other claims in the lawsuit in the future. “So, [the hospital] is a little more optimistic than the reality of what the government agrees is the situation.”

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

Catholic Medical Center has agreed to pay $3.8 million to settle claims it provided free call coverage to a cardiologist in exchange for patient referrals to the Manchester, N.H., hospital, according to federal officials.

“The cardiologist who received the free call coverage referred millions of dollars in medical procedures and services to CMC over the decade in which the free services were provided,” the Department of Justice said in a news release.

Because the hospital submitted claims for payment to Medicare, Medicaid, and other federal health care programs for the services referred by the cardiologist, the government alleged the claims were the result of unlawful kickbacks.

The settlement resolves allegations brought in a whistleblower lawsuit filed in 2018 by cardiologist David Goldberg, MD, who previously worked at Catholic Medical Center (CMC) and is represented by Douglas, Leonard & Garvey.

The news release did not name the cardiologist involved in the alleged kickback scheme but the recently unsealed lawsuit says CMC paid its cardiologists above market rates ($10,000 per weekend, $3,000 per night) to provide free coverage services for Mary-Claire Paicopolis, MD.

The lawsuit also claims Dr. Paicopolis insisted the hospital implant only Boston Scientific devices in her patients and that her preferred electrophysiologist use only its Rhythmia mapping system during ablation procedures. To keep CMC from objecting, the suit alleges Boston Scientific offered CMC early access to its Watchman left atrial appendage occluder and provided “unprecedented” support to a nonacademic community hospital site.

“It went back several years, and that and the other issues in the suit were strong motivators for Dr. Goldberg to try to rectify the situation and he deserves a lot of credit for having done so,” attorney Charles G. Douglas III told this news organization.

Dr. Goldberg will receive $570,000 of the $3.8 million settlement as well as $145,361 in expenses, attorney fees, and costs.

Although not addressed in the federal news release, the lawsuit also alleges that CMC staff manipulated mortality data by discharging patients from the ICU and then readmitting them to hospice with a new patient number, “thereby avoiding the need to claim a surgical mortality.”

The lawsuit also says CMC “created a practice of covering up medical errors” and detailed 12 patient deaths between 2012 and 2018, alleging that these deaths were the result of substandard care.

CMC spokesperson Lauren Collins-Cline said in an email that the call coverage arrangement is no longer in place and originated almost 15 years ago with the input of legal counsel in order to provide high-quality care for patients.

“While CMC vigorously disagrees with the government’s allegations that this arrangement violated federal law, we have agreed to settle in order to avoid long costly civil litigation,” she said.

As to the other claims in the complaint, Ms. Collins-Cline said they were investigated by the government and dismissed per the settlement agreement. “CMC holds itself to the highest ethical standards in patient care and business conduct. That’s embedded in our mission and will always remain our highest priority.”

Mr. Douglas, however, said the government retains the right to pursue other claims in the lawsuit in the future. “So, [the hospital] is a little more optimistic than the reality of what the government agrees is the situation.”

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

An infliximab biosimilar (infliximab-axxq) delivered via subcutaneous injection was superior to intravenous vedolizumab (Entyvio) for induction and maintenance therapy of Crohn’s disease (CD), according to a systematic review and meta-analysis from French researchers.  

In contrast, the same research showed no significant differences in efficacy between these agents for people with ulcerative colitis (UC).

The subcutaneous injection formulation of infliximab-axxq, also known as CT-P13 SC, is approved by the European Medicines Agency for both CD and UC (Remsima SC). This formulation is not yet approved by the U.S. Food and Drug Administration.

“It’s kind of a small revolution, because now we have access, and in France, we are using a lot of subcutaneous infliximab,” Laurent Peyrin-Biroulet, MD, said during a digital oral presentation at ECCO ‘22 Virtual, the European Crohn’s and Colitis Organisation 2022 Congress. He is ECCO president and a gastroenterologist at University Hospital of Nancy in France.

Dr. Peyrin-Biroulet and colleagues compared the efficacy and safety of the two agents in major randomized controlled trials looking at moderate-to-severe CD or UC from January 2010 to April 2021.

Subcutaneous infliximab-axxq data came from NCT02883452, an ongoing phase 1 study started in 2016. The vedolizumab data come from GEMINI I, II, and III; VISIBLE 1 and 2; and VARSITY trials.
 

Key findings

In CD, induction efficacy was 79% for subcutaneous infliximab-axxq versus a 45% response for vedolizumab, as measured by the Crohn’s Disease Activity Index-70 (CDAI-70).

In addition, the study showed a 62% induction efficacy for subcutaneous infliximab-axxq versus 36% for vedolizumab on the CDAI-100.

The maintenance response on the CDAI-100 was achieved by 64% of the infliximab-axxq patients versus 47% of the vedolizumab patients.

“You can see better efficacy results of subcutaneous infliximab compared to vedolizumab in CD for both induction and maintenance,” Dr. Peyrin-Biroulet said, adding that what is seen here is probably what has been observed.
 

Similar results for UC

“We know vedolizumab is a good drug in UC, and there was not a difference between UC and CD,” Dr. Peyrin-Biroulet said.

There were no significant differences between subcutaneous infliximab-axxq and vedolizumab in terms of clinical response for induction (77% vs. 69%, respectively) or clinical response for maintenance (62% vs. 63%, respectively).

Similarly, no significant differences emerged in rates of clinical remission or mucosal healing.
 

Safety so far

Safety profiles for both agents in both indications were similar over 1 year.

However, Dr. Peyrin-Biroulet shared a caveat about that timeline. “It’s a 1-year follow-up, not a 10-year follow-up with 100,000 patients,” he said. “But still, what we see here is a confirmation of what we see in other analyses. There is not a significant [safety] difference between these two drugs.”

The rate of any adverse event in CD was 76% for subcutaneous infliximab-axxq versus 77% for vedolizumab, for example. Rates of any serious adverse event were 9% and 14%, respectively.

In UC studies, the rate of any adverse event was 67% for subcutaneous infliximab-axxq versus 64% for vedolizumab. Rates of serious adverse events were 12% and 11%, respectively.

Rates of discontinuation over 1 year differed between agents. Five percent of subcutaneous infliximab-axxq participants with CD discontinued treatment as because of lack of efficacy compared with 32% with vedolizumab. In UC participants, discontinuation for the same reason was reported for 3% of subcutaneous infliximab-axxq patients versus 15% of vedolizumab.

Although all participants in the subcutaneous infliximab-axxq trial were anti-tumor necrosis factor treatment naive, some in the vedolizumab may have been previously exposed to such therapy, Dr. Peyrin-Biroulet said. “Subgroup analyses would be need to further explore that.”

“It’s interesting and a clinically relevant piece of work,” said Mark Samaan, MD, session moderator and consultant gastroenterologist at Guy’s and St. Thomas’ NHS Foundation Trust in London, who was not involved in the study.

“The results are in keeping with what one might expect from IV infliximab administration. In that sense, [it is] reassuring that the two routes of administration appear to perform in a broadly similar manner,” Dr. Samaan said.

“So long as adequate exposure is achieved, I wouldn’t have expected route of administration to be a significant determinant of efficacy,” he added.

Dr. Peyrin-Biroulet reports receiving personal fees from Galapagos, AbbVie, Janssen, Genetech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Samsung Bioepis, Alma, Sterna, Nestle, Inotrem, Enterome, Allergen, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgene, Mylan, Lilly, Fresenius Kabi, Opplian Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, and Theravance. Dr. Samaan reports receiving advisory fees from Janssen, Takeda, Sandoz, Samsung Bioepis, Galapagos, and AbbVie and lecture fees from Bristol-Myers Squibb, Janssen, Takeda, MSD, Falk, AbbVie, and Galapagos.

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

An infliximab biosimilar (infliximab-axxq) delivered via subcutaneous injection was superior to intravenous vedolizumab (Entyvio) for induction and maintenance therapy of Crohn’s disease (CD), according to a systematic review and meta-analysis from French researchers.  

In contrast, the same research showed no significant differences in efficacy between these agents for people with ulcerative colitis (UC).

The subcutaneous injection formulation of infliximab-axxq, also known as CT-P13 SC, is approved by the European Medicines Agency for both CD and UC (Remsima SC). This formulation is not yet approved by the U.S. Food and Drug Administration.

“It’s kind of a small revolution, because now we have access, and in France, we are using a lot of subcutaneous infliximab,” Laurent Peyrin-Biroulet, MD, said during a digital oral presentation at ECCO ‘22 Virtual, the European Crohn’s and Colitis Organisation 2022 Congress. He is ECCO president and a gastroenterologist at University Hospital of Nancy in France.

Dr. Peyrin-Biroulet and colleagues compared the efficacy and safety of the two agents in major randomized controlled trials looking at moderate-to-severe CD or UC from January 2010 to April 2021.

Subcutaneous infliximab-axxq data came from NCT02883452, an ongoing phase 1 study started in 2016. The vedolizumab data come from GEMINI I, II, and III; VISIBLE 1 and 2; and VARSITY trials.
 

Key findings

In CD, induction efficacy was 79% for subcutaneous infliximab-axxq versus a 45% response for vedolizumab, as measured by the Crohn’s Disease Activity Index-70 (CDAI-70).

In addition, the study showed a 62% induction efficacy for subcutaneous infliximab-axxq versus 36% for vedolizumab on the CDAI-100.

The maintenance response on the CDAI-100 was achieved by 64% of the infliximab-axxq patients versus 47% of the vedolizumab patients.

“You can see better efficacy results of subcutaneous infliximab compared to vedolizumab in CD for both induction and maintenance,” Dr. Peyrin-Biroulet said, adding that what is seen here is probably what has been observed.
 

Similar results for UC

“We know vedolizumab is a good drug in UC, and there was not a difference between UC and CD,” Dr. Peyrin-Biroulet said.

There were no significant differences between subcutaneous infliximab-axxq and vedolizumab in terms of clinical response for induction (77% vs. 69%, respectively) or clinical response for maintenance (62% vs. 63%, respectively).

Similarly, no significant differences emerged in rates of clinical remission or mucosal healing.
 

Safety so far

Safety profiles for both agents in both indications were similar over 1 year.

However, Dr. Peyrin-Biroulet shared a caveat about that timeline. “It’s a 1-year follow-up, not a 10-year follow-up with 100,000 patients,” he said. “But still, what we see here is a confirmation of what we see in other analyses. There is not a significant [safety] difference between these two drugs.”

The rate of any adverse event in CD was 76% for subcutaneous infliximab-axxq versus 77% for vedolizumab, for example. Rates of any serious adverse event were 9% and 14%, respectively.

In UC studies, the rate of any adverse event was 67% for subcutaneous infliximab-axxq versus 64% for vedolizumab. Rates of serious adverse events were 12% and 11%, respectively.

Rates of discontinuation over 1 year differed between agents. Five percent of subcutaneous infliximab-axxq participants with CD discontinued treatment as because of lack of efficacy compared with 32% with vedolizumab. In UC participants, discontinuation for the same reason was reported for 3% of subcutaneous infliximab-axxq patients versus 15% of vedolizumab.

Although all participants in the subcutaneous infliximab-axxq trial were anti-tumor necrosis factor treatment naive, some in the vedolizumab may have been previously exposed to such therapy, Dr. Peyrin-Biroulet said. “Subgroup analyses would be need to further explore that.”

“It’s interesting and a clinically relevant piece of work,” said Mark Samaan, MD, session moderator and consultant gastroenterologist at Guy’s and St. Thomas’ NHS Foundation Trust in London, who was not involved in the study.

“The results are in keeping with what one might expect from IV infliximab administration. In that sense, [it is] reassuring that the two routes of administration appear to perform in a broadly similar manner,” Dr. Samaan said.

“So long as adequate exposure is achieved, I wouldn’t have expected route of administration to be a significant determinant of efficacy,” he added.

Dr. Peyrin-Biroulet reports receiving personal fees from Galapagos, AbbVie, Janssen, Genetech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Samsung Bioepis, Alma, Sterna, Nestle, Inotrem, Enterome, Allergen, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgene, Mylan, Lilly, Fresenius Kabi, Opplian Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, and Theravance. Dr. Samaan reports receiving advisory fees from Janssen, Takeda, Sandoz, Samsung Bioepis, Galapagos, and AbbVie and lecture fees from Bristol-Myers Squibb, Janssen, Takeda, MSD, Falk, AbbVie, and Galapagos.

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

An infliximab biosimilar (infliximab-axxq) delivered via subcutaneous injection was superior to intravenous vedolizumab (Entyvio) for induction and maintenance therapy of Crohn’s disease (CD), according to a systematic review and meta-analysis from French researchers.  

In contrast, the same research showed no significant differences in efficacy between these agents for people with ulcerative colitis (UC).

The subcutaneous injection formulation of infliximab-axxq, also known as CT-P13 SC, is approved by the European Medicines Agency for both CD and UC (Remsima SC). This formulation is not yet approved by the U.S. Food and Drug Administration.

“It’s kind of a small revolution, because now we have access, and in France, we are using a lot of subcutaneous infliximab,” Laurent Peyrin-Biroulet, MD, said during a digital oral presentation at ECCO ‘22 Virtual, the European Crohn’s and Colitis Organisation 2022 Congress. He is ECCO president and a gastroenterologist at University Hospital of Nancy in France.

Dr. Peyrin-Biroulet and colleagues compared the efficacy and safety of the two agents in major randomized controlled trials looking at moderate-to-severe CD or UC from January 2010 to April 2021.

Subcutaneous infliximab-axxq data came from NCT02883452, an ongoing phase 1 study started in 2016. The vedolizumab data come from GEMINI I, II, and III; VISIBLE 1 and 2; and VARSITY trials.
 

Key findings

In CD, induction efficacy was 79% for subcutaneous infliximab-axxq versus a 45% response for vedolizumab, as measured by the Crohn’s Disease Activity Index-70 (CDAI-70).

In addition, the study showed a 62% induction efficacy for subcutaneous infliximab-axxq versus 36% for vedolizumab on the CDAI-100.

The maintenance response on the CDAI-100 was achieved by 64% of the infliximab-axxq patients versus 47% of the vedolizumab patients.

“You can see better efficacy results of subcutaneous infliximab compared to vedolizumab in CD for both induction and maintenance,” Dr. Peyrin-Biroulet said, adding that what is seen here is probably what has been observed.
 

Similar results for UC

“We know vedolizumab is a good drug in UC, and there was not a difference between UC and CD,” Dr. Peyrin-Biroulet said.

There were no significant differences between subcutaneous infliximab-axxq and vedolizumab in terms of clinical response for induction (77% vs. 69%, respectively) or clinical response for maintenance (62% vs. 63%, respectively).

Similarly, no significant differences emerged in rates of clinical remission or mucosal healing.
 

Safety so far

Safety profiles for both agents in both indications were similar over 1 year.

However, Dr. Peyrin-Biroulet shared a caveat about that timeline. “It’s a 1-year follow-up, not a 10-year follow-up with 100,000 patients,” he said. “But still, what we see here is a confirmation of what we see in other analyses. There is not a significant [safety] difference between these two drugs.”

The rate of any adverse event in CD was 76% for subcutaneous infliximab-axxq versus 77% for vedolizumab, for example. Rates of any serious adverse event were 9% and 14%, respectively.

In UC studies, the rate of any adverse event was 67% for subcutaneous infliximab-axxq versus 64% for vedolizumab. Rates of serious adverse events were 12% and 11%, respectively.

Rates of discontinuation over 1 year differed between agents. Five percent of subcutaneous infliximab-axxq participants with CD discontinued treatment as because of lack of efficacy compared with 32% with vedolizumab. In UC participants, discontinuation for the same reason was reported for 3% of subcutaneous infliximab-axxq patients versus 15% of vedolizumab.

Although all participants in the subcutaneous infliximab-axxq trial were anti-tumor necrosis factor treatment naive, some in the vedolizumab may have been previously exposed to such therapy, Dr. Peyrin-Biroulet said. “Subgroup analyses would be need to further explore that.”

“It’s interesting and a clinically relevant piece of work,” said Mark Samaan, MD, session moderator and consultant gastroenterologist at Guy’s and St. Thomas’ NHS Foundation Trust in London, who was not involved in the study.

“The results are in keeping with what one might expect from IV infliximab administration. In that sense, [it is] reassuring that the two routes of administration appear to perform in a broadly similar manner,” Dr. Samaan said.

“So long as adequate exposure is achieved, I wouldn’t have expected route of administration to be a significant determinant of efficacy,” he added.

Dr. Peyrin-Biroulet reports receiving personal fees from Galapagos, AbbVie, Janssen, Genetech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Samsung Bioepis, Alma, Sterna, Nestle, Inotrem, Enterome, Allergen, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgene, Mylan, Lilly, Fresenius Kabi, Opplian Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, and Theravance. Dr. Samaan reports receiving advisory fees from Janssen, Takeda, Sandoz, Samsung Bioepis, Galapagos, and AbbVie and lecture fees from Bristol-Myers Squibb, Janssen, Takeda, MSD, Falk, AbbVie, and Galapagos.

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

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹ assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴ demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). doi: 10.1093/aje/kwac009. Epub ahead of print. PMID: 35029650.
5.    Walscheid K, Rothaus K, Niewerth M, Klotsche J, Minden K, Heiligenhaus A. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15). doi: 10.3899/jrheum.210755. Epub ahead of print. PMID: 35034000.
 

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹ assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴ demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). doi: 10.1093/aje/kwac009. Epub ahead of print. PMID: 35029650.
5.    Walscheid K, Rothaus K, Niewerth M, Klotsche J, Minden K, Heiligenhaus A. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15). doi: 10.3899/jrheum.210755. Epub ahead of print. PMID: 35034000.
 

The influence of sex and gender on psoriatic arthritis (PsA) continues to be of interest. Using data from the Dutch south-west Early Psoriatic Arthritis cohort (DEPAR), Passia et al¹ assessed sex-related differences in demographics, disease characteristics, and evolution over 1 year in 273 men and 294 women newly diagnosed with PsA. They found that at baseline, women had a significantly longer duration of symptoms, higher tender joint count and enthesitis, higher disease activity, higher levels of pain, more severe limitations in function and worse quality of life. During the 1 year follow up, composite measures of disease activity declined in men and women, but women continued to have higher levels than men. At the end of 1 year, fewer women achieved the criteria for minimal disease activity (MDA). Thus, the disease burden of PsA was higher in women vs. men at all time points and even after 1 year of standard-of-care treatment. Sex-specific treatment strategies might help a higher proportion of women achieve MDA.

Although, enthesitis is believed to be a primary pathogenetic lesion in PsA, the relationship between active enthesitis and disease severity as measured by the presence of joint erosions is less well studied. In a cross-sectional study of 104 PsA patients, Smerilli et al² explored the association between ultrasound (US) entheseal abnormalities and the presence of US detected bone erosions in PsA joints. At least 1 joint bone erosion was found in 45.2% of patients and was associated with power Doppler signal at enthesis (odds ratio [OR] 1.74; P < .01), entheseal bone erosions (OR 3.17; P = .01), and greyscale synovitis (OR 2.59; P = .02). Thus, Doppler signal and bone erosions at entheses indicate more severe PsA and patients with such abnormalities should therefore be treated aggressively.

Comorbidities and associated conditions were a focus of several publications last month. Venous thromboembolism (VTE) is associated with inflammatory diseases, including PsA. In a retrospective cohort study including 5,275 patients with newly diagnosed PsA, Gazitt et al³ assessed the association between PsA and VTE events using a large population-based database in Israel. During follow-up, 1.2% vs. 0.8% patients in the PsA vs. control group were diagnosed with VTE, but this association was not statistically significant after adjusting for demographic factors and comorbidities (adjusted hazard ratio [aHR] 1.27; P = .16) with only older age (aHR 1.08; P < .0001) and history of VTE (aHR 31.63; P < .0001) remaining associated with an increased risk for VTE. Thus, VTE in patients with PsA may be associated with underlying comorbidities rather than PsA per se. In another study, Harris et al⁴ demonstrated that PsA was associated with increased risk of endometriosis. In an analysis of 4112 patients with laparoscopically confirmed endometriosis from the Nurses’ Health Study II, they found that psoriasis with concomitant PsA was associated with increased risk for subsequent endometriosis (HR 2.01; 95% CI 1.23-3.30), which persisted even after adjusting for comorbidities. Finally, in a cross-sectional study using data from 1862 juvenile PsA (jPsA) patients (122 [6.6%] of whom developed uveitis) in the German National Pediatric Rheumatological Database, Walscheid et al⁵ showed that patients with jPsA were more likely to develop uveitis if they were diagnosed with PsA at a younger age or were antinuclear antibody positive, with higher disease activity being the only factor significantly associated with the presence of uveitis.

References

1.    Passia E et al. Sex-specific differences and how to handle them in early psoriatic arthritis. Arthritis Res Ther. 2022;24(1):22 (Jan 11). 
2.    Smerilli G et al. Doppler signal and bone erosions at the enthesis are independently associated with ultrasound joint erosive damage in psoriatic arthritis. J Rheumatol. 2022 (Feb 1). 
3.    Gazitt T et al. The association between psoriatic arthritis and venous thromboembolism: a population-based cohort study. Arthritis Res Ther. 2022;24(1):16 (Jan 7). 
4.    Harris HR et al. Endometriosis, psoriasis and psoriatic arthritis: A prospective cohort study. Am J Epidemiol. 2022 (Jan 13). doi: 10.1093/aje/kwac009. Epub ahead of print. PMID: 35029650.
5.    Walscheid K, Rothaus K, Niewerth M, Klotsche J, Minden K, Heiligenhaus A. Occurrence and risk factors of uveitis in juvenile psoriatic arthritis: Data from a population-based nationwide study in Germany. J Rheumatol. 2022 (Jan 15). doi: 10.3899/jrheum.210755. Epub ahead of print. PMID: 35034000.
 

The pandemic has significantly affected the mental health of family members of patients with COVID-19, including high rates of posttraumatic stress disorder (PTSD), anxiety, and depression, new research suggests.

In a prospective cohort study of more than 500 individuals, those related to intensive care unit patients with COVID-19 acute respiratory distress syndrome (ARDS) had a significantly higher prevalence of, and were at increased risk for, PTSD-related symptoms 90 days after discharge compared with their peers who were related to ICU patients with non-COVID ARDS.

They also had a higher prevalence of depression and anxiety symptoms.

The results illustrate how the mental health of families has been adversely affected by strict isolation measures instituted at the height of the COVID pandemic, lead author Elie Azoulay, MD, PhD, professor of medicine at Diderot University and director of the Medical Intensive Care Unit, Saint Louis Hospital, Paris, told this news organization.

Such restrictions were unnecessary, Dr. Azoulay noted, adding that everyone, including health care professionals, benefits when families are allowed to interact with their loved ones in the ICU.

He added the study findings also emphasize the importance of social supports.

“We need to develop and really increase what we can do for family members”  of patients staying in the ICU, said Dr. Azoulay.

The findings were published online Feb. 18 in JAMA.
 

Twenty-three ICUs in France

The study included adult family members of patients admitted with ARDS to 23 ICUs in France from January to October 2020.

Patients had a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO₂/FiO₂) of less than 300, and bilateral opacities on chest radiography not fully explained by cardiac failure or fluid overload.

Two trained clinical psychologists interviewed family members and patients by telephone a median of 112 days after ICU discharge. During this interview, participants completed the Impact of Event Scale Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS).

The IES-R score ranges from 0 (best) to 88 (worst) with a score of more than 22 indicating presence of PTSD-related symptoms of clinical concern. The HADS has separate subscales for anxiety and depression, with a score of 7 or greater on a 21-point scale indicating symptoms of anxiety or depression.

Family members also rated social supports on a scale from 0 (extremely limited) to 10 (extremely effective). Dr. Azoulay noted that social support is the subjective perception of the extent to which friends, mental health specialists, and others are available and helpful.

Investigators divided patients into two groups depending on whether or not the cause of ARDS was COVID-19. Causes other than COVID-19 mainly included community-acquired pneumonia and influenza.

The primary outcome was the prevalence of PTSD-related symptoms among family members. Secondary outcomes were the prevalence of anxiety and depression in family members.

The analysis included 303 family members of patients with COVID-19 ARDS and 214 family members of patients with non–COVID-19 ARDS. Almost half of the family members were spouses.

Those with family members with COVID-19 were younger than the non-COVID group (median age, 50 vs. 55 years). They were less frequently allowed to visit the ICU (35% vs. 88%) and more commonly received patient information by phone (84% vs. 20%).
 

Better strategies needed

Results showed PTSD symptoms were significantly more common in family members of patients with than without COVID-10 (35% vs. 19%; difference of 16%; 95% confidence interval, 8%-24%; P < .001).

Anxiety symptoms were significantly more common in the COVID-19 group (41% vs. 34%; difference of 8%; 95% CI, 0%-16%; P = .05), as were depression symptoms (31% vs. 18%; difference of 13%; 95% CI, 6%-21%; P < .001).

About 26% of the hospitalized relatives died. PTSD symptoms were more common among bereaved family members of patients who died from COVID-19 than of patients without COVID-19 (63% vs. 39%; difference of 24%; 95% CI, 7%-40%; P = .008).

In the COVID-19 group, significantly fewer family members reported having attended the funeral (77% vs. 91%, P = .04). This could be because of concerns over transmitting the virus, the investigators noted.

After adjustment for age, sex, and level of social support in a multivariable analysis, COVID-19 ARDS was significantly associated with increased risk for PTSD-related symptoms in family members (odds ratio, 2.05; 95% CI, 1.30-3.23; P =.002).

Other factors independently associated with PTSD symptoms were age, level of social support, and being male.

Factors associated with anxiety included having COVID-19 ARDS, age, being male, and level of social support. COVID-19 ARDS and level of social support were independently associated with depression.

Although isolation measures were implemented to prevent viral transmission during the pandemic, severely restricting family members from interacting with their sick loved ones in the ICU is “very destructive [and] deeply distressing,” said Dr. Azoulay. “It’s almost cruel.”

Fear may be at the heart of the “psycho-trauma” experienced by family members, he said.

“I would say one of the main sources is fear of getting infected, fear of abandoning family members, fear of leaving the kids alone without any support, and fear of infecting others,” he added.

Health care providers should develop strategies to better communicate with family members, who also feel a lot of guilt when they’re unable to be with their sick loved ones, said Dr. Azoulay.
 

‘Element of fear’

Commenting on the findings for this news organization, O. Joseph Bienvenu, MD, PhD, professor of psychiatry and behavioral sciences at Johns Hopkins Medicine, Baltimore, called the study “solid” and noted the lead author is “a well-recognized clinical researcher.”

It was “remarkable” that investigators were able to include a control group of family members of patients with ARDS not due to COVID-19, added Dr. Bienvenu, who was not involved with the research.

“It sounds like the bottom line is COVID adds an additional element of fear in loved ones,” he said.

Dr. Bienvenu added this fits with his own clinical experience – and noted that some COVID-19 follow-up clinics now include family members in their assessments and care.

“I think this study nicely illustrates the utility of this,” he concluded.

The study received funding from the French Ministry of Health. Dr. Azoulay reported receipt of personal fees from lectures from Pfizer, Gilead, Baxter, and Alexion, and institutional research grants from Merck Sharp and Dohme, Pfizer, Baxter, and Alexion. Dr. Bienvenu has disclosed no relevant financial relationships.

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

The pandemic has significantly affected the mental health of family members of patients with COVID-19, including high rates of posttraumatic stress disorder (PTSD), anxiety, and depression, new research suggests.

In a prospective cohort study of more than 500 individuals, those related to intensive care unit patients with COVID-19 acute respiratory distress syndrome (ARDS) had a significantly higher prevalence of, and were at increased risk for, PTSD-related symptoms 90 days after discharge compared with their peers who were related to ICU patients with non-COVID ARDS.

They also had a higher prevalence of depression and anxiety symptoms.

The results illustrate how the mental health of families has been adversely affected by strict isolation measures instituted at the height of the COVID pandemic, lead author Elie Azoulay, MD, PhD, professor of medicine at Diderot University and director of the Medical Intensive Care Unit, Saint Louis Hospital, Paris, told this news organization.

Such restrictions were unnecessary, Dr. Azoulay noted, adding that everyone, including health care professionals, benefits when families are allowed to interact with their loved ones in the ICU.

He added the study findings also emphasize the importance of social supports.

“We need to develop and really increase what we can do for family members”  of patients staying in the ICU, said Dr. Azoulay.

The findings were published online Feb. 18 in JAMA.
 

Twenty-three ICUs in France

The study included adult family members of patients admitted with ARDS to 23 ICUs in France from January to October 2020.

Patients had a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO₂/FiO₂) of less than 300, and bilateral opacities on chest radiography not fully explained by cardiac failure or fluid overload.

Two trained clinical psychologists interviewed family members and patients by telephone a median of 112 days after ICU discharge. During this interview, participants completed the Impact of Event Scale Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS).

The IES-R score ranges from 0 (best) to 88 (worst) with a score of more than 22 indicating presence of PTSD-related symptoms of clinical concern. The HADS has separate subscales for anxiety and depression, with a score of 7 or greater on a 21-point scale indicating symptoms of anxiety or depression.

Family members also rated social supports on a scale from 0 (extremely limited) to 10 (extremely effective). Dr. Azoulay noted that social support is the subjective perception of the extent to which friends, mental health specialists, and others are available and helpful.

Investigators divided patients into two groups depending on whether or not the cause of ARDS was COVID-19. Causes other than COVID-19 mainly included community-acquired pneumonia and influenza.

The primary outcome was the prevalence of PTSD-related symptoms among family members. Secondary outcomes were the prevalence of anxiety and depression in family members.

The analysis included 303 family members of patients with COVID-19 ARDS and 214 family members of patients with non–COVID-19 ARDS. Almost half of the family members were spouses.

Those with family members with COVID-19 were younger than the non-COVID group (median age, 50 vs. 55 years). They were less frequently allowed to visit the ICU (35% vs. 88%) and more commonly received patient information by phone (84% vs. 20%).
 

Better strategies needed

Results showed PTSD symptoms were significantly more common in family members of patients with than without COVID-10 (35% vs. 19%; difference of 16%; 95% confidence interval, 8%-24%; P < .001).

Anxiety symptoms were significantly more common in the COVID-19 group (41% vs. 34%; difference of 8%; 95% CI, 0%-16%; P = .05), as were depression symptoms (31% vs. 18%; difference of 13%; 95% CI, 6%-21%; P < .001).

About 26% of the hospitalized relatives died. PTSD symptoms were more common among bereaved family members of patients who died from COVID-19 than of patients without COVID-19 (63% vs. 39%; difference of 24%; 95% CI, 7%-40%; P = .008).

In the COVID-19 group, significantly fewer family members reported having attended the funeral (77% vs. 91%, P = .04). This could be because of concerns over transmitting the virus, the investigators noted.

After adjustment for age, sex, and level of social support in a multivariable analysis, COVID-19 ARDS was significantly associated with increased risk for PTSD-related symptoms in family members (odds ratio, 2.05; 95% CI, 1.30-3.23; P =.002).

Other factors independently associated with PTSD symptoms were age, level of social support, and being male.

Factors associated with anxiety included having COVID-19 ARDS, age, being male, and level of social support. COVID-19 ARDS and level of social support were independently associated with depression.

Although isolation measures were implemented to prevent viral transmission during the pandemic, severely restricting family members from interacting with their sick loved ones in the ICU is “very destructive [and] deeply distressing,” said Dr. Azoulay. “It’s almost cruel.”

Fear may be at the heart of the “psycho-trauma” experienced by family members, he said.

“I would say one of the main sources is fear of getting infected, fear of abandoning family members, fear of leaving the kids alone without any support, and fear of infecting others,” he added.

Health care providers should develop strategies to better communicate with family members, who also feel a lot of guilt when they’re unable to be with their sick loved ones, said Dr. Azoulay.
 

‘Element of fear’

Commenting on the findings for this news organization, O. Joseph Bienvenu, MD, PhD, professor of psychiatry and behavioral sciences at Johns Hopkins Medicine, Baltimore, called the study “solid” and noted the lead author is “a well-recognized clinical researcher.”

It was “remarkable” that investigators were able to include a control group of family members of patients with ARDS not due to COVID-19, added Dr. Bienvenu, who was not involved with the research.

“It sounds like the bottom line is COVID adds an additional element of fear in loved ones,” he said.

Dr. Bienvenu added this fits with his own clinical experience – and noted that some COVID-19 follow-up clinics now include family members in their assessments and care.

“I think this study nicely illustrates the utility of this,” he concluded.

The study received funding from the French Ministry of Health. Dr. Azoulay reported receipt of personal fees from lectures from Pfizer, Gilead, Baxter, and Alexion, and institutional research grants from Merck Sharp and Dohme, Pfizer, Baxter, and Alexion. Dr. Bienvenu has disclosed no relevant financial relationships.

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

The pandemic has significantly affected the mental health of family members of patients with COVID-19, including high rates of posttraumatic stress disorder (PTSD), anxiety, and depression, new research suggests.

In a prospective cohort study of more than 500 individuals, those related to intensive care unit patients with COVID-19 acute respiratory distress syndrome (ARDS) had a significantly higher prevalence of, and were at increased risk for, PTSD-related symptoms 90 days after discharge compared with their peers who were related to ICU patients with non-COVID ARDS.

They also had a higher prevalence of depression and anxiety symptoms.

The results illustrate how the mental health of families has been adversely affected by strict isolation measures instituted at the height of the COVID pandemic, lead author Elie Azoulay, MD, PhD, professor of medicine at Diderot University and director of the Medical Intensive Care Unit, Saint Louis Hospital, Paris, told this news organization.

Such restrictions were unnecessary, Dr. Azoulay noted, adding that everyone, including health care professionals, benefits when families are allowed to interact with their loved ones in the ICU.

He added the study findings also emphasize the importance of social supports.

“We need to develop and really increase what we can do for family members”  of patients staying in the ICU, said Dr. Azoulay.

The findings were published online Feb. 18 in JAMA.
 

Twenty-three ICUs in France

The study included adult family members of patients admitted with ARDS to 23 ICUs in France from January to October 2020.

Patients had a partial pressure of arterial oxygen to fraction of inspired oxygen ratio (PaO₂/FiO₂) of less than 300, and bilateral opacities on chest radiography not fully explained by cardiac failure or fluid overload.

Two trained clinical psychologists interviewed family members and patients by telephone a median of 112 days after ICU discharge. During this interview, participants completed the Impact of Event Scale Revised (IES-R) and the Hospital Anxiety and Depression Scale (HADS).

The IES-R score ranges from 0 (best) to 88 (worst) with a score of more than 22 indicating presence of PTSD-related symptoms of clinical concern. The HADS has separate subscales for anxiety and depression, with a score of 7 or greater on a 21-point scale indicating symptoms of anxiety or depression.

Family members also rated social supports on a scale from 0 (extremely limited) to 10 (extremely effective). Dr. Azoulay noted that social support is the subjective perception of the extent to which friends, mental health specialists, and others are available and helpful.

Investigators divided patients into two groups depending on whether or not the cause of ARDS was COVID-19. Causes other than COVID-19 mainly included community-acquired pneumonia and influenza.

The primary outcome was the prevalence of PTSD-related symptoms among family members. Secondary outcomes were the prevalence of anxiety and depression in family members.

The analysis included 303 family members of patients with COVID-19 ARDS and 214 family members of patients with non–COVID-19 ARDS. Almost half of the family members were spouses.

Those with family members with COVID-19 were younger than the non-COVID group (median age, 50 vs. 55 years). They were less frequently allowed to visit the ICU (35% vs. 88%) and more commonly received patient information by phone (84% vs. 20%).
 

Better strategies needed

Results showed PTSD symptoms were significantly more common in family members of patients with than without COVID-10 (35% vs. 19%; difference of 16%; 95% confidence interval, 8%-24%; P < .001).

Anxiety symptoms were significantly more common in the COVID-19 group (41% vs. 34%; difference of 8%; 95% CI, 0%-16%; P = .05), as were depression symptoms (31% vs. 18%; difference of 13%; 95% CI, 6%-21%; P < .001).

About 26% of the hospitalized relatives died. PTSD symptoms were more common among bereaved family members of patients who died from COVID-19 than of patients without COVID-19 (63% vs. 39%; difference of 24%; 95% CI, 7%-40%; P = .008).

In the COVID-19 group, significantly fewer family members reported having attended the funeral (77% vs. 91%, P = .04). This could be because of concerns over transmitting the virus, the investigators noted.

After adjustment for age, sex, and level of social support in a multivariable analysis, COVID-19 ARDS was significantly associated with increased risk for PTSD-related symptoms in family members (odds ratio, 2.05; 95% CI, 1.30-3.23; P =.002).

Other factors independently associated with PTSD symptoms were age, level of social support, and being male.

Factors associated with anxiety included having COVID-19 ARDS, age, being male, and level of social support. COVID-19 ARDS and level of social support were independently associated with depression.

Although isolation measures were implemented to prevent viral transmission during the pandemic, severely restricting family members from interacting with their sick loved ones in the ICU is “very destructive [and] deeply distressing,” said Dr. Azoulay. “It’s almost cruel.”

Fear may be at the heart of the “psycho-trauma” experienced by family members, he said.

“I would say one of the main sources is fear of getting infected, fear of abandoning family members, fear of leaving the kids alone without any support, and fear of infecting others,” he added.

Health care providers should develop strategies to better communicate with family members, who also feel a lot of guilt when they’re unable to be with their sick loved ones, said Dr. Azoulay.
 

‘Element of fear’

Commenting on the findings for this news organization, O. Joseph Bienvenu, MD, PhD, professor of psychiatry and behavioral sciences at Johns Hopkins Medicine, Baltimore, called the study “solid” and noted the lead author is “a well-recognized clinical researcher.”

It was “remarkable” that investigators were able to include a control group of family members of patients with ARDS not due to COVID-19, added Dr. Bienvenu, who was not involved with the research.

“It sounds like the bottom line is COVID adds an additional element of fear in loved ones,” he said.

Dr. Bienvenu added this fits with his own clinical experience – and noted that some COVID-19 follow-up clinics now include family members in their assessments and care.

“I think this study nicely illustrates the utility of this,” he concluded.

The study received funding from the French Ministry of Health. Dr. Azoulay reported receipt of personal fees from lectures from Pfizer, Gilead, Baxter, and Alexion, and institutional research grants from Merck Sharp and Dohme, Pfizer, Baxter, and Alexion. Dr. Bienvenu has disclosed no relevant financial relationships.

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

The Dexcom G7 continuous glucose monitor (CGM) is as accurate or better than other currently marketed CGM devices for measuring glucose in those with diabetes, new data from a pivotal study suggest.  

Currently under review by the U.S. Food and Drug Administration, the G7 is expected to be an improvement over the Dexcom G6 version in several ways.

The on-body size will be 60% smaller, “roughly the size of three stacked quarters,” according to the authors, and will incorporate the sensor with a single-use transmitter, as opposed to the current separate 3-month transmitter used with the G6 sensor. This will eliminate the need for using a transmitter across multiple sensor sessions (as is the case for G6).

The warm-up period after insertion is reduced from 2 hours to 27 minutes, and users are given an extra 12-hour “grace period” after the 10-day wear period to change the device before it stops displaying glucose data. Up to 24 hours of missed data can also be recaptured.

“The enhanced features of G7 may increase clinical adoption, encourage sustained use, and reduce the burden of diabetes management,” write Satish K. Garg, MD, of the University of Colorado, Aurora, and colleagues, in their article, published online Feb. 14 in Diabetes Technology & Therapeutics.  

Several features of the G6 remain unchanged, including factory calibration, but also the capacity for optional user calibrations, use of Bluetooth to transmit data up to 20 feet (approximately 6 meters), and data displays on either a dedicated receiver or a variety of iOS and Android smart devices.

It will also allow for user-customized settings and alerts, as well as the option for real-time remote “share” monitoring with caregivers or providers. The G7 will also not be susceptible to interference by acetaminophen (paracetamol) or ascorbic acid.

And, like the G6, the G7 was submitted for approval to the FDA as an “integrated CGM,” meaning that it will be interoperable with other compatible devices, including insulin pumps, glucose meters, or other electronic devices used for diabetes management.

Accuracy shown on abdomen, arm

The prospective, multicenter, single-arm study reported by Dr. Garg and colleagues was conducted at 12 U.S. sites between February and June 2021.

In-clinic visits were conducted on days 1 or 2, 4 or 7, and one additional day for comparisons with a reference glucose measure (YSI 2300 Stat Plus glucose analyzer). Participants wore blinded G7 sensors concurrently on the upper arm and abdomen while continuing to use their own personal glucose monitoring method (CGM or fingerstick) at home.

A total of 316 insulin-using adults with type 1 or type 2 diabetes contributed data from 308 arm- and 311 abdomen-placed blinded devices, which generated 77,774 matched pairs of data within the blood glucose reportable range of 40-400 mg/dL.  

The overall mean absolute relative difference (MARD) of each CGM-YSI pair (a standard metric for CGM analysis) was 8.2%, with 9.1% for the abdomen and 8.2% for the arm.

Accuracy remained high in both arm- and abdomen-placed sensors across the 10-day wear period through the 12-hour grace period and across glucose ranges. There were no significant differences between G7 accuracy by diabetes type, insulin regimen, or body mass index.

The highest agreement rates and lowest MARDs occurred when CGM readings were increasing or decreasing by no more than 1 mg/dL per minute. However, even at the highest rates of glucose concentration change, MARD values below 10% were found for arm-placed sensors and below 10.5% for abdomen-placed sensors, Dr. Garg and colleagues report.

When the hypoglycemia threshold alert was set to 55 mg/dL, true alert rates for detection of hypoglycemia below 70 mg/dL by sensors worn on the arm and abdomen were 91.3% and 85.2%, respectively. With hyperglycemia threshold alerts set to 300 mg/dL, the true alert rates for detection of hyperglycemia greater than 250 mg/dL by sensors worn on the arm and abdomen were 99.9% and 99.8% respectively.

The overall mean time lag for the sensors was 3.5 minutes, 3.6 minutes for the arm, and 3.4 minutes for the abdomen. There were no serious adverse events during the study.

The study excluded children and adolescents; data from these populations will be reported separately, the authors note.
 

Accuracy at least as good as prior Dexcom versions, competitors

The MARD values of 8.2% on the arm and 9.1% on the abdomen were similar to or better than accuracy measurements of other commercially available CGM systems, note Dr. Garg and colleagues, although they acknowledge that few head-to-head studies at different anatomic locations have been conducted.

A study of an older Dexcom version (G4 Platinum) found MARD estimates of 12.0% on the arm and 12.3% on the abdomen, the authors note.  

The newly FDA-approved implantable Eversense E3 (Senseonics) CGM, worn on the upper arm, has a MARD of 9.1%, while the arm-placed Abbott FreeStyle Libre 2, approved in the U.S. in June 2020, has an overall MARD of 9.3%.

Lag-time differences between the reference and G7 were also similar to or better than time delays in prior-generation Dexcom CGMs, Dr. Garg and colleagues say.

Participants also completed a survey. “The redesigned applicator allows for sensor deployment with one hand, and most participants found G7 easier to insert than their prior CGM system,” the researchers say.

Finally, “unlike G6, G7 allows for temporary silencing of all audible alerts, including Urgent Low. Taken together, these attributes are anticipated to provide for a better end-user experience with G7 and help reduce diabetes burden,” they conclude.

The study was supported by a grant from Dexcom. Dr. Garg has reported receiving consultant fees from Medtronic, Novo Nordisk, Zealand, LifeScan, Roche, and Lilly, as well as research grants through the University of Colorado from Lilly, Novo Nordisk, Medtronic, Dexcom, T1D Exchange, Helmsley Trust, NIDDK, and JDRF.

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

The Dexcom G7 continuous glucose monitor (CGM) is as accurate or better than other currently marketed CGM devices for measuring glucose in those with diabetes, new data from a pivotal study suggest.  

Currently under review by the U.S. Food and Drug Administration, the G7 is expected to be an improvement over the Dexcom G6 version in several ways.

The on-body size will be 60% smaller, “roughly the size of three stacked quarters,” according to the authors, and will incorporate the sensor with a single-use transmitter, as opposed to the current separate 3-month transmitter used with the G6 sensor. This will eliminate the need for using a transmitter across multiple sensor sessions (as is the case for G6).

The warm-up period after insertion is reduced from 2 hours to 27 minutes, and users are given an extra 12-hour “grace period” after the 10-day wear period to change the device before it stops displaying glucose data. Up to 24 hours of missed data can also be recaptured.

“The enhanced features of G7 may increase clinical adoption, encourage sustained use, and reduce the burden of diabetes management,” write Satish K. Garg, MD, of the University of Colorado, Aurora, and colleagues, in their article, published online Feb. 14 in Diabetes Technology & Therapeutics.  

Several features of the G6 remain unchanged, including factory calibration, but also the capacity for optional user calibrations, use of Bluetooth to transmit data up to 20 feet (approximately 6 meters), and data displays on either a dedicated receiver or a variety of iOS and Android smart devices.

It will also allow for user-customized settings and alerts, as well as the option for real-time remote “share” monitoring with caregivers or providers. The G7 will also not be susceptible to interference by acetaminophen (paracetamol) or ascorbic acid.

And, like the G6, the G7 was submitted for approval to the FDA as an “integrated CGM,” meaning that it will be interoperable with other compatible devices, including insulin pumps, glucose meters, or other electronic devices used for diabetes management.

Accuracy shown on abdomen, arm

The prospective, multicenter, single-arm study reported by Dr. Garg and colleagues was conducted at 12 U.S. sites between February and June 2021.

In-clinic visits were conducted on days 1 or 2, 4 or 7, and one additional day for comparisons with a reference glucose measure (YSI 2300 Stat Plus glucose analyzer). Participants wore blinded G7 sensors concurrently on the upper arm and abdomen while continuing to use their own personal glucose monitoring method (CGM or fingerstick) at home.

A total of 316 insulin-using adults with type 1 or type 2 diabetes contributed data from 308 arm- and 311 abdomen-placed blinded devices, which generated 77,774 matched pairs of data within the blood glucose reportable range of 40-400 mg/dL.  

The overall mean absolute relative difference (MARD) of each CGM-YSI pair (a standard metric for CGM analysis) was 8.2%, with 9.1% for the abdomen and 8.2% for the arm.

Accuracy remained high in both arm- and abdomen-placed sensors across the 10-day wear period through the 12-hour grace period and across glucose ranges. There were no significant differences between G7 accuracy by diabetes type, insulin regimen, or body mass index.

The highest agreement rates and lowest MARDs occurred when CGM readings were increasing or decreasing by no more than 1 mg/dL per minute. However, even at the highest rates of glucose concentration change, MARD values below 10% were found for arm-placed sensors and below 10.5% for abdomen-placed sensors, Dr. Garg and colleagues report.

When the hypoglycemia threshold alert was set to 55 mg/dL, true alert rates for detection of hypoglycemia below 70 mg/dL by sensors worn on the arm and abdomen were 91.3% and 85.2%, respectively. With hyperglycemia threshold alerts set to 300 mg/dL, the true alert rates for detection of hyperglycemia greater than 250 mg/dL by sensors worn on the arm and abdomen were 99.9% and 99.8% respectively.

The overall mean time lag for the sensors was 3.5 minutes, 3.6 minutes for the arm, and 3.4 minutes for the abdomen. There were no serious adverse events during the study.

The study excluded children and adolescents; data from these populations will be reported separately, the authors note.
 

Accuracy at least as good as prior Dexcom versions, competitors

The MARD values of 8.2% on the arm and 9.1% on the abdomen were similar to or better than accuracy measurements of other commercially available CGM systems, note Dr. Garg and colleagues, although they acknowledge that few head-to-head studies at different anatomic locations have been conducted.

A study of an older Dexcom version (G4 Platinum) found MARD estimates of 12.0% on the arm and 12.3% on the abdomen, the authors note.  

The newly FDA-approved implantable Eversense E3 (Senseonics) CGM, worn on the upper arm, has a MARD of 9.1%, while the arm-placed Abbott FreeStyle Libre 2, approved in the U.S. in June 2020, has an overall MARD of 9.3%.

Lag-time differences between the reference and G7 were also similar to or better than time delays in prior-generation Dexcom CGMs, Dr. Garg and colleagues say.

Participants also completed a survey. “The redesigned applicator allows for sensor deployment with one hand, and most participants found G7 easier to insert than their prior CGM system,” the researchers say.

Finally, “unlike G6, G7 allows for temporary silencing of all audible alerts, including Urgent Low. Taken together, these attributes are anticipated to provide for a better end-user experience with G7 and help reduce diabetes burden,” they conclude.

The study was supported by a grant from Dexcom. Dr. Garg has reported receiving consultant fees from Medtronic, Novo Nordisk, Zealand, LifeScan, Roche, and Lilly, as well as research grants through the University of Colorado from Lilly, Novo Nordisk, Medtronic, Dexcom, T1D Exchange, Helmsley Trust, NIDDK, and JDRF.

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

The Dexcom G7 continuous glucose monitor (CGM) is as accurate or better than other currently marketed CGM devices for measuring glucose in those with diabetes, new data from a pivotal study suggest.  

Currently under review by the U.S. Food and Drug Administration, the G7 is expected to be an improvement over the Dexcom G6 version in several ways.

The on-body size will be 60% smaller, “roughly the size of three stacked quarters,” according to the authors, and will incorporate the sensor with a single-use transmitter, as opposed to the current separate 3-month transmitter used with the G6 sensor. This will eliminate the need for using a transmitter across multiple sensor sessions (as is the case for G6).

The warm-up period after insertion is reduced from 2 hours to 27 minutes, and users are given an extra 12-hour “grace period” after the 10-day wear period to change the device before it stops displaying glucose data. Up to 24 hours of missed data can also be recaptured.

“The enhanced features of G7 may increase clinical adoption, encourage sustained use, and reduce the burden of diabetes management,” write Satish K. Garg, MD, of the University of Colorado, Aurora, and colleagues, in their article, published online Feb. 14 in Diabetes Technology & Therapeutics.  

Several features of the G6 remain unchanged, including factory calibration, but also the capacity for optional user calibrations, use of Bluetooth to transmit data up to 20 feet (approximately 6 meters), and data displays on either a dedicated receiver or a variety of iOS and Android smart devices.

It will also allow for user-customized settings and alerts, as well as the option for real-time remote “share” monitoring with caregivers or providers. The G7 will also not be susceptible to interference by acetaminophen (paracetamol) or ascorbic acid.

And, like the G6, the G7 was submitted for approval to the FDA as an “integrated CGM,” meaning that it will be interoperable with other compatible devices, including insulin pumps, glucose meters, or other electronic devices used for diabetes management.

Accuracy shown on abdomen, arm

The prospective, multicenter, single-arm study reported by Dr. Garg and colleagues was conducted at 12 U.S. sites between February and June 2021.

In-clinic visits were conducted on days 1 or 2, 4 or 7, and one additional day for comparisons with a reference glucose measure (YSI 2300 Stat Plus glucose analyzer). Participants wore blinded G7 sensors concurrently on the upper arm and abdomen while continuing to use their own personal glucose monitoring method (CGM or fingerstick) at home.

A total of 316 insulin-using adults with type 1 or type 2 diabetes contributed data from 308 arm- and 311 abdomen-placed blinded devices, which generated 77,774 matched pairs of data within the blood glucose reportable range of 40-400 mg/dL.  

The overall mean absolute relative difference (MARD) of each CGM-YSI pair (a standard metric for CGM analysis) was 8.2%, with 9.1% for the abdomen and 8.2% for the arm.

Accuracy remained high in both arm- and abdomen-placed sensors across the 10-day wear period through the 12-hour grace period and across glucose ranges. There were no significant differences between G7 accuracy by diabetes type, insulin regimen, or body mass index.

The highest agreement rates and lowest MARDs occurred when CGM readings were increasing or decreasing by no more than 1 mg/dL per minute. However, even at the highest rates of glucose concentration change, MARD values below 10% were found for arm-placed sensors and below 10.5% for abdomen-placed sensors, Dr. Garg and colleagues report.

When the hypoglycemia threshold alert was set to 55 mg/dL, true alert rates for detection of hypoglycemia below 70 mg/dL by sensors worn on the arm and abdomen were 91.3% and 85.2%, respectively. With hyperglycemia threshold alerts set to 300 mg/dL, the true alert rates for detection of hyperglycemia greater than 250 mg/dL by sensors worn on the arm and abdomen were 99.9% and 99.8% respectively.

The overall mean time lag for the sensors was 3.5 minutes, 3.6 minutes for the arm, and 3.4 minutes for the abdomen. There were no serious adverse events during the study.

The study excluded children and adolescents; data from these populations will be reported separately, the authors note.
 

Accuracy at least as good as prior Dexcom versions, competitors

The MARD values of 8.2% on the arm and 9.1% on the abdomen were similar to or better than accuracy measurements of other commercially available CGM systems, note Dr. Garg and colleagues, although they acknowledge that few head-to-head studies at different anatomic locations have been conducted.

A study of an older Dexcom version (G4 Platinum) found MARD estimates of 12.0% on the arm and 12.3% on the abdomen, the authors note.  

The newly FDA-approved implantable Eversense E3 (Senseonics) CGM, worn on the upper arm, has a MARD of 9.1%, while the arm-placed Abbott FreeStyle Libre 2, approved in the U.S. in June 2020, has an overall MARD of 9.3%.

Lag-time differences between the reference and G7 were also similar to or better than time delays in prior-generation Dexcom CGMs, Dr. Garg and colleagues say.

Participants also completed a survey. “The redesigned applicator allows for sensor deployment with one hand, and most participants found G7 easier to insert than their prior CGM system,” the researchers say.

Finally, “unlike G6, G7 allows for temporary silencing of all audible alerts, including Urgent Low. Taken together, these attributes are anticipated to provide for a better end-user experience with G7 and help reduce diabetes burden,” they conclude.

The study was supported by a grant from Dexcom. Dr. Garg has reported receiving consultant fees from Medtronic, Novo Nordisk, Zealand, LifeScan, Roche, and Lilly, as well as research grants through the University of Colorado from Lilly, Novo Nordisk, Medtronic, Dexcom, T1D Exchange, Helmsley Trust, NIDDK, and JDRF.

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

When counseling patients with warts, Adam Friedman, MD, admits that he feels like a character from “Game of Thrones” since many treatment options are “medieval and painful,” from duct tape occlusion to the stings of liquid nitrogen and salicylic acid.

“We can combine destructive, immunologic, and cytotoxic approaches,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic & Surgical Conference. “It’s not one or the other, we want to be aggressive. Combining therapies in the office and at home will accelerate clearance of warts; monotherapy just doesn’t cut it.”

At the initial clinic visit, he advises asking patients how long the warts have been present, because sometimes they will go away within a year or two without treatment. “If someone says, ‘I’ve had these for years,’ you know you’re in for the long haul and you have to be aggressive with their therapy,” Dr. Friedman said. “Sometimes you’ll pick up plantar warts on a full-body skin exam and the patient may say, ‘I really don’t care. Please don’t touch them,’ so it’s important to understand how they are impacting quality of life.”

Patients should also be asked what treatments they have used previously, and it is important to set some realistic expectations and dispel some myths, Dr. Friedman said. “One of the most important things is that you must get these patients back. This is not often a one and done approach; you need to keep hitting them [with therapy], because if you let one infected keratinocyte survive, it’s going to come back and it’s still going to be contagious – more likely for that patient than for anyone else.”

The application of liquid nitrogen is a popular, inexpensive destructive treatment option, with spray canisters that cost about $600. “You have to consider the temperature of the liquid nitrogen spray because melanocytes die at negative 5 degrees Celsius, so you have to be mindful in patients with darker skin tones that you may leave with permanent dyschromia, meaning hypopigmentation or depigmentation when you do this,” he said. Because it is painful, “we’re limited when it comes to treating children with warts who are younger than 9 or 10. I don’t think the Q-tip method or dipping a hemostat in cryogen and touching the tip really works. You’ve got to create a nice ice ball that thaws and kills the infected keratinocytes.”

Dr. Friedman favors a 10-second freeze of the wart, usually for two to three cycles depending on its anatomic location, and he may give patients imiquimod or 5-FU to use at home for 5 nights of the week. A recently published study found that the use of ultrasound gel increases the efficacy of cryotherapy in the treatment of warts.

Another destructive treatment approach is cantharidin 0.7% applied topically in the office. It is believed to activate neutral serine proteases that cause degeneration of the desmosomal plaque, leading to detachment of tonofilaments from desmosomes. Repeat in-office applications within 14-21 days may be necessary for this treatment, which is not approved by the Food and Drug Administration. “It is painless on application unless there’s a break in the skin,” Dr. Friedman said.

For warts on thicker areas such as palms and soles, he often employs combination therapy with cantharidin 1%, salicylic acid 30%, and podophyllotoxin 5%. “This can hurt a little bit, but some patients require only one treatment for cure,” he said. “Efficacy depends on the size of the wart.”

VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% “is coming down the pike,” Dr. Friedman said. “From the data we have, it seems that pairing with a curette or a #15 blade first gets better penetration, which makes sense. Patients come back every 3-4 weeks for treatment. It is a big investment, but it is worth it. I tell patients it’s not worth starting if you’re not going to see it through. I tell them, ‘we’re going to see a lot of each other until this is clear.’ ”

As for immunomodulatory approaches, imiquimod 5% cream is approved for treating genital and perianal warts. In Dr. Friedman’s clinical experience, it has limited efficacy on keratinized skin unless the surface has been disrupted, “so don’t even waste your time unless you are using some approach to enhance skin penetration,” he advised. “Insurance coverage can be a challenge,” he added.

He recommends application with salicylic acid alternating with imiquimod 5% cream every night at bedtime – under occlusion for thicker skinned areas.

For patients who favor use of natural products, off-label ingenol mebutate is an option. A case series of its use in 17 patients with anogenital warts found that 16 experienced clearance of all warts treated with either 0.05% or 0.015% ingenol mebutate gel. Local irritation occurred within 24-48 hours and lasted 2-5 days.

A natural alternative treatment is Candida albicans skin test antigen (Candin), especially for cases of multiple lesions on the hands and feet, because a field effect can be achieved, Dr. Friedman said. “The idea here is simple. At most, you’re talking about injecting a sentinel wart with 0.3 mL Candin 2-10 times every 3 weeks. The wart may be in a field of warts. That will induce an immune reaction that brings in the cavalry. I find that it works very well but it is painful, so when you’re injecting the feet, get the foot positioned well, because that patient may inadvertently kick you in the face [upon injection].”

Authors of a recent systematic review and meta-analysis highlighted the efficacy for systemic retinoids in the treatment of warts, particularly recalcitrant or recurrent types (Dermatol Ther 2021 34[2]:e14793). “Tazarotene is going to be your best bet if you can get it,” Dr. Friedman said. “If you have to go lower like OTC adapalene or tretinoin, be my guest, but tazarotene works best by slowing down that rapid turnover that the virus is imparting on the basal keratinocyte layer. It can enhance penetration of drug but also thin the warts out.”

Dr. Friedman characterized human papilloma virus (HPV) vaccines, such as Gardasil 9, as “one of the greatest innovations” in the treatment of warts. While indicated as a preventive strategy, “it also works as treatment. I’ve had patients with recalcitrant genital warts who will clear after taking the vaccine. It is something to think about as an adjuvant to everything we do, because it can function as a treatment.”

Another immunologic treatment option is the oral H2-receptor antagonist cimetidine taken 30 mg/kg per day for 3-5 months. “There is mixed evidence of efficacy with this,” Dr. Friedman said. “I tend to use it in cases of innumerable flat warts.”

As for cytotoxic options for treating warts, bleomycin works at 250-1,000 U/mL injected per lesion, with lidocaine. “This is painful to patients both on application and post treatment,” he said. “But it works really well when used properly.”

In one study of 46 patients who received intralesional bleomycin, 74% patients had complete resolution of all warts with an average of 1.7 treatments. About 70% of patients experienced pain that lasted less than 2 days after treatment. In a separate study of patients treated with bleomycin for warts, researchers in India diluted bleomycin with lidocaine to help mitigate some of that pain.

An additional cytotoxic option, 5-FU in formulations of 5% cream/solution or 1% cream, can effectively treat warts. Dr. Friedman typically suggests application to the affected area twice daily for 3-5 weeks. “The cost can be high especially for off-label use,” he said. He noted that Skin Medicinals makes a compounded wart solution composed of 5% 5-FU and salicylic acid 30% solution. A 50 mL container sells for about $50.

Dr. Friedman had no relevant disclosures related to his presentation.

When counseling patients with warts, Adam Friedman, MD, admits that he feels like a character from “Game of Thrones” since many treatment options are “medieval and painful,” from duct tape occlusion to the stings of liquid nitrogen and salicylic acid.

“We can combine destructive, immunologic, and cytotoxic approaches,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic & Surgical Conference. “It’s not one or the other, we want to be aggressive. Combining therapies in the office and at home will accelerate clearance of warts; monotherapy just doesn’t cut it.”

At the initial clinic visit, he advises asking patients how long the warts have been present, because sometimes they will go away within a year or two without treatment. “If someone says, ‘I’ve had these for years,’ you know you’re in for the long haul and you have to be aggressive with their therapy,” Dr. Friedman said. “Sometimes you’ll pick up plantar warts on a full-body skin exam and the patient may say, ‘I really don’t care. Please don’t touch them,’ so it’s important to understand how they are impacting quality of life.”

Patients should also be asked what treatments they have used previously, and it is important to set some realistic expectations and dispel some myths, Dr. Friedman said. “One of the most important things is that you must get these patients back. This is not often a one and done approach; you need to keep hitting them [with therapy], because if you let one infected keratinocyte survive, it’s going to come back and it’s still going to be contagious – more likely for that patient than for anyone else.”

The application of liquid nitrogen is a popular, inexpensive destructive treatment option, with spray canisters that cost about $600. “You have to consider the temperature of the liquid nitrogen spray because melanocytes die at negative 5 degrees Celsius, so you have to be mindful in patients with darker skin tones that you may leave with permanent dyschromia, meaning hypopigmentation or depigmentation when you do this,” he said. Because it is painful, “we’re limited when it comes to treating children with warts who are younger than 9 or 10. I don’t think the Q-tip method or dipping a hemostat in cryogen and touching the tip really works. You’ve got to create a nice ice ball that thaws and kills the infected keratinocytes.”

Dr. Friedman favors a 10-second freeze of the wart, usually for two to three cycles depending on its anatomic location, and he may give patients imiquimod or 5-FU to use at home for 5 nights of the week. A recently published study found that the use of ultrasound gel increases the efficacy of cryotherapy in the treatment of warts.

Another destructive treatment approach is cantharidin 0.7% applied topically in the office. It is believed to activate neutral serine proteases that cause degeneration of the desmosomal plaque, leading to detachment of tonofilaments from desmosomes. Repeat in-office applications within 14-21 days may be necessary for this treatment, which is not approved by the Food and Drug Administration. “It is painless on application unless there’s a break in the skin,” Dr. Friedman said.

For warts on thicker areas such as palms and soles, he often employs combination therapy with cantharidin 1%, salicylic acid 30%, and podophyllotoxin 5%. “This can hurt a little bit, but some patients require only one treatment for cure,” he said. “Efficacy depends on the size of the wart.”

VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% “is coming down the pike,” Dr. Friedman said. “From the data we have, it seems that pairing with a curette or a #15 blade first gets better penetration, which makes sense. Patients come back every 3-4 weeks for treatment. It is a big investment, but it is worth it. I tell patients it’s not worth starting if you’re not going to see it through. I tell them, ‘we’re going to see a lot of each other until this is clear.’ ”

As for immunomodulatory approaches, imiquimod 5% cream is approved for treating genital and perianal warts. In Dr. Friedman’s clinical experience, it has limited efficacy on keratinized skin unless the surface has been disrupted, “so don’t even waste your time unless you are using some approach to enhance skin penetration,” he advised. “Insurance coverage can be a challenge,” he added.

He recommends application with salicylic acid alternating with imiquimod 5% cream every night at bedtime – under occlusion for thicker skinned areas.

For patients who favor use of natural products, off-label ingenol mebutate is an option. A case series of its use in 17 patients with anogenital warts found that 16 experienced clearance of all warts treated with either 0.05% or 0.015% ingenol mebutate gel. Local irritation occurred within 24-48 hours and lasted 2-5 days.

A natural alternative treatment is Candida albicans skin test antigen (Candin), especially for cases of multiple lesions on the hands and feet, because a field effect can be achieved, Dr. Friedman said. “The idea here is simple. At most, you’re talking about injecting a sentinel wart with 0.3 mL Candin 2-10 times every 3 weeks. The wart may be in a field of warts. That will induce an immune reaction that brings in the cavalry. I find that it works very well but it is painful, so when you’re injecting the feet, get the foot positioned well, because that patient may inadvertently kick you in the face [upon injection].”

Authors of a recent systematic review and meta-analysis highlighted the efficacy for systemic retinoids in the treatment of warts, particularly recalcitrant or recurrent types (Dermatol Ther 2021 34[2]:e14793). “Tazarotene is going to be your best bet if you can get it,” Dr. Friedman said. “If you have to go lower like OTC adapalene or tretinoin, be my guest, but tazarotene works best by slowing down that rapid turnover that the virus is imparting on the basal keratinocyte layer. It can enhance penetration of drug but also thin the warts out.”

Dr. Friedman characterized human papilloma virus (HPV) vaccines, such as Gardasil 9, as “one of the greatest innovations” in the treatment of warts. While indicated as a preventive strategy, “it also works as treatment. I’ve had patients with recalcitrant genital warts who will clear after taking the vaccine. It is something to think about as an adjuvant to everything we do, because it can function as a treatment.”

Another immunologic treatment option is the oral H2-receptor antagonist cimetidine taken 30 mg/kg per day for 3-5 months. “There is mixed evidence of efficacy with this,” Dr. Friedman said. “I tend to use it in cases of innumerable flat warts.”

As for cytotoxic options for treating warts, bleomycin works at 250-1,000 U/mL injected per lesion, with lidocaine. “This is painful to patients both on application and post treatment,” he said. “But it works really well when used properly.”

In one study of 46 patients who received intralesional bleomycin, 74% patients had complete resolution of all warts with an average of 1.7 treatments. About 70% of patients experienced pain that lasted less than 2 days after treatment. In a separate study of patients treated with bleomycin for warts, researchers in India diluted bleomycin with lidocaine to help mitigate some of that pain.

An additional cytotoxic option, 5-FU in formulations of 5% cream/solution or 1% cream, can effectively treat warts. Dr. Friedman typically suggests application to the affected area twice daily for 3-5 weeks. “The cost can be high especially for off-label use,” he said. He noted that Skin Medicinals makes a compounded wart solution composed of 5% 5-FU and salicylic acid 30% solution. A 50 mL container sells for about $50.

Dr. Friedman had no relevant disclosures related to his presentation.

When counseling patients with warts, Adam Friedman, MD, admits that he feels like a character from “Game of Thrones” since many treatment options are “medieval and painful,” from duct tape occlusion to the stings of liquid nitrogen and salicylic acid.

“We can combine destructive, immunologic, and cytotoxic approaches,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic & Surgical Conference. “It’s not one or the other, we want to be aggressive. Combining therapies in the office and at home will accelerate clearance of warts; monotherapy just doesn’t cut it.”

At the initial clinic visit, he advises asking patients how long the warts have been present, because sometimes they will go away within a year or two without treatment. “If someone says, ‘I’ve had these for years,’ you know you’re in for the long haul and you have to be aggressive with their therapy,” Dr. Friedman said. “Sometimes you’ll pick up plantar warts on a full-body skin exam and the patient may say, ‘I really don’t care. Please don’t touch them,’ so it’s important to understand how they are impacting quality of life.”

Patients should also be asked what treatments they have used previously, and it is important to set some realistic expectations and dispel some myths, Dr. Friedman said. “One of the most important things is that you must get these patients back. This is not often a one and done approach; you need to keep hitting them [with therapy], because if you let one infected keratinocyte survive, it’s going to come back and it’s still going to be contagious – more likely for that patient than for anyone else.”

The application of liquid nitrogen is a popular, inexpensive destructive treatment option, with spray canisters that cost about $600. “You have to consider the temperature of the liquid nitrogen spray because melanocytes die at negative 5 degrees Celsius, so you have to be mindful in patients with darker skin tones that you may leave with permanent dyschromia, meaning hypopigmentation or depigmentation when you do this,” he said. Because it is painful, “we’re limited when it comes to treating children with warts who are younger than 9 or 10. I don’t think the Q-tip method or dipping a hemostat in cryogen and touching the tip really works. You’ve got to create a nice ice ball that thaws and kills the infected keratinocytes.”

Dr. Friedman favors a 10-second freeze of the wart, usually for two to three cycles depending on its anatomic location, and he may give patients imiquimod or 5-FU to use at home for 5 nights of the week. A recently published study found that the use of ultrasound gel increases the efficacy of cryotherapy in the treatment of warts.

Another destructive treatment approach is cantharidin 0.7% applied topically in the office. It is believed to activate neutral serine proteases that cause degeneration of the desmosomal plaque, leading to detachment of tonofilaments from desmosomes. Repeat in-office applications within 14-21 days may be necessary for this treatment, which is not approved by the Food and Drug Administration. “It is painless on application unless there’s a break in the skin,” Dr. Friedman said.

For warts on thicker areas such as palms and soles, he often employs combination therapy with cantharidin 1%, salicylic acid 30%, and podophyllotoxin 5%. “This can hurt a little bit, but some patients require only one treatment for cure,” he said. “Efficacy depends on the size of the wart.”

VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% “is coming down the pike,” Dr. Friedman said. “From the data we have, it seems that pairing with a curette or a #15 blade first gets better penetration, which makes sense. Patients come back every 3-4 weeks for treatment. It is a big investment, but it is worth it. I tell patients it’s not worth starting if you’re not going to see it through. I tell them, ‘we’re going to see a lot of each other until this is clear.’ ”

As for immunomodulatory approaches, imiquimod 5% cream is approved for treating genital and perianal warts. In Dr. Friedman’s clinical experience, it has limited efficacy on keratinized skin unless the surface has been disrupted, “so don’t even waste your time unless you are using some approach to enhance skin penetration,” he advised. “Insurance coverage can be a challenge,” he added.

He recommends application with salicylic acid alternating with imiquimod 5% cream every night at bedtime – under occlusion for thicker skinned areas.

For patients who favor use of natural products, off-label ingenol mebutate is an option. A case series of its use in 17 patients with anogenital warts found that 16 experienced clearance of all warts treated with either 0.05% or 0.015% ingenol mebutate gel. Local irritation occurred within 24-48 hours and lasted 2-5 days.

A natural alternative treatment is Candida albicans skin test antigen (Candin), especially for cases of multiple lesions on the hands and feet, because a field effect can be achieved, Dr. Friedman said. “The idea here is simple. At most, you’re talking about injecting a sentinel wart with 0.3 mL Candin 2-10 times every 3 weeks. The wart may be in a field of warts. That will induce an immune reaction that brings in the cavalry. I find that it works very well but it is painful, so when you’re injecting the feet, get the foot positioned well, because that patient may inadvertently kick you in the face [upon injection].”

Authors of a recent systematic review and meta-analysis highlighted the efficacy for systemic retinoids in the treatment of warts, particularly recalcitrant or recurrent types (Dermatol Ther 2021 34[2]:e14793). “Tazarotene is going to be your best bet if you can get it,” Dr. Friedman said. “If you have to go lower like OTC adapalene or tretinoin, be my guest, but tazarotene works best by slowing down that rapid turnover that the virus is imparting on the basal keratinocyte layer. It can enhance penetration of drug but also thin the warts out.”

Dr. Friedman characterized human papilloma virus (HPV) vaccines, such as Gardasil 9, as “one of the greatest innovations” in the treatment of warts. While indicated as a preventive strategy, “it also works as treatment. I’ve had patients with recalcitrant genital warts who will clear after taking the vaccine. It is something to think about as an adjuvant to everything we do, because it can function as a treatment.”

Another immunologic treatment option is the oral H2-receptor antagonist cimetidine taken 30 mg/kg per day for 3-5 months. “There is mixed evidence of efficacy with this,” Dr. Friedman said. “I tend to use it in cases of innumerable flat warts.”

As for cytotoxic options for treating warts, bleomycin works at 250-1,000 U/mL injected per lesion, with lidocaine. “This is painful to patients both on application and post treatment,” he said. “But it works really well when used properly.”

In one study of 46 patients who received intralesional bleomycin, 74% patients had complete resolution of all warts with an average of 1.7 treatments. About 70% of patients experienced pain that lasted less than 2 days after treatment. In a separate study of patients treated with bleomycin for warts, researchers in India diluted bleomycin with lidocaine to help mitigate some of that pain.

An additional cytotoxic option, 5-FU in formulations of 5% cream/solution or 1% cream, can effectively treat warts. Dr. Friedman typically suggests application to the affected area twice daily for 3-5 weeks. “The cost can be high especially for off-label use,” he said. He noted that Skin Medicinals makes a compounded wart solution composed of 5% 5-FU and salicylic acid 30% solution. A 50 mL container sells for about $50.

Dr. Friedman had no relevant disclosures related to his presentation.

The perception of an inadequate milk supply can contribute to a new mother’s decision to cease breastfeeding prematurely, but identifying at-risk women is difficult. Now a new study suggests that, for some women, this impression, known as perceived inadequacy of milk supply (PIMS) appears to have a basis in genetics.

Steven D. Hicks, MD, PhD, associate professor of pediatrics at Penn State University, Hershey, and colleagues found that variations in the MFGE8 gene was associated with perceived breast milk supply.

“Genotyping one lactogenic gene aided identification of mothers at risk for PIMS. If validated in a larger cohort, such an approach could be used to identify mothers who may benefit from increased lactation support.” Dr. Hicks’ group wrote in Breastfeeding Medicine.

A simple 24-hour polymerase chain reaction test around the time of delivery could identify vulnerable mothers, who could receive targeted lactation support including galactagogue supplementation and early scheduling of “nurse and pump” routines.

“Also, if a woman is found to have PIMS, she would definitely want to avoid going on oral contraceptives after delivery as these can affect milk supply,” Dr. Hicks said in an interview. “That would be like a double hit in a woman already at risk.“

In other measures, she would meet once a week with a lactation consultant for the first 6 months to make sure good breastfeeding practices as to frequency and duration of placing the baby on the breast are being maintained, Dr. Hicks continued. “She needs to make sure her supply isn’t going backwards because once it starts to dry up, it’s really hard to turn the ship around.”

Dietary interventions to promote lactation may also help.
 

The study

In the context of a larger study on breast milk factors protecting children from developing allergies, the prospective observational analysis collected data on 221 breastfeeding mothers aged 19-42 years (mean age, 29 years) for 12 months.

All mothers had initially planned to nurse their babies for at least 6 months but some stopped well short of their goal.

“At least a third told us they gave up because they felt their milk supply had run out,” Dr. Hicks said in an interview.

Using salivas swabs, the investigators assessed 18 genes secreted from mammary tissue and previously linked in cows to secretory function for single-nucleotide polymorphisms in 88 age-, race-, and parity-matched women. Of these, 45 had PIMS and 43 had perceived adequate milk supply (PAMS).

Among differences between the two groups:

• PIMS mothers breastfed exclusively for a shorter period than PAMS mothers: 7 ± 12 weeks versus 22 ± 19 weeks(P = .001)
• At 1 month after delivery, their reported milk production was lower: 17.6 ± 13.3 oz/day versus 27.0 ± 12.2 oz/day (P = .0001). This shortfall persisted at 4 months: 16.0 ± 14.1 oz/day versus 27.3 ± 14.9 oz/day (P < .0010.
• Between birth and 1 month, infants of PIMS mothers also showed a smaller average increase in weight-for-length z score between birth and 1 month: 0.74 ± 1.4 versus 1.4 ± 1.5 (P = .038).

Furthermore, maternal genotype for the rs2271714 variant within MFGE8 was associated with PIMS status (P = .009; adjusted P = .09; likelihood ratio, 9.33), and duration of exclusive breastfeeding (P = .009; adjusted P = .09; chi square, 9.39).

Adding the MFGE8 genotype to a model including maternal age, parity, previous breastfeeding duration, body mass index, education, and depression status significantly increased predictive accuracy for PIMS status, the authors noted.

“This is a very exciting observation made by Dr. Hicks and his team, and the first study to identify a genetic variant associated with perceived insufficient milk supply,” said Shannon L. Kelleher, PhD, professor of biological and nutritional sciences at University of Massachusetts, Lowell.

“It provides compelling evidence that insufficient milk supply is very common and supports the urgent need to identify the risk factors and develop interventions to improve breastfeeding success,” added Dr. Kelleher, who was not involved in the study.

“If genetic variants such as the one identified in MFGE8 are confirmed to be common in mothers with insufficient milk supply, the development of lactation-focused genetic tests to identify women at risk for low milk supply would revolutionize our ability to support breastfeeding mothers and help them achieve their breastfeeding goals.”

Although 83% of new mothers initiate breastfeeding, only 57% are still breastfeeding at 6 months and only 35% breastfeed until 12 months, according to the Centers for Disease Control and Prevention’s Breastfeeding Report Card.

This study was funded by grants to Dr. Hicks from the Gerber Foundation and the Center for Research on Women and Newborns Foundation. The authors disclosed no competing interests. Dr. Kelleher reported no conflicts of interest relevant to her comments.

The perception of an inadequate milk supply can contribute to a new mother’s decision to cease breastfeeding prematurely, but identifying at-risk women is difficult. Now a new study suggests that, for some women, this impression, known as perceived inadequacy of milk supply (PIMS) appears to have a basis in genetics.

Steven D. Hicks, MD, PhD, associate professor of pediatrics at Penn State University, Hershey, and colleagues found that variations in the MFGE8 gene was associated with perceived breast milk supply.

“Genotyping one lactogenic gene aided identification of mothers at risk for PIMS. If validated in a larger cohort, such an approach could be used to identify mothers who may benefit from increased lactation support.” Dr. Hicks’ group wrote in Breastfeeding Medicine.

A simple 24-hour polymerase chain reaction test around the time of delivery could identify vulnerable mothers, who could receive targeted lactation support including galactagogue supplementation and early scheduling of “nurse and pump” routines.

“Also, if a woman is found to have PIMS, she would definitely want to avoid going on oral contraceptives after delivery as these can affect milk supply,” Dr. Hicks said in an interview. “That would be like a double hit in a woman already at risk.“

In other measures, she would meet once a week with a lactation consultant for the first 6 months to make sure good breastfeeding practices as to frequency and duration of placing the baby on the breast are being maintained, Dr. Hicks continued. “She needs to make sure her supply isn’t going backwards because once it starts to dry up, it’s really hard to turn the ship around.”

Dietary interventions to promote lactation may also help.
 

The study

In the context of a larger study on breast milk factors protecting children from developing allergies, the prospective observational analysis collected data on 221 breastfeeding mothers aged 19-42 years (mean age, 29 years) for 12 months.

All mothers had initially planned to nurse their babies for at least 6 months but some stopped well short of their goal.

“At least a third told us they gave up because they felt their milk supply had run out,” Dr. Hicks said in an interview.

Using salivas swabs, the investigators assessed 18 genes secreted from mammary tissue and previously linked in cows to secretory function for single-nucleotide polymorphisms in 88 age-, race-, and parity-matched women. Of these, 45 had PIMS and 43 had perceived adequate milk supply (PAMS).

Among differences between the two groups:

• PIMS mothers breastfed exclusively for a shorter period than PAMS mothers: 7 ± 12 weeks versus 22 ± 19 weeks(P = .001)
• At 1 month after delivery, their reported milk production was lower: 17.6 ± 13.3 oz/day versus 27.0 ± 12.2 oz/day (P = .0001). This shortfall persisted at 4 months: 16.0 ± 14.1 oz/day versus 27.3 ± 14.9 oz/day (P < .0010.
• Between birth and 1 month, infants of PIMS mothers also showed a smaller average increase in weight-for-length z score between birth and 1 month: 0.74 ± 1.4 versus 1.4 ± 1.5 (P = .038).

Furthermore, maternal genotype for the rs2271714 variant within MFGE8 was associated with PIMS status (P = .009; adjusted P = .09; likelihood ratio, 9.33), and duration of exclusive breastfeeding (P = .009; adjusted P = .09; chi square, 9.39).

Adding the MFGE8 genotype to a model including maternal age, parity, previous breastfeeding duration, body mass index, education, and depression status significantly increased predictive accuracy for PIMS status, the authors noted.

“This is a very exciting observation made by Dr. Hicks and his team, and the first study to identify a genetic variant associated with perceived insufficient milk supply,” said Shannon L. Kelleher, PhD, professor of biological and nutritional sciences at University of Massachusetts, Lowell.

“It provides compelling evidence that insufficient milk supply is very common and supports the urgent need to identify the risk factors and develop interventions to improve breastfeeding success,” added Dr. Kelleher, who was not involved in the study.

“If genetic variants such as the one identified in MFGE8 are confirmed to be common in mothers with insufficient milk supply, the development of lactation-focused genetic tests to identify women at risk for low milk supply would revolutionize our ability to support breastfeeding mothers and help them achieve their breastfeeding goals.”

Although 83% of new mothers initiate breastfeeding, only 57% are still breastfeeding at 6 months and only 35% breastfeed until 12 months, according to the Centers for Disease Control and Prevention’s Breastfeeding Report Card.

This study was funded by grants to Dr. Hicks from the Gerber Foundation and the Center for Research on Women and Newborns Foundation. The authors disclosed no competing interests. Dr. Kelleher reported no conflicts of interest relevant to her comments.

The perception of an inadequate milk supply can contribute to a new mother’s decision to cease breastfeeding prematurely, but identifying at-risk women is difficult. Now a new study suggests that, for some women, this impression, known as perceived inadequacy of milk supply (PIMS) appears to have a basis in genetics.

Steven D. Hicks, MD, PhD, associate professor of pediatrics at Penn State University, Hershey, and colleagues found that variations in the MFGE8 gene was associated with perceived breast milk supply.

“Genotyping one lactogenic gene aided identification of mothers at risk for PIMS. If validated in a larger cohort, such an approach could be used to identify mothers who may benefit from increased lactation support.” Dr. Hicks’ group wrote in Breastfeeding Medicine.

A simple 24-hour polymerase chain reaction test around the time of delivery could identify vulnerable mothers, who could receive targeted lactation support including galactagogue supplementation and early scheduling of “nurse and pump” routines.

“Also, if a woman is found to have PIMS, she would definitely want to avoid going on oral contraceptives after delivery as these can affect milk supply,” Dr. Hicks said in an interview. “That would be like a double hit in a woman already at risk.“

In other measures, she would meet once a week with a lactation consultant for the first 6 months to make sure good breastfeeding practices as to frequency and duration of placing the baby on the breast are being maintained, Dr. Hicks continued. “She needs to make sure her supply isn’t going backwards because once it starts to dry up, it’s really hard to turn the ship around.”

Dietary interventions to promote lactation may also help.
 

The study

In the context of a larger study on breast milk factors protecting children from developing allergies, the prospective observational analysis collected data on 221 breastfeeding mothers aged 19-42 years (mean age, 29 years) for 12 months.

All mothers had initially planned to nurse their babies for at least 6 months but some stopped well short of their goal.

“At least a third told us they gave up because they felt their milk supply had run out,” Dr. Hicks said in an interview.

Using salivas swabs, the investigators assessed 18 genes secreted from mammary tissue and previously linked in cows to secretory function for single-nucleotide polymorphisms in 88 age-, race-, and parity-matched women. Of these, 45 had PIMS and 43 had perceived adequate milk supply (PAMS).

Among differences between the two groups:

• PIMS mothers breastfed exclusively for a shorter period than PAMS mothers: 7 ± 12 weeks versus 22 ± 19 weeks(P = .001)
• At 1 month after delivery, their reported milk production was lower: 17.6 ± 13.3 oz/day versus 27.0 ± 12.2 oz/day (P = .0001). This shortfall persisted at 4 months: 16.0 ± 14.1 oz/day versus 27.3 ± 14.9 oz/day (P < .0010.
• Between birth and 1 month, infants of PIMS mothers also showed a smaller average increase in weight-for-length z score between birth and 1 month: 0.74 ± 1.4 versus 1.4 ± 1.5 (P = .038).

Furthermore, maternal genotype for the rs2271714 variant within MFGE8 was associated with PIMS status (P = .009; adjusted P = .09; likelihood ratio, 9.33), and duration of exclusive breastfeeding (P = .009; adjusted P = .09; chi square, 9.39).

Adding the MFGE8 genotype to a model including maternal age, parity, previous breastfeeding duration, body mass index, education, and depression status significantly increased predictive accuracy for PIMS status, the authors noted.

“This is a very exciting observation made by Dr. Hicks and his team, and the first study to identify a genetic variant associated with perceived insufficient milk supply,” said Shannon L. Kelleher, PhD, professor of biological and nutritional sciences at University of Massachusetts, Lowell.

“It provides compelling evidence that insufficient milk supply is very common and supports the urgent need to identify the risk factors and develop interventions to improve breastfeeding success,” added Dr. Kelleher, who was not involved in the study.

“If genetic variants such as the one identified in MFGE8 are confirmed to be common in mothers with insufficient milk supply, the development of lactation-focused genetic tests to identify women at risk for low milk supply would revolutionize our ability to support breastfeeding mothers and help them achieve their breastfeeding goals.”

Although 83% of new mothers initiate breastfeeding, only 57% are still breastfeeding at 6 months and only 35% breastfeed until 12 months, according to the Centers for Disease Control and Prevention’s Breastfeeding Report Card.

This study was funded by grants to Dr. Hicks from the Gerber Foundation and the Center for Research on Women and Newborns Foundation. The authors disclosed no competing interests. Dr. Kelleher reported no conflicts of interest relevant to her comments.

Kaseb et al report the results of a Phase 2 study where 27 patients with resectable HCC were randomized to receive either nivolumab alone or the combination of nivolumab and ipilimumab for 6 weeks before surgery, and then for up to 2 years after resection. Estimated median progression-free survival (PFS) was 9.4 months with nivolumab and 19.53 months with nivolumab plus ipilimumab (hazard ratio [HR] 0.99, 95% CI 0.31–2.54); median time to progression was 9.4 months in the nivolumab group and 19.53 months in the nivolumab plus ipilimumab group (HR 0.89, 95% CI 0.31–2.54). Three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumor area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. Grade 3–4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The authors concluded that immunotherapy is safe and feasible in patients with resectable hepatocellular carcinoma.

Marron et al. evaluated the clinical activity of cemiplimab (an anti-PD-1) in 21 patients with resectable hepatocellular carcinoma. Cemiplimab was administered twice every 3 weeks before and 8 times after surgery. Of the 20 patients with resected tumors, four (20%) had significant (>70%) tumor necrosis with 15% showing complete (100%) tumor necrosis. Three (15%) of 20 patients had a radiologic partial response, and all other patients maintained stable disease. Seven (33%) patients had grade 3 adverse events. No grade 4 or 5 events were observed. The investigators concluded that perioperative cemiplimab should be studied further in patients with resectable HCC.

Finally, Guan et al. compared outcomes of 498 patients with resected HCC who also had hepatitis B virus infection (defined as HBsAg-positivity for >90 days). Of those, 367 patients (73.69%) received at least 3 months of postoperative anti-viral treatment (AVT), while 131 (27.31%) did not (non-AVT group). Propensity score matching (PSM) analysis was performed on 206 patients. AVT was associated with better recurrence-free survival (RFS) and overall survival (OS) either before or after PSM.  After PSM, the 1-, 3-, and 5-year RFS rates were 85.3%, 65.7%, and 19.1% vs. 76.7%, 46.6%, and 5.8% in the AVT and non-AVT groups, respectively (P = .001). The corresponding 1-, 3-, and 5-year OS rates were 99.0%, 89.8%, and 64.0% vs. 96.1%, 70.5%, and 43.2% in the AVT and non-AVT groups (P < .001). Risk factors that were independently associated with a poor RFS included HBV DNA positivity (P = .002), preoperative alpha fetoprotein (AFP) level of ≥20 ng/mL (P < .001), poor differentiation (P = .022), multiple tumors (P = .037), and microvascular invasion (P < .001). The conclusion was that AVT improves outcomes in patients with HBV and resectable HCC.

Kaseb et al report the results of a Phase 2 study where 27 patients with resectable HCC were randomized to receive either nivolumab alone or the combination of nivolumab and ipilimumab for 6 weeks before surgery, and then for up to 2 years after resection. Estimated median progression-free survival (PFS) was 9.4 months with nivolumab and 19.53 months with nivolumab plus ipilimumab (hazard ratio [HR] 0.99, 95% CI 0.31–2.54); median time to progression was 9.4 months in the nivolumab group and 19.53 months in the nivolumab plus ipilimumab group (HR 0.89, 95% CI 0.31–2.54). Three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumor area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. Grade 3–4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The authors concluded that immunotherapy is safe and feasible in patients with resectable hepatocellular carcinoma.

Marron et al. evaluated the clinical activity of cemiplimab (an anti-PD-1) in 21 patients with resectable hepatocellular carcinoma. Cemiplimab was administered twice every 3 weeks before and 8 times after surgery. Of the 20 patients with resected tumors, four (20%) had significant (>70%) tumor necrosis with 15% showing complete (100%) tumor necrosis. Three (15%) of 20 patients had a radiologic partial response, and all other patients maintained stable disease. Seven (33%) patients had grade 3 adverse events. No grade 4 or 5 events were observed. The investigators concluded that perioperative cemiplimab should be studied further in patients with resectable HCC.

Finally, Guan et al. compared outcomes of 498 patients with resected HCC who also had hepatitis B virus infection (defined as HBsAg-positivity for >90 days). Of those, 367 patients (73.69%) received at least 3 months of postoperative anti-viral treatment (AVT), while 131 (27.31%) did not (non-AVT group). Propensity score matching (PSM) analysis was performed on 206 patients. AVT was associated with better recurrence-free survival (RFS) and overall survival (OS) either before or after PSM.  After PSM, the 1-, 3-, and 5-year RFS rates were 85.3%, 65.7%, and 19.1% vs. 76.7%, 46.6%, and 5.8% in the AVT and non-AVT groups, respectively (P = .001). The corresponding 1-, 3-, and 5-year OS rates were 99.0%, 89.8%, and 64.0% vs. 96.1%, 70.5%, and 43.2% in the AVT and non-AVT groups (P < .001). Risk factors that were independently associated with a poor RFS included HBV DNA positivity (P = .002), preoperative alpha fetoprotein (AFP) level of ≥20 ng/mL (P < .001), poor differentiation (P = .022), multiple tumors (P = .037), and microvascular invasion (P < .001). The conclusion was that AVT improves outcomes in patients with HBV and resectable HCC.

Kaseb et al report the results of a Phase 2 study where 27 patients with resectable HCC were randomized to receive either nivolumab alone or the combination of nivolumab and ipilimumab for 6 weeks before surgery, and then for up to 2 years after resection. Estimated median progression-free survival (PFS) was 9.4 months with nivolumab and 19.53 months with nivolumab plus ipilimumab (hazard ratio [HR] 0.99, 95% CI 0.31–2.54); median time to progression was 9.4 months in the nivolumab group and 19.53 months in the nivolumab plus ipilimumab group (HR 0.89, 95% CI 0.31–2.54). Three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumor area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. Grade 3–4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The authors concluded that immunotherapy is safe and feasible in patients with resectable hepatocellular carcinoma.

Marron et al. evaluated the clinical activity of cemiplimab (an anti-PD-1) in 21 patients with resectable hepatocellular carcinoma. Cemiplimab was administered twice every 3 weeks before and 8 times after surgery. Of the 20 patients with resected tumors, four (20%) had significant (>70%) tumor necrosis with 15% showing complete (100%) tumor necrosis. Three (15%) of 20 patients had a radiologic partial response, and all other patients maintained stable disease. Seven (33%) patients had grade 3 adverse events. No grade 4 or 5 events were observed. The investigators concluded that perioperative cemiplimab should be studied further in patients with resectable HCC.

Finally, Guan et al. compared outcomes of 498 patients with resected HCC who also had hepatitis B virus infection (defined as HBsAg-positivity for >90 days). Of those, 367 patients (73.69%) received at least 3 months of postoperative anti-viral treatment (AVT), while 131 (27.31%) did not (non-AVT group). Propensity score matching (PSM) analysis was performed on 206 patients. AVT was associated with better recurrence-free survival (RFS) and overall survival (OS) either before or after PSM.  After PSM, the 1-, 3-, and 5-year RFS rates were 85.3%, 65.7%, and 19.1% vs. 76.7%, 46.6%, and 5.8% in the AVT and non-AVT groups, respectively (P = .001). The corresponding 1-, 3-, and 5-year OS rates were 99.0%, 89.8%, and 64.0% vs. 96.1%, 70.5%, and 43.2% in the AVT and non-AVT groups (P < .001). Risk factors that were independently associated with a poor RFS included HBV DNA positivity (P = .002), preoperative alpha fetoprotein (AFP) level of ≥20 ng/mL (P < .001), poor differentiation (P = .022), multiple tumors (P = .037), and microvascular invasion (P < .001). The conclusion was that AVT improves outcomes in patients with HBV and resectable HCC.

Investigators presenting at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium called for neoadjuvant chemotherapy to be a new standard of care for high-grade upper tract urothelial carcinoma.

They made the call after finding that 63% of patients (36/57) had a pathologic response to gemcitabine/cisplatin before extirpative surgery, with pathologic response defined as less than pT2NO disease on postoperative pathology. Nineteen percent (11/57) had complete responses, with no evidence of the main tumor (ypT0N0).

The approach has a “favorable pathologic response, is well tolerated ... and thus should be considered a new standard of care option,” said investigators led by Wesley Yip, MD, a urologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York.

There was no comparator arm, but the results are in line with previous reports, including a 2014 investigation that found a 5-year disease specific survival (DSS) of 90.1% and 5-year overall survival (OS) of 80.2% among 31 upper tract urothelial carcinoma patients who received neoadjuvant chemotherapy, versus a 5-year DSS and OS of 57.6% among 81 historical controls.

Presentation moderator Stephen Boorjian, MD, chair of urology at the Mayo Clinic in Rochester, Minn., called the findings “valuable” but noted there’s level 1 evidence for an alternative approach, chemotherapy or nivolumab after surgery for patients with particularly worrisome postop pathology. It makes it tough to know if patients should be treated beforehand or afterwards.

“What do we do?” he asked.

Dr. Yip said it’s an open question at this point but that trials are underway to address the issue. In the meantime, “it’s definitely a multidisciplinary discussion to know what’s best for each patient,” he said. One of the factors that argues for the neoadjuvant approach is that substantially fewer patients are eligible for chemotherapy after nephroureterectomy because of diminished renal function. “Patients who might not be eligible ... are the ones we’d be targeting for” neoadjuvant chemotherapy (NAC), he said.

In the study, gemcitabine 1000 mg/m² and cisplatin 35 mg/m² were administered on days 1 and 8 of four 21-day cycles, followed by radical nephroureterectomy or ureterectomy.

Fifty-three of the subjects had high-grade disease by endoscopic biopsy, and the remaining four were enrolled based on imaging and selective cytology. There was no nodal disease on CT within 30 days of neoadjuvant chemotherapy initiation.

Two-year progression-free survival (PFS) was 91% among pathologic responders but only 52% among nonresponders. Every responder was alive at 2 years versus 80% of nonresponders.

Across the entire cohort, 5-year PFS was 61% and 5-year OS 79%; 89.5% of patients were alive at a median follow-up of 3.5 years.

Almost all of the patients completed at least three NAC cycles, and all of them went to surgery, which had a 90-day grade 3 or higher complication rate of 7%.

Sixty-three percent were men, and 95% were White. The median age was 66 years.

The work was funded by the National Institutes of Health and Memorial Sloan Kettering. Dr. Yip had no disclosures. Dr. Boorjian advises ArTara Therapeutics, FerGene, and Ferring.

Investigators presenting at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium called for neoadjuvant chemotherapy to be a new standard of care for high-grade upper tract urothelial carcinoma.

They made the call after finding that 63% of patients (36/57) had a pathologic response to gemcitabine/cisplatin before extirpative surgery, with pathologic response defined as less than pT2NO disease on postoperative pathology. Nineteen percent (11/57) had complete responses, with no evidence of the main tumor (ypT0N0).

The approach has a “favorable pathologic response, is well tolerated ... and thus should be considered a new standard of care option,” said investigators led by Wesley Yip, MD, a urologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York.

There was no comparator arm, but the results are in line with previous reports, including a 2014 investigation that found a 5-year disease specific survival (DSS) of 90.1% and 5-year overall survival (OS) of 80.2% among 31 upper tract urothelial carcinoma patients who received neoadjuvant chemotherapy, versus a 5-year DSS and OS of 57.6% among 81 historical controls.

Presentation moderator Stephen Boorjian, MD, chair of urology at the Mayo Clinic in Rochester, Minn., called the findings “valuable” but noted there’s level 1 evidence for an alternative approach, chemotherapy or nivolumab after surgery for patients with particularly worrisome postop pathology. It makes it tough to know if patients should be treated beforehand or afterwards.

“What do we do?” he asked.

Dr. Yip said it’s an open question at this point but that trials are underway to address the issue. In the meantime, “it’s definitely a multidisciplinary discussion to know what’s best for each patient,” he said. One of the factors that argues for the neoadjuvant approach is that substantially fewer patients are eligible for chemotherapy after nephroureterectomy because of diminished renal function. “Patients who might not be eligible ... are the ones we’d be targeting for” neoadjuvant chemotherapy (NAC), he said.

In the study, gemcitabine 1000 mg/m² and cisplatin 35 mg/m² were administered on days 1 and 8 of four 21-day cycles, followed by radical nephroureterectomy or ureterectomy.

Fifty-three of the subjects had high-grade disease by endoscopic biopsy, and the remaining four were enrolled based on imaging and selective cytology. There was no nodal disease on CT within 30 days of neoadjuvant chemotherapy initiation.

Two-year progression-free survival (PFS) was 91% among pathologic responders but only 52% among nonresponders. Every responder was alive at 2 years versus 80% of nonresponders.

Across the entire cohort, 5-year PFS was 61% and 5-year OS 79%; 89.5% of patients were alive at a median follow-up of 3.5 years.

Almost all of the patients completed at least three NAC cycles, and all of them went to surgery, which had a 90-day grade 3 or higher complication rate of 7%.

Sixty-three percent were men, and 95% were White. The median age was 66 years.

The work was funded by the National Institutes of Health and Memorial Sloan Kettering. Dr. Yip had no disclosures. Dr. Boorjian advises ArTara Therapeutics, FerGene, and Ferring.

Investigators presenting at the American Society of Clinical Oncology’s Genitourinary Cancers Symposium called for neoadjuvant chemotherapy to be a new standard of care for high-grade upper tract urothelial carcinoma.

They made the call after finding that 63% of patients (36/57) had a pathologic response to gemcitabine/cisplatin before extirpative surgery, with pathologic response defined as less than pT2NO disease on postoperative pathology. Nineteen percent (11/57) had complete responses, with no evidence of the main tumor (ypT0N0).

The approach has a “favorable pathologic response, is well tolerated ... and thus should be considered a new standard of care option,” said investigators led by Wesley Yip, MD, a urologic oncology fellow at Memorial Sloan Kettering Cancer Center, New York.

There was no comparator arm, but the results are in line with previous reports, including a 2014 investigation that found a 5-year disease specific survival (DSS) of 90.1% and 5-year overall survival (OS) of 80.2% among 31 upper tract urothelial carcinoma patients who received neoadjuvant chemotherapy, versus a 5-year DSS and OS of 57.6% among 81 historical controls.

Presentation moderator Stephen Boorjian, MD, chair of urology at the Mayo Clinic in Rochester, Minn., called the findings “valuable” but noted there’s level 1 evidence for an alternative approach, chemotherapy or nivolumab after surgery for patients with particularly worrisome postop pathology. It makes it tough to know if patients should be treated beforehand or afterwards.

“What do we do?” he asked.

Dr. Yip said it’s an open question at this point but that trials are underway to address the issue. In the meantime, “it’s definitely a multidisciplinary discussion to know what’s best for each patient,” he said. One of the factors that argues for the neoadjuvant approach is that substantially fewer patients are eligible for chemotherapy after nephroureterectomy because of diminished renal function. “Patients who might not be eligible ... are the ones we’d be targeting for” neoadjuvant chemotherapy (NAC), he said.

In the study, gemcitabine 1000 mg/m² and cisplatin 35 mg/m² were administered on days 1 and 8 of four 21-day cycles, followed by radical nephroureterectomy or ureterectomy.

Fifty-three of the subjects had high-grade disease by endoscopic biopsy, and the remaining four were enrolled based on imaging and selective cytology. There was no nodal disease on CT within 30 days of neoadjuvant chemotherapy initiation.

Two-year progression-free survival (PFS) was 91% among pathologic responders but only 52% among nonresponders. Every responder was alive at 2 years versus 80% of nonresponders.

Across the entire cohort, 5-year PFS was 61% and 5-year OS 79%; 89.5% of patients were alive at a median follow-up of 3.5 years.

Almost all of the patients completed at least three NAC cycles, and all of them went to surgery, which had a 90-day grade 3 or higher complication rate of 7%.

Sixty-three percent were men, and 95% were White. The median age was 66 years.

The work was funded by the National Institutes of Health and Memorial Sloan Kettering. Dr. Yip had no disclosures. Dr. Boorjian advises ArTara Therapeutics, FerGene, and Ferring.