User login
What Markers Are Helpful to Diagnose Infection in Tocilizumab Users?
TOPLINE:
Eosinopenia and low ratio between eosinophil count (EC) and neutrophil count (NC) are potential indicators of infection for patients with inflammatory disease who are treated with tocilizumab.
METHODOLOGY:
- The researchers reviewed data from 163 patients treated for an inflammatory disease (mostly rheumatoid arthritis) with tocilizumab at a single center between 2009 and 2020.
- The study population included 41 patients with unscheduled hospitalizations for suspected infections. Patients’ median age was 59 years, and 83% were female.
- The researchers assessed the association in tocilizumab-treated patients between infections and eosinopenia (defined as EC < 0.05 g/L) and a low ratio between EC and NC, defined as EC/NC × 1000 < 11.8.
TAKEAWAY:
- Infectious diseases were diagnosed in 20 of the hospitalized patients (49%); the most common diseases were pneumonia (30%), joint or bone infections (25%), and gastrointestinal tract infections (15%).
- The median absolute EC at hospital admission was significantly lower for patients with infections than for those without infections (0.06 g/L vs 0.20 g/L).
- The median EC/NC × 1000 ratios were significantly lower in infected patients vs noninfected patients (6.54 vs 48.50).
- No differences appeared between patients with and without infections in age, sex, type of inflammatory disease, and steroid treatment.
IN PRACTICE:
“This original study suggests that all those easily available parameters should be used to maximize [sensitivity] in the screening of infection in patients undergoing treatment with IL-6 pathway antagonists,” the researchers wrote.
SOURCE:
The lead author on the study was Audrey Glatre, MD, of University Hospital Centre Reims, France. The study was published online in RMD Open on February 9.
LIMITATIONS:
The retrospective, observational design; relatively small study population; and use of data from a single center were potential limitations of the findings.
DISCLOSURES:
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
TOPLINE:
Eosinopenia and low ratio between eosinophil count (EC) and neutrophil count (NC) are potential indicators of infection for patients with inflammatory disease who are treated with tocilizumab.
METHODOLOGY:
- The researchers reviewed data from 163 patients treated for an inflammatory disease (mostly rheumatoid arthritis) with tocilizumab at a single center between 2009 and 2020.
- The study population included 41 patients with unscheduled hospitalizations for suspected infections. Patients’ median age was 59 years, and 83% were female.
- The researchers assessed the association in tocilizumab-treated patients between infections and eosinopenia (defined as EC < 0.05 g/L) and a low ratio between EC and NC, defined as EC/NC × 1000 < 11.8.
TAKEAWAY:
- Infectious diseases were diagnosed in 20 of the hospitalized patients (49%); the most common diseases were pneumonia (30%), joint or bone infections (25%), and gastrointestinal tract infections (15%).
- The median absolute EC at hospital admission was significantly lower for patients with infections than for those without infections (0.06 g/L vs 0.20 g/L).
- The median EC/NC × 1000 ratios were significantly lower in infected patients vs noninfected patients (6.54 vs 48.50).
- No differences appeared between patients with and without infections in age, sex, type of inflammatory disease, and steroid treatment.
IN PRACTICE:
“This original study suggests that all those easily available parameters should be used to maximize [sensitivity] in the screening of infection in patients undergoing treatment with IL-6 pathway antagonists,” the researchers wrote.
SOURCE:
The lead author on the study was Audrey Glatre, MD, of University Hospital Centre Reims, France. The study was published online in RMD Open on February 9.
LIMITATIONS:
The retrospective, observational design; relatively small study population; and use of data from a single center were potential limitations of the findings.
DISCLOSURES:
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
TOPLINE:
Eosinopenia and low ratio between eosinophil count (EC) and neutrophil count (NC) are potential indicators of infection for patients with inflammatory disease who are treated with tocilizumab.
METHODOLOGY:
- The researchers reviewed data from 163 patients treated for an inflammatory disease (mostly rheumatoid arthritis) with tocilizumab at a single center between 2009 and 2020.
- The study population included 41 patients with unscheduled hospitalizations for suspected infections. Patients’ median age was 59 years, and 83% were female.
- The researchers assessed the association in tocilizumab-treated patients between infections and eosinopenia (defined as EC < 0.05 g/L) and a low ratio between EC and NC, defined as EC/NC × 1000 < 11.8.
TAKEAWAY:
- Infectious diseases were diagnosed in 20 of the hospitalized patients (49%); the most common diseases were pneumonia (30%), joint or bone infections (25%), and gastrointestinal tract infections (15%).
- The median absolute EC at hospital admission was significantly lower for patients with infections than for those without infections (0.06 g/L vs 0.20 g/L).
- The median EC/NC × 1000 ratios were significantly lower in infected patients vs noninfected patients (6.54 vs 48.50).
- No differences appeared between patients with and without infections in age, sex, type of inflammatory disease, and steroid treatment.
IN PRACTICE:
“This original study suggests that all those easily available parameters should be used to maximize [sensitivity] in the screening of infection in patients undergoing treatment with IL-6 pathway antagonists,” the researchers wrote.
SOURCE:
The lead author on the study was Audrey Glatre, MD, of University Hospital Centre Reims, France. The study was published online in RMD Open on February 9.
LIMITATIONS:
The retrospective, observational design; relatively small study population; and use of data from a single center were potential limitations of the findings.
DISCLOSURES:
The study received no outside funding. The researchers had no financial conflicts to disclose.
A version of this article appeared on Medscape.com.
Democratic Lawmakers Press Pfizer on Chemotherapy Drug Shortages
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
In a statement about their February 21 action, the legislators, led by Rep. Jamie Raskin (D-Md.), the committee’s ranking minority member, described their work as a follow up to an earlier investigation into price hikes of generic drugs. While the committee members queried Pfizer over the three oncology medications only, they also sent letters to drugmakers Teva and Sandoz with respect to shortages in other drug classes.
A representative for Pfizer confirmed to MDedge Oncology that the company had received the representatives’ letter but said “we have no further details to provide at this time.”
What is the basis for concern?
All three generic chemotherapy drugs are mainstay treatments used across a broad array of cancers. Though shortages have been reported for several years, they became especially acute after December 2022, when an inspection by the US Food and Drug Administration (FDA) led to regulatory action against an Indian manufacturer, Intas, that produced up to half of the platinum-based therapies supplied globally. The National Comprehensive Cancer Care Network reported in October 2023 that more than 90% of its member centers were struggling to maintain adequate supplies of carboplatin, and 70% had trouble obtaining cisplatin, while the American Society of Clinical Oncology published clinical guidance on alternative treatment strategies.
What has the government done in response to the recent shortages?
The White House and the FDA announced in September that they were working with several manufacturers to help increase supplies of the platinum-based chemotherapies and of methotrexate, and taking measures that included relaxing rules on imports. Recent guidance under a pandemic-era federal law, the 2020 CARES Act, strengthened manufacturer reporting requirements related to drug shortages, and other measures have been proposed. While federal regulators have many tools with which to address drug shortages, they cannot legally oblige a manufacturer to increase production of a drug.
What can the lawmakers expect to achieve with their letter?
By pressuring Pfizer publicly, the lawmakers may be able to nudge the company to take measures to assure more consistent supplies of the three drugs. The lawmakers also said they hoped to glean from Pfizer more insight into the root causes of the shortages and potential remedies. They noted that, in a May 2023 letter by Pfizer to customers, the company had warned of depleted and limited supplies of the three drugs and said it was “working diligently” to increase output. However, the lawmakers wrote, “the root cause is not yet resolved and carboplatin, cisplatin, and methotrexate continue to experience residual delays.”
Why did the committee target Pfizer specifically?
Pfizer and its subsidiaries are among the major manufacturers of the three generic chemotherapy agents mentioned in the letter. The legislators noted that “pharmaceutical companies may not be motivated to produce generic drugs like carboplatin, cisplatin, and methotrexate, because they are not as lucrative as producing patented brand name drugs,” and that “as a principal supplier of carboplatin, cisplatin, and methotrexate, it is critical that Pfizer continues to increase production of these life-sustaining cancer medications, even amidst potential lower profitability.”
The committee members also made reference to news reports of price-gouging with these medications, as smaller hospitals or oncology centers are forced to turn to unscrupulous third-party suppliers.
What is being demanded of Pfizer?
Pfizer was given until March 6 to respond, in writing and in a briefing with committee staff, to a six questions. These queries concern what specific steps the company has taken to increase supplies of the three generic oncology drugs, what Pfizer is doing to help avert price-gouging, whether further oncology drug shortages are anticipated, and how the company is working with the FDA on the matter.
Stimulants for ADHD Not Linked to Prescription Drug Misuse
TOPLINE:
The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.
METHODOLOGY:
- Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
- Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
- The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
- Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.
TAKEAWAY:
- Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
- Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
- The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
- The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.
IN PRACTICE:
“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.
SOURCE:
Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.
LIMITATIONS:
Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.
DISCLOSURES:
This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.
METHODOLOGY:
- Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
- Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
- The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
- Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.
TAKEAWAY:
- Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
- Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
- The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
- The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.
IN PRACTICE:
“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.
SOURCE:
Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.
LIMITATIONS:
Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.
DISCLOSURES:
This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
TOPLINE:
The use of stimulant therapy by adolescents with attention-deficit/hyperactivity disorder (ADHD) was not associated with later prescription drug misuse (PDM), a new study showed. However, misuse of prescription stimulants during adolescence was associated with significantly higher odds of later PDM.
METHODOLOGY:
- Data came from 11,066 participants in the ongoing Monitoring the Future panel study (baseline cohort years 2005-2017), a multicohort US national longitudinal study of adolescents followed into adulthood, in which procedures and measures are kept consistent across time.
- Participants (ages 17 and 18 years, 51.7% female, 11.2% Black, 15.7% Hispanic, and 59.6% White) completed self-administered questionnaires, with biennial follow-up during young adulthood (ages 19-24 years).
- The questionnaires asked about the number of occasions (if any) in which respondents used a prescription drug (benzodiazepine, opioid, or stimulant) on their own, without a physician’s order.
- Baseline covariates included sex, race, ethnicity, grade point average during high school, parental education, past 2-week binge drinking, past-month cigarette use, and past-year marijuana use, as well as demographic factors.
TAKEAWAY:
- Overall, 9.9% of participants reported lifetime stimulant therapy for ADHD, and 18.6% reported lifetime prescription stimulant misuse at baseline.
- Adolescents who received stimulant therapy for ADHD were less likely to report past-year prescription stimulant misuse as young adults compared with their same-age peers who did not receive stimulant therapy (adjusted odds ratio, 0.71; 95% CI, 0.52-0.99).
- The researchers found no significant differences between adolescents with or without lifetime stimulants in later incidence or prevalence of past-year PDM during young adulthood.
- The most robust predictor of prescription stimulant misuse during young adulthood was prescription stimulant misuse during adolescence; similarly, the most robust predictors of prescription opioid and prescription benzodiazepine misuse during young adulthood were prescription opioid and prescription benzodiazepine misuse (respectively) during adolescence.
IN PRACTICE:
“These findings amplify accumulating evidence suggesting that careful monitoring and screening during adolescence could identify individuals who are at relatively greater risk for PDM and need more comprehensive substance use assessment,” the authors wrote.
SOURCE:
Sean Esteban McCabe, PhD, professor and director, Center for the Study of Drugs, Alcohol, Smoking and Health, University of Michigan School of Nursing, Ann Arbor, was the lead and corresponding author of the study. It was published online on February 7 in Psychiatric Sciences.
LIMITATIONS:
Some subpopulations with higher rates of substance use, including youths who left school before completion and institutionalized populations, were excluded from the study, which may have led to an underestimation of PDM. Moreover, some potential confounders (eg, comorbid psychiatric conditions) were not assessed.
DISCLOSURES:
This study was supported by a research award from the US Food and Drug Administration and research awards from the National Institute on Drug Abuse of the NIH. Dr. McCabe reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.
A version of this article appeared on Medscape.com.
Mental Health Interventions for Refugee Children
In my previous article, “Mental Health Characteristics of Refugee Children,” we learned that in recent decades, refugeeism has become a growing problem that disproportionately affects children. Refugee children and their families experience a variety of traumas, often sustained across years and even decades, because of armed conflict, persecution, social upheavals, or environmental disasters. Refugees are at greater risks for PTSD and affective and psychotic disorders presumably due to increased traumatic life events before, during, and after migration. I used my own experience as a child refugee from Vietnam to elucidate the stressors evident in various phases of forced displacement.1
Risk Factors and Protective Factors
To a certain extent, the experiences of refugees are universal. All refugees experience some sort of humanitarian crisis that forces an emergent escape from their home across international borders to a new resettlement area. It is important to note that internally displaced people do not meet the United Nations’ (UN) official designation of refugee status; however, some agencies use a broader definition where they are designated as such.2,3 We will refer to those not meeting the UN criteria as displaced people, while refugees are those that do meet the UN criteria. Dr. Mina Fazel’s 2012 systematic review in The Lancet of mental health risk factors and protective factors for displaced and refugee children is the most comprehensive of its kind.4 It will be summarized in this section with some relevant personal reflection.
In terms of risk factors, external displacement likely results in additional stress and trauma, presumably from the lack of assess to one’s culture and the host country’s language. Understandably, this makes rebuilding of one’s life more difficult. Several studies show that displaced/refugee children experience more difficulty with psychosocial adaptation than non-displaced children. Violence, directly experienced or indirectly feared, both to the child and their parents, was the strongest predictor of mental health problems and withdrawn behavior. Children who were separated from their parents clearly fared worst in their mental health than those who did not, which is not surprising given the nature of their dependence on caregivers for protection and guidance. During resettlement, experienced or perceived discrimination from the host country was also a risk factor, as well as instability in housing and a drawn-out resettlement process. Female sex was a risk factor mainly for emotional problems. Poor financial support post-migration is associated with depression, but it is unclear whether pre-migration financial status was protective. From my own experience, it is likely not, given that once one becomes a refugee one does not have access to one’s wealth, except that which could be hidden on one’s body. Another risk factor was also if one’s parent had psychiatric problems or was single. Due to the migration, my mother was separated permanently from her husband, which caused her extraordinary isolation and loneliness, something that was palpably felt by myself as I grew up.
In terms of protective factors, family cohesion and cultural continuity appear critical. For myself, not only would I not have survived without my mother and aunt, but they constantly protected me from the harsh realities. My mother would distract me with seemingly trivial goals once we got to America, like finally tasting a hamburger, or talking about school and being reunited with my uncle. This is in line with another finding — that children have better mental health outcomes when their parents do not talk about their hardships. Once my family was resettled with my uncle and his family, they played a critical role in smoothing our transition, not only by providing us with housing, but also cultural knowledge. Cultural havens can restore some of the social position and way of life that refugees lose when they are able to reconnect with a society that recognizes their previous achievements and status. Finally, religion also seemed to be a protective factor.
Mental Health Interventions
In 2018, Dr. Fazel identified mental health interventions for refugee children in a narrative review.5 She acknowledged that these conclusions are limited by the paucity of preventive mental health research in children in general, as well as the mobile nature and complex cultural differences of refugee children. This is exacerbated by the small evidence base. Given that, she makes these recommendations for varying levels of interventions: individual, group, family, living circumstances, social interactions, and school.
On an individual level, effective interventions developed to address PTSD include narrative exposure therapy, trauma-focused cognitive behavior therapy, and eye-movement and desensitization therapy. Group-based interventions for trauma, for example school-based PTSD intervention programs in conflicted areas, have either been shown to not be effective, or only effective for reducing depression. The mental health of unaccompanied children separated from family fare better when placed in foster care, rather than other types of social support. This is further enhanced if the foster family is the same ethnicity.
On a family level, improvements in parenting style and parental mental health, family engagement with local culture and structures, and family-based mental health interventions all positively impact refugee children. Not surprisingly, refugee parents have a greater prevalence of mental health conditions. Several studies on refugeeism point out a greater occurrence of intimate partner violence (that negatively affects children) as well has harsher discipline and maltreatment of refugee children. Thus, mental health treatment for parents also directly improves the well-being of their children. Teaching parenting skills to mitigate the violent effect of their PTSD symptoms, as well as parenting classes that teach gentler styles, have been shown to reduce harsh parenting and mitigate aggressive behaviors in these children. These improvements are enhanced when these classes are taught by other refugees themselves.
School is key for helping refugee children since it is a site where they can access language proficiency, successful acculturation, and medical and mental health services. Several studies have identified the positive effects of better parental engagement with school, resulting in improved academic performance and reduced levels of depressive and PTSD symptoms. A review of learning problems in refugee children identified several factors for success. These include high academic and life ambition, parental involvement in education, accurate educational assessment and grade placement, teacher understanding of linguistic and cultural heritage, culturally appropriate school transition, supportive peer relationships, and successful acculturation. School certainly was key for my acculturation and language proficiency. When I arrived at 6 years old I was selectively mute for my year in first grade, namely because I did not know how to speak English and because I did not share the culture. However, my teacher correctly identified my deficiency and chose to place me in kindergarten, which allowed me the time to gain English proficiency. Though I was always the oldest one in class, that remediation was key in allowing eventual success in school leading up to my admission to UC Berkeley.
Summary
In recent decades, refugeeism has become a growing problem that disproportionately affects children leading to traumas sustained across years and even decades, and greater risks for PTSD, as well as affective and psychotic disorders. Risk factors include the experience of violence, the separation from family, female gender, discrimination in the host country, unstable housing, and a drawn-out resettlement process. Protective factors consist of family cohesion, cultural continuity, support at schools, being protected from the truth of their harsh reality, stable housing, language acquisition, and quick resettlement. From these factors, effective mental interventions have been found to be the promotion of these protective factors as well as support for parental mental health and parenting skills, better parental engagement at school, and schools that correctly identify and address these children’s educational needs.
Dr. Nguyen is a second-year resident at UCSF Fresno Psychiatry Residency. He was a public high school English teacher for 15 years previously.*
References
1. Nguyen D. Mental Health Characteristics of Refugee Children. Pediatric News. 2023 Nov. 14. https://www.mdedge.com/pediatrics/article/266518/mental-health/mental-health-characteristics-refugee-children.
2. Office of the United Nations High Commissioner for Refugees. The Refugee Concept Under International Law. Global Compact for Safe, Orderly and Regular Migration. 2018 March 8. https://www.unhcr.org/sites/default/files/legacy-pdf/5aa290937.pdf.
3. Winer JP. Mental Health Practice with Immigrant and Refugee Youth [Power Point Slides]. Michigan Medicine. 2021 June 24. https://www.youtube.com/watch?v=ICkg4132SQY
4. Fazel M et al. Mental Health of Displaced and Refugee Children Resettled in High-Income Countries: Risk and Protective Factors. Lancet. 2012 Jan 21;379(9812):266-282. doi: 10.1016/S0140-6736(11)60051-2.
5. Fazel M, Betancourt TS. Preventive Mental Health Interventions for Refugee Children and Adolescents in High-Income Settings. Lancet Child Adolesc Health. 2018 Feb;2(2):121-132. doi: 10.1016/S2352-4642(17)30147-5.
*Correction, 2/27: An earlier version of this article misstated Dr. Nguyen's affiliation.
In my previous article, “Mental Health Characteristics of Refugee Children,” we learned that in recent decades, refugeeism has become a growing problem that disproportionately affects children. Refugee children and their families experience a variety of traumas, often sustained across years and even decades, because of armed conflict, persecution, social upheavals, or environmental disasters. Refugees are at greater risks for PTSD and affective and psychotic disorders presumably due to increased traumatic life events before, during, and after migration. I used my own experience as a child refugee from Vietnam to elucidate the stressors evident in various phases of forced displacement.1
Risk Factors and Protective Factors
To a certain extent, the experiences of refugees are universal. All refugees experience some sort of humanitarian crisis that forces an emergent escape from their home across international borders to a new resettlement area. It is important to note that internally displaced people do not meet the United Nations’ (UN) official designation of refugee status; however, some agencies use a broader definition where they are designated as such.2,3 We will refer to those not meeting the UN criteria as displaced people, while refugees are those that do meet the UN criteria. Dr. Mina Fazel’s 2012 systematic review in The Lancet of mental health risk factors and protective factors for displaced and refugee children is the most comprehensive of its kind.4 It will be summarized in this section with some relevant personal reflection.
In terms of risk factors, external displacement likely results in additional stress and trauma, presumably from the lack of assess to one’s culture and the host country’s language. Understandably, this makes rebuilding of one’s life more difficult. Several studies show that displaced/refugee children experience more difficulty with psychosocial adaptation than non-displaced children. Violence, directly experienced or indirectly feared, both to the child and their parents, was the strongest predictor of mental health problems and withdrawn behavior. Children who were separated from their parents clearly fared worst in their mental health than those who did not, which is not surprising given the nature of their dependence on caregivers for protection and guidance. During resettlement, experienced or perceived discrimination from the host country was also a risk factor, as well as instability in housing and a drawn-out resettlement process. Female sex was a risk factor mainly for emotional problems. Poor financial support post-migration is associated with depression, but it is unclear whether pre-migration financial status was protective. From my own experience, it is likely not, given that once one becomes a refugee one does not have access to one’s wealth, except that which could be hidden on one’s body. Another risk factor was also if one’s parent had psychiatric problems or was single. Due to the migration, my mother was separated permanently from her husband, which caused her extraordinary isolation and loneliness, something that was palpably felt by myself as I grew up.
In terms of protective factors, family cohesion and cultural continuity appear critical. For myself, not only would I not have survived without my mother and aunt, but they constantly protected me from the harsh realities. My mother would distract me with seemingly trivial goals once we got to America, like finally tasting a hamburger, or talking about school and being reunited with my uncle. This is in line with another finding — that children have better mental health outcomes when their parents do not talk about their hardships. Once my family was resettled with my uncle and his family, they played a critical role in smoothing our transition, not only by providing us with housing, but also cultural knowledge. Cultural havens can restore some of the social position and way of life that refugees lose when they are able to reconnect with a society that recognizes their previous achievements and status. Finally, religion also seemed to be a protective factor.
Mental Health Interventions
In 2018, Dr. Fazel identified mental health interventions for refugee children in a narrative review.5 She acknowledged that these conclusions are limited by the paucity of preventive mental health research in children in general, as well as the mobile nature and complex cultural differences of refugee children. This is exacerbated by the small evidence base. Given that, she makes these recommendations for varying levels of interventions: individual, group, family, living circumstances, social interactions, and school.
On an individual level, effective interventions developed to address PTSD include narrative exposure therapy, trauma-focused cognitive behavior therapy, and eye-movement and desensitization therapy. Group-based interventions for trauma, for example school-based PTSD intervention programs in conflicted areas, have either been shown to not be effective, or only effective for reducing depression. The mental health of unaccompanied children separated from family fare better when placed in foster care, rather than other types of social support. This is further enhanced if the foster family is the same ethnicity.
On a family level, improvements in parenting style and parental mental health, family engagement with local culture and structures, and family-based mental health interventions all positively impact refugee children. Not surprisingly, refugee parents have a greater prevalence of mental health conditions. Several studies on refugeeism point out a greater occurrence of intimate partner violence (that negatively affects children) as well has harsher discipline and maltreatment of refugee children. Thus, mental health treatment for parents also directly improves the well-being of their children. Teaching parenting skills to mitigate the violent effect of their PTSD symptoms, as well as parenting classes that teach gentler styles, have been shown to reduce harsh parenting and mitigate aggressive behaviors in these children. These improvements are enhanced when these classes are taught by other refugees themselves.
School is key for helping refugee children since it is a site where they can access language proficiency, successful acculturation, and medical and mental health services. Several studies have identified the positive effects of better parental engagement with school, resulting in improved academic performance and reduced levels of depressive and PTSD symptoms. A review of learning problems in refugee children identified several factors for success. These include high academic and life ambition, parental involvement in education, accurate educational assessment and grade placement, teacher understanding of linguistic and cultural heritage, culturally appropriate school transition, supportive peer relationships, and successful acculturation. School certainly was key for my acculturation and language proficiency. When I arrived at 6 years old I was selectively mute for my year in first grade, namely because I did not know how to speak English and because I did not share the culture. However, my teacher correctly identified my deficiency and chose to place me in kindergarten, which allowed me the time to gain English proficiency. Though I was always the oldest one in class, that remediation was key in allowing eventual success in school leading up to my admission to UC Berkeley.
Summary
In recent decades, refugeeism has become a growing problem that disproportionately affects children leading to traumas sustained across years and even decades, and greater risks for PTSD, as well as affective and psychotic disorders. Risk factors include the experience of violence, the separation from family, female gender, discrimination in the host country, unstable housing, and a drawn-out resettlement process. Protective factors consist of family cohesion, cultural continuity, support at schools, being protected from the truth of their harsh reality, stable housing, language acquisition, and quick resettlement. From these factors, effective mental interventions have been found to be the promotion of these protective factors as well as support for parental mental health and parenting skills, better parental engagement at school, and schools that correctly identify and address these children’s educational needs.
Dr. Nguyen is a second-year resident at UCSF Fresno Psychiatry Residency. He was a public high school English teacher for 15 years previously.*
References
1. Nguyen D. Mental Health Characteristics of Refugee Children. Pediatric News. 2023 Nov. 14. https://www.mdedge.com/pediatrics/article/266518/mental-health/mental-health-characteristics-refugee-children.
2. Office of the United Nations High Commissioner for Refugees. The Refugee Concept Under International Law. Global Compact for Safe, Orderly and Regular Migration. 2018 March 8. https://www.unhcr.org/sites/default/files/legacy-pdf/5aa290937.pdf.
3. Winer JP. Mental Health Practice with Immigrant and Refugee Youth [Power Point Slides]. Michigan Medicine. 2021 June 24. https://www.youtube.com/watch?v=ICkg4132SQY
4. Fazel M et al. Mental Health of Displaced and Refugee Children Resettled in High-Income Countries: Risk and Protective Factors. Lancet. 2012 Jan 21;379(9812):266-282. doi: 10.1016/S0140-6736(11)60051-2.
5. Fazel M, Betancourt TS. Preventive Mental Health Interventions for Refugee Children and Adolescents in High-Income Settings. Lancet Child Adolesc Health. 2018 Feb;2(2):121-132. doi: 10.1016/S2352-4642(17)30147-5.
*Correction, 2/27: An earlier version of this article misstated Dr. Nguyen's affiliation.
In my previous article, “Mental Health Characteristics of Refugee Children,” we learned that in recent decades, refugeeism has become a growing problem that disproportionately affects children. Refugee children and their families experience a variety of traumas, often sustained across years and even decades, because of armed conflict, persecution, social upheavals, or environmental disasters. Refugees are at greater risks for PTSD and affective and psychotic disorders presumably due to increased traumatic life events before, during, and after migration. I used my own experience as a child refugee from Vietnam to elucidate the stressors evident in various phases of forced displacement.1
Risk Factors and Protective Factors
To a certain extent, the experiences of refugees are universal. All refugees experience some sort of humanitarian crisis that forces an emergent escape from their home across international borders to a new resettlement area. It is important to note that internally displaced people do not meet the United Nations’ (UN) official designation of refugee status; however, some agencies use a broader definition where they are designated as such.2,3 We will refer to those not meeting the UN criteria as displaced people, while refugees are those that do meet the UN criteria. Dr. Mina Fazel’s 2012 systematic review in The Lancet of mental health risk factors and protective factors for displaced and refugee children is the most comprehensive of its kind.4 It will be summarized in this section with some relevant personal reflection.
In terms of risk factors, external displacement likely results in additional stress and trauma, presumably from the lack of assess to one’s culture and the host country’s language. Understandably, this makes rebuilding of one’s life more difficult. Several studies show that displaced/refugee children experience more difficulty with psychosocial adaptation than non-displaced children. Violence, directly experienced or indirectly feared, both to the child and their parents, was the strongest predictor of mental health problems and withdrawn behavior. Children who were separated from their parents clearly fared worst in their mental health than those who did not, which is not surprising given the nature of their dependence on caregivers for protection and guidance. During resettlement, experienced or perceived discrimination from the host country was also a risk factor, as well as instability in housing and a drawn-out resettlement process. Female sex was a risk factor mainly for emotional problems. Poor financial support post-migration is associated with depression, but it is unclear whether pre-migration financial status was protective. From my own experience, it is likely not, given that once one becomes a refugee one does not have access to one’s wealth, except that which could be hidden on one’s body. Another risk factor was also if one’s parent had psychiatric problems or was single. Due to the migration, my mother was separated permanently from her husband, which caused her extraordinary isolation and loneliness, something that was palpably felt by myself as I grew up.
In terms of protective factors, family cohesion and cultural continuity appear critical. For myself, not only would I not have survived without my mother and aunt, but they constantly protected me from the harsh realities. My mother would distract me with seemingly trivial goals once we got to America, like finally tasting a hamburger, or talking about school and being reunited with my uncle. This is in line with another finding — that children have better mental health outcomes when their parents do not talk about their hardships. Once my family was resettled with my uncle and his family, they played a critical role in smoothing our transition, not only by providing us with housing, but also cultural knowledge. Cultural havens can restore some of the social position and way of life that refugees lose when they are able to reconnect with a society that recognizes their previous achievements and status. Finally, religion also seemed to be a protective factor.
Mental Health Interventions
In 2018, Dr. Fazel identified mental health interventions for refugee children in a narrative review.5 She acknowledged that these conclusions are limited by the paucity of preventive mental health research in children in general, as well as the mobile nature and complex cultural differences of refugee children. This is exacerbated by the small evidence base. Given that, she makes these recommendations for varying levels of interventions: individual, group, family, living circumstances, social interactions, and school.
On an individual level, effective interventions developed to address PTSD include narrative exposure therapy, trauma-focused cognitive behavior therapy, and eye-movement and desensitization therapy. Group-based interventions for trauma, for example school-based PTSD intervention programs in conflicted areas, have either been shown to not be effective, or only effective for reducing depression. The mental health of unaccompanied children separated from family fare better when placed in foster care, rather than other types of social support. This is further enhanced if the foster family is the same ethnicity.
On a family level, improvements in parenting style and parental mental health, family engagement with local culture and structures, and family-based mental health interventions all positively impact refugee children. Not surprisingly, refugee parents have a greater prevalence of mental health conditions. Several studies on refugeeism point out a greater occurrence of intimate partner violence (that negatively affects children) as well has harsher discipline and maltreatment of refugee children. Thus, mental health treatment for parents also directly improves the well-being of their children. Teaching parenting skills to mitigate the violent effect of their PTSD symptoms, as well as parenting classes that teach gentler styles, have been shown to reduce harsh parenting and mitigate aggressive behaviors in these children. These improvements are enhanced when these classes are taught by other refugees themselves.
School is key for helping refugee children since it is a site where they can access language proficiency, successful acculturation, and medical and mental health services. Several studies have identified the positive effects of better parental engagement with school, resulting in improved academic performance and reduced levels of depressive and PTSD symptoms. A review of learning problems in refugee children identified several factors for success. These include high academic and life ambition, parental involvement in education, accurate educational assessment and grade placement, teacher understanding of linguistic and cultural heritage, culturally appropriate school transition, supportive peer relationships, and successful acculturation. School certainly was key for my acculturation and language proficiency. When I arrived at 6 years old I was selectively mute for my year in first grade, namely because I did not know how to speak English and because I did not share the culture. However, my teacher correctly identified my deficiency and chose to place me in kindergarten, which allowed me the time to gain English proficiency. Though I was always the oldest one in class, that remediation was key in allowing eventual success in school leading up to my admission to UC Berkeley.
Summary
In recent decades, refugeeism has become a growing problem that disproportionately affects children leading to traumas sustained across years and even decades, and greater risks for PTSD, as well as affective and psychotic disorders. Risk factors include the experience of violence, the separation from family, female gender, discrimination in the host country, unstable housing, and a drawn-out resettlement process. Protective factors consist of family cohesion, cultural continuity, support at schools, being protected from the truth of their harsh reality, stable housing, language acquisition, and quick resettlement. From these factors, effective mental interventions have been found to be the promotion of these protective factors as well as support for parental mental health and parenting skills, better parental engagement at school, and schools that correctly identify and address these children’s educational needs.
Dr. Nguyen is a second-year resident at UCSF Fresno Psychiatry Residency. He was a public high school English teacher for 15 years previously.*
References
1. Nguyen D. Mental Health Characteristics of Refugee Children. Pediatric News. 2023 Nov. 14. https://www.mdedge.com/pediatrics/article/266518/mental-health/mental-health-characteristics-refugee-children.
2. Office of the United Nations High Commissioner for Refugees. The Refugee Concept Under International Law. Global Compact for Safe, Orderly and Regular Migration. 2018 March 8. https://www.unhcr.org/sites/default/files/legacy-pdf/5aa290937.pdf.
3. Winer JP. Mental Health Practice with Immigrant and Refugee Youth [Power Point Slides]. Michigan Medicine. 2021 June 24. https://www.youtube.com/watch?v=ICkg4132SQY
4. Fazel M et al. Mental Health of Displaced and Refugee Children Resettled in High-Income Countries: Risk and Protective Factors. Lancet. 2012 Jan 21;379(9812):266-282. doi: 10.1016/S0140-6736(11)60051-2.
5. Fazel M, Betancourt TS. Preventive Mental Health Interventions for Refugee Children and Adolescents in High-Income Settings. Lancet Child Adolesc Health. 2018 Feb;2(2):121-132. doi: 10.1016/S2352-4642(17)30147-5.
*Correction, 2/27: An earlier version of this article misstated Dr. Nguyen's affiliation.
Unleashing Our Immune Response to Quash Cancer
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
This article was originally published on February 10 in Eric Topol’s substack “Ground Truths.”
It’s astounding how devious cancer cells and tumor tissue can be. This week in Science we learned how certain lung cancer cells can function like “Catch Me If You Can” — changing their driver mutation and cell identity to escape targeted therapy. This histologic transformation, as seen in an experimental model, is just one of so many cancer tricks that we are learning about.
Recently, as shown by single-cell sequencing, cancer cells can steal the mitochondria from T cells, a double whammy that turbocharges cancer cells with the hijacked fuel supply and, at the same time, dismantles the immune response.
Last week, we saw how tumor cells can release a virus-like protein that unleashes a vicious autoimmune response.
And then there’s the finding that cancer cell spread predominantly is occurring while we sleep.
As I previously reviewed, the ability for cancer cells to hijack neurons and neural circuits is now well established, no less their ability to reprogram neurons to become adrenergic and stimulate tumor progression, and interfere with the immune response. Stay tuned on that for a new Ground Truths podcast with Prof Michelle Monje, a leader in cancer neuroscience, which will post soon.
Add advancing age’s immunosenescence as yet another challenge to the long and growing list of formidable ways that cancer cells, and the tumor microenvironment, evade our immune response.
An Ever-Expanding Armamentarium
Immune Checkpoint Inhibitors
The field of immunotherapies took off with the immune checkpoint inhibitors, first approved by the FDA in 2011, that take the brakes off of T cells, with the programmed death-1 (PD-1), PD-ligand1, and anti-CTLA-4 monoclonal antibodies.
But we’re clearly learning they are not enough to prevail over cancer with common recurrences, only short term success in most patients, with some notable exceptions. Adding other immune response strategies, such as a vaccine, or antibody-drug conjugates, or engineered T cells, are showing improved chances for success.
Therapeutic Cancer Vaccines
There are many therapeutic cancer vaccines in the works, as reviewed in depth here.
Here’s a list of ongoing clinical trials of cancer vaccines. You’ll note most of these are on top of a checkpoint inhibitor and use personalized neoantigens (cancer cell surface proteins) derived from sequencing (whole-exome or whole genome, RNA-sequencing and HLA-profiling) the patient’s tumor.
An example of positive findings is with the combination of an mRNA-nanoparticle vaccine with up to 34 personalized neoantigens and pembrolizumab (Keytruda) vs pembrolizumab alone in advanced melanoma after resection, with improved outcomes at 3-year follow-up, cutting death or relapse rate in half.
Antibody-Drug Conjugates (ADC)
There is considerable excitement about antibody-drug conjugates (ADC) whereby a linker is used to attach a chemotherapy agent to the checkpoint inhibitor antibody, specifically targeting the cancer cell and facilitating entry of the chemotherapy into the cell. Akin to these are bispecific antibodies (BiTEs, binding to a tumor antigen and T cell receptor simultaneously), both of these conjugates acting as “biologic” or “guided” missiles.
A very good example of the potency of an ADC was seen in a “HER2-low” breast cancer randomized trial. The absence or very low expression or amplification of the HER2 receptor is common in breast cancer and successful treatment has been elusive. A randomized trial of an ADC (trastuzumab deruxtecan) compared to physician’s choice therapy demonstrated a marked success for progression-free survival in HER2-low patients, which was characterized as “unheard-of success” by media coverage.
This strategy is being used to target some of the most difficult cancer driver mutations such as TP53 and KRAS.
Oncolytic Viruses
Modifying viruses to infect the tumor and make it more visible to the immune system, potentiating anti-tumor responses, known as oncolytic viruses, have been proposed as a way to rev up the immune response for a long time but without positive Phase 3 clinical trials.
After decades of failure, a recent trial in refractory bladder cancer showed marked success, along with others, summarized here, now providing very encouraging results. It looks like oncolytic viruses are on a comeback path.
Engineering T Cells (Chimeric Antigen Receptor [CAR-T])
As I recently reviewed, there are over 500 ongoing clinical trials to build on the success of the first CAR-T approval for leukemia 7 years ago. I won’t go through that all again here, but to reiterate most of the success to date has been in “liquid” blood (leukemia and lymphoma) cancer tumors. This week in Nature is the discovery of a T cell cancer mutation, a gene fusion CARD11-PIK3R3, from a T cell lymphoma that can potentially be used to augment CAR-T efficacy. It has pronounced and prolonged effects in the experimental model. Instead of 1 million cells needed for treatment, even 20,000 were enough to melt the tumor. This is a noteworthy discovery since CAR-T work to date has largely not exploited such naturally occurring mutations, while instead concentrating on those seen in the patient’s set of key tumor mutations.
As currently conceived, CAR-T, and what is being referred to more broadly as adoptive cell therapies, involves removing T cells from the patient’s body and engineering their activation, then reintroducing them back to the patient. This is laborious, technically difficult, and very expensive. Recently, the idea of achieving all of this via an injection of virus that specifically infects T cells and inserts the genes needed, was advanced by two biotech companies with preclinical results, one in non-human primates.
Gearing up to meet the challenge of solid tumor CAR-T intervention, there’s more work using CRISPR genome editing of T cell receptors. A.I. is increasingly being exploited to process the data from sequencing and identify optimal neoantigens.
Instead of just CAR-T, we’re seeing the emergence of CAR-macrophage and CAR-natural killer (NK) cells strategies, and rapidly expanding potential combinations of all the strategies I’ve mentioned. No less, there’s been maturation of on-off suicide switches programmed in, to limit cytokine release and promote safety of these interventions. Overall, major side effects of immunotherapies are not only cytokine release syndromes, but also include interstitial pneumonitis and neurotoxicity.
Summary
Given the multitude of ways cancer cells and tumor tissue can evade our immune response, durably successful treatment remains a daunting challenge. But the ingenuity of so many different approaches to unleash our immune response, and their combinations, provides considerable hope that we’ll increasingly meet the challenge in the years ahead. We have clearly learned that combining different immunotherapy strategies will be essential for many patients with the most resilient solid tumors.
Of concern, as noted by a recent editorial in The Lancet, entitled “Cancer Research Equity: Innovations For The Many, Not The Few,” is that these individualized, sophisticated strategies are not scalable; they will have limited reach and benefit. The movement towards “off the shelf” CAR-T and inexpensive, orally active checkpoint inhibitors may help mitigate this issue.
Notwithstanding this important concern, we’re seeing an array of diverse and potent immunotherapy strategies that are providing highly encouraging results, engendering more excitement than we’ve seen in this space for some time. These should propel substantial improvements in outcomes for patients in the years ahead. It can’t happen soon enough.
Thanks for reading this edition of Ground Truths. If you found it informative, please share it with your colleagues.
Dr. Topol has disclosed the following relevant financial relationships: Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for Dexcom; Illumina; Molecular Stethoscope; Quest Diagnostics; Blue Cross Blue Shield Association. Received research grant from National Institutes of Health.
A version of this article appeared on Medscape.com.
Most Sudden Infant Deaths Occur in Shared Sleep Space
, according to new data published online in Pediatrics.
SUID occur in infants less than 1 year old. The deaths happen without an obvious cause before investigation and account for 3,400 deaths per year in the United States.
Alexa B. Erck Lambert, MPH, Maternal and Infant Health Branch of the Centers for Disease Control and Prevention (CDC), led the study that examined 7,595 such deaths in 23 US jurisdictions from 2011 to 2020, using data from the CDC’s SUID Case Registry.
The researchers reported that the prevalence of surface sharing ranges from 34% to 64% among living infants and about 50% among SUID.
Common Factors
They found common factors when infants share sleep space compared with infants who did not. Those who shared space, for example, were often 0-3 months old; publicly insured; non-Hispanic Black; found in an adult bed, couch, or chair; exposed to maternal cigarette smoking prenatally; and supervised by a parent when they died or had a supervisor who was impaired by drugs or alcohol at the time of death.
Having a supervisor who was impaired by drugs or alcohol was much more common among sharing (16.3%) than nonsharing infants (4.7%).
The American Academy of Pediatrics (AAP) guidance says a safe sleep environment for infants includes a place to sleep on a nonshared sleep surface (in a crib or bassinet) without soft bedding, and lying on the back facing up.
Most Who Died had Multiple Unsafe Sleep Factors
At least 76% of all SUID had multiple unsafe sleep factors present, regardless of whether the infants shared sleep space. Unsafe sleep factors include an inclined or soft sleep surface, sleeping on the side or stomach, sleeping with soft or loose bedding or objects, not breastfeeding, prenatal or environmental exposure to cigarette smoke, and overheating.
Sharing sleep space combined with parents’ smoking and maternal alcohol or drug use greatly increases risk of sudden infant death, the authors noted.
Sharing More Common With Multiples
Among SUID, surface sharing was more common among multiples than singletons and more common in an adult bed than in the same crib. The authors noted that parents often cite financial reasons for such arrangements.
However, AAP recommends multiples sleep on separate surfaces. The authors say pediatricians and other healthcare providers should be aware of free crib distribution programs. A study by Hauck et al. found “crib distribution and safe sleep education positively influence knowledge and practices about safe sleep.”
Robin Haynes, PhD, who studies causes underlying the pathology of SIDS at Boston Children’s Hospital, pointed to the Cribs for Kids website as a place for parents and clinicians to start for help with providing separate sleeping surfaces.
Dr. Haynes said the large number of infants included is a strength of the study. The findings help confirm the risk of sharing a sleep surface, she said, but the details on characteristics of sleep-sharing environments provide “novel insight into this problem,” she said.
“For basic researchers,” Dr. Haynes said, “it reiterates that most cases of sudden and unexpected infant deaths are exposed to multiple risk factors. It also highlights the role that young infant age and maternal smoking have as risk factors that contribute to biological vulnerabilities in infants.”
The results also give clinicians more information on characteristics of bedsharing families and some of the factors related to bedsharing, including socioeconomic and behavioral factors, she said. She highlighted the higher risk of SUID when drug or alcohol impairment is involved while bedsharing.
“All of this information is really important and helps clinicians shape the safe sleep messages to families,” she said.
The study authors and Dr. Haynes report no relevant financial relationships.
, according to new data published online in Pediatrics.
SUID occur in infants less than 1 year old. The deaths happen without an obvious cause before investigation and account for 3,400 deaths per year in the United States.
Alexa B. Erck Lambert, MPH, Maternal and Infant Health Branch of the Centers for Disease Control and Prevention (CDC), led the study that examined 7,595 such deaths in 23 US jurisdictions from 2011 to 2020, using data from the CDC’s SUID Case Registry.
The researchers reported that the prevalence of surface sharing ranges from 34% to 64% among living infants and about 50% among SUID.
Common Factors
They found common factors when infants share sleep space compared with infants who did not. Those who shared space, for example, were often 0-3 months old; publicly insured; non-Hispanic Black; found in an adult bed, couch, or chair; exposed to maternal cigarette smoking prenatally; and supervised by a parent when they died or had a supervisor who was impaired by drugs or alcohol at the time of death.
Having a supervisor who was impaired by drugs or alcohol was much more common among sharing (16.3%) than nonsharing infants (4.7%).
The American Academy of Pediatrics (AAP) guidance says a safe sleep environment for infants includes a place to sleep on a nonshared sleep surface (in a crib or bassinet) without soft bedding, and lying on the back facing up.
Most Who Died had Multiple Unsafe Sleep Factors
At least 76% of all SUID had multiple unsafe sleep factors present, regardless of whether the infants shared sleep space. Unsafe sleep factors include an inclined or soft sleep surface, sleeping on the side or stomach, sleeping with soft or loose bedding or objects, not breastfeeding, prenatal or environmental exposure to cigarette smoke, and overheating.
Sharing sleep space combined with parents’ smoking and maternal alcohol or drug use greatly increases risk of sudden infant death, the authors noted.
Sharing More Common With Multiples
Among SUID, surface sharing was more common among multiples than singletons and more common in an adult bed than in the same crib. The authors noted that parents often cite financial reasons for such arrangements.
However, AAP recommends multiples sleep on separate surfaces. The authors say pediatricians and other healthcare providers should be aware of free crib distribution programs. A study by Hauck et al. found “crib distribution and safe sleep education positively influence knowledge and practices about safe sleep.”
Robin Haynes, PhD, who studies causes underlying the pathology of SIDS at Boston Children’s Hospital, pointed to the Cribs for Kids website as a place for parents and clinicians to start for help with providing separate sleeping surfaces.
Dr. Haynes said the large number of infants included is a strength of the study. The findings help confirm the risk of sharing a sleep surface, she said, but the details on characteristics of sleep-sharing environments provide “novel insight into this problem,” she said.
“For basic researchers,” Dr. Haynes said, “it reiterates that most cases of sudden and unexpected infant deaths are exposed to multiple risk factors. It also highlights the role that young infant age and maternal smoking have as risk factors that contribute to biological vulnerabilities in infants.”
The results also give clinicians more information on characteristics of bedsharing families and some of the factors related to bedsharing, including socioeconomic and behavioral factors, she said. She highlighted the higher risk of SUID when drug or alcohol impairment is involved while bedsharing.
“All of this information is really important and helps clinicians shape the safe sleep messages to families,” she said.
The study authors and Dr. Haynes report no relevant financial relationships.
, according to new data published online in Pediatrics.
SUID occur in infants less than 1 year old. The deaths happen without an obvious cause before investigation and account for 3,400 deaths per year in the United States.
Alexa B. Erck Lambert, MPH, Maternal and Infant Health Branch of the Centers for Disease Control and Prevention (CDC), led the study that examined 7,595 such deaths in 23 US jurisdictions from 2011 to 2020, using data from the CDC’s SUID Case Registry.
The researchers reported that the prevalence of surface sharing ranges from 34% to 64% among living infants and about 50% among SUID.
Common Factors
They found common factors when infants share sleep space compared with infants who did not. Those who shared space, for example, were often 0-3 months old; publicly insured; non-Hispanic Black; found in an adult bed, couch, or chair; exposed to maternal cigarette smoking prenatally; and supervised by a parent when they died or had a supervisor who was impaired by drugs or alcohol at the time of death.
Having a supervisor who was impaired by drugs or alcohol was much more common among sharing (16.3%) than nonsharing infants (4.7%).
The American Academy of Pediatrics (AAP) guidance says a safe sleep environment for infants includes a place to sleep on a nonshared sleep surface (in a crib or bassinet) without soft bedding, and lying on the back facing up.
Most Who Died had Multiple Unsafe Sleep Factors
At least 76% of all SUID had multiple unsafe sleep factors present, regardless of whether the infants shared sleep space. Unsafe sleep factors include an inclined or soft sleep surface, sleeping on the side or stomach, sleeping with soft or loose bedding or objects, not breastfeeding, prenatal or environmental exposure to cigarette smoke, and overheating.
Sharing sleep space combined with parents’ smoking and maternal alcohol or drug use greatly increases risk of sudden infant death, the authors noted.
Sharing More Common With Multiples
Among SUID, surface sharing was more common among multiples than singletons and more common in an adult bed than in the same crib. The authors noted that parents often cite financial reasons for such arrangements.
However, AAP recommends multiples sleep on separate surfaces. The authors say pediatricians and other healthcare providers should be aware of free crib distribution programs. A study by Hauck et al. found “crib distribution and safe sleep education positively influence knowledge and practices about safe sleep.”
Robin Haynes, PhD, who studies causes underlying the pathology of SIDS at Boston Children’s Hospital, pointed to the Cribs for Kids website as a place for parents and clinicians to start for help with providing separate sleeping surfaces.
Dr. Haynes said the large number of infants included is a strength of the study. The findings help confirm the risk of sharing a sleep surface, she said, but the details on characteristics of sleep-sharing environments provide “novel insight into this problem,” she said.
“For basic researchers,” Dr. Haynes said, “it reiterates that most cases of sudden and unexpected infant deaths are exposed to multiple risk factors. It also highlights the role that young infant age and maternal smoking have as risk factors that contribute to biological vulnerabilities in infants.”
The results also give clinicians more information on characteristics of bedsharing families and some of the factors related to bedsharing, including socioeconomic and behavioral factors, she said. She highlighted the higher risk of SUID when drug or alcohol impairment is involved while bedsharing.
“All of this information is really important and helps clinicians shape the safe sleep messages to families,” she said.
The study authors and Dr. Haynes report no relevant financial relationships.
FROM PEDIATRICS
What Skin Manifestations Are Associated With Pediatric IBD?
TOPLINE:
Skin conditions burden many children with inflammatory bowel disease (IBD), according to the authors of a single-center study.
METHODOLOGY:
- Researchers retrospectively reviewed the medical charts of 425 children and adolescents with (CD) or ulcerative (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
- Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
- They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.
- Researchers retrospectively reviewed the medical charts of 425 children and adolescents with Crohn’s disease (CD) or ulcerative colitis (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
- Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
- They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.
TAKEAWAY:
- The most common noninfectious dermatologic condition among the 425 children and adolescents was (30.8%), followed by eczema (15.8%) and perianal skin tags (14.6%).
- Angular cheilitis was more common among those with CD than those with UC (7.2% vs 2%, respectively; P = .024) as was keratosis pilaris (6.9% vs 0.7%; P = .003), and perianal skin complications such as skin tags (20.3% vs 4%), fistulas (13.4% vs 2.7%), and abscesses (13.4% vs 2%; P < .001 for all associations).
- Fungal skin infections were more frequently diagnosed in children with UC than those with CD (15.4% vs 8%; P = .017).
- The researchers observed that the severity of IBD correlated with a higher prevalence of perianal fistula (P = .003), perianal region abscess (P = .041), psoriasis (P < .001), and pyoderma gangrenosum (P = .003).
IN PRACTICE:
“Early identification of common dermatologic conditions in children and adolescents with IBD and recognizing their characteristic associations may alter management and improve skin-related outcomes in this patient population,” the authors wrote.
SOURCE:
Corresponding author Megha M. Tollefson, MD, of the Department of Dermatology at Mayo Clinic, Rochester, Minnesota, and colleagues conducted the research, which was published in Pediatric Dermatology.
LIMITATIONS:
The single-center design and the fact that database studies are subject to extraction error. There was no age- and sex-matched cohort to determine whether the prevalence of cutaneous infections, acne, eczema, and other inflammatory disorders was truly increased in IBD.
DISCLOSURES:
The researchers reported having no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
Skin conditions burden many children with inflammatory bowel disease (IBD), according to the authors of a single-center study.
METHODOLOGY:
- Researchers retrospectively reviewed the medical charts of 425 children and adolescents with (CD) or ulcerative (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
- Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
- They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.
- Researchers retrospectively reviewed the medical charts of 425 children and adolescents with Crohn’s disease (CD) or ulcerative colitis (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
- Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
- They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.
TAKEAWAY:
- The most common noninfectious dermatologic condition among the 425 children and adolescents was (30.8%), followed by eczema (15.8%) and perianal skin tags (14.6%).
- Angular cheilitis was more common among those with CD than those with UC (7.2% vs 2%, respectively; P = .024) as was keratosis pilaris (6.9% vs 0.7%; P = .003), and perianal skin complications such as skin tags (20.3% vs 4%), fistulas (13.4% vs 2.7%), and abscesses (13.4% vs 2%; P < .001 for all associations).
- Fungal skin infections were more frequently diagnosed in children with UC than those with CD (15.4% vs 8%; P = .017).
- The researchers observed that the severity of IBD correlated with a higher prevalence of perianal fistula (P = .003), perianal region abscess (P = .041), psoriasis (P < .001), and pyoderma gangrenosum (P = .003).
IN PRACTICE:
“Early identification of common dermatologic conditions in children and adolescents with IBD and recognizing their characteristic associations may alter management and improve skin-related outcomes in this patient population,” the authors wrote.
SOURCE:
Corresponding author Megha M. Tollefson, MD, of the Department of Dermatology at Mayo Clinic, Rochester, Minnesota, and colleagues conducted the research, which was published in Pediatric Dermatology.
LIMITATIONS:
The single-center design and the fact that database studies are subject to extraction error. There was no age- and sex-matched cohort to determine whether the prevalence of cutaneous infections, acne, eczema, and other inflammatory disorders was truly increased in IBD.
DISCLOSURES:
The researchers reported having no disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
Skin conditions burden many children with inflammatory bowel disease (IBD), according to the authors of a single-center study.
METHODOLOGY:
- Researchers retrospectively reviewed the medical charts of 425 children and adolescents with (CD) or ulcerative (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
- Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
- They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.
- Researchers retrospectively reviewed the medical charts of 425 children and adolescents with Crohn’s disease (CD) or ulcerative colitis (UC) at one or more dermatologic diagnoses who were seen at Mayo Clinic, Rochester, Minnesota, between 1999 and 2017.
- Of the children studied, 53% were male, 64.9% had CD, and 42.8% had one or more cutaneous infections.
- They used the chi-square/Fischer’s exact test to compare categorical outcomes between patients with CD and UC and to detect differences in IBD/CD/UC disease severity and skin conditions.
TAKEAWAY:
- The most common noninfectious dermatologic condition among the 425 children and adolescents was (30.8%), followed by eczema (15.8%) and perianal skin tags (14.6%).
- Angular cheilitis was more common among those with CD than those with UC (7.2% vs 2%, respectively; P = .024) as was keratosis pilaris (6.9% vs 0.7%; P = .003), and perianal skin complications such as skin tags (20.3% vs 4%), fistulas (13.4% vs 2.7%), and abscesses (13.4% vs 2%; P < .001 for all associations).
- Fungal skin infections were more frequently diagnosed in children with UC than those with CD (15.4% vs 8%; P = .017).
- The researchers observed that the severity of IBD correlated with a higher prevalence of perianal fistula (P = .003), perianal region abscess (P = .041), psoriasis (P < .001), and pyoderma gangrenosum (P = .003).
IN PRACTICE:
“Early identification of common dermatologic conditions in children and adolescents with IBD and recognizing their characteristic associations may alter management and improve skin-related outcomes in this patient population,” the authors wrote.
SOURCE:
Corresponding author Megha M. Tollefson, MD, of the Department of Dermatology at Mayo Clinic, Rochester, Minnesota, and colleagues conducted the research, which was published in Pediatric Dermatology.
LIMITATIONS:
The single-center design and the fact that database studies are subject to extraction error. There was no age- and sex-matched cohort to determine whether the prevalence of cutaneous infections, acne, eczema, and other inflammatory disorders was truly increased in IBD.
DISCLOSURES:
The researchers reported having no disclosures.
A version of this article appeared on Medscape.com.
Company Announces Regulatory Filing for Nemolizumab for Two Indications
On February 14, 2024, Galderma announced that .
A first-in-class investigational monoclonal antibody specifically designed to inhibit interleukin (IL) IL-31 signaling, nemolizumab has also been granted FDA Priority Review for prurigo nodularis, according to a press release from the company. The European Medicines Agency has also accepted Galderma’s Marketing Authorization Applications for nemolizumab for both prurigo nodularis and atopic dermatitis.
The regulatory developments follow data from the phase III OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in patients with prurigo nodularis (NCT04501679 and NCT04501666). According to the press release, in OLYMPIA 1 and 2, 58% and 56% of patients, respectively, achieved at least a least four-point reduction in itch intensity as measured by the peak-pruritus numerical rating scale (PP-NRS), compared with 17% and 21% in the placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the investigator’s global assessment (IGA) score, compared with 7% and 11% in the placebo groups (P < .0001).
On February 14, 2024, Galderma announced that .
A first-in-class investigational monoclonal antibody specifically designed to inhibit interleukin (IL) IL-31 signaling, nemolizumab has also been granted FDA Priority Review for prurigo nodularis, according to a press release from the company. The European Medicines Agency has also accepted Galderma’s Marketing Authorization Applications for nemolizumab for both prurigo nodularis and atopic dermatitis.
The regulatory developments follow data from the phase III OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in patients with prurigo nodularis (NCT04501679 and NCT04501666). According to the press release, in OLYMPIA 1 and 2, 58% and 56% of patients, respectively, achieved at least a least four-point reduction in itch intensity as measured by the peak-pruritus numerical rating scale (PP-NRS), compared with 17% and 21% in the placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the investigator’s global assessment (IGA) score, compared with 7% and 11% in the placebo groups (P < .0001).
On February 14, 2024, Galderma announced that .
A first-in-class investigational monoclonal antibody specifically designed to inhibit interleukin (IL) IL-31 signaling, nemolizumab has also been granted FDA Priority Review for prurigo nodularis, according to a press release from the company. The European Medicines Agency has also accepted Galderma’s Marketing Authorization Applications for nemolizumab for both prurigo nodularis and atopic dermatitis.
The regulatory developments follow data from the phase III OLYMPIA clinical trial program, which evaluated the efficacy and safety of nemolizumab administered subcutaneously every 4 weeks in patients with prurigo nodularis (NCT04501679 and NCT04501666). According to the press release, in OLYMPIA 1 and 2, 58% and 56% of patients, respectively, achieved at least a least four-point reduction in itch intensity as measured by the peak-pruritus numerical rating scale (PP-NRS), compared with 17% and 21% in the placebo groups (P < .0001). At the same time, 26% and 38% of nemolizumab-treated patients reached clearance or almost-clearance of skin lesions on the investigator’s global assessment (IGA) score, compared with 7% and 11% in the placebo groups (P < .0001).
An 8-Year-Old Male With Asymptomatic Brown Rough Plaques on the Dorsum of the Right Hand and Fingers, Accompanied by Widening of the Knuckles
During examination, the patient was observed repetitively cracking his knuckles, making a fist with the right hand, placing the left hand on top, and rubbing the hand, a behavior he routinely did multiple times daily. The observed pattern of finger involvement on the dorsum of the right hand corresponded to areas subjected to significant pressure during the described activity. Consequently, a diagnosis of lichen simplex chronicus (LSC) secondary to mechanical rubbing, along with associated pachydermodactyly on the fingers of the right hand, was established.
Lichen simplex chronicus and pachydermodactyly are both attributed to microtrauma inflicted upon the skin. Lichen simplex chronicus often constitutes a diagnosis of exclusion and is characterized by repetitive trauma-induced keratinocyte proliferation and melanocyte activation, resulting in hyperpigmentation and skin thickening. Although typically observed in women between the fourth and fifth decades of life, LSC is rarely reported in children. In adults, LSC-related rubbing or scratching frequently arises from chronic pruritic dermatitis such as eczema or psoriasis, neurodermatitis from dysesthesia, or habitual movements, as exhibited by this young patient. While generally benign, LSC may become infected. In rare instances, malignant transformation may occur.
The association with pachydermodactyly implicates microtrauma, necessitating careful observation and questioning to elucidate the cause, as demonstrated in this case. Lesions are typically hyperpigmented, though cases of associated hypopigmentation or depigmentation have been documented. Affected areas typically fall within the patient’s hand and finger reach, with lesion improvement over several months achievable through trigger avoidance.
Pachydermodactyly, a rare but benign fibromatosis around the proximal interphalangeal joints, is often misdiagnosed as juvenile idiopathic arthritis, potentially leading to unnecessary treatments and patient anxiety. Microtrauma history due to digit manipulation is prevalent among affected individuals, with most also exhibiting neuropsychiatric disorders. Histological examination of pachydermodactyly reveals hypergranulosis and dermal thickening, accompanied by increased fibroblasts and collagen types I, III, and V, differing from the epidermal changes seen in LSC.
The differential diagnosis also included phytophotodermatitis, a phototoxic dermatologic reaction following exposure to ultraviolet light subsequent to contact with furocoumarin-containing plant chemicals. However, the persistence of the patient’s lesions for over a year precluded this diagnosis. Secondary hyperpigmentation was also contemplated but excluded due to the absence of preceding inflammatory dermatitis.
Treatment of LSC primarily involves identifying and addressing any underlying conditions, repairing the skin barrier, reducing inflammation, and modifying behaviors contributing to chronic microtrauma, as observed in this patient. Topical corticosteroids may aid in decreasing epidermal thickening and discoloration, though lesion resolution necessitates behavior cessation.
It’s important to identify these types of skin changes in children to avoid unnecessary medical treatments for these benign conditions.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
Suggested Reading
Seier JA, Dissemond J. Lichen Simplex Chronicus Due to Mechanical Irritation. Dtsch Arztebl Int. 2022 Nov 18;119(46):802. doi: 10.3238/arztebl.m2022.0213.
Small S et al. A 12-Year-Old Boy Presenting With Unilateral Proximal Interphalangeal Joint Swelling. BMJ Case Rep. 2011 Apr 13:2011:bcr0120113719. doi: 10.1136/bcr.01.2011.3719.
Voicu C et al Lichen Simplex Chronicus as an Essential Part of the Dermatologic Masquerade. Open Access Maced J Med Sci. 2017 Jul 24;5(4):556-557. doi: 10.3889/oamjms.2017.133.
During examination, the patient was observed repetitively cracking his knuckles, making a fist with the right hand, placing the left hand on top, and rubbing the hand, a behavior he routinely did multiple times daily. The observed pattern of finger involvement on the dorsum of the right hand corresponded to areas subjected to significant pressure during the described activity. Consequently, a diagnosis of lichen simplex chronicus (LSC) secondary to mechanical rubbing, along with associated pachydermodactyly on the fingers of the right hand, was established.
Lichen simplex chronicus and pachydermodactyly are both attributed to microtrauma inflicted upon the skin. Lichen simplex chronicus often constitutes a diagnosis of exclusion and is characterized by repetitive trauma-induced keratinocyte proliferation and melanocyte activation, resulting in hyperpigmentation and skin thickening. Although typically observed in women between the fourth and fifth decades of life, LSC is rarely reported in children. In adults, LSC-related rubbing or scratching frequently arises from chronic pruritic dermatitis such as eczema or psoriasis, neurodermatitis from dysesthesia, or habitual movements, as exhibited by this young patient. While generally benign, LSC may become infected. In rare instances, malignant transformation may occur.
The association with pachydermodactyly implicates microtrauma, necessitating careful observation and questioning to elucidate the cause, as demonstrated in this case. Lesions are typically hyperpigmented, though cases of associated hypopigmentation or depigmentation have been documented. Affected areas typically fall within the patient’s hand and finger reach, with lesion improvement over several months achievable through trigger avoidance.
Pachydermodactyly, a rare but benign fibromatosis around the proximal interphalangeal joints, is often misdiagnosed as juvenile idiopathic arthritis, potentially leading to unnecessary treatments and patient anxiety. Microtrauma history due to digit manipulation is prevalent among affected individuals, with most also exhibiting neuropsychiatric disorders. Histological examination of pachydermodactyly reveals hypergranulosis and dermal thickening, accompanied by increased fibroblasts and collagen types I, III, and V, differing from the epidermal changes seen in LSC.
The differential diagnosis also included phytophotodermatitis, a phototoxic dermatologic reaction following exposure to ultraviolet light subsequent to contact with furocoumarin-containing plant chemicals. However, the persistence of the patient’s lesions for over a year precluded this diagnosis. Secondary hyperpigmentation was also contemplated but excluded due to the absence of preceding inflammatory dermatitis.
Treatment of LSC primarily involves identifying and addressing any underlying conditions, repairing the skin barrier, reducing inflammation, and modifying behaviors contributing to chronic microtrauma, as observed in this patient. Topical corticosteroids may aid in decreasing epidermal thickening and discoloration, though lesion resolution necessitates behavior cessation.
It’s important to identify these types of skin changes in children to avoid unnecessary medical treatments for these benign conditions.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
Suggested Reading
Seier JA, Dissemond J. Lichen Simplex Chronicus Due to Mechanical Irritation. Dtsch Arztebl Int. 2022 Nov 18;119(46):802. doi: 10.3238/arztebl.m2022.0213.
Small S et al. A 12-Year-Old Boy Presenting With Unilateral Proximal Interphalangeal Joint Swelling. BMJ Case Rep. 2011 Apr 13:2011:bcr0120113719. doi: 10.1136/bcr.01.2011.3719.
Voicu C et al Lichen Simplex Chronicus as an Essential Part of the Dermatologic Masquerade. Open Access Maced J Med Sci. 2017 Jul 24;5(4):556-557. doi: 10.3889/oamjms.2017.133.
During examination, the patient was observed repetitively cracking his knuckles, making a fist with the right hand, placing the left hand on top, and rubbing the hand, a behavior he routinely did multiple times daily. The observed pattern of finger involvement on the dorsum of the right hand corresponded to areas subjected to significant pressure during the described activity. Consequently, a diagnosis of lichen simplex chronicus (LSC) secondary to mechanical rubbing, along with associated pachydermodactyly on the fingers of the right hand, was established.
Lichen simplex chronicus and pachydermodactyly are both attributed to microtrauma inflicted upon the skin. Lichen simplex chronicus often constitutes a diagnosis of exclusion and is characterized by repetitive trauma-induced keratinocyte proliferation and melanocyte activation, resulting in hyperpigmentation and skin thickening. Although typically observed in women between the fourth and fifth decades of life, LSC is rarely reported in children. In adults, LSC-related rubbing or scratching frequently arises from chronic pruritic dermatitis such as eczema or psoriasis, neurodermatitis from dysesthesia, or habitual movements, as exhibited by this young patient. While generally benign, LSC may become infected. In rare instances, malignant transformation may occur.
The association with pachydermodactyly implicates microtrauma, necessitating careful observation and questioning to elucidate the cause, as demonstrated in this case. Lesions are typically hyperpigmented, though cases of associated hypopigmentation or depigmentation have been documented. Affected areas typically fall within the patient’s hand and finger reach, with lesion improvement over several months achievable through trigger avoidance.
Pachydermodactyly, a rare but benign fibromatosis around the proximal interphalangeal joints, is often misdiagnosed as juvenile idiopathic arthritis, potentially leading to unnecessary treatments and patient anxiety. Microtrauma history due to digit manipulation is prevalent among affected individuals, with most also exhibiting neuropsychiatric disorders. Histological examination of pachydermodactyly reveals hypergranulosis and dermal thickening, accompanied by increased fibroblasts and collagen types I, III, and V, differing from the epidermal changes seen in LSC.
The differential diagnosis also included phytophotodermatitis, a phototoxic dermatologic reaction following exposure to ultraviolet light subsequent to contact with furocoumarin-containing plant chemicals. However, the persistence of the patient’s lesions for over a year precluded this diagnosis. Secondary hyperpigmentation was also contemplated but excluded due to the absence of preceding inflammatory dermatitis.
Treatment of LSC primarily involves identifying and addressing any underlying conditions, repairing the skin barrier, reducing inflammation, and modifying behaviors contributing to chronic microtrauma, as observed in this patient. Topical corticosteroids may aid in decreasing epidermal thickening and discoloration, though lesion resolution necessitates behavior cessation.
It’s important to identify these types of skin changes in children to avoid unnecessary medical treatments for these benign conditions.
Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego.
Suggested Reading
Seier JA, Dissemond J. Lichen Simplex Chronicus Due to Mechanical Irritation. Dtsch Arztebl Int. 2022 Nov 18;119(46):802. doi: 10.3238/arztebl.m2022.0213.
Small S et al. A 12-Year-Old Boy Presenting With Unilateral Proximal Interphalangeal Joint Swelling. BMJ Case Rep. 2011 Apr 13:2011:bcr0120113719. doi: 10.1136/bcr.01.2011.3719.
Voicu C et al Lichen Simplex Chronicus as an Essential Part of the Dermatologic Masquerade. Open Access Maced J Med Sci. 2017 Jul 24;5(4):556-557. doi: 10.3889/oamjms.2017.133.
The patient was otherwise healthy, with no current medication intake, and he engaged in baseball and soccer activities. Upon physical examination, a hyperpigmented lichenified irregular plaque was observed on the dorsum of the right hand, along with irregular hyperpigmented macules and plaques on the fingers. Fusiform widening of the interphalangeal joints on the second, third, and fourth fingers of the right hand was noted, without associated pain, edema, or erythema.
Obesity’s Effect on Neonatal Outcomes Is Dose Dependent
TOPLINE:
Higher body mass index (BMI) at the start of pregnancy is associated with increased risk for adverse maternal outcomes, including preeclampsia, and neonatal complications, such as respiratory distress syndrome (RDS), in a dose-dependent manner, new research shows.
METHODOLOGY:
- Researchers conducted a retrospective study of 58,497 singleton pregnancies delivered at an urban hospital between 2013 and 2021.
- They focused on pregnancies delivered between 24 and 42 weeks of gestation, for which information about BMI at the first prenatal visit was available.
- 21.1% of mothers had class I , 9.3% had class II obesity, and 6% had class III obesity.
TAKEAWAY:
- Obesity was associated with a dose-dependent increase in cesarean deliveries (27% of deliveries without obesity vs 46% of deliveries with class III obesity).
- Severe preeclampsia occurred in 8% of mothers without obesity and in 19% of mothers with class III obesity.
- Infants born to mothers with class III obesity were more likely than were infants born to mothers without obesity to have RDS, with a relative risk (RR) of 2.66.
- With class II obesity, the RR was 1.77. With class I obesity, the RR was 1.3.
- Obesity also was associated with increased risk for grade III-IV (RR), 4.58 for class III obesity) and (RR, 3.76).
IN PRACTICE:
“Infants born to patients with higher classes of obesity have significant associated morbidity including a 2 to 4 times increased risk of neonatal acidosis, grades III-IV intraventricular hemorrhage, sepsis, and RDS,” the researchers reported.
SOURCE:
Sara I. Jones, MD, with University of Texas Southwestern Medical Center in Dallas, presented the study on February 14 at the 2024 Pregnancy Meeting of the Society for Maternal-Fetal Medicine, in National Harbor, Maryland.
DISCLOSURES:
The researchers had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
TOPLINE:
Higher body mass index (BMI) at the start of pregnancy is associated with increased risk for adverse maternal outcomes, including preeclampsia, and neonatal complications, such as respiratory distress syndrome (RDS), in a dose-dependent manner, new research shows.
METHODOLOGY:
- Researchers conducted a retrospective study of 58,497 singleton pregnancies delivered at an urban hospital between 2013 and 2021.
- They focused on pregnancies delivered between 24 and 42 weeks of gestation, for which information about BMI at the first prenatal visit was available.
- 21.1% of mothers had class I , 9.3% had class II obesity, and 6% had class III obesity.
TAKEAWAY:
- Obesity was associated with a dose-dependent increase in cesarean deliveries (27% of deliveries without obesity vs 46% of deliveries with class III obesity).
- Severe preeclampsia occurred in 8% of mothers without obesity and in 19% of mothers with class III obesity.
- Infants born to mothers with class III obesity were more likely than were infants born to mothers without obesity to have RDS, with a relative risk (RR) of 2.66.
- With class II obesity, the RR was 1.77. With class I obesity, the RR was 1.3.
- Obesity also was associated with increased risk for grade III-IV (RR), 4.58 for class III obesity) and (RR, 3.76).
IN PRACTICE:
“Infants born to patients with higher classes of obesity have significant associated morbidity including a 2 to 4 times increased risk of neonatal acidosis, grades III-IV intraventricular hemorrhage, sepsis, and RDS,” the researchers reported.
SOURCE:
Sara I. Jones, MD, with University of Texas Southwestern Medical Center in Dallas, presented the study on February 14 at the 2024 Pregnancy Meeting of the Society for Maternal-Fetal Medicine, in National Harbor, Maryland.
DISCLOSURES:
The researchers had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com.
TOPLINE:
Higher body mass index (BMI) at the start of pregnancy is associated with increased risk for adverse maternal outcomes, including preeclampsia, and neonatal complications, such as respiratory distress syndrome (RDS), in a dose-dependent manner, new research shows.
METHODOLOGY:
- Researchers conducted a retrospective study of 58,497 singleton pregnancies delivered at an urban hospital between 2013 and 2021.
- They focused on pregnancies delivered between 24 and 42 weeks of gestation, for which information about BMI at the first prenatal visit was available.
- 21.1% of mothers had class I , 9.3% had class II obesity, and 6% had class III obesity.
TAKEAWAY:
- Obesity was associated with a dose-dependent increase in cesarean deliveries (27% of deliveries without obesity vs 46% of deliveries with class III obesity).
- Severe preeclampsia occurred in 8% of mothers without obesity and in 19% of mothers with class III obesity.
- Infants born to mothers with class III obesity were more likely than were infants born to mothers without obesity to have RDS, with a relative risk (RR) of 2.66.
- With class II obesity, the RR was 1.77. With class I obesity, the RR was 1.3.
- Obesity also was associated with increased risk for grade III-IV (RR), 4.58 for class III obesity) and (RR, 3.76).
IN PRACTICE:
“Infants born to patients with higher classes of obesity have significant associated morbidity including a 2 to 4 times increased risk of neonatal acidosis, grades III-IV intraventricular hemorrhage, sepsis, and RDS,” the researchers reported.
SOURCE:
Sara I. Jones, MD, with University of Texas Southwestern Medical Center in Dallas, presented the study on February 14 at the 2024 Pregnancy Meeting of the Society for Maternal-Fetal Medicine, in National Harbor, Maryland.
DISCLOSURES:
The researchers had no conflicts of interest to disclose.
A version of this article appeared on Medscape.com.