Pediatrics

A quadrivalent human papillomavirus vaccine provided adequate seroconversion response rates in immunocompromised children, according to Dr. C. Raina MacIntyre, MBBS, PhD, and her associates.

In a clinical trial of 59 immunocompromised children aged 5-18, seroconversion rates for HPV types 6, 11, 16, and 18 were 93.3%, 100%, 100%, and 88.9%, respectively, 7 months after receiving the first dose of vaccine. After 2 years, seroconversion rates for HPV types 6, 11, 16, and 18 were 82.2%, 91.1%, 91.1%, and 68.9%, respectively.

Thinkstockimages (yangna)

Local adverse events occurred in 16 patients after the first dose, but incidence decreased after the second and third doses. Injection site erythema, pain, and swelling were the most commonly reported adverse events. Minor disease flare occurred in two patients during the follow-up period, and one patient developed a squamous cell oral carcinoma, but the tumor could not be tested for HPV.

The data suggest “that HPV vaccine could be given earlier for immunosuppressed children, who are at higher risk of earlier onset cancers, but long-term follow-up studies are required to determine persistence of immunity,” the investigators said.

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.06.049).

lfranki@frontlinemedcom.com

A quadrivalent human papillomavirus vaccine provided adequate seroconversion response rates in immunocompromised children, according to Dr. C. Raina MacIntyre, MBBS, PhD, and her associates.

In a clinical trial of 59 immunocompromised children aged 5-18, seroconversion rates for HPV types 6, 11, 16, and 18 were 93.3%, 100%, 100%, and 88.9%, respectively, 7 months after receiving the first dose of vaccine. After 2 years, seroconversion rates for HPV types 6, 11, 16, and 18 were 82.2%, 91.1%, 91.1%, and 68.9%, respectively.

Thinkstockimages (yangna)

Local adverse events occurred in 16 patients after the first dose, but incidence decreased after the second and third doses. Injection site erythema, pain, and swelling were the most commonly reported adverse events. Minor disease flare occurred in two patients during the follow-up period, and one patient developed a squamous cell oral carcinoma, but the tumor could not be tested for HPV.

The data suggest “that HPV vaccine could be given earlier for immunosuppressed children, who are at higher risk of earlier onset cancers, but long-term follow-up studies are required to determine persistence of immunity,” the investigators said.

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.06.049).

lfranki@frontlinemedcom.com

A quadrivalent human papillomavirus vaccine provided adequate seroconversion response rates in immunocompromised children, according to Dr. C. Raina MacIntyre, MBBS, PhD, and her associates.

In a clinical trial of 59 immunocompromised children aged 5-18, seroconversion rates for HPV types 6, 11, 16, and 18 were 93.3%, 100%, 100%, and 88.9%, respectively, 7 months after receiving the first dose of vaccine. After 2 years, seroconversion rates for HPV types 6, 11, 16, and 18 were 82.2%, 91.1%, 91.1%, and 68.9%, respectively.

Thinkstockimages (yangna)

Local adverse events occurred in 16 patients after the first dose, but incidence decreased after the second and third doses. Injection site erythema, pain, and swelling were the most commonly reported adverse events. Minor disease flare occurred in two patients during the follow-up period, and one patient developed a squamous cell oral carcinoma, but the tumor could not be tested for HPV.

The data suggest “that HPV vaccine could be given earlier for immunosuppressed children, who are at higher risk of earlier onset cancers, but long-term follow-up studies are required to determine persistence of immunity,” the investigators said.

Find the full study in Vaccine (doi: 10.1016/j.vaccine.2016.06.049).

lfranki@frontlinemedcom.com

While vaginal lidocaine gel does not significantly reduce pain from intrauterine device (IUD) insertion, it does appear to reduce the pain from tenaculum placement in nulliparous women and the likelihood that women will need cervical dilation for insertion, according to the results of a randomized controlled trial.

Despite the effectiveness of IUDs in preventing pregnancy, some women don’t choose this contraception method because they fear the pain of insertion, past research has found. Pain is also more likely in women who have not given birth. In fact, just 5.9% of nulliparous women use IUDs, compared with 16.8% of women with one or two prior births, wrote Rachel B. Rapkin, MD, MPH, of the University of South Florida in Tampa, and her colleagues (Obstet Gynecol. 2016;128:621-8. doi: 10.1097/AOG.0000000000001596).

flocu/ThinkStock.com

The researchers tested the effectiveness of self-administered lidocaine gel as pain relief with 59 nulliparous women aged 14-50 years from University of Pittsburgh Medical Center clinics between July 2012 and May 2013. All of the women requested an IUD. A total of 30 women were randomized to apply the 2% lidocaine vaginal gel 5 minutes before the IUD insertion. Another 29 women were randomized to apply a placebo gel. Nearly all the women reported that inserting the gel was somewhat or very easy and that they had no pain after insertion.

There was one unsuccessful IUD insertion in the placebo group. That woman had intolerable pain while attempting uterine sound so the procedure was aborted. She was included in the intention-to-treat analysis with all missing data set to 100 mm on a 100-mm visual analog scale.

In the intention-to-treat analysis, the median change in pain from baseline to IUD insertion was 61 mm for women who used the lidocaine gel. Women using placebo reported a median score of 69 mm, which was not significantly different from those using the lidocaine gel (P = .06). However, women using lidocaine did report significantly less pain when the tenaculum was placed: a median 32 mm on the pain scale, compared with 56 mm reported by those who used the placebo gel (P = .02).

Although 87% of the physicians reported that insertion was easy in the women with lidocaine, compared with 64% who said it was easy in women using the placebo gel, the difference was not significant (P = .07). However, significantly more women needed cervical dilation before IUD placement if they used the placebo (34.5%), compared with those using the lidocaine (3.3%, P = .002). The women also reported pain scores after speculum placement, uterine sounding, and 5 minutes after speculum removal, but none of these showed significant differences.

Overall, more than one-third of the women needed to take pain medication for at least 3 days after the IUD was inserted, but the majority of women (86%) would probably or definitely recommend an IUD to a friend, and 76% reported satisfaction with the insertion experience. Cramping and pain medication use after insertion did not vary between the two groups.

The generalizability of the trial may be limited because it enrolled participants who were largely white and college educated and it used clinicians with at least 4 years of IUD insertion experience.

The research was funded by the Society of Family Planning Research Fund. Dr. Rapkin reported having no financial disclosures. Her coauthors reported consulting work for Merck and research funding from Bayer Healthcare and Medicines 360 Inc. One of the coauthors is founder and president of the nonprofit Basic Health International.

While vaginal lidocaine gel does not significantly reduce pain from intrauterine device (IUD) insertion, it does appear to reduce the pain from tenaculum placement in nulliparous women and the likelihood that women will need cervical dilation for insertion, according to the results of a randomized controlled trial.

Despite the effectiveness of IUDs in preventing pregnancy, some women don’t choose this contraception method because they fear the pain of insertion, past research has found. Pain is also more likely in women who have not given birth. In fact, just 5.9% of nulliparous women use IUDs, compared with 16.8% of women with one or two prior births, wrote Rachel B. Rapkin, MD, MPH, of the University of South Florida in Tampa, and her colleagues (Obstet Gynecol. 2016;128:621-8. doi: 10.1097/AOG.0000000000001596).

flocu/ThinkStock.com

The researchers tested the effectiveness of self-administered lidocaine gel as pain relief with 59 nulliparous women aged 14-50 years from University of Pittsburgh Medical Center clinics between July 2012 and May 2013. All of the women requested an IUD. A total of 30 women were randomized to apply the 2% lidocaine vaginal gel 5 minutes before the IUD insertion. Another 29 women were randomized to apply a placebo gel. Nearly all the women reported that inserting the gel was somewhat or very easy and that they had no pain after insertion.

There was one unsuccessful IUD insertion in the placebo group. That woman had intolerable pain while attempting uterine sound so the procedure was aborted. She was included in the intention-to-treat analysis with all missing data set to 100 mm on a 100-mm visual analog scale.

In the intention-to-treat analysis, the median change in pain from baseline to IUD insertion was 61 mm for women who used the lidocaine gel. Women using placebo reported a median score of 69 mm, which was not significantly different from those using the lidocaine gel (P = .06). However, women using lidocaine did report significantly less pain when the tenaculum was placed: a median 32 mm on the pain scale, compared with 56 mm reported by those who used the placebo gel (P = .02).

Although 87% of the physicians reported that insertion was easy in the women with lidocaine, compared with 64% who said it was easy in women using the placebo gel, the difference was not significant (P = .07). However, significantly more women needed cervical dilation before IUD placement if they used the placebo (34.5%), compared with those using the lidocaine (3.3%, P = .002). The women also reported pain scores after speculum placement, uterine sounding, and 5 minutes after speculum removal, but none of these showed significant differences.

Overall, more than one-third of the women needed to take pain medication for at least 3 days after the IUD was inserted, but the majority of women (86%) would probably or definitely recommend an IUD to a friend, and 76% reported satisfaction with the insertion experience. Cramping and pain medication use after insertion did not vary between the two groups.

The generalizability of the trial may be limited because it enrolled participants who were largely white and college educated and it used clinicians with at least 4 years of IUD insertion experience.

The research was funded by the Society of Family Planning Research Fund. Dr. Rapkin reported having no financial disclosures. Her coauthors reported consulting work for Merck and research funding from Bayer Healthcare and Medicines 360 Inc. One of the coauthors is founder and president of the nonprofit Basic Health International.

While vaginal lidocaine gel does not significantly reduce pain from intrauterine device (IUD) insertion, it does appear to reduce the pain from tenaculum placement in nulliparous women and the likelihood that women will need cervical dilation for insertion, according to the results of a randomized controlled trial.

Despite the effectiveness of IUDs in preventing pregnancy, some women don’t choose this contraception method because they fear the pain of insertion, past research has found. Pain is also more likely in women who have not given birth. In fact, just 5.9% of nulliparous women use IUDs, compared with 16.8% of women with one or two prior births, wrote Rachel B. Rapkin, MD, MPH, of the University of South Florida in Tampa, and her colleagues (Obstet Gynecol. 2016;128:621-8. doi: 10.1097/AOG.0000000000001596).

flocu/ThinkStock.com

The researchers tested the effectiveness of self-administered lidocaine gel as pain relief with 59 nulliparous women aged 14-50 years from University of Pittsburgh Medical Center clinics between July 2012 and May 2013. All of the women requested an IUD. A total of 30 women were randomized to apply the 2% lidocaine vaginal gel 5 minutes before the IUD insertion. Another 29 women were randomized to apply a placebo gel. Nearly all the women reported that inserting the gel was somewhat or very easy and that they had no pain after insertion.

There was one unsuccessful IUD insertion in the placebo group. That woman had intolerable pain while attempting uterine sound so the procedure was aborted. She was included in the intention-to-treat analysis with all missing data set to 100 mm on a 100-mm visual analog scale.

In the intention-to-treat analysis, the median change in pain from baseline to IUD insertion was 61 mm for women who used the lidocaine gel. Women using placebo reported a median score of 69 mm, which was not significantly different from those using the lidocaine gel (P = .06). However, women using lidocaine did report significantly less pain when the tenaculum was placed: a median 32 mm on the pain scale, compared with 56 mm reported by those who used the placebo gel (P = .02).

Although 87% of the physicians reported that insertion was easy in the women with lidocaine, compared with 64% who said it was easy in women using the placebo gel, the difference was not significant (P = .07). However, significantly more women needed cervical dilation before IUD placement if they used the placebo (34.5%), compared with those using the lidocaine (3.3%, P = .002). The women also reported pain scores after speculum placement, uterine sounding, and 5 minutes after speculum removal, but none of these showed significant differences.

Overall, more than one-third of the women needed to take pain medication for at least 3 days after the IUD was inserted, but the majority of women (86%) would probably or definitely recommend an IUD to a friend, and 76% reported satisfaction with the insertion experience. Cramping and pain medication use after insertion did not vary between the two groups.

The generalizability of the trial may be limited because it enrolled participants who were largely white and college educated and it used clinicians with at least 4 years of IUD insertion experience.

The research was funded by the Society of Family Planning Research Fund. Dr. Rapkin reported having no financial disclosures. Her coauthors reported consulting work for Merck and research funding from Bayer Healthcare and Medicines 360 Inc. One of the coauthors is founder and president of the nonprofit Basic Health International.

The European Commission has proposed regulatory criteria on endocrine-disrupting chemicals that are too strict and so fall short of protecting the public, as they were intended to do, experts contend.

Endocrine-disrupting chemicals cost Europe billions in health care costs each year (Andrology. 2016 Jul;4[4]:565-72).

Published in June, the criteria would require proof that chemicals harm human endocrine health to define them as endocrine-disrupting chemicals (EDCs) – even if data from animal and in vitro studies already suggest so. “Because health effects can take years or even generations to become apparent, this proposal will not protect public health,” the Endocrine Society noted in a sharp formal critique.

Endocrine-disrupting chemicals mimic or block hormones central to brain development, reproduction, metabolism, growth, and other key physiologic processes. The European Union is the largest single economy to regulate EDCs specifically, which more than 1,300 studies have linked to health problems such as infertility, diabetes, obesity, hormone-related cancers, and neurological disorders, the Endocrine Society concluded in a 2015 scientific statement.

Exposure to even low doses of EDCs such as bisphenol A (BPA) can cause adverse effects. But to fulfill the regulatory definition of the European Commission, EDCs would have to meet an even greater burden of proof than carcinogens – a backward step that “defeats the purpose of the regulations – to shield the public from EDCs that pose a threat to human health,” Rémy Slama, PhD, a member of the Society’s European Union Endocrine-Disrupting Chemicals Task Force, stated in an Endocrine Society news release. Of particular concern is the proposal that EDCs must have a single known “mode of action,” which “represents a fundamental misunderstanding of how endocrine signaling works by connecting different organ systems within the body,” said Dr. Slama, senior investigator at Inserm (the National Institute of Health and Medical Research) in Paris.

Deborah M. Kurrasch, PhD, assistant professor and principal investigator at the University of Calgary (Alta.), agreed. The “mode of action” criterion misses the point that EDCs are “messy” compounds that target various proteins and elicit a range of potential cellular responses based on dose, target tissue, and age, she said in an interview. An EDC may lack a single mode of action, or its mode of action may be far harder to pinpoint than its effects on processes such as reproduction, sleep, mood, and growth, she added. “In my opinion, an endocrine-disrupting chemical is one that disrupts the endocrine system. Despite some internal dialogue, the name for this broad and diverse group of chemicals is, and likely will remain, EDCs because the name so accurately describes their one unifying effect – they all perturb normal endocrine function.”

Ultimately, enacting such tight criteria would tie the hands of regulators with regard to newly recognized and even some well-studied EDCs, “despite evidence that they affect endocrine signaling, because their mode of action is not yet known,” Dr. Kurrasch said.

Experts also noted that the EC criteria would keep regulatory bodies from ranking chemicals based on the strength of evidence that they disrupt endocrine function. Instead, the Endocrine Society advocates for a tiered ranking system based on available data. “As the European Parliament and member countries consider whether to implement the European Commission’s criteria, the Society will continue to advocate for criteria that reflect the state of the science,” the organization emphasized.

Dr. Kurrasch is a member of the Endocrine Society and had no other disclosures.

The European Commission has proposed regulatory criteria on endocrine-disrupting chemicals that are too strict and so fall short of protecting the public, as they were intended to do, experts contend.

Endocrine-disrupting chemicals cost Europe billions in health care costs each year (Andrology. 2016 Jul;4[4]:565-72).

Published in June, the criteria would require proof that chemicals harm human endocrine health to define them as endocrine-disrupting chemicals (EDCs) – even if data from animal and in vitro studies already suggest so. “Because health effects can take years or even generations to become apparent, this proposal will not protect public health,” the Endocrine Society noted in a sharp formal critique.

Endocrine-disrupting chemicals mimic or block hormones central to brain development, reproduction, metabolism, growth, and other key physiologic processes. The European Union is the largest single economy to regulate EDCs specifically, which more than 1,300 studies have linked to health problems such as infertility, diabetes, obesity, hormone-related cancers, and neurological disorders, the Endocrine Society concluded in a 2015 scientific statement.

Exposure to even low doses of EDCs such as bisphenol A (BPA) can cause adverse effects. But to fulfill the regulatory definition of the European Commission, EDCs would have to meet an even greater burden of proof than carcinogens – a backward step that “defeats the purpose of the regulations – to shield the public from EDCs that pose a threat to human health,” Rémy Slama, PhD, a member of the Society’s European Union Endocrine-Disrupting Chemicals Task Force, stated in an Endocrine Society news release. Of particular concern is the proposal that EDCs must have a single known “mode of action,” which “represents a fundamental misunderstanding of how endocrine signaling works by connecting different organ systems within the body,” said Dr. Slama, senior investigator at Inserm (the National Institute of Health and Medical Research) in Paris.

Deborah M. Kurrasch, PhD, assistant professor and principal investigator at the University of Calgary (Alta.), agreed. The “mode of action” criterion misses the point that EDCs are “messy” compounds that target various proteins and elicit a range of potential cellular responses based on dose, target tissue, and age, she said in an interview. An EDC may lack a single mode of action, or its mode of action may be far harder to pinpoint than its effects on processes such as reproduction, sleep, mood, and growth, she added. “In my opinion, an endocrine-disrupting chemical is one that disrupts the endocrine system. Despite some internal dialogue, the name for this broad and diverse group of chemicals is, and likely will remain, EDCs because the name so accurately describes their one unifying effect – they all perturb normal endocrine function.”

Ultimately, enacting such tight criteria would tie the hands of regulators with regard to newly recognized and even some well-studied EDCs, “despite evidence that they affect endocrine signaling, because their mode of action is not yet known,” Dr. Kurrasch said.

Experts also noted that the EC criteria would keep regulatory bodies from ranking chemicals based on the strength of evidence that they disrupt endocrine function. Instead, the Endocrine Society advocates for a tiered ranking system based on available data. “As the European Parliament and member countries consider whether to implement the European Commission’s criteria, the Society will continue to advocate for criteria that reflect the state of the science,” the organization emphasized.

Dr. Kurrasch is a member of the Endocrine Society and had no other disclosures.

The European Commission has proposed regulatory criteria on endocrine-disrupting chemicals that are too strict and so fall short of protecting the public, as they were intended to do, experts contend.

Endocrine-disrupting chemicals cost Europe billions in health care costs each year (Andrology. 2016 Jul;4[4]:565-72).

Published in June, the criteria would require proof that chemicals harm human endocrine health to define them as endocrine-disrupting chemicals (EDCs) – even if data from animal and in vitro studies already suggest so. “Because health effects can take years or even generations to become apparent, this proposal will not protect public health,” the Endocrine Society noted in a sharp formal critique.

Endocrine-disrupting chemicals mimic or block hormones central to brain development, reproduction, metabolism, growth, and other key physiologic processes. The European Union is the largest single economy to regulate EDCs specifically, which more than 1,300 studies have linked to health problems such as infertility, diabetes, obesity, hormone-related cancers, and neurological disorders, the Endocrine Society concluded in a 2015 scientific statement.

Exposure to even low doses of EDCs such as bisphenol A (BPA) can cause adverse effects. But to fulfill the regulatory definition of the European Commission, EDCs would have to meet an even greater burden of proof than carcinogens – a backward step that “defeats the purpose of the regulations – to shield the public from EDCs that pose a threat to human health,” Rémy Slama, PhD, a member of the Society’s European Union Endocrine-Disrupting Chemicals Task Force, stated in an Endocrine Society news release. Of particular concern is the proposal that EDCs must have a single known “mode of action,” which “represents a fundamental misunderstanding of how endocrine signaling works by connecting different organ systems within the body,” said Dr. Slama, senior investigator at Inserm (the National Institute of Health and Medical Research) in Paris.

Deborah M. Kurrasch, PhD, assistant professor and principal investigator at the University of Calgary (Alta.), agreed. The “mode of action” criterion misses the point that EDCs are “messy” compounds that target various proteins and elicit a range of potential cellular responses based on dose, target tissue, and age, she said in an interview. An EDC may lack a single mode of action, or its mode of action may be far harder to pinpoint than its effects on processes such as reproduction, sleep, mood, and growth, she added. “In my opinion, an endocrine-disrupting chemical is one that disrupts the endocrine system. Despite some internal dialogue, the name for this broad and diverse group of chemicals is, and likely will remain, EDCs because the name so accurately describes their one unifying effect – they all perturb normal endocrine function.”

Ultimately, enacting such tight criteria would tie the hands of regulators with regard to newly recognized and even some well-studied EDCs, “despite evidence that they affect endocrine signaling, because their mode of action is not yet known,” Dr. Kurrasch said.

Experts also noted that the EC criteria would keep regulatory bodies from ranking chemicals based on the strength of evidence that they disrupt endocrine function. Instead, the Endocrine Society advocates for a tiered ranking system based on available data. “As the European Parliament and member countries consider whether to implement the European Commission’s criteria, the Society will continue to advocate for criteria that reflect the state of the science,” the organization emphasized.

Dr. Kurrasch is a member of the Endocrine Society and had no other disclosures.

SAN DIEGO – Readmission rates and the underlying reasons for them vary between medical specialties following surgery in children, a study of national data suggests.

“Hospital readmission is a very hot topic, particularly in light of the Affordable Care Act,” Afif N. Kulaylat, MD, said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference. “Beyond economic costs there are very tangible costs to patients that we must consider. Readmissions have been associated with significant morbidity for patients. They often herald or implicate a postoperative complication. There are also indirect costs to patients and families such as time off from school or work.”

Dr. Kulaylat, of the division of pediatric surgery at Penn State Children’s Hospital, Hershey, Penn., presented findings from a retrospective analysis of NSQIP Pediatric (NSQIP-P), an ongoing collaboration between the ACS and the American Pediatric Surgical Association to improve the care of young patients. The researchers evaluated NSQIP-P data from 2013 and 2014 and focused on unplanned readmission within 30 days, including reasons for readmission based on NSQIP-P readmission categories and ICD-9 readmission codes as categorized by the AHRQ Clinical Classification Software. Multivariate logistic regression was used to evaluate factors associated with unplanned readmission.

Dr. Kulaylat reported results from a cohort of 129,849 patients cared for by 64 NSQIP-P participating hospitals. Among these, the all-cause readmission rate was 4.7%. After excluding patients with planned readmissions, the unplanned readmission rate was found to be 3.9%. From this cohort, 28% required reoperation within 30 days, and the median time from discharge to unplanned readmission was 8 days, with an interquartile range between 3 and 14 days.

Among the procedures captured in NSQIP-P, neurosurgery accounted for the highest readmission rate (10.8%), followed by general/thoracic surgery (5.2%), urology (2.6%), ENT (2%), orthopedic (1.9%), and plastic and reconstructive surgery (1.3%). The most common reason for readmission was surgical site infection at 23%, followed by GI complications such as ileus, obstruction, and constipation (17%); pulmonary-related complications (9%); device-related complications including shunt malfunction (8%); neurologic (7%); pain (6%); other medical diseases (6%); sepsis (5%); electrolytes/dehydration (5%); and urinary tract infection (UTI, 3%). It is estimated that at least two-thirds of unplanned readmissions (63%) were directly related to surgery. “These reasons for readmission and their frequency closely parallel what is seen in adults, with the exception of bleeding complications, which were rare in children compared to adults,” Dr. Kulaylat said.

The top five CPT codes associated with readmissions were laparoscopic appendectomy, laparoscopic gastrostomy tube placement, and three additional codes related to placement and replacement/revision of ventricular shunts/catheters.

Reasons for readmission varied among specialties. For example, among general and thoracic surgery, surgical-site infections (SSI) and GI-related issues dominated, while in neurosurgery SSI and device issues dominated. In urology, UTIs were the most frequent, while ENT had a greater proportion of pulmonary complications. Certain patient variables were also associated with an increased risk of hospital readmission, including comorbidities related to GI, CNS, renal, and immunosuppression and nutrition (P less than .001 for all). The strongest association was the occurrence of a postoperative complication, namely a post-discharge complication.

“The granularity of NSQIP-P can continue to be refined to help predict who is likely to get readmitted or if specific follow-up strategies might identify those headed to readmission,” remarked Robert E. Cilley, MD, a senior author and surgeon-in-chief at Penn State Children’s Hospital. Dr. Kulaylat acknowledged certain limitations of the study, including its retrospective design, the potential for data entry/data interpretation error, and that the researchers were unable to adjust for clustering at the hospital level. Directions of future research include a plan to study readmissions and predictive factors at the procedural level, establish risk-adjusted specialty/procedural-specific benchmarks for readmission rates, and refine the accuracy and reliability of the readmission data. “With these NSQIP-P data there is substantial opportunity for quality improvement as we strive to improve the care of children everywhere,” Dr. Kulaylat said. He reported having no relevant disclosures.

dbrunk@frontlinemedcom.com

SAN DIEGO – Readmission rates and the underlying reasons for them vary between medical specialties following surgery in children, a study of national data suggests.

“Hospital readmission is a very hot topic, particularly in light of the Affordable Care Act,” Afif N. Kulaylat, MD, said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference. “Beyond economic costs there are very tangible costs to patients that we must consider. Readmissions have been associated with significant morbidity for patients. They often herald or implicate a postoperative complication. There are also indirect costs to patients and families such as time off from school or work.”

Dr. Kulaylat, of the division of pediatric surgery at Penn State Children’s Hospital, Hershey, Penn., presented findings from a retrospective analysis of NSQIP Pediatric (NSQIP-P), an ongoing collaboration between the ACS and the American Pediatric Surgical Association to improve the care of young patients. The researchers evaluated NSQIP-P data from 2013 and 2014 and focused on unplanned readmission within 30 days, including reasons for readmission based on NSQIP-P readmission categories and ICD-9 readmission codes as categorized by the AHRQ Clinical Classification Software. Multivariate logistic regression was used to evaluate factors associated with unplanned readmission.

Dr. Kulaylat reported results from a cohort of 129,849 patients cared for by 64 NSQIP-P participating hospitals. Among these, the all-cause readmission rate was 4.7%. After excluding patients with planned readmissions, the unplanned readmission rate was found to be 3.9%. From this cohort, 28% required reoperation within 30 days, and the median time from discharge to unplanned readmission was 8 days, with an interquartile range between 3 and 14 days.

Among the procedures captured in NSQIP-P, neurosurgery accounted for the highest readmission rate (10.8%), followed by general/thoracic surgery (5.2%), urology (2.6%), ENT (2%), orthopedic (1.9%), and plastic and reconstructive surgery (1.3%). The most common reason for readmission was surgical site infection at 23%, followed by GI complications such as ileus, obstruction, and constipation (17%); pulmonary-related complications (9%); device-related complications including shunt malfunction (8%); neurologic (7%); pain (6%); other medical diseases (6%); sepsis (5%); electrolytes/dehydration (5%); and urinary tract infection (UTI, 3%). It is estimated that at least two-thirds of unplanned readmissions (63%) were directly related to surgery. “These reasons for readmission and their frequency closely parallel what is seen in adults, with the exception of bleeding complications, which were rare in children compared to adults,” Dr. Kulaylat said.

The top five CPT codes associated with readmissions were laparoscopic appendectomy, laparoscopic gastrostomy tube placement, and three additional codes related to placement and replacement/revision of ventricular shunts/catheters.

Reasons for readmission varied among specialties. For example, among general and thoracic surgery, surgical-site infections (SSI) and GI-related issues dominated, while in neurosurgery SSI and device issues dominated. In urology, UTIs were the most frequent, while ENT had a greater proportion of pulmonary complications. Certain patient variables were also associated with an increased risk of hospital readmission, including comorbidities related to GI, CNS, renal, and immunosuppression and nutrition (P less than .001 for all). The strongest association was the occurrence of a postoperative complication, namely a post-discharge complication.

“The granularity of NSQIP-P can continue to be refined to help predict who is likely to get readmitted or if specific follow-up strategies might identify those headed to readmission,” remarked Robert E. Cilley, MD, a senior author and surgeon-in-chief at Penn State Children’s Hospital. Dr. Kulaylat acknowledged certain limitations of the study, including its retrospective design, the potential for data entry/data interpretation error, and that the researchers were unable to adjust for clustering at the hospital level. Directions of future research include a plan to study readmissions and predictive factors at the procedural level, establish risk-adjusted specialty/procedural-specific benchmarks for readmission rates, and refine the accuracy and reliability of the readmission data. “With these NSQIP-P data there is substantial opportunity for quality improvement as we strive to improve the care of children everywhere,” Dr. Kulaylat said. He reported having no relevant disclosures.

dbrunk@frontlinemedcom.com

SAN DIEGO – Readmission rates and the underlying reasons for them vary between medical specialties following surgery in children, a study of national data suggests.

“Hospital readmission is a very hot topic, particularly in light of the Affordable Care Act,” Afif N. Kulaylat, MD, said at the American College of Surgeons/National Surgical Quality Improvement Program National Conference. “Beyond economic costs there are very tangible costs to patients that we must consider. Readmissions have been associated with significant morbidity for patients. They often herald or implicate a postoperative complication. There are also indirect costs to patients and families such as time off from school or work.”

Dr. Kulaylat, of the division of pediatric surgery at Penn State Children’s Hospital, Hershey, Penn., presented findings from a retrospective analysis of NSQIP Pediatric (NSQIP-P), an ongoing collaboration between the ACS and the American Pediatric Surgical Association to improve the care of young patients. The researchers evaluated NSQIP-P data from 2013 and 2014 and focused on unplanned readmission within 30 days, including reasons for readmission based on NSQIP-P readmission categories and ICD-9 readmission codes as categorized by the AHRQ Clinical Classification Software. Multivariate logistic regression was used to evaluate factors associated with unplanned readmission.

Dr. Kulaylat reported results from a cohort of 129,849 patients cared for by 64 NSQIP-P participating hospitals. Among these, the all-cause readmission rate was 4.7%. After excluding patients with planned readmissions, the unplanned readmission rate was found to be 3.9%. From this cohort, 28% required reoperation within 30 days, and the median time from discharge to unplanned readmission was 8 days, with an interquartile range between 3 and 14 days.

Among the procedures captured in NSQIP-P, neurosurgery accounted for the highest readmission rate (10.8%), followed by general/thoracic surgery (5.2%), urology (2.6%), ENT (2%), orthopedic (1.9%), and plastic and reconstructive surgery (1.3%). The most common reason for readmission was surgical site infection at 23%, followed by GI complications such as ileus, obstruction, and constipation (17%); pulmonary-related complications (9%); device-related complications including shunt malfunction (8%); neurologic (7%); pain (6%); other medical diseases (6%); sepsis (5%); electrolytes/dehydration (5%); and urinary tract infection (UTI, 3%). It is estimated that at least two-thirds of unplanned readmissions (63%) were directly related to surgery. “These reasons for readmission and their frequency closely parallel what is seen in adults, with the exception of bleeding complications, which were rare in children compared to adults,” Dr. Kulaylat said.

The top five CPT codes associated with readmissions were laparoscopic appendectomy, laparoscopic gastrostomy tube placement, and three additional codes related to placement and replacement/revision of ventricular shunts/catheters.

Reasons for readmission varied among specialties. For example, among general and thoracic surgery, surgical-site infections (SSI) and GI-related issues dominated, while in neurosurgery SSI and device issues dominated. In urology, UTIs were the most frequent, while ENT had a greater proportion of pulmonary complications. Certain patient variables were also associated with an increased risk of hospital readmission, including comorbidities related to GI, CNS, renal, and immunosuppression and nutrition (P less than .001 for all). The strongest association was the occurrence of a postoperative complication, namely a post-discharge complication.

“The granularity of NSQIP-P can continue to be refined to help predict who is likely to get readmitted or if specific follow-up strategies might identify those headed to readmission,” remarked Robert E. Cilley, MD, a senior author and surgeon-in-chief at Penn State Children’s Hospital. Dr. Kulaylat acknowledged certain limitations of the study, including its retrospective design, the potential for data entry/data interpretation error, and that the researchers were unable to adjust for clustering at the hospital level. Directions of future research include a plan to study readmissions and predictive factors at the procedural level, establish risk-adjusted specialty/procedural-specific benchmarks for readmission rates, and refine the accuracy and reliability of the readmission data. “With these NSQIP-P data there is substantial opportunity for quality improvement as we strive to improve the care of children everywhere,” Dr. Kulaylat said. He reported having no relevant disclosures.

dbrunk@frontlinemedcom.com

A randomized clinical trial evaluating three dosing strategies for 13-valent pneumococcal vaccine (PCV13) in preterm infants found that more widely spaced priming vaccinations resulted in higher immunoglobulin G (IgG) during the first 12 months of life, but reduced the immune response seen after the 12-month booster was given.

After the primary schedule, the percent of infants lacking seroprotection for more than one half of the serotypes in the PCV13 formulation was 25% on a reduced two-dose schedule, 12% on an accelerated schedule, and 3% on an extended schedule (P less than .001).

Conversely, “A reduced priming schedule of PCV13 resulted in higher post-booster IgG concentrations but lower post-primary concentrations,” wrote Alison Kent, MBChB, and her coinvestigators in the PUNS (Prems Under New Schedule) Study Group (Pediatrics. 2016;138[3]:e20153945).

©dina2001/Thinkstock

“Infants who received the extended schedule had lower fold increases in concentrations after booster vaccination than the other groups,” wrote Dr. Kent of the Pediatric Infectious Diseases Research Group and Vaccine Institute, St. George’s, University of London, and her collaborators. Participants receiving the extended schedule had lower geometric mean concentrations (GMCs) of antibodies than did those on the reduced schedule for nine serotypes and those on the accelerated schedule for four serotypes.

The study enrolled 210 premature infants in a phase IV, controlled, open-label trial at 12 sites in the United Kingdom. Infants of less than 35 weeks gestation, and between 7 and 12 weeks of age, were randomly assigned to receive PCV13 on one of three schedules. The reduced schedule gave two priming doses at 2 and 4 months of age; the accelerated schedule gave the doses at 2, 3, and 4 months of age; and the extended schedule gave doses at 2, 4, and 6 months of age. All infants received a booster vaccination at 12 or 13 months of age, and all received a standard suite of childhood immunizations for other diseases. The entire study was completed by 194 patients.

Serotype-specific IgG concentrations were obtained pre-vaccination, 1 month after the primary vaccination, and before and 1 month after the booster vaccination was given. IgG levels were reported for each PCV serotype; “there was considerable variation between serotypes,” ranging from 0.16 ng/mL for serotype 6b on the reduced schedule to 8.49 ng/mL for serotype 14 on the extended schedule, the investigators said.

Dr. Kent and her collaborators also used logistic regression analysis to explore how the vaccine’s effectiveness was affected by a number of factors. These included gestational length, the receipt of blood transfusions or pre- or post-natal steroids, BCG vaccination, early postvaccination acetaminophen, and the presence of chronic lung disease.

Later gestation was associated with increased seroprotection for four serotypes at 2 months of age, and with an increase in post-primary vaccination IgG concentrations for three others (P-values ranging from P less than .001 to P = .021).

No other factors were associated with protective IgG levels at any point, except that receipt of prenatal steroids had a negative association with seroprotection for several serotypes. “At no time points were antenatal steroids associated with higher antibody concentrations,” wrote the investigators.

Most studies of immunogenicity of infant vaccination schedules have been completed using term infants, with limited knowledge about efficacy in preterm infants. Previous work had shown that preterm infants had lower IgG concentrations after the primary and booster vaccinations for eight serotypes of PCV, compared with term infants. “The lower immunogenicity ... is concerning because premature infants are also less likely to benefit from the protective maternal antibodies transferred during late pregnancy,” Dr. Kent and her coauthors wrote.

The lower booster immunogenicity after the extended schedule is an effect that has been previously observed with other vaccinations and may be related to the formation of immune complexes with previously existing antibodies with the vaccine antigen, said Dr. Kent and her coauthors. The variation in immunogenicity timing for the various priming schedules, they said, will be helpful for those caring for preterm infants, enabling them “to consider this finding in the context of their own immunization programs and epidemiologic situations.”

The study was funded by Pfizer as an investigator-led study, without Pfizer’s input on the conduct of the trial, analysis of data, interpretation of results, or the preparation of this manuscript. Pfizer manufactures Prevnar 13.

koakes@frontlinemedcom.com

On Twitter @karioakes

A randomized clinical trial evaluating three dosing strategies for 13-valent pneumococcal vaccine (PCV13) in preterm infants found that more widely spaced priming vaccinations resulted in higher immunoglobulin G (IgG) during the first 12 months of life, but reduced the immune response seen after the 12-month booster was given.

After the primary schedule, the percent of infants lacking seroprotection for more than one half of the serotypes in the PCV13 formulation was 25% on a reduced two-dose schedule, 12% on an accelerated schedule, and 3% on an extended schedule (P less than .001).

Conversely, “A reduced priming schedule of PCV13 resulted in higher post-booster IgG concentrations but lower post-primary concentrations,” wrote Alison Kent, MBChB, and her coinvestigators in the PUNS (Prems Under New Schedule) Study Group (Pediatrics. 2016;138[3]:e20153945).

©dina2001/Thinkstock

“Infants who received the extended schedule had lower fold increases in concentrations after booster vaccination than the other groups,” wrote Dr. Kent of the Pediatric Infectious Diseases Research Group and Vaccine Institute, St. George’s, University of London, and her collaborators. Participants receiving the extended schedule had lower geometric mean concentrations (GMCs) of antibodies than did those on the reduced schedule for nine serotypes and those on the accelerated schedule for four serotypes.

The study enrolled 210 premature infants in a phase IV, controlled, open-label trial at 12 sites in the United Kingdom. Infants of less than 35 weeks gestation, and between 7 and 12 weeks of age, were randomly assigned to receive PCV13 on one of three schedules. The reduced schedule gave two priming doses at 2 and 4 months of age; the accelerated schedule gave the doses at 2, 3, and 4 months of age; and the extended schedule gave doses at 2, 4, and 6 months of age. All infants received a booster vaccination at 12 or 13 months of age, and all received a standard suite of childhood immunizations for other diseases. The entire study was completed by 194 patients.

Serotype-specific IgG concentrations were obtained pre-vaccination, 1 month after the primary vaccination, and before and 1 month after the booster vaccination was given. IgG levels were reported for each PCV serotype; “there was considerable variation between serotypes,” ranging from 0.16 ng/mL for serotype 6b on the reduced schedule to 8.49 ng/mL for serotype 14 on the extended schedule, the investigators said.

Dr. Kent and her collaborators also used logistic regression analysis to explore how the vaccine’s effectiveness was affected by a number of factors. These included gestational length, the receipt of blood transfusions or pre- or post-natal steroids, BCG vaccination, early postvaccination acetaminophen, and the presence of chronic lung disease.

Later gestation was associated with increased seroprotection for four serotypes at 2 months of age, and with an increase in post-primary vaccination IgG concentrations for three others (P-values ranging from P less than .001 to P = .021).

No other factors were associated with protective IgG levels at any point, except that receipt of prenatal steroids had a negative association with seroprotection for several serotypes. “At no time points were antenatal steroids associated with higher antibody concentrations,” wrote the investigators.

Most studies of immunogenicity of infant vaccination schedules have been completed using term infants, with limited knowledge about efficacy in preterm infants. Previous work had shown that preterm infants had lower IgG concentrations after the primary and booster vaccinations for eight serotypes of PCV, compared with term infants. “The lower immunogenicity ... is concerning because premature infants are also less likely to benefit from the protective maternal antibodies transferred during late pregnancy,” Dr. Kent and her coauthors wrote.

The lower booster immunogenicity after the extended schedule is an effect that has been previously observed with other vaccinations and may be related to the formation of immune complexes with previously existing antibodies with the vaccine antigen, said Dr. Kent and her coauthors. The variation in immunogenicity timing for the various priming schedules, they said, will be helpful for those caring for preterm infants, enabling them “to consider this finding in the context of their own immunization programs and epidemiologic situations.”

The study was funded by Pfizer as an investigator-led study, without Pfizer’s input on the conduct of the trial, analysis of data, interpretation of results, or the preparation of this manuscript. Pfizer manufactures Prevnar 13.

koakes@frontlinemedcom.com

On Twitter @karioakes

A randomized clinical trial evaluating three dosing strategies for 13-valent pneumococcal vaccine (PCV13) in preterm infants found that more widely spaced priming vaccinations resulted in higher immunoglobulin G (IgG) during the first 12 months of life, but reduced the immune response seen after the 12-month booster was given.

After the primary schedule, the percent of infants lacking seroprotection for more than one half of the serotypes in the PCV13 formulation was 25% on a reduced two-dose schedule, 12% on an accelerated schedule, and 3% on an extended schedule (P less than .001).

Conversely, “A reduced priming schedule of PCV13 resulted in higher post-booster IgG concentrations but lower post-primary concentrations,” wrote Alison Kent, MBChB, and her coinvestigators in the PUNS (Prems Under New Schedule) Study Group (Pediatrics. 2016;138[3]:e20153945).

©dina2001/Thinkstock

“Infants who received the extended schedule had lower fold increases in concentrations after booster vaccination than the other groups,” wrote Dr. Kent of the Pediatric Infectious Diseases Research Group and Vaccine Institute, St. George’s, University of London, and her collaborators. Participants receiving the extended schedule had lower geometric mean concentrations (GMCs) of antibodies than did those on the reduced schedule for nine serotypes and those on the accelerated schedule for four serotypes.

The study enrolled 210 premature infants in a phase IV, controlled, open-label trial at 12 sites in the United Kingdom. Infants of less than 35 weeks gestation, and between 7 and 12 weeks of age, were randomly assigned to receive PCV13 on one of three schedules. The reduced schedule gave two priming doses at 2 and 4 months of age; the accelerated schedule gave the doses at 2, 3, and 4 months of age; and the extended schedule gave doses at 2, 4, and 6 months of age. All infants received a booster vaccination at 12 or 13 months of age, and all received a standard suite of childhood immunizations for other diseases. The entire study was completed by 194 patients.

Serotype-specific IgG concentrations were obtained pre-vaccination, 1 month after the primary vaccination, and before and 1 month after the booster vaccination was given. IgG levels were reported for each PCV serotype; “there was considerable variation between serotypes,” ranging from 0.16 ng/mL for serotype 6b on the reduced schedule to 8.49 ng/mL for serotype 14 on the extended schedule, the investigators said.

Dr. Kent and her collaborators also used logistic regression analysis to explore how the vaccine’s effectiveness was affected by a number of factors. These included gestational length, the receipt of blood transfusions or pre- or post-natal steroids, BCG vaccination, early postvaccination acetaminophen, and the presence of chronic lung disease.

Later gestation was associated with increased seroprotection for four serotypes at 2 months of age, and with an increase in post-primary vaccination IgG concentrations for three others (P-values ranging from P less than .001 to P = .021).

No other factors were associated with protective IgG levels at any point, except that receipt of prenatal steroids had a negative association with seroprotection for several serotypes. “At no time points were antenatal steroids associated with higher antibody concentrations,” wrote the investigators.

Most studies of immunogenicity of infant vaccination schedules have been completed using term infants, with limited knowledge about efficacy in preterm infants. Previous work had shown that preterm infants had lower IgG concentrations after the primary and booster vaccinations for eight serotypes of PCV, compared with term infants. “The lower immunogenicity ... is concerning because premature infants are also less likely to benefit from the protective maternal antibodies transferred during late pregnancy,” Dr. Kent and her coauthors wrote.

The lower booster immunogenicity after the extended schedule is an effect that has been previously observed with other vaccinations and may be related to the formation of immune complexes with previously existing antibodies with the vaccine antigen, said Dr. Kent and her coauthors. The variation in immunogenicity timing for the various priming schedules, they said, will be helpful for those caring for preterm infants, enabling them “to consider this finding in the context of their own immunization programs and epidemiologic situations.”

The study was funded by Pfizer as an investigator-led study, without Pfizer’s input on the conduct of the trial, analysis of data, interpretation of results, or the preparation of this manuscript. Pfizer manufactures Prevnar 13.

koakes@frontlinemedcom.com

On Twitter @karioakes

ORLANDO – The frequency of prophylactic clotting factor infusions does not appear to adversely affect adherence to hemophilia therapy in children, but age seems to play a role in compliance to prescribed regimens, investigators in two separate studies report.

A study of pediatric patients with moderate to severe hemophilia A or B on bleeding prophylaxis showed no significant differences in adherence between patients receiving two clotting factor infusions per week and those receiving three or four per week, reported Karen Strike, a physiotherapist at McMaster Children’s Hospital in Hamilton, Ont., and colleagues.

“This study demonstrates that our patients have a very high degree of adherence, and it doesn’t appear to be related to infusion frequency,” she said in an interview at a scientific poster session at the World Federation of Hemophilia World Congress.

Although their sample size was small – just 23 patients – the median levels of adherence were high for both twice-weekly infusers (99.5%) and 3-4 times per week infusers (96%; P = .053).

Ms. Strike acknowledges that the borderline P value could be due to the small sample size instead of a lack of association. Additionally, because the patients are managed by a regional hemophilia treatment center, they tend to be more engaged and more likely to cooperate with clinician instructions, she said.

“Basically, patients are either going to do what’s prescribed or they’re not. What that actual prescription is doesn’t seem to matter. If they prescribe you twice a week or they prescribe me every other day, you’re going to be adherent to twice a week or you’re not.

The investigators have expanded their study to include adult patients on primary prophylaxis and to look at additional co-variates that might have an effect on adherence, including interactions with a health care team, geographical distance from a hemophilia treatment center, joint health status, and infusion delivery method (peripheral vs. port).

Age may be a factor

In a separate study, German investigators report that adherence appears to vary by age.

Wolfgang Miesbach, MD, from Goethe University Hospital in Frankfurt, Germany, and colleagues asked all members of the German hemophilia patient organization with moderate or severe hemophilia to fill out the VERITAS-PRO (Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis) questionnaire and compared scores across age groups.

Data were available on a total of 364 patients. The investigators found that among 131 children from birth to age 19, adherence to prescribed regimens was 100%. In contrast, the adherence rate among 189 adults aged 20-59 was 88.1%. After age 59, adherence rates began to improve as those 60 and older (44 patients) reported 93.9% adherence.

“Within the patients aged 20+, care by a hemophilia center was the only significant indicator for better adherence. The tendency of better adherence of patients aged greater than 60 compared to patients 20-59 may be explained by the significant association of the occurrence of pain with increasing age although a significant influence of pain on the adherence levels could not be demonstrated,” the investigators wrote.

Their findings point the way to possible interventions to facilitate adherence to prophylaxis among patients with hemophilia, they wrote.

Both studies were internally funded. The authors reported no relevant disclosures.

ORLANDO – The frequency of prophylactic clotting factor infusions does not appear to adversely affect adherence to hemophilia therapy in children, but age seems to play a role in compliance to prescribed regimens, investigators in two separate studies report.

A study of pediatric patients with moderate to severe hemophilia A or B on bleeding prophylaxis showed no significant differences in adherence between patients receiving two clotting factor infusions per week and those receiving three or four per week, reported Karen Strike, a physiotherapist at McMaster Children’s Hospital in Hamilton, Ont., and colleagues.

“This study demonstrates that our patients have a very high degree of adherence, and it doesn’t appear to be related to infusion frequency,” she said in an interview at a scientific poster session at the World Federation of Hemophilia World Congress.

Although their sample size was small – just 23 patients – the median levels of adherence were high for both twice-weekly infusers (99.5%) and 3-4 times per week infusers (96%; P = .053).

Ms. Strike acknowledges that the borderline P value could be due to the small sample size instead of a lack of association. Additionally, because the patients are managed by a regional hemophilia treatment center, they tend to be more engaged and more likely to cooperate with clinician instructions, she said.

“Basically, patients are either going to do what’s prescribed or they’re not. What that actual prescription is doesn’t seem to matter. If they prescribe you twice a week or they prescribe me every other day, you’re going to be adherent to twice a week or you’re not.

The investigators have expanded their study to include adult patients on primary prophylaxis and to look at additional co-variates that might have an effect on adherence, including interactions with a health care team, geographical distance from a hemophilia treatment center, joint health status, and infusion delivery method (peripheral vs. port).

Age may be a factor

In a separate study, German investigators report that adherence appears to vary by age.

Wolfgang Miesbach, MD, from Goethe University Hospital in Frankfurt, Germany, and colleagues asked all members of the German hemophilia patient organization with moderate or severe hemophilia to fill out the VERITAS-PRO (Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis) questionnaire and compared scores across age groups.

Data were available on a total of 364 patients. The investigators found that among 131 children from birth to age 19, adherence to prescribed regimens was 100%. In contrast, the adherence rate among 189 adults aged 20-59 was 88.1%. After age 59, adherence rates began to improve as those 60 and older (44 patients) reported 93.9% adherence.

“Within the patients aged 20+, care by a hemophilia center was the only significant indicator for better adherence. The tendency of better adherence of patients aged greater than 60 compared to patients 20-59 may be explained by the significant association of the occurrence of pain with increasing age although a significant influence of pain on the adherence levels could not be demonstrated,” the investigators wrote.

Their findings point the way to possible interventions to facilitate adherence to prophylaxis among patients with hemophilia, they wrote.

Both studies were internally funded. The authors reported no relevant disclosures.

ORLANDO – The frequency of prophylactic clotting factor infusions does not appear to adversely affect adherence to hemophilia therapy in children, but age seems to play a role in compliance to prescribed regimens, investigators in two separate studies report.

A study of pediatric patients with moderate to severe hemophilia A or B on bleeding prophylaxis showed no significant differences in adherence between patients receiving two clotting factor infusions per week and those receiving three or four per week, reported Karen Strike, a physiotherapist at McMaster Children’s Hospital in Hamilton, Ont., and colleagues.

“This study demonstrates that our patients have a very high degree of adherence, and it doesn’t appear to be related to infusion frequency,” she said in an interview at a scientific poster session at the World Federation of Hemophilia World Congress.

Although their sample size was small – just 23 patients – the median levels of adherence were high for both twice-weekly infusers (99.5%) and 3-4 times per week infusers (96%; P = .053).

Ms. Strike acknowledges that the borderline P value could be due to the small sample size instead of a lack of association. Additionally, because the patients are managed by a regional hemophilia treatment center, they tend to be more engaged and more likely to cooperate with clinician instructions, she said.

“Basically, patients are either going to do what’s prescribed or they’re not. What that actual prescription is doesn’t seem to matter. If they prescribe you twice a week or they prescribe me every other day, you’re going to be adherent to twice a week or you’re not.

The investigators have expanded their study to include adult patients on primary prophylaxis and to look at additional co-variates that might have an effect on adherence, including interactions with a health care team, geographical distance from a hemophilia treatment center, joint health status, and infusion delivery method (peripheral vs. port).

Age may be a factor

In a separate study, German investigators report that adherence appears to vary by age.

Wolfgang Miesbach, MD, from Goethe University Hospital in Frankfurt, Germany, and colleagues asked all members of the German hemophilia patient organization with moderate or severe hemophilia to fill out the VERITAS-PRO (Validated Hemophilia Regimen Treatment Adherence Scale-Prophylaxis) questionnaire and compared scores across age groups.

Data were available on a total of 364 patients. The investigators found that among 131 children from birth to age 19, adherence to prescribed regimens was 100%. In contrast, the adherence rate among 189 adults aged 20-59 was 88.1%. After age 59, adherence rates began to improve as those 60 and older (44 patients) reported 93.9% adherence.

“Within the patients aged 20+, care by a hemophilia center was the only significant indicator for better adherence. The tendency of better adherence of patients aged greater than 60 compared to patients 20-59 may be explained by the significant association of the occurrence of pain with increasing age although a significant influence of pain on the adherence levels could not be demonstrated,” the investigators wrote.

Their findings point the way to possible interventions to facilitate adherence to prophylaxis among patients with hemophilia, they wrote.

Both studies were internally funded. The authors reported no relevant disclosures.

DURBAN, SOUTH AFRICA – Oral emtricitabine/tenofovir for pre-exposure prophylaxis against HIV acquisition in high-risk 15- to 17-year-old males proved safe and effective in the first clinical trial looking at the drug’s effects in a population so young, Sybil Hosek, PhD, reported at the 21st International AIDS Conference.

Based upon these encouraging findings, the drug’s manufacturer, Gilead Sciences, plans to file a request for the Food and Drug Administration to grant an expanded indication for emtricitabine/tenofovir (Truvada) for pre-exposure prophylaxis (PrEP) against HIV infection in teens as young as 15 years. The drug is currently approved for use only in patients aged 18 and up because there were no data in younger patients, said Dr. Hosek of John H. Stroger, Jr. Hospital, Chicago.

The prospect of an expanded indication in younger adolescents is most welcome news, she added.

“I really want to strongly, strongly, strongly say that adolescents need access to PrEP,” Dr. Hosek declared. “This is one of the best prevention options we’ve had in a long time.”

Co-investigator Craig M. Wilson, MD, concurred. “The epicenter of the HIV/AIDS epidemic in the U.S. is in 13- to 24-year-old males who have sex with males, particular MSM of color,” noted Dr. Wilson, professor of epidemiology, pediatrics, and director of the Sparkman Center for Global Health at the University of Alabama, Birmingham.

Dr. Hosek reported on 77 male teens ages 15-17 at high self-reported risk for HIV infection because of behaviors such as condomless anal intercourse with an HIV-positive or unknown-status partner. All 77 were negative for HIV at enrollment, which didn’t require parental permission. Prior to embarking on 48 months of once-daily, open-label emtricitabine/tenofovir for PrEP in this multicenter U.S. trial, they received personalized risk reduction, adherence, and behavior counseling. As part of the study protocol they had clinic visits monthly for the first 12 weeks. At that point the visits, which included testing for HIV and other STIs as well as measurement of blood drug levels as an indicator of adherence, were scaled back to once every 3 months.

The PrEP was safe and well tolerated. No one discontinued treatment because of side effects. The only adverse event of note was weight loss of 10%-19% in two patients. New STIs were diagnosed and treated in 12.3% of participants in the first 24 weeks of the study and in 10.6% in the next 24 weeks.

Three patients seroconverted during the 48-week study, for a hefty HIV infection rate of 6.41% per year. One of these patients never took the PrEP medication, the other two did so on and off but had no or very low blood levels of the drug at the time of seroconversion.

Adherence was a major issue, according to Dr. Hosek. She deemed adherence to be “really good” during the first 12 weeks of the study. During that period, the majority of participants had blood levels indicating they were taking their medication at least 4 days per week, providing high-level protection. More than 95% of subjects had detectable levels of drug, indicating they were at least trying to keep up with their medication schedule. However, once the clinic visits were scaled back from monthly to quarterly, adherence fell off drastically.

Audience member Carlos del Rio, MD, commented that he found the poor adherence over time to be really discouraging.

“The adolescent challenge is tremendous. All the studies show us that this group isn’t getting any protection. Are we trying to fit a square peg in a round hole? Is this something that’s just not going to happen, so we should look at alternatives such as long-acting injectables? It looks to me like we’re not going to get the adherence we need in adolescents with any of the things that are out there at this moment,” said Dr. del Rio, professor and chair of the department of global health and codirector of the center for AIDS research at Emory University in Atlanta.

Dr. Hosek replied that she found heartening the “outstanding” treatment adherence rate when patients were being seen monthly.

“Young people need more time,” Dr. Hosek observed. “And if they need that time from us, we have to give it to them. If they need to see us more frequently, if they need to text with us, if they need interim phone calls, a peer support group, an adherence club – whatever they need, if they want PrEP and they want to make it work, then we need to help them make it work. That’s our responsibility, to give them the time and attention they need.”

Loss of bone mineral density with PrEP

Dr. Wilson said an issue that bears watching, assuming a large increase in the use of emtricitabine/tenofovir for HIV PrEP in adolescents is in store in the near future, is drug-related loss in bone mineral density.

He presented data on changes in bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry with results assessed at a core laboratory every 6 months in a companion study to the one presented by Dr. Hosek, this one involving 72 high-HIV-risk patients aged 18-22 years on 48 weeks of open-label emtricitabine/tenofovir followed by 48 weeks off PrEP.

Consistent with what’s been seen in studies of adults on emtricitabine/tenofovir, statistically significant decreases in mean Z-scores adjusted for age, sex, and race were seen at the hip and lumbar spine in this younger population between baseline and week 48 of PrEP. The reductions in BMD were in the range of 0.1-0.2 standard deviation. That’s noteworthy because up until age 20, people are supposed to be accruing bone mineralization, he observed.

During the subsequent 48 weeks off-PrEP patients showed evidence of partial but not full remineralization.

“There’s nothing here to indicate we should stop using PrEP in this age group, but given that we’d like to see high-risk young patients remain on therapy for longer than in this 48-week study, I think it would be smart to get longer-term exposure data to ensure that we still believe it’s safe,” the pediatrician commented.

Reassuringly, there is no evidence of an increase in fractures or complaints of bone pain in any studies of HIV-positive patients on tenofovir, he observed.

Because it’s unrealistic to expect to be able to routinely do serial DEXA scans in young patients on emtricitabine/tenofovir once PrEP is ramped up to the scale HIV specialists are hoping for, Dr. Wilson said he and his coinvestigators are now looking at potential biomarkers of clinically significant bone loss in young patients on chemoprophylaxis.

Dr. Wilson drew attention to the disturbingly high HIV seroconversion rate of 7.2% per year following discontinuation of PrEP after 48 weeks.

“Remember, this is a population that had already gone through extensive counseling, behavioral interventions, and personalized prevention and adherence support during the 48 weeks they were on the study drug, so they had been informed as to what the risks were. Yet we still end up with one of the highest seroconversion rates observed in any PrEP study. That tells us we still have a lot of work to do in these particular young populations,” according to Dr. Wilson.

These clinical trials of PrEP in 15- to 17- and 18- to 22-year-olds were carried out by the Adolescent Medicine Trials Network for HIV/AIDS Interventions with funding from the National Institutes of Health. Dr. Husek and Dr. Wilson reported having no financial conflicts.

bjancin@frontlinemedcom.com

DURBAN, SOUTH AFRICA – Oral emtricitabine/tenofovir for pre-exposure prophylaxis against HIV acquisition in high-risk 15- to 17-year-old males proved safe and effective in the first clinical trial looking at the drug’s effects in a population so young, Sybil Hosek, PhD, reported at the 21st International AIDS Conference.

Based upon these encouraging findings, the drug’s manufacturer, Gilead Sciences, plans to file a request for the Food and Drug Administration to grant an expanded indication for emtricitabine/tenofovir (Truvada) for pre-exposure prophylaxis (PrEP) against HIV infection in teens as young as 15 years. The drug is currently approved for use only in patients aged 18 and up because there were no data in younger patients, said Dr. Hosek of John H. Stroger, Jr. Hospital, Chicago.

The prospect of an expanded indication in younger adolescents is most welcome news, she added.

“I really want to strongly, strongly, strongly say that adolescents need access to PrEP,” Dr. Hosek declared. “This is one of the best prevention options we’ve had in a long time.”

Co-investigator Craig M. Wilson, MD, concurred. “The epicenter of the HIV/AIDS epidemic in the U.S. is in 13- to 24-year-old males who have sex with males, particular MSM of color,” noted Dr. Wilson, professor of epidemiology, pediatrics, and director of the Sparkman Center for Global Health at the University of Alabama, Birmingham.

Dr. Hosek reported on 77 male teens ages 15-17 at high self-reported risk for HIV infection because of behaviors such as condomless anal intercourse with an HIV-positive or unknown-status partner. All 77 were negative for HIV at enrollment, which didn’t require parental permission. Prior to embarking on 48 months of once-daily, open-label emtricitabine/tenofovir for PrEP in this multicenter U.S. trial, they received personalized risk reduction, adherence, and behavior counseling. As part of the study protocol they had clinic visits monthly for the first 12 weeks. At that point the visits, which included testing for HIV and other STIs as well as measurement of blood drug levels as an indicator of adherence, were scaled back to once every 3 months.

The PrEP was safe and well tolerated. No one discontinued treatment because of side effects. The only adverse event of note was weight loss of 10%-19% in two patients. New STIs were diagnosed and treated in 12.3% of participants in the first 24 weeks of the study and in 10.6% in the next 24 weeks.

Three patients seroconverted during the 48-week study, for a hefty HIV infection rate of 6.41% per year. One of these patients never took the PrEP medication, the other two did so on and off but had no or very low blood levels of the drug at the time of seroconversion.

Adherence was a major issue, according to Dr. Hosek. She deemed adherence to be “really good” during the first 12 weeks of the study. During that period, the majority of participants had blood levels indicating they were taking their medication at least 4 days per week, providing high-level protection. More than 95% of subjects had detectable levels of drug, indicating they were at least trying to keep up with their medication schedule. However, once the clinic visits were scaled back from monthly to quarterly, adherence fell off drastically.

Audience member Carlos del Rio, MD, commented that he found the poor adherence over time to be really discouraging.

“The adolescent challenge is tremendous. All the studies show us that this group isn’t getting any protection. Are we trying to fit a square peg in a round hole? Is this something that’s just not going to happen, so we should look at alternatives such as long-acting injectables? It looks to me like we’re not going to get the adherence we need in adolescents with any of the things that are out there at this moment,” said Dr. del Rio, professor and chair of the department of global health and codirector of the center for AIDS research at Emory University in Atlanta.

Dr. Hosek replied that she found heartening the “outstanding” treatment adherence rate when patients were being seen monthly.

“Young people need more time,” Dr. Hosek observed. “And if they need that time from us, we have to give it to them. If they need to see us more frequently, if they need to text with us, if they need interim phone calls, a peer support group, an adherence club – whatever they need, if they want PrEP and they want to make it work, then we need to help them make it work. That’s our responsibility, to give them the time and attention they need.”

Loss of bone mineral density with PrEP

Dr. Wilson said an issue that bears watching, assuming a large increase in the use of emtricitabine/tenofovir for HIV PrEP in adolescents is in store in the near future, is drug-related loss in bone mineral density.

He presented data on changes in bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry with results assessed at a core laboratory every 6 months in a companion study to the one presented by Dr. Hosek, this one involving 72 high-HIV-risk patients aged 18-22 years on 48 weeks of open-label emtricitabine/tenofovir followed by 48 weeks off PrEP.

Consistent with what’s been seen in studies of adults on emtricitabine/tenofovir, statistically significant decreases in mean Z-scores adjusted for age, sex, and race were seen at the hip and lumbar spine in this younger population between baseline and week 48 of PrEP. The reductions in BMD were in the range of 0.1-0.2 standard deviation. That’s noteworthy because up until age 20, people are supposed to be accruing bone mineralization, he observed.

During the subsequent 48 weeks off-PrEP patients showed evidence of partial but not full remineralization.

“There’s nothing here to indicate we should stop using PrEP in this age group, but given that we’d like to see high-risk young patients remain on therapy for longer than in this 48-week study, I think it would be smart to get longer-term exposure data to ensure that we still believe it’s safe,” the pediatrician commented.

Reassuringly, there is no evidence of an increase in fractures or complaints of bone pain in any studies of HIV-positive patients on tenofovir, he observed.

Because it’s unrealistic to expect to be able to routinely do serial DEXA scans in young patients on emtricitabine/tenofovir once PrEP is ramped up to the scale HIV specialists are hoping for, Dr. Wilson said he and his coinvestigators are now looking at potential biomarkers of clinically significant bone loss in young patients on chemoprophylaxis.

Dr. Wilson drew attention to the disturbingly high HIV seroconversion rate of 7.2% per year following discontinuation of PrEP after 48 weeks.

“Remember, this is a population that had already gone through extensive counseling, behavioral interventions, and personalized prevention and adherence support during the 48 weeks they were on the study drug, so they had been informed as to what the risks were. Yet we still end up with one of the highest seroconversion rates observed in any PrEP study. That tells us we still have a lot of work to do in these particular young populations,” according to Dr. Wilson.

These clinical trials of PrEP in 15- to 17- and 18- to 22-year-olds were carried out by the Adolescent Medicine Trials Network for HIV/AIDS Interventions with funding from the National Institutes of Health. Dr. Husek and Dr. Wilson reported having no financial conflicts.

bjancin@frontlinemedcom.com

DURBAN, SOUTH AFRICA – Oral emtricitabine/tenofovir for pre-exposure prophylaxis against HIV acquisition in high-risk 15- to 17-year-old males proved safe and effective in the first clinical trial looking at the drug’s effects in a population so young, Sybil Hosek, PhD, reported at the 21st International AIDS Conference.

Based upon these encouraging findings, the drug’s manufacturer, Gilead Sciences, plans to file a request for the Food and Drug Administration to grant an expanded indication for emtricitabine/tenofovir (Truvada) for pre-exposure prophylaxis (PrEP) against HIV infection in teens as young as 15 years. The drug is currently approved for use only in patients aged 18 and up because there were no data in younger patients, said Dr. Hosek of John H. Stroger, Jr. Hospital, Chicago.

The prospect of an expanded indication in younger adolescents is most welcome news, she added.

“I really want to strongly, strongly, strongly say that adolescents need access to PrEP,” Dr. Hosek declared. “This is one of the best prevention options we’ve had in a long time.”

Co-investigator Craig M. Wilson, MD, concurred. “The epicenter of the HIV/AIDS epidemic in the U.S. is in 13- to 24-year-old males who have sex with males, particular MSM of color,” noted Dr. Wilson, professor of epidemiology, pediatrics, and director of the Sparkman Center for Global Health at the University of Alabama, Birmingham.

Dr. Hosek reported on 77 male teens ages 15-17 at high self-reported risk for HIV infection because of behaviors such as condomless anal intercourse with an HIV-positive or unknown-status partner. All 77 were negative for HIV at enrollment, which didn’t require parental permission. Prior to embarking on 48 months of once-daily, open-label emtricitabine/tenofovir for PrEP in this multicenter U.S. trial, they received personalized risk reduction, adherence, and behavior counseling. As part of the study protocol they had clinic visits monthly for the first 12 weeks. At that point the visits, which included testing for HIV and other STIs as well as measurement of blood drug levels as an indicator of adherence, were scaled back to once every 3 months.

The PrEP was safe and well tolerated. No one discontinued treatment because of side effects. The only adverse event of note was weight loss of 10%-19% in two patients. New STIs were diagnosed and treated in 12.3% of participants in the first 24 weeks of the study and in 10.6% in the next 24 weeks.

Three patients seroconverted during the 48-week study, for a hefty HIV infection rate of 6.41% per year. One of these patients never took the PrEP medication, the other two did so on and off but had no or very low blood levels of the drug at the time of seroconversion.

Adherence was a major issue, according to Dr. Hosek. She deemed adherence to be “really good” during the first 12 weeks of the study. During that period, the majority of participants had blood levels indicating they were taking their medication at least 4 days per week, providing high-level protection. More than 95% of subjects had detectable levels of drug, indicating they were at least trying to keep up with their medication schedule. However, once the clinic visits were scaled back from monthly to quarterly, adherence fell off drastically.

Audience member Carlos del Rio, MD, commented that he found the poor adherence over time to be really discouraging.

“The adolescent challenge is tremendous. All the studies show us that this group isn’t getting any protection. Are we trying to fit a square peg in a round hole? Is this something that’s just not going to happen, so we should look at alternatives such as long-acting injectables? It looks to me like we’re not going to get the adherence we need in adolescents with any of the things that are out there at this moment,” said Dr. del Rio, professor and chair of the department of global health and codirector of the center for AIDS research at Emory University in Atlanta.

Dr. Hosek replied that she found heartening the “outstanding” treatment adherence rate when patients were being seen monthly.

“Young people need more time,” Dr. Hosek observed. “And if they need that time from us, we have to give it to them. If they need to see us more frequently, if they need to text with us, if they need interim phone calls, a peer support group, an adherence club – whatever they need, if they want PrEP and they want to make it work, then we need to help them make it work. That’s our responsibility, to give them the time and attention they need.”

Loss of bone mineral density with PrEP

Dr. Wilson said an issue that bears watching, assuming a large increase in the use of emtricitabine/tenofovir for HIV PrEP in adolescents is in store in the near future, is drug-related loss in bone mineral density.

He presented data on changes in bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry with results assessed at a core laboratory every 6 months in a companion study to the one presented by Dr. Hosek, this one involving 72 high-HIV-risk patients aged 18-22 years on 48 weeks of open-label emtricitabine/tenofovir followed by 48 weeks off PrEP.

Consistent with what’s been seen in studies of adults on emtricitabine/tenofovir, statistically significant decreases in mean Z-scores adjusted for age, sex, and race were seen at the hip and lumbar spine in this younger population between baseline and week 48 of PrEP. The reductions in BMD were in the range of 0.1-0.2 standard deviation. That’s noteworthy because up until age 20, people are supposed to be accruing bone mineralization, he observed.

During the subsequent 48 weeks off-PrEP patients showed evidence of partial but not full remineralization.

“There’s nothing here to indicate we should stop using PrEP in this age group, but given that we’d like to see high-risk young patients remain on therapy for longer than in this 48-week study, I think it would be smart to get longer-term exposure data to ensure that we still believe it’s safe,” the pediatrician commented.

Reassuringly, there is no evidence of an increase in fractures or complaints of bone pain in any studies of HIV-positive patients on tenofovir, he observed.

Because it’s unrealistic to expect to be able to routinely do serial DEXA scans in young patients on emtricitabine/tenofovir once PrEP is ramped up to the scale HIV specialists are hoping for, Dr. Wilson said he and his coinvestigators are now looking at potential biomarkers of clinically significant bone loss in young patients on chemoprophylaxis.

Dr. Wilson drew attention to the disturbingly high HIV seroconversion rate of 7.2% per year following discontinuation of PrEP after 48 weeks.

“Remember, this is a population that had already gone through extensive counseling, behavioral interventions, and personalized prevention and adherence support during the 48 weeks they were on the study drug, so they had been informed as to what the risks were. Yet we still end up with one of the highest seroconversion rates observed in any PrEP study. That tells us we still have a lot of work to do in these particular young populations,” according to Dr. Wilson.

These clinical trials of PrEP in 15- to 17- and 18- to 22-year-olds were carried out by the Adolescent Medicine Trials Network for HIV/AIDS Interventions with funding from the National Institutes of Health. Dr. Husek and Dr. Wilson reported having no financial conflicts.

bjancin@frontlinemedcom.com

The European Commission has granted orphan drug designation for the T-cell therapy product candidate BPX-501 and the small molecule rimiducid.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Haplo-HSCT recipients receive BPX-501 to speed immune reconstitution and provide control over viral infections. And rimiducid is used to eliminate BPX-501 alloreactive T cells if severe graft-vs-host disease (GVHD) occurs.

If a patient develops severe GVHD, rimiducid is used to trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About orphan designation

Orphan drug designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat serious or life-threatening conditions that affect no more than 5 in 10,000 people in the European Union (EU), and where no treatment is currently approved.

In addition to a 10-year period of marketing exclusivity in the EU upon product approval, orphan drug designation provides fee waivers, protocol assistance, and marketing authorization under the centralized procedure granting approval in all EU countries.

BPX-501/rimiducid development

BPX-501 and rimiducid are being developed by Bellicum Pharmaceuticals.

The company has met with regulatory authorities in Europe to discuss the potential approval pathway for BPX-501 and rimiducid for the treatment of immunodeficiency and GVHD following haplo-HSCT in pediatric patients with leukemias, lymphomas, and rare inherited blood diseases who do not have a matched donor.

These discussions have resulted in an initial agreement regarding the company’s development plans, subject to further refinement in a formal protocol assistance process that is available for orphan drug products.

Based on regulatory discussions, Bellicum believes that data from the European arm of its BP-004 trial, with a 6-month follow-up time and expanded to enroll additional patients, could form the basis of marketing authorization applications for BPX-501 and rimiducid.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has agreed that review and approval under “exceptional circumstances” may be suitable, recognizing that a randomized trial may not be feasible in the pediatric setting. In place of a randomized trial, Bellicum intends to collect data from a concurrent observational study of allogeneic HSCT outcomes in the pediatric setting.

The European Medicines Agency can grant early market authorization to orphan drug products under exceptional circumstances. Exceptional circumstances can be granted for medicines that treat very rare diseases or where controlled studies are impractical or not consistent with accepted principles of medical ethics.

BP-004 trial

BP-004 is a phase 1/2 dose-escalation trial of BPX-501 and rimiducid in pediatric patients with malignant and nonmalignant diseases. Interim results from this trial were reported in 2 presentations at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation in April 2016.

One presentation involved patients with acute leukemia who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free. There were several cases of GVHD, but nearly all were resolved.

The other presentation covered patients with nonmalignant disorders who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, all 24 patients studied were still alive and disease-free. The incidence of GVHD was considered “very low.” 

The European Commission has granted orphan drug designation for the T-cell therapy product candidate BPX-501 and the small molecule rimiducid.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Haplo-HSCT recipients receive BPX-501 to speed immune reconstitution and provide control over viral infections. And rimiducid is used to eliminate BPX-501 alloreactive T cells if severe graft-vs-host disease (GVHD) occurs.

If a patient develops severe GVHD, rimiducid is used to trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About orphan designation

Orphan drug designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat serious or life-threatening conditions that affect no more than 5 in 10,000 people in the European Union (EU), and where no treatment is currently approved.

In addition to a 10-year period of marketing exclusivity in the EU upon product approval, orphan drug designation provides fee waivers, protocol assistance, and marketing authorization under the centralized procedure granting approval in all EU countries.

BPX-501/rimiducid development

BPX-501 and rimiducid are being developed by Bellicum Pharmaceuticals.

The company has met with regulatory authorities in Europe to discuss the potential approval pathway for BPX-501 and rimiducid for the treatment of immunodeficiency and GVHD following haplo-HSCT in pediatric patients with leukemias, lymphomas, and rare inherited blood diseases who do not have a matched donor.

These discussions have resulted in an initial agreement regarding the company’s development plans, subject to further refinement in a formal protocol assistance process that is available for orphan drug products.

Based on regulatory discussions, Bellicum believes that data from the European arm of its BP-004 trial, with a 6-month follow-up time and expanded to enroll additional patients, could form the basis of marketing authorization applications for BPX-501 and rimiducid.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has agreed that review and approval under “exceptional circumstances” may be suitable, recognizing that a randomized trial may not be feasible in the pediatric setting. In place of a randomized trial, Bellicum intends to collect data from a concurrent observational study of allogeneic HSCT outcomes in the pediatric setting.

The European Medicines Agency can grant early market authorization to orphan drug products under exceptional circumstances. Exceptional circumstances can be granted for medicines that treat very rare diseases or where controlled studies are impractical or not consistent with accepted principles of medical ethics.

BP-004 trial

BP-004 is a phase 1/2 dose-escalation trial of BPX-501 and rimiducid in pediatric patients with malignant and nonmalignant diseases. Interim results from this trial were reported in 2 presentations at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation in April 2016.

One presentation involved patients with acute leukemia who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free. There were several cases of GVHD, but nearly all were resolved.

The other presentation covered patients with nonmalignant disorders who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, all 24 patients studied were still alive and disease-free. The incidence of GVHD was considered “very low.” 

The European Commission has granted orphan drug designation for the T-cell therapy product candidate BPX-501 and the small molecule rimiducid.

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haploidentical hematopoietic stem cell transplant (haplo-HSCT).

Haplo-HSCT recipients receive BPX-501 to speed immune reconstitution and provide control over viral infections. And rimiducid is used to eliminate BPX-501 alloreactive T cells if severe graft-vs-host disease (GVHD) occurs.

If a patient develops severe GVHD, rimiducid is used to trigger activation of the domain of caspase-9, which leads to selective apoptosis of the CaspaCIDe-containing cells.

About orphan designation

Orphan drug designation from the European Commission provides regulatory and financial incentives for companies to develop and market therapies that treat serious or life-threatening conditions that affect no more than 5 in 10,000 people in the European Union (EU), and where no treatment is currently approved.

In addition to a 10-year period of marketing exclusivity in the EU upon product approval, orphan drug designation provides fee waivers, protocol assistance, and marketing authorization under the centralized procedure granting approval in all EU countries.

BPX-501/rimiducid development

BPX-501 and rimiducid are being developed by Bellicum Pharmaceuticals.

The company has met with regulatory authorities in Europe to discuss the potential approval pathway for BPX-501 and rimiducid for the treatment of immunodeficiency and GVHD following haplo-HSCT in pediatric patients with leukemias, lymphomas, and rare inherited blood diseases who do not have a matched donor.

These discussions have resulted in an initial agreement regarding the company’s development plans, subject to further refinement in a formal protocol assistance process that is available for orphan drug products.

Based on regulatory discussions, Bellicum believes that data from the European arm of its BP-004 trial, with a 6-month follow-up time and expanded to enroll additional patients, could form the basis of marketing authorization applications for BPX-501 and rimiducid.

The European Medicines Agency’s Committee for Medicinal Products for Human Use has agreed that review and approval under “exceptional circumstances” may be suitable, recognizing that a randomized trial may not be feasible in the pediatric setting. In place of a randomized trial, Bellicum intends to collect data from a concurrent observational study of allogeneic HSCT outcomes in the pediatric setting.

The European Medicines Agency can grant early market authorization to orphan drug products under exceptional circumstances. Exceptional circumstances can be granted for medicines that treat very rare diseases or where controlled studies are impractical or not consistent with accepted principles of medical ethics.

BP-004 trial

BP-004 is a phase 1/2 dose-escalation trial of BPX-501 and rimiducid in pediatric patients with malignant and nonmalignant diseases. Interim results from this trial were reported in 2 presentations at the 42nd Annual Meeting of the European Society for Blood and Marrow Transplantation in April 2016.

One presentation involved patients with acute leukemia who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, 16 of the 17 patients were alive and disease-free. There were several cases of GVHD, but nearly all were resolved.

The other presentation covered patients with nonmalignant disorders who received BPX-501 after haplo-HSCT. At a median follow-up of 7 months, all 24 patients studied were still alive and disease-free. The incidence of GVHD was considered “very low.” 

MINNEAPOLIS – A large single-site case review found that most pediatric patients with staphylococcal scalded skin syndrome (SSSS) had a classic presentation, often preceded by an upper respiratory tract infection.

In the review, surgical debridement increased hospital length of stay, and the use of clindamycin gave none of the benefit that might be expected from an antitoxin-specific antibiotic, according to Carmen Liy-Wong, MD, a pediatric medicine fellow at the Hospital for Sick Children in Toronto.

Kari Oakes/Frontline Medical News

All children in the 84-patient study had a skin rash, which was also the first symptom noticed for 94% of the patients (n = 79). All children also had the classic SSSS clinical signs of skin erythema and exfoliation or desquamation; most (88%, n = 74) had skin tenderness. In more than half of the children in the study, erythema, exfoliation, and bullae formation first presented on the head or neck.

Dr. Liy-Wong presented her findings at the annual meeting of the Society for Pediatric Dermatology. She and her collaborators used a retrospective chart review to develop the largest case series to date of SSSS in pediatric hospitalized children to describe both the clinical presentation of SSSS and antimicrobial use and susceptibilities. Study objectives, she said, included identifying the clinical characteristics of children with SSSS, as well as identifying management practices and associated outcomes for hospitalized children with SSSS.

Of the 84 patients who met inclusion criteria, 49 (58%) were male, and the mean age at SSSS diagnosis was 3.1 (plus or minus 2.4) years. Children, aged 0-18 years, were included if they had a clinical diagnosis of SSSS. Children with localized exfoliative staphylococcal infections, such as bullous impetigo, were excluded from the study.

In addition to erythema, exfoliation, and bullae formation, most children also had a history of skin tenderness (68%, n = 79); a little over a third had a history of fever or pruritus (38%, n = 32 for both). Thirty-five of the children (42%) had an upper respiratory tract infection in the 2 weeks preceding the SSSS diagnosis.

Facial edema, perioral or periocular crusting, and vesicles or bullae were seen in more than half of children. A few patients had conjunctivitis (11%, n = 9), mucous membrane involvement (5%, n = 4), or a sandpaper-like scarlatiniform rash (11%, n = 9).

No patients in the study died. Complications were rare: shock syndrome in one patient, and generalized bacteremia in three patients (4%).

Pain management was a mainstay of inpatient care for children with SSSS; 75 children (89%) required pain medication, and opioids were used in more than half. One in five children received morphine by continuous intravenous infusion.

Patients who underwent surgical debridement stayed a mean 5.8 (plus or minus 4.1) days, compared with a mean 3.6 (plus or minus 2.1) days for those children not receiving debridement (P = 0.03).

The study also aimed to identify antibiotic resistance patterns for SSSS in the single-site study population. Blood cultures were obtained from all but five patients and were positive in three patients. Bullae were cultured in 28 patients (33%), and periorificial lesions were cultured in 57 patients (68%). Throat cultures were obtained in 31 patients, but culture results were not reported.

“Periorificial cultures were more useful than other sites in identification of the causative organism,” Dr. Liy-Wong noted, since 74% (42 of 57) of periorificial cultures were positive. In all, 50 of 195 cultures (26%) were positive for Staphylococcus aureus. Almost all of the 50 isolates (98%, n = 49) were sensitive to oxacillin. Just under half of isolates were sensitive to clindamycin (48%, n = 24,) and erythromycin (46%, n = 23).

The use of clindamycin, an antibiotic known to be effective in inhibiting exotoxin production by staphylococcus species, was not associated with reduced hospital length of stay (P = .63 for comparison with nonantitoxin antibiotics). Dr. Liy-Wong and her collaborators noted that “no statistically significant difference in outcomes was found in patients treated with specific antitoxin medication (clindamycin),” a practice that requires further study.

SSSS was diagnosed by dermatologists in 35 of the 84 cases, followed by emergency department physicians in 29 cases (34%), pediatricians in 16 cases (19%), and family physicians in 4 cases (5%).

Dr. Liy-Wong and her colleagues reported no external sources of funding, and no conflicts of interest.

MINNEAPOLIS – A large single-site case review found that most pediatric patients with staphylococcal scalded skin syndrome (SSSS) had a classic presentation, often preceded by an upper respiratory tract infection.

In the review, surgical debridement increased hospital length of stay, and the use of clindamycin gave none of the benefit that might be expected from an antitoxin-specific antibiotic, according to Carmen Liy-Wong, MD, a pediatric medicine fellow at the Hospital for Sick Children in Toronto.

Kari Oakes/Frontline Medical News

All children in the 84-patient study had a skin rash, which was also the first symptom noticed for 94% of the patients (n = 79). All children also had the classic SSSS clinical signs of skin erythema and exfoliation or desquamation; most (88%, n = 74) had skin tenderness. In more than half of the children in the study, erythema, exfoliation, and bullae formation first presented on the head or neck.

Dr. Liy-Wong presented her findings at the annual meeting of the Society for Pediatric Dermatology. She and her collaborators used a retrospective chart review to develop the largest case series to date of SSSS in pediatric hospitalized children to describe both the clinical presentation of SSSS and antimicrobial use and susceptibilities. Study objectives, she said, included identifying the clinical characteristics of children with SSSS, as well as identifying management practices and associated outcomes for hospitalized children with SSSS.

Of the 84 patients who met inclusion criteria, 49 (58%) were male, and the mean age at SSSS diagnosis was 3.1 (plus or minus 2.4) years. Children, aged 0-18 years, were included if they had a clinical diagnosis of SSSS. Children with localized exfoliative staphylococcal infections, such as bullous impetigo, were excluded from the study.

In addition to erythema, exfoliation, and bullae formation, most children also had a history of skin tenderness (68%, n = 79); a little over a third had a history of fever or pruritus (38%, n = 32 for both). Thirty-five of the children (42%) had an upper respiratory tract infection in the 2 weeks preceding the SSSS diagnosis.

Facial edema, perioral or periocular crusting, and vesicles or bullae were seen in more than half of children. A few patients had conjunctivitis (11%, n = 9), mucous membrane involvement (5%, n = 4), or a sandpaper-like scarlatiniform rash (11%, n = 9).

No patients in the study died. Complications were rare: shock syndrome in one patient, and generalized bacteremia in three patients (4%).

Pain management was a mainstay of inpatient care for children with SSSS; 75 children (89%) required pain medication, and opioids were used in more than half. One in five children received morphine by continuous intravenous infusion.

Patients who underwent surgical debridement stayed a mean 5.8 (plus or minus 4.1) days, compared with a mean 3.6 (plus or minus 2.1) days for those children not receiving debridement (P = 0.03).

The study also aimed to identify antibiotic resistance patterns for SSSS in the single-site study population. Blood cultures were obtained from all but five patients and were positive in three patients. Bullae were cultured in 28 patients (33%), and periorificial lesions were cultured in 57 patients (68%). Throat cultures were obtained in 31 patients, but culture results were not reported.

“Periorificial cultures were more useful than other sites in identification of the causative organism,” Dr. Liy-Wong noted, since 74% (42 of 57) of periorificial cultures were positive. In all, 50 of 195 cultures (26%) were positive for Staphylococcus aureus. Almost all of the 50 isolates (98%, n = 49) were sensitive to oxacillin. Just under half of isolates were sensitive to clindamycin (48%, n = 24,) and erythromycin (46%, n = 23).

The use of clindamycin, an antibiotic known to be effective in inhibiting exotoxin production by staphylococcus species, was not associated with reduced hospital length of stay (P = .63 for comparison with nonantitoxin antibiotics). Dr. Liy-Wong and her collaborators noted that “no statistically significant difference in outcomes was found in patients treated with specific antitoxin medication (clindamycin),” a practice that requires further study.

SSSS was diagnosed by dermatologists in 35 of the 84 cases, followed by emergency department physicians in 29 cases (34%), pediatricians in 16 cases (19%), and family physicians in 4 cases (5%).

Dr. Liy-Wong and her colleagues reported no external sources of funding, and no conflicts of interest.

MINNEAPOLIS – A large single-site case review found that most pediatric patients with staphylococcal scalded skin syndrome (SSSS) had a classic presentation, often preceded by an upper respiratory tract infection.

In the review, surgical debridement increased hospital length of stay, and the use of clindamycin gave none of the benefit that might be expected from an antitoxin-specific antibiotic, according to Carmen Liy-Wong, MD, a pediatric medicine fellow at the Hospital for Sick Children in Toronto.

Kari Oakes/Frontline Medical News

All children in the 84-patient study had a skin rash, which was also the first symptom noticed for 94% of the patients (n = 79). All children also had the classic SSSS clinical signs of skin erythema and exfoliation or desquamation; most (88%, n = 74) had skin tenderness. In more than half of the children in the study, erythema, exfoliation, and bullae formation first presented on the head or neck.

Dr. Liy-Wong presented her findings at the annual meeting of the Society for Pediatric Dermatology. She and her collaborators used a retrospective chart review to develop the largest case series to date of SSSS in pediatric hospitalized children to describe both the clinical presentation of SSSS and antimicrobial use and susceptibilities. Study objectives, she said, included identifying the clinical characteristics of children with SSSS, as well as identifying management practices and associated outcomes for hospitalized children with SSSS.

Of the 84 patients who met inclusion criteria, 49 (58%) were male, and the mean age at SSSS diagnosis was 3.1 (plus or minus 2.4) years. Children, aged 0-18 years, were included if they had a clinical diagnosis of SSSS. Children with localized exfoliative staphylococcal infections, such as bullous impetigo, were excluded from the study.

In addition to erythema, exfoliation, and bullae formation, most children also had a history of skin tenderness (68%, n = 79); a little over a third had a history of fever or pruritus (38%, n = 32 for both). Thirty-five of the children (42%) had an upper respiratory tract infection in the 2 weeks preceding the SSSS diagnosis.

Facial edema, perioral or periocular crusting, and vesicles or bullae were seen in more than half of children. A few patients had conjunctivitis (11%, n = 9), mucous membrane involvement (5%, n = 4), or a sandpaper-like scarlatiniform rash (11%, n = 9).

No patients in the study died. Complications were rare: shock syndrome in one patient, and generalized bacteremia in three patients (4%).

Pain management was a mainstay of inpatient care for children with SSSS; 75 children (89%) required pain medication, and opioids were used in more than half. One in five children received morphine by continuous intravenous infusion.

Patients who underwent surgical debridement stayed a mean 5.8 (plus or minus 4.1) days, compared with a mean 3.6 (plus or minus 2.1) days for those children not receiving debridement (P = 0.03).

The study also aimed to identify antibiotic resistance patterns for SSSS in the single-site study population. Blood cultures were obtained from all but five patients and were positive in three patients. Bullae were cultured in 28 patients (33%), and periorificial lesions were cultured in 57 patients (68%). Throat cultures were obtained in 31 patients, but culture results were not reported.

“Periorificial cultures were more useful than other sites in identification of the causative organism,” Dr. Liy-Wong noted, since 74% (42 of 57) of periorificial cultures were positive. In all, 50 of 195 cultures (26%) were positive for Staphylococcus aureus. Almost all of the 50 isolates (98%, n = 49) were sensitive to oxacillin. Just under half of isolates were sensitive to clindamycin (48%, n = 24,) and erythromycin (46%, n = 23).

The use of clindamycin, an antibiotic known to be effective in inhibiting exotoxin production by staphylococcus species, was not associated with reduced hospital length of stay (P = .63 for comparison with nonantitoxin antibiotics). Dr. Liy-Wong and her collaborators noted that “no statistically significant difference in outcomes was found in patients treated with specific antitoxin medication (clindamycin),” a practice that requires further study.

SSSS was diagnosed by dermatologists in 35 of the 84 cases, followed by emergency department physicians in 29 cases (34%), pediatricians in 16 cases (19%), and family physicians in 4 cases (5%).

Dr. Liy-Wong and her colleagues reported no external sources of funding, and no conflicts of interest.

MINNEAPOLIS – A large single-site case review found that most pediatric patients with staphylococcal scalded skin syndrome (SSSS) had a classic presentation, often preceded by an upper respiratory tract infection.

In the review, surgical debridement increased hospital length of stay, and the use of clindamycin gave none of the benefit that might be expected from an antitoxin-specific antibiotic, according to Carmen Liy-Wong, MD, a pediatric medicine fellow at the Hospital for Sick Children in Toronto.

Kari Oakes/Frontline Medical News

All children in the 84-patient study had a skin rash, which was also the first symptom noticed for 94% of the patients (n = 79). All children also had the classic SSSS clinical signs of skin erythema and exfoliation or desquamation; most (88%, n = 74) had skin tenderness. In more than half of the children in the study, erythema, exfoliation, and bullae formation first presented on the head or neck.

Dr. Liy-Wong presented her findings at the annual meeting of the Society for Pediatric Dermatology. She and her collaborators used a retrospective chart review to develop the largest case series to date of SSSS in pediatric hospitalized children to describe both the clinical presentation of SSSS and antimicrobial use and susceptibilities. Study objectives, she said, included identifying the clinical characteristics of children with SSSS, as well as identifying management practices and associated outcomes for hospitalized children with SSSS.

Of the 84 patients who met inclusion criteria, 49 (58%) were male, and the mean age at SSSS diagnosis was 3.1 (plus or minus 2.4) years. Children, aged 0-18 years, were included if they had a clinical diagnosis of SSSS. Children with localized exfoliative staphylococcal infections, such as bullous impetigo, were excluded from the study.

In addition to erythema, exfoliation, and bullae formation, most children also had a history of skin tenderness (68%, n = 79); a little over a third had a history of fever or pruritus (38%, n = 32 for both). Thirty-five of the children (42%) had an upper respiratory tract infection in the 2 weeks preceding the SSSS diagnosis.

Facial edema, perioral or periocular crusting, and vesicles or bullae were seen in more than half of children. A few patients had conjunctivitis (11%, n = 9), mucous membrane involvement (5%, n = 4), or a sandpaper-like scarlatiniform rash (11%, n = 9).

No patients in the study died. Complications were rare: shock syndrome in one patient, and generalized bacteremia in three patients (4%).

Pain management was a mainstay of inpatient care for children with SSSS; 75 children (89%) required pain medication, and opioids were used in more than half. One in five children received morphine by continuous intravenous infusion.

Patients who underwent surgical debridement stayed a mean 5.8 (plus or minus 4.1) days, compared with a mean 3.6 (plus or minus 2.1) days for those children not receiving debridement (P = 0.03).

The study also aimed to identify antibiotic resistance patterns for SSSS in the single-site study population. Blood cultures were obtained from all but five patients and were positive in three patients. Bullae were cultured in 28 patients (33%), and periorificial lesions were cultured in 57 patients (68%). Throat cultures were obtained in 31 patients, but culture results were not reported.

“Periorificial cultures were more useful than other sites in identification of the causative organism,” Dr. Liy-Wong noted, since 74% (42 of 57) of periorificial cultures were positive. In all, 50 of 195 cultures (26%) were positive for Staphylococcus aureus. Almost all of the 50 isolates (98%, n = 49) were sensitive to oxacillin. Just under half of isolates were sensitive to clindamycin (48%, n = 24,) and erythromycin (46%, n = 23).

The use of clindamycin, an antibiotic known to be effective in inhibiting exotoxin production by staphylococcus species, was not associated with reduced hospital length of stay (P = .63 for comparison with nonantitoxin antibiotics). Dr. Liy-Wong and her collaborators noted that “no statistically significant difference in outcomes was found in patients treated with specific antitoxin medication (clindamycin),” a practice that requires further study.

SSSS was diagnosed by dermatologists in 35 of the 84 cases, followed by emergency department physicians in 29 cases (34%), pediatricians in 16 cases (19%), and family physicians in 4 cases (5%).

Dr. Liy-Wong and her colleagues reported no external sources of funding, and no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

MINNEAPOLIS – A large single-site case review found that most pediatric patients with staphylococcal scalded skin syndrome (SSSS) had a classic presentation, often preceded by an upper respiratory tract infection.

In the review, surgical debridement increased hospital length of stay, and the use of clindamycin gave none of the benefit that might be expected from an antitoxin-specific antibiotic, according to Carmen Liy-Wong, MD, a pediatric medicine fellow at the Hospital for Sick Children in Toronto.

Kari Oakes/Frontline Medical News

All children in the 84-patient study had a skin rash, which was also the first symptom noticed for 94% of the patients (n = 79). All children also had the classic SSSS clinical signs of skin erythema and exfoliation or desquamation; most (88%, n = 74) had skin tenderness. In more than half of the children in the study, erythema, exfoliation, and bullae formation first presented on the head or neck.

Dr. Liy-Wong presented her findings at the annual meeting of the Society for Pediatric Dermatology. She and her collaborators used a retrospective chart review to develop the largest case series to date of SSSS in pediatric hospitalized children to describe both the clinical presentation of SSSS and antimicrobial use and susceptibilities. Study objectives, she said, included identifying the clinical characteristics of children with SSSS, as well as identifying management practices and associated outcomes for hospitalized children with SSSS.

Of the 84 patients who met inclusion criteria, 49 (58%) were male, and the mean age at SSSS diagnosis was 3.1 (plus or minus 2.4) years. Children, aged 0-18 years, were included if they had a clinical diagnosis of SSSS. Children with localized exfoliative staphylococcal infections, such as bullous impetigo, were excluded from the study.

In addition to erythema, exfoliation, and bullae formation, most children also had a history of skin tenderness (68%, n = 79); a little over a third had a history of fever or pruritus (38%, n = 32 for both). Thirty-five of the children (42%) had an upper respiratory tract infection in the 2 weeks preceding the SSSS diagnosis.

Facial edema, perioral or periocular crusting, and vesicles or bullae were seen in more than half of children. A few patients had conjunctivitis (11%, n = 9), mucous membrane involvement (5%, n = 4), or a sandpaper-like scarlatiniform rash (11%, n = 9).

No patients in the study died. Complications were rare: shock syndrome in one patient, and generalized bacteremia in three patients (4%).

Pain management was a mainstay of inpatient care for children with SSSS; 75 children (89%) required pain medication, and opioids were used in more than half. One in five children received morphine by continuous intravenous infusion.

Patients who underwent surgical debridement stayed a mean 5.8 (plus or minus 4.1) days, compared with a mean 3.6 (plus or minus 2.1) days for those children not receiving debridement (P = 0.03).

The study also aimed to identify antibiotic resistance patterns for SSSS in the single-site study population. Blood cultures were obtained from all but five patients and were positive in three patients. Bullae were cultured in 28 patients (33%), and periorificial lesions were cultured in 57 patients (68%). Throat cultures were obtained in 31 patients, but culture results were not reported.

“Periorificial cultures were more useful than other sites in identification of the causative organism,” Dr. Liy-Wong noted, since 74% (42 of 57) of periorificial cultures were positive. In all, 50 of 195 cultures (26%) were positive for Staphylococcus aureus. Almost all of the 50 isolates (98%, n = 49) were sensitive to oxacillin. Just under half of isolates were sensitive to clindamycin (48%, n = 24,) and erythromycin (46%, n = 23).

The use of clindamycin, an antibiotic known to be effective in inhibiting exotoxin production by staphylococcus species, was not associated with reduced hospital length of stay (P = .63 for comparison with nonantitoxin antibiotics). Dr. Liy-Wong and her collaborators noted that “no statistically significant difference in outcomes was found in patients treated with specific antitoxin medication (clindamycin),” a practice that requires further study.

SSSS was diagnosed by dermatologists in 35 of the 84 cases, followed by emergency department physicians in 29 cases (34%), pediatricians in 16 cases (19%), and family physicians in 4 cases (5%).

Dr. Liy-Wong and her colleagues reported no external sources of funding, and no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes

MINNEAPOLIS – A large single-site case review found that most pediatric patients with staphylococcal scalded skin syndrome (SSSS) had a classic presentation, often preceded by an upper respiratory tract infection.

In the review, surgical debridement increased hospital length of stay, and the use of clindamycin gave none of the benefit that might be expected from an antitoxin-specific antibiotic, according to Carmen Liy-Wong, MD, a pediatric medicine fellow at the Hospital for Sick Children in Toronto.

Kari Oakes/Frontline Medical News

All children in the 84-patient study had a skin rash, which was also the first symptom noticed for 94% of the patients (n = 79). All children also had the classic SSSS clinical signs of skin erythema and exfoliation or desquamation; most (88%, n = 74) had skin tenderness. In more than half of the children in the study, erythema, exfoliation, and bullae formation first presented on the head or neck.

Dr. Liy-Wong presented her findings at the annual meeting of the Society for Pediatric Dermatology. She and her collaborators used a retrospective chart review to develop the largest case series to date of SSSS in pediatric hospitalized children to describe both the clinical presentation of SSSS and antimicrobial use and susceptibilities. Study objectives, she said, included identifying the clinical characteristics of children with SSSS, as well as identifying management practices and associated outcomes for hospitalized children with SSSS.

Of the 84 patients who met inclusion criteria, 49 (58%) were male, and the mean age at SSSS diagnosis was 3.1 (plus or minus 2.4) years. Children, aged 0-18 years, were included if they had a clinical diagnosis of SSSS. Children with localized exfoliative staphylococcal infections, such as bullous impetigo, were excluded from the study.

In addition to erythema, exfoliation, and bullae formation, most children also had a history of skin tenderness (68%, n = 79); a little over a third had a history of fever or pruritus (38%, n = 32 for both). Thirty-five of the children (42%) had an upper respiratory tract infection in the 2 weeks preceding the SSSS diagnosis.

Facial edema, perioral or periocular crusting, and vesicles or bullae were seen in more than half of children. A few patients had conjunctivitis (11%, n = 9), mucous membrane involvement (5%, n = 4), or a sandpaper-like scarlatiniform rash (11%, n = 9).

No patients in the study died. Complications were rare: shock syndrome in one patient, and generalized bacteremia in three patients (4%).

Pain management was a mainstay of inpatient care for children with SSSS; 75 children (89%) required pain medication, and opioids were used in more than half. One in five children received morphine by continuous intravenous infusion.

Patients who underwent surgical debridement stayed a mean 5.8 (plus or minus 4.1) days, compared with a mean 3.6 (plus or minus 2.1) days for those children not receiving debridement (P = 0.03).

The study also aimed to identify antibiotic resistance patterns for SSSS in the single-site study population. Blood cultures were obtained from all but five patients and were positive in three patients. Bullae were cultured in 28 patients (33%), and periorificial lesions were cultured in 57 patients (68%). Throat cultures were obtained in 31 patients, but culture results were not reported.

“Periorificial cultures were more useful than other sites in identification of the causative organism,” Dr. Liy-Wong noted, since 74% (42 of 57) of periorificial cultures were positive. In all, 50 of 195 cultures (26%) were positive for Staphylococcus aureus. Almost all of the 50 isolates (98%, n = 49) were sensitive to oxacillin. Just under half of isolates were sensitive to clindamycin (48%, n = 24,) and erythromycin (46%, n = 23).

The use of clindamycin, an antibiotic known to be effective in inhibiting exotoxin production by staphylococcus species, was not associated with reduced hospital length of stay (P = .63 for comparison with nonantitoxin antibiotics). Dr. Liy-Wong and her collaborators noted that “no statistically significant difference in outcomes was found in patients treated with specific antitoxin medication (clindamycin),” a practice that requires further study.

SSSS was diagnosed by dermatologists in 35 of the 84 cases, followed by emergency department physicians in 29 cases (34%), pediatricians in 16 cases (19%), and family physicians in 4 cases (5%).

Dr. Liy-Wong and her colleagues reported no external sources of funding, and no conflicts of interest.

koakes@frontlinemedcom.com

On Twitter @karioakes