Heidi Splete

Approximately 20% of sexually active high schoolers reported testing for a sexually transmitted infection in the previous year, based on data from 2,501 respondents to the 2019 national Youth Risk Behavior Survey.

Data suggest that half of all new STIs in the United States occur in youth aged 15-24 years, and that 25% of sexually active young women in the United States have an STI, wrote Nicole Liddon, PhD, of the Centers for Disease Control and Prevention, Atlanta, and colleagues.

Although organizations including the American Academy of Pediatrics and the U.S. Preventive Services Task Force recommend varying degrees of routine STI screening for adolescents, data on the prevalence of testing in this population are limited, the researchers said.

However, the addition in 2019 of a question on STI testing to the national Youth Risk Behavior Survey (YRBS) provided an opportunity to assess prevalence of STI testing, identify potential barriers, and increase screening rates, they wrote.

In a study published in Pediatrics, the researchers reviewed data from the 2019 national YRBS, an anonymous survey administered biannually to public and private high school students across the United States.

The study population included 2,501 individuals who reported sexual activity with at least one person during the 3 months prior to the survey.

Overall, 20.4% of the respondents reported being tested for an STI in the previous year, including significantly more females than males (26.1% vs. 13.7%).

The prevalence of testing among females was not significantly different according to race/ethnicity, sexual identity, or the sex of sexual contacts, but the prevalence increased with age; 12.6%, 22.8%, 28.5%, and 36.9% for females aged 15 years and younger, 16 years, 17 years, and 18 years, respectively.

Among males, no significant differences in STI testing were noted according to race/ethnicity, age, sexual identity, or sex of sexual contacts.

The researchers also analyzed prevalence of STI tested based on sexual behaviors. Among female students, the prevalence of STI testing was higher among those who reported the following behaviors, compared with those who did not: nonuse of condoms at last sexual intercourse (34.1% vs. 18.2%), substance use at last sexual intercourse (32.0% vs. 24.7%), and having four or more lifetime sex partners (31.9% vs. 24.7%).

Among male students, the prevalence of STI testing was higher among those who reported the following behaviors, compared with those who did not: sex before age 13 years (27.1% vs. 12.1%), having two or more recent sex partners (22.4% vs. 10.4%), having four or more lifetime sex partners (22.3% vs. 9.5%), and substance use at last sexual intercourse (19.2% vs. 12.1%).

The low prevalence of STI testing in teens has become more urgent in the wake of the coronavirus pandemic, the researchers wrote. “These prevalence estimates were derived before the possible profound impacts of the pandemic on adolescent sexual behavior and access to and use of health care services.”

Current guidelines allow health care providers the options for opt-out STI screening as a strategy to improve screening rates and testing; however, this option does not eliminate the need for conversations with adolescent patients about sexual activity, they emphasized.

The study findings were limited by several other factors including the inability to directly assess adherence to screening recommendations specifically, the inability to determine whether low testing rates resulted from limited access to health care or missed screening opportunities at visits, and the inclusion only of high school students but not out-of-school youth who may have more limited access to testing.

However, the results highlight the need to improve STI testing services for adolescents, and to address barriers at the individual and clinic level, they said. The addition of a question about past-year STI testing to the 2019 and future YRBS survey will promote ongoing monitoring of efforts to increase testing rates.

Teen sexual health goes beyond testing

The current study shows that routine testing for STIs according to published guidelines is low, Cynthia Holland-Hall, MD, and Andrea E. Bonny, MD, of Nationwide Children’s Hospital and Ohio State University, both in Columbus, wrote in an accompanying editorial.

Notably, sexually active females and males who had sex with male partners, two groups for whom annual testing is specifically recommended by multiple organizations, had testing rates of less than 30%, they said. The authors highlighted the study’s lack of information on which specific barriers, such as lack of access to the health care system, lack of knowledge, and fear of disclosure, contributed to overall low rates of testing.

However, STI testing is only one element of sexual and reproductive health care. Although opt-out testing may improve detection rates, the editorialists emphasized the need for patient-provider conversations about sex, citing recent studies showing that adolescents who spent some time alone with providers were more likely to receive sexual and reproductive health (SRH) services in the past year.

“Resources such as confidentiality policies, checklists, and written screening tools may facilitate SRH discussions,” Dr. Holland-Hall and Dr. Bonny said. “With a little practice, respect, and intention, a caring provider can take the awkward out of discussing sexual health but must not opt out of the conversation.”
 

Privacy and time issues exacerbate low testing rates

The current study is especially important at this time because many adolescents have likely missed well visits, and therefore important STI screens, because of disruptions caused by the COVID-19 pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

“I was surprised that the rate of screening was only one in five,” said Dr. Kinsella. “I knew it would be suboptimal, but not that low.”

According to Dr. Kinsella, there are two major barriers to increasing STI testing in adolescents in primary care. One barrier is that insurance companies will often state on the bill what the testing was for, which will lead to an uncomfortable conversation at a later date for the adolescent and parent when the bill arrives in the mail. A second barrier is when to test during a visit,. “If we obtain urine samples on all adolescents and many of them are not sexually active, we are wasting a lot of time in the short visit to obtain urine,” she explained. “If testing is scheduled for the end of the visit, they often leave without providing a urine sample.”

Overall, the study is an important reminder to general pediatricians about STI testing for sexually active teens, she emphasized. 

The study received no outside funding. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Approximately 20% of sexually active high schoolers reported testing for a sexually transmitted infection in the previous year, based on data from 2,501 respondents to the 2019 national Youth Risk Behavior Survey.

Data suggest that half of all new STIs in the United States occur in youth aged 15-24 years, and that 25% of sexually active young women in the United States have an STI, wrote Nicole Liddon, PhD, of the Centers for Disease Control and Prevention, Atlanta, and colleagues.

Although organizations including the American Academy of Pediatrics and the U.S. Preventive Services Task Force recommend varying degrees of routine STI screening for adolescents, data on the prevalence of testing in this population are limited, the researchers said.

However, the addition in 2019 of a question on STI testing to the national Youth Risk Behavior Survey (YRBS) provided an opportunity to assess prevalence of STI testing, identify potential barriers, and increase screening rates, they wrote.

In a study published in Pediatrics, the researchers reviewed data from the 2019 national YRBS, an anonymous survey administered biannually to public and private high school students across the United States.

The study population included 2,501 individuals who reported sexual activity with at least one person during the 3 months prior to the survey.

Overall, 20.4% of the respondents reported being tested for an STI in the previous year, including significantly more females than males (26.1% vs. 13.7%).

The prevalence of testing among females was not significantly different according to race/ethnicity, sexual identity, or the sex of sexual contacts, but the prevalence increased with age; 12.6%, 22.8%, 28.5%, and 36.9% for females aged 15 years and younger, 16 years, 17 years, and 18 years, respectively.

Among males, no significant differences in STI testing were noted according to race/ethnicity, age, sexual identity, or sex of sexual contacts.

The researchers also analyzed prevalence of STI tested based on sexual behaviors. Among female students, the prevalence of STI testing was higher among those who reported the following behaviors, compared with those who did not: nonuse of condoms at last sexual intercourse (34.1% vs. 18.2%), substance use at last sexual intercourse (32.0% vs. 24.7%), and having four or more lifetime sex partners (31.9% vs. 24.7%).

Among male students, the prevalence of STI testing was higher among those who reported the following behaviors, compared with those who did not: sex before age 13 years (27.1% vs. 12.1%), having two or more recent sex partners (22.4% vs. 10.4%), having four or more lifetime sex partners (22.3% vs. 9.5%), and substance use at last sexual intercourse (19.2% vs. 12.1%).

The low prevalence of STI testing in teens has become more urgent in the wake of the coronavirus pandemic, the researchers wrote. “These prevalence estimates were derived before the possible profound impacts of the pandemic on adolescent sexual behavior and access to and use of health care services.”

Current guidelines allow health care providers the options for opt-out STI screening as a strategy to improve screening rates and testing; however, this option does not eliminate the need for conversations with adolescent patients about sexual activity, they emphasized.

The study findings were limited by several other factors including the inability to directly assess adherence to screening recommendations specifically, the inability to determine whether low testing rates resulted from limited access to health care or missed screening opportunities at visits, and the inclusion only of high school students but not out-of-school youth who may have more limited access to testing.

However, the results highlight the need to improve STI testing services for adolescents, and to address barriers at the individual and clinic level, they said. The addition of a question about past-year STI testing to the 2019 and future YRBS survey will promote ongoing monitoring of efforts to increase testing rates.

Teen sexual health goes beyond testing

The current study shows that routine testing for STIs according to published guidelines is low, Cynthia Holland-Hall, MD, and Andrea E. Bonny, MD, of Nationwide Children’s Hospital and Ohio State University, both in Columbus, wrote in an accompanying editorial.

Notably, sexually active females and males who had sex with male partners, two groups for whom annual testing is specifically recommended by multiple organizations, had testing rates of less than 30%, they said. The authors highlighted the study’s lack of information on which specific barriers, such as lack of access to the health care system, lack of knowledge, and fear of disclosure, contributed to overall low rates of testing.

However, STI testing is only one element of sexual and reproductive health care. Although opt-out testing may improve detection rates, the editorialists emphasized the need for patient-provider conversations about sex, citing recent studies showing that adolescents who spent some time alone with providers were more likely to receive sexual and reproductive health (SRH) services in the past year.

“Resources such as confidentiality policies, checklists, and written screening tools may facilitate SRH discussions,” Dr. Holland-Hall and Dr. Bonny said. “With a little practice, respect, and intention, a caring provider can take the awkward out of discussing sexual health but must not opt out of the conversation.”
 

Privacy and time issues exacerbate low testing rates

The current study is especially important at this time because many adolescents have likely missed well visits, and therefore important STI screens, because of disruptions caused by the COVID-19 pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

“I was surprised that the rate of screening was only one in five,” said Dr. Kinsella. “I knew it would be suboptimal, but not that low.”

According to Dr. Kinsella, there are two major barriers to increasing STI testing in adolescents in primary care. One barrier is that insurance companies will often state on the bill what the testing was for, which will lead to an uncomfortable conversation at a later date for the adolescent and parent when the bill arrives in the mail. A second barrier is when to test during a visit,. “If we obtain urine samples on all adolescents and many of them are not sexually active, we are wasting a lot of time in the short visit to obtain urine,” she explained. “If testing is scheduled for the end of the visit, they often leave without providing a urine sample.”

Overall, the study is an important reminder to general pediatricians about STI testing for sexually active teens, she emphasized. 

The study received no outside funding. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Approximately 20% of sexually active high schoolers reported testing for a sexually transmitted infection in the previous year, based on data from 2,501 respondents to the 2019 national Youth Risk Behavior Survey.

Data suggest that half of all new STIs in the United States occur in youth aged 15-24 years, and that 25% of sexually active young women in the United States have an STI, wrote Nicole Liddon, PhD, of the Centers for Disease Control and Prevention, Atlanta, and colleagues.

Although organizations including the American Academy of Pediatrics and the U.S. Preventive Services Task Force recommend varying degrees of routine STI screening for adolescents, data on the prevalence of testing in this population are limited, the researchers said.

However, the addition in 2019 of a question on STI testing to the national Youth Risk Behavior Survey (YRBS) provided an opportunity to assess prevalence of STI testing, identify potential barriers, and increase screening rates, they wrote.

In a study published in Pediatrics, the researchers reviewed data from the 2019 national YRBS, an anonymous survey administered biannually to public and private high school students across the United States.

The study population included 2,501 individuals who reported sexual activity with at least one person during the 3 months prior to the survey.

Overall, 20.4% of the respondents reported being tested for an STI in the previous year, including significantly more females than males (26.1% vs. 13.7%).

The prevalence of testing among females was not significantly different according to race/ethnicity, sexual identity, or the sex of sexual contacts, but the prevalence increased with age; 12.6%, 22.8%, 28.5%, and 36.9% for females aged 15 years and younger, 16 years, 17 years, and 18 years, respectively.

Among males, no significant differences in STI testing were noted according to race/ethnicity, age, sexual identity, or sex of sexual contacts.

The researchers also analyzed prevalence of STI tested based on sexual behaviors. Among female students, the prevalence of STI testing was higher among those who reported the following behaviors, compared with those who did not: nonuse of condoms at last sexual intercourse (34.1% vs. 18.2%), substance use at last sexual intercourse (32.0% vs. 24.7%), and having four or more lifetime sex partners (31.9% vs. 24.7%).

Among male students, the prevalence of STI testing was higher among those who reported the following behaviors, compared with those who did not: sex before age 13 years (27.1% vs. 12.1%), having two or more recent sex partners (22.4% vs. 10.4%), having four or more lifetime sex partners (22.3% vs. 9.5%), and substance use at last sexual intercourse (19.2% vs. 12.1%).

The low prevalence of STI testing in teens has become more urgent in the wake of the coronavirus pandemic, the researchers wrote. “These prevalence estimates were derived before the possible profound impacts of the pandemic on adolescent sexual behavior and access to and use of health care services.”

Current guidelines allow health care providers the options for opt-out STI screening as a strategy to improve screening rates and testing; however, this option does not eliminate the need for conversations with adolescent patients about sexual activity, they emphasized.

The study findings were limited by several other factors including the inability to directly assess adherence to screening recommendations specifically, the inability to determine whether low testing rates resulted from limited access to health care or missed screening opportunities at visits, and the inclusion only of high school students but not out-of-school youth who may have more limited access to testing.

However, the results highlight the need to improve STI testing services for adolescents, and to address barriers at the individual and clinic level, they said. The addition of a question about past-year STI testing to the 2019 and future YRBS survey will promote ongoing monitoring of efforts to increase testing rates.

Teen sexual health goes beyond testing

The current study shows that routine testing for STIs according to published guidelines is low, Cynthia Holland-Hall, MD, and Andrea E. Bonny, MD, of Nationwide Children’s Hospital and Ohio State University, both in Columbus, wrote in an accompanying editorial.

Notably, sexually active females and males who had sex with male partners, two groups for whom annual testing is specifically recommended by multiple organizations, had testing rates of less than 30%, they said. The authors highlighted the study’s lack of information on which specific barriers, such as lack of access to the health care system, lack of knowledge, and fear of disclosure, contributed to overall low rates of testing.

However, STI testing is only one element of sexual and reproductive health care. Although opt-out testing may improve detection rates, the editorialists emphasized the need for patient-provider conversations about sex, citing recent studies showing that adolescents who spent some time alone with providers were more likely to receive sexual and reproductive health (SRH) services in the past year.

“Resources such as confidentiality policies, checklists, and written screening tools may facilitate SRH discussions,” Dr. Holland-Hall and Dr. Bonny said. “With a little practice, respect, and intention, a caring provider can take the awkward out of discussing sexual health but must not opt out of the conversation.”
 

Privacy and time issues exacerbate low testing rates

The current study is especially important at this time because many adolescents have likely missed well visits, and therefore important STI screens, because of disruptions caused by the COVID-19 pandemic, Karalyn Kinsella, MD, a pediatrician in private practice in Cheshire, Conn., said in an interview.

“I was surprised that the rate of screening was only one in five,” said Dr. Kinsella. “I knew it would be suboptimal, but not that low.”

According to Dr. Kinsella, there are two major barriers to increasing STI testing in adolescents in primary care. One barrier is that insurance companies will often state on the bill what the testing was for, which will lead to an uncomfortable conversation at a later date for the adolescent and parent when the bill arrives in the mail. A second barrier is when to test during a visit,. “If we obtain urine samples on all adolescents and many of them are not sexually active, we are wasting a lot of time in the short visit to obtain urine,” she explained. “If testing is scheduled for the end of the visit, they often leave without providing a urine sample.”

Overall, the study is an important reminder to general pediatricians about STI testing for sexually active teens, she emphasized. 

The study received no outside funding. The researchers had no financial conflicts to disclose. The editorialists had no financial conflicts to disclose. Dr. Kinsella had no financial conflicts to disclose and serves on the editorial advisory board of Pediatric News.

Restless legs syndrome occurred in approximately 40% of adults with X-linked adrenoleukodystrophy, based on data from 32 individuals.

Patients with X-linked adrenoleukodystrophy (ALD), a neurodegenerative disease, often experience gait and balance problems, as well as leg discomfort, sleep disturbances, and pain, wrote John W. Winkelman, MD, of Massachusetts General Hospital, Boston, and colleagues. Restless legs syndrome (RLS) has been associated with neurological conditions including Parkinson’s disease, but the prevalence of RLS in ALD patients has not been examined, they said.

Courtesy Brigham and Women's Hospital

In a pilot study published in Sleep Medicine, the researchers identified 21 women and 11 men with ALD who were treated at a single center. The median age of the patients was 45.9 years. Twenty-seven patients had symptoms of myelopathy, with a median age of onset of 34 years.

The researchers assessed RLS severity using questionnaires and the Hopkins Telephone Diagnostic Interview (HTDI), a validated RLS assessment tool. They also reviewed patients’ charts for data on neurological examinations, functional gait measures, and laboratory assessments. Functional gait assessments included the 25-Foot Walk test (25-FW), the Timed Up and Go test (TUG), and Six Minute Walk test (6MW).

Thirteen patients (10 women and 3 men) met criteria for RLS based on the HTDI. The median age of RLS onset was 35 years. Six RLS patients (46.2%) reported using medication to relieve symptoms, and eight RLS patients had a history of antidepressant use.

In addition, six patients with RLS reported a history of anemia or iron deficiency. Ferritin levels were available for 14 patients: 8 women with RLS and 4 women and 2 men without RLS; the mean ferritin levels were 74.0 mcg/L in RLS patients and 99.5 mcg/L in those without RLS.

Of the seven ALD patients with brain lesions, all were men, only two were diagnosed with RLS, and all seven cases were mild, the researchers noted.

Overall, patients with RLS had more neurological signs and symptoms than those without RLS; the most significant were pain and gait difficulty. However, patients with RLS also were more likely than were those without RLS to report spasticity, muscle weakness, impaired coordination, hyperreflexia, impaired sensation, and paraesthesia, as well as bladder, bowel, and erectile dysfunction.

The 40.6% prevalence of RLS in patients with ALD is notably higher than that of the general population, in which the prevalence of RLS is 5%-10%, the researchers wrote in their discussion.

“Consistent with patterns observed in the general population, risk factors for RLS in this cohort of adults with ALD included female gender, increased age, lower iron indices, and use of serotonergic antidepressants,” they said.

The study findings were limited by several factors including the small size and the possible contribution of antidepressant use to the high rate of RLS, the researchers noted.

“Awareness of RLS in patients with ALD would allow for its effective treatment, which may improve the functional impairments as well as quality of life, mood, and anxiety issues in those with ALD,” they concluded.

The study received no outside funding.

Dr. Winkelman disclosed ties with Advance Medical, Avadel, Disc Medicine, Eisai, Emalex, Idorsia, Noctrix, UpToDate, and Merck Pharmaceuticals, as well as research support from the National Institute on Drug Abuse and the Baszucki Brain Research Foundation. The study also was supported by grants from the National Institute of Neurological Disorders and Stroke, the European Leukodystrophy Association, the Arrivederci Foundation, the Leblang Foundation, and the Hammer Family Fund Journal Preproof for ALD Research and Therapies for Women.

Restless legs syndrome occurred in approximately 40% of adults with X-linked adrenoleukodystrophy, based on data from 32 individuals.

Patients with X-linked adrenoleukodystrophy (ALD), a neurodegenerative disease, often experience gait and balance problems, as well as leg discomfort, sleep disturbances, and pain, wrote John W. Winkelman, MD, of Massachusetts General Hospital, Boston, and colleagues. Restless legs syndrome (RLS) has been associated with neurological conditions including Parkinson’s disease, but the prevalence of RLS in ALD patients has not been examined, they said.

Courtesy Brigham and Women's Hospital

In a pilot study published in Sleep Medicine, the researchers identified 21 women and 11 men with ALD who were treated at a single center. The median age of the patients was 45.9 years. Twenty-seven patients had symptoms of myelopathy, with a median age of onset of 34 years.

The researchers assessed RLS severity using questionnaires and the Hopkins Telephone Diagnostic Interview (HTDI), a validated RLS assessment tool. They also reviewed patients’ charts for data on neurological examinations, functional gait measures, and laboratory assessments. Functional gait assessments included the 25-Foot Walk test (25-FW), the Timed Up and Go test (TUG), and Six Minute Walk test (6MW).

Thirteen patients (10 women and 3 men) met criteria for RLS based on the HTDI. The median age of RLS onset was 35 years. Six RLS patients (46.2%) reported using medication to relieve symptoms, and eight RLS patients had a history of antidepressant use.

In addition, six patients with RLS reported a history of anemia or iron deficiency. Ferritin levels were available for 14 patients: 8 women with RLS and 4 women and 2 men without RLS; the mean ferritin levels were 74.0 mcg/L in RLS patients and 99.5 mcg/L in those without RLS.

Of the seven ALD patients with brain lesions, all were men, only two were diagnosed with RLS, and all seven cases were mild, the researchers noted.

Overall, patients with RLS had more neurological signs and symptoms than those without RLS; the most significant were pain and gait difficulty. However, patients with RLS also were more likely than were those without RLS to report spasticity, muscle weakness, impaired coordination, hyperreflexia, impaired sensation, and paraesthesia, as well as bladder, bowel, and erectile dysfunction.

The 40.6% prevalence of RLS in patients with ALD is notably higher than that of the general population, in which the prevalence of RLS is 5%-10%, the researchers wrote in their discussion.

“Consistent with patterns observed in the general population, risk factors for RLS in this cohort of adults with ALD included female gender, increased age, lower iron indices, and use of serotonergic antidepressants,” they said.

The study findings were limited by several factors including the small size and the possible contribution of antidepressant use to the high rate of RLS, the researchers noted.

“Awareness of RLS in patients with ALD would allow for its effective treatment, which may improve the functional impairments as well as quality of life, mood, and anxiety issues in those with ALD,” they concluded.

The study received no outside funding.

Dr. Winkelman disclosed ties with Advance Medical, Avadel, Disc Medicine, Eisai, Emalex, Idorsia, Noctrix, UpToDate, and Merck Pharmaceuticals, as well as research support from the National Institute on Drug Abuse and the Baszucki Brain Research Foundation. The study also was supported by grants from the National Institute of Neurological Disorders and Stroke, the European Leukodystrophy Association, the Arrivederci Foundation, the Leblang Foundation, and the Hammer Family Fund Journal Preproof for ALD Research and Therapies for Women.

Restless legs syndrome occurred in approximately 40% of adults with X-linked adrenoleukodystrophy, based on data from 32 individuals.

Patients with X-linked adrenoleukodystrophy (ALD), a neurodegenerative disease, often experience gait and balance problems, as well as leg discomfort, sleep disturbances, and pain, wrote John W. Winkelman, MD, of Massachusetts General Hospital, Boston, and colleagues. Restless legs syndrome (RLS) has been associated with neurological conditions including Parkinson’s disease, but the prevalence of RLS in ALD patients has not been examined, they said.

Courtesy Brigham and Women's Hospital

In a pilot study published in Sleep Medicine, the researchers identified 21 women and 11 men with ALD who were treated at a single center. The median age of the patients was 45.9 years. Twenty-seven patients had symptoms of myelopathy, with a median age of onset of 34 years.

The researchers assessed RLS severity using questionnaires and the Hopkins Telephone Diagnostic Interview (HTDI), a validated RLS assessment tool. They also reviewed patients’ charts for data on neurological examinations, functional gait measures, and laboratory assessments. Functional gait assessments included the 25-Foot Walk test (25-FW), the Timed Up and Go test (TUG), and Six Minute Walk test (6MW).

Thirteen patients (10 women and 3 men) met criteria for RLS based on the HTDI. The median age of RLS onset was 35 years. Six RLS patients (46.2%) reported using medication to relieve symptoms, and eight RLS patients had a history of antidepressant use.

In addition, six patients with RLS reported a history of anemia or iron deficiency. Ferritin levels were available for 14 patients: 8 women with RLS and 4 women and 2 men without RLS; the mean ferritin levels were 74.0 mcg/L in RLS patients and 99.5 mcg/L in those without RLS.

Of the seven ALD patients with brain lesions, all were men, only two were diagnosed with RLS, and all seven cases were mild, the researchers noted.

Overall, patients with RLS had more neurological signs and symptoms than those without RLS; the most significant were pain and gait difficulty. However, patients with RLS also were more likely than were those without RLS to report spasticity, muscle weakness, impaired coordination, hyperreflexia, impaired sensation, and paraesthesia, as well as bladder, bowel, and erectile dysfunction.

The 40.6% prevalence of RLS in patients with ALD is notably higher than that of the general population, in which the prevalence of RLS is 5%-10%, the researchers wrote in their discussion.

“Consistent with patterns observed in the general population, risk factors for RLS in this cohort of adults with ALD included female gender, increased age, lower iron indices, and use of serotonergic antidepressants,” they said.

The study findings were limited by several factors including the small size and the possible contribution of antidepressant use to the high rate of RLS, the researchers noted.

“Awareness of RLS in patients with ALD would allow for its effective treatment, which may improve the functional impairments as well as quality of life, mood, and anxiety issues in those with ALD,” they concluded.

The study received no outside funding.

Dr. Winkelman disclosed ties with Advance Medical, Avadel, Disc Medicine, Eisai, Emalex, Idorsia, Noctrix, UpToDate, and Merck Pharmaceuticals, as well as research support from the National Institute on Drug Abuse and the Baszucki Brain Research Foundation. The study also was supported by grants from the National Institute of Neurological Disorders and Stroke, the European Leukodystrophy Association, the Arrivederci Foundation, the Leblang Foundation, and the Hammer Family Fund Journal Preproof for ALD Research and Therapies for Women.

Individuals with a prior diagnosis of pneumonia were significantly more likely to develop chronic otitis media (COM) than were those without a history of pneumonia, based on data from a nationwide cohort study of more than 100,000 patients.

“Recently, middle ear diseases, including COM, have been recognized as respiratory tract diseases beyond the pathophysiological concepts of ventilation dysfunction, with recurrent infection that occurs from anatomically adjacent structures such as the middle ear, mastoid cavity, and eustachian tube,” but the potential link between pneumonia and chronic otitis media and adults in particular has not been examined, wrote Sung Kyun Kim, MD, of Hallym University, Dongtan, South Korea, and colleagues.

In a study recently published in the International Journal of Infectious Diseases, the researchers identified 23,436 adults with COM and 93,744 controls aged 40 years and older from a Korean health insurance database between 2002 and 2015.

The overall incidence of pneumonia in the study population was significantly higher in the COM group compared with controls (9.3% vs. 7.2%, P <.001). The odds ratios of pneumonia were significantly higher in the COM group compared with controls, and a history of pneumonia increased the odds of COM regardless of sex and across all ages.

Pneumonia was defined as when a patient had a diagnosis of pneumonia based on ICD-10 codes and underwent a chest x-ray or chest CT scan. Chronic otitis media was defined as when a patient had a diagnosis based on ICD-10 codes at least two times with one of the following conditions: chronic serous otitis media, chronic mucoid otitis media, other chronic nonsuppurative otitis media, unspecified nonsuppurative otitis media, chronic tubotympanic suppurative otitis media, chronic atticoantral suppurative otitis media, other chronic suppurative otitis media, or unspecified suppurative otitis media.

Age groups were divided into 5-year intervals, and patients were classified into income groups and rural vs. urban residence.

In a further sensitivity analysis, individuals who were diagnosed with pneumonia five or more times before the index date had a significantly higher odds ratio for COM compared with those with less than five diagnoses of pneumonia (adjusted odds ratio, 1.34; P < .001).

Microbiome dysbiosis may explain part of the connection between pneumonia and COM, the researchers wrote in their discussion. Pathogens in the lungs can prompt changes in the microbiome dynamics, as might the use of antibiotics, they said. In addition, “Mucus plugging in the airway caused by pneumonia induces hypoxic conditions and leads to the expression of inflammatory markers in the eustachian tube and middle ear mucosa,” they noted.

The study findings were limited by several factors, including the retrospective design and lack of data on microbiological cultures for antibiotic susceptibility, radiologic findings on the severity of pneumonia, results of pulmonary function tests, and hearing thresholds, the researchers noted. Other limitations were the exclusion of the frequency of upper respiratory infections and antibiotic use due to lack of data, they said.

However, the results show an association between pneumonia diagnoses and increased incidence of COM, which suggests a novel perspective that “infection of the lower respiratory tract may affect the function of the eustachian tube and the middle ear to later cause COM,” they concluded.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

Individuals with a prior diagnosis of pneumonia were significantly more likely to develop chronic otitis media (COM) than were those without a history of pneumonia, based on data from a nationwide cohort study of more than 100,000 patients.

“Recently, middle ear diseases, including COM, have been recognized as respiratory tract diseases beyond the pathophysiological concepts of ventilation dysfunction, with recurrent infection that occurs from anatomically adjacent structures such as the middle ear, mastoid cavity, and eustachian tube,” but the potential link between pneumonia and chronic otitis media and adults in particular has not been examined, wrote Sung Kyun Kim, MD, of Hallym University, Dongtan, South Korea, and colleagues.

In a study recently published in the International Journal of Infectious Diseases, the researchers identified 23,436 adults with COM and 93,744 controls aged 40 years and older from a Korean health insurance database between 2002 and 2015.

The overall incidence of pneumonia in the study population was significantly higher in the COM group compared with controls (9.3% vs. 7.2%, P <.001). The odds ratios of pneumonia were significantly higher in the COM group compared with controls, and a history of pneumonia increased the odds of COM regardless of sex and across all ages.

Pneumonia was defined as when a patient had a diagnosis of pneumonia based on ICD-10 codes and underwent a chest x-ray or chest CT scan. Chronic otitis media was defined as when a patient had a diagnosis based on ICD-10 codes at least two times with one of the following conditions: chronic serous otitis media, chronic mucoid otitis media, other chronic nonsuppurative otitis media, unspecified nonsuppurative otitis media, chronic tubotympanic suppurative otitis media, chronic atticoantral suppurative otitis media, other chronic suppurative otitis media, or unspecified suppurative otitis media.

Age groups were divided into 5-year intervals, and patients were classified into income groups and rural vs. urban residence.

In a further sensitivity analysis, individuals who were diagnosed with pneumonia five or more times before the index date had a significantly higher odds ratio for COM compared with those with less than five diagnoses of pneumonia (adjusted odds ratio, 1.34; P < .001).

Microbiome dysbiosis may explain part of the connection between pneumonia and COM, the researchers wrote in their discussion. Pathogens in the lungs can prompt changes in the microbiome dynamics, as might the use of antibiotics, they said. In addition, “Mucus plugging in the airway caused by pneumonia induces hypoxic conditions and leads to the expression of inflammatory markers in the eustachian tube and middle ear mucosa,” they noted.

The study findings were limited by several factors, including the retrospective design and lack of data on microbiological cultures for antibiotic susceptibility, radiologic findings on the severity of pneumonia, results of pulmonary function tests, and hearing thresholds, the researchers noted. Other limitations were the exclusion of the frequency of upper respiratory infections and antibiotic use due to lack of data, they said.

However, the results show an association between pneumonia diagnoses and increased incidence of COM, which suggests a novel perspective that “infection of the lower respiratory tract may affect the function of the eustachian tube and the middle ear to later cause COM,” they concluded.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

Individuals with a prior diagnosis of pneumonia were significantly more likely to develop chronic otitis media (COM) than were those without a history of pneumonia, based on data from a nationwide cohort study of more than 100,000 patients.

“Recently, middle ear diseases, including COM, have been recognized as respiratory tract diseases beyond the pathophysiological concepts of ventilation dysfunction, with recurrent infection that occurs from anatomically adjacent structures such as the middle ear, mastoid cavity, and eustachian tube,” but the potential link between pneumonia and chronic otitis media and adults in particular has not been examined, wrote Sung Kyun Kim, MD, of Hallym University, Dongtan, South Korea, and colleagues.

In a study recently published in the International Journal of Infectious Diseases, the researchers identified 23,436 adults with COM and 93,744 controls aged 40 years and older from a Korean health insurance database between 2002 and 2015.

The overall incidence of pneumonia in the study population was significantly higher in the COM group compared with controls (9.3% vs. 7.2%, P <.001). The odds ratios of pneumonia were significantly higher in the COM group compared with controls, and a history of pneumonia increased the odds of COM regardless of sex and across all ages.

Pneumonia was defined as when a patient had a diagnosis of pneumonia based on ICD-10 codes and underwent a chest x-ray or chest CT scan. Chronic otitis media was defined as when a patient had a diagnosis based on ICD-10 codes at least two times with one of the following conditions: chronic serous otitis media, chronic mucoid otitis media, other chronic nonsuppurative otitis media, unspecified nonsuppurative otitis media, chronic tubotympanic suppurative otitis media, chronic atticoantral suppurative otitis media, other chronic suppurative otitis media, or unspecified suppurative otitis media.

Age groups were divided into 5-year intervals, and patients were classified into income groups and rural vs. urban residence.

In a further sensitivity analysis, individuals who were diagnosed with pneumonia five or more times before the index date had a significantly higher odds ratio for COM compared with those with less than five diagnoses of pneumonia (adjusted odds ratio, 1.34; P < .001).

Microbiome dysbiosis may explain part of the connection between pneumonia and COM, the researchers wrote in their discussion. Pathogens in the lungs can prompt changes in the microbiome dynamics, as might the use of antibiotics, they said. In addition, “Mucus plugging in the airway caused by pneumonia induces hypoxic conditions and leads to the expression of inflammatory markers in the eustachian tube and middle ear mucosa,” they noted.

The study findings were limited by several factors, including the retrospective design and lack of data on microbiological cultures for antibiotic susceptibility, radiologic findings on the severity of pneumonia, results of pulmonary function tests, and hearing thresholds, the researchers noted. Other limitations were the exclusion of the frequency of upper respiratory infections and antibiotic use due to lack of data, they said.

However, the results show an association between pneumonia diagnoses and increased incidence of COM, which suggests a novel perspective that “infection of the lower respiratory tract may affect the function of the eustachian tube and the middle ear to later cause COM,” they concluded.

The study received no outside funding. The researchers have disclosed no relevant financial relationships.

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

Oral tebipenem pivoxil hydrobromide (TBP-PI-HBr) offers a safe and effective strategy for treating patients with complicated urinary tract infections, according to a new study.

“No new oral antibiotic alternative has emerged to treat these conditions in more than 25 years,” corresponding author Angela K. Talley, MD, said in an interview. The new research was published in the New England Journal of Medicine.

Courtesy Spero Therapeutics

Patients with complicated urinary tract infection (cUTI), including acute pyelonephritis (AP), are often hospitalized and treated with intravenous therapy because of the lack of oral options, especially in cases of antibiotic-resistant pathogens, explained Dr. Talley, of Spero Therapeutics.

In their new phase 3, double-blind randomized trial, the researchers evaluated the safety and effectiveness of oral TBP-PI-HBr, compared with intravenous ertapenem in hospitalized patients with cUTIs or AP. Oral tebipenem is an investigational carbapenem with demonstrated activity against uropathogenic Enterobacterales, and it has shown effectiveness in animal models, the researchers noted in their paper.
 

Methods and results

The researchers randomized 1,372 adult patients. The microbiologic intent-to-treat population included 449 patients who received TBP-PI-HBr (600 mg every 8 hours) and 419 who received ertapenem (1 g every 24 hours) for 7-10 days or up to 14 days for patients with bacteremia.

The primary endpoint was a composite of clinical cure and favorable microbiologic response, assessed at a test-of-cure visit on day 19. Clinical cure was defined as “complete resolution or clinically significant alleviation of baseline signs and symptoms of complicated urinary tract infection or acute pyelonephritis and no new symptoms, such that no further antimicrobial therapy was warranted,” the researchers wrote. Microbiologic response was defined as a reduction to less than 103 CFU per milliliter in uropathogen levels from baseline at day 19.

Overall, the clinical response occurred in 58.8% of patients who received TBP-PI-HBr and 61.6% of those who received ertapenem at the test-of-cure visit.

Clinical cure rates were similar in the TBP-PI-HBr and ertapenem groups (93.1% vs. 93.6%) at the test-of-cure visit.

Both treatment groups showed similar responses to Enterobacterales pathogens at the test-of-cure visit (62.7% for TBP-PI-HBr and 65.2% for ertapenem).

Among patients with bacteremia at baseline, overall response rates were 72.3% and 66.0% for TBP-PI-HBr and ertapenem, respectively, at the test-of-cure visit, and 93.6% and 96.2%, respectively, at the end-of-treatment visit on or around day 25.

The overall incidence of adverse events was approximately 26% in both treatment groups. Most adverse events were mild or moderate in severity and did not limit treatment, the researchers wrote.

The mean age of the patients was 58.1 years; 46.1% were aged 65 and older, and 11.5% had bacteremia at baseline.

The study findings were limited by several factors, including the mandated 7- to 10-day course of antibiotics, which may not reflect the standard of care in other settings in the United States. The study’s trial sites were located in the United States, South Africa, and Europe. The study population was primarily White and from Central and Eastern Europe. Other limitations included the randomization of patients before confirming the baseline pathogen, although this was done to limit potential confounding from previous antibiotics, the researchers noted.
 

Safety and efficacy support application for approval

“To our knowledge, this is the first head-to-head evaluation of an IV vs. an oral drug for the treatment of cUTI and acute pyelonephritis,” Dr. Talley said in an interview.  

“The findings demonstrate that almost all patients in the study achieved complete resolution of the signs and symptoms of their infection,” she said.

TBP-PI-HBr has not been approved by the Food and Drug Administration, but a new drug application that included data from the current study was submitted to the FDA and is currently under review, Dr. Talley noted.

As for additional research, the current study was conducted in hospitalized patients, and the use of TBP-PI-HBr in the outpatient setting has not yet been evaluated, she said.
 

Approval and use of oral carbapenem will change practice

The current study is very important because it provides a viable and effective alternative form of antibiotic delivery for the patients with complicated UTI, Noel N. Deep, MD, emphasized in an interview.

“Currently these patients have to be treated with IV carbapenem antibiotics either in a hospital or through a home health nurse,” Dr. Deep, a general internist in group practice in Antigo, Wisc., explained.

Current IV strategies also carry the inherent risk associated with the insertion of an IV catheter that is left in place for several days or replaced periodically. “The oral antibiotic eliminates these risks and higher health care costs and provides a safer and equally efficacious option,” Dr. Deep said.

In the current study, “I was definitely surprised at the effectiveness of the oral carbapenem,” Dr. Deep said. “I am absolutely delighted with this new treatment option that physicians can now add to their armamentarium [assuming FDA approval] as we provide care to our patients,” he said.

If approved, TBP-PI-HBr will definitely change the treatment spectrum for the multidrug-resistant bacterial UTIs, said Dr. Deep. “Carbapenems have continued to be effective and low antibiotic resistance to carbapenems has been recorded.”

As for additional research, “I would like to see studies done in other ethnicities and different countries to ascertain the effectiveness of this antibiotic in those populations and against other bacterial strains with potentially different resistance mechanisms,” Dr. Deep said.

The study was supported by Spero Therapeutics and the Department of Health and Human Services. Lead author Paul B. Eckburg, MD, of Stanford (Calif.) University, and Dr. Talley are employees of Spero Therapeutics. Dr. Deep had no financial conflicts to disclose, but serves on the editorial advisory board of Internal Medicine News.

Oral tebipenem pivoxil hydrobromide (TBP-PI-HBr) offers a safe and effective strategy for treating patients with complicated urinary tract infections, according to a new study.

“No new oral antibiotic alternative has emerged to treat these conditions in more than 25 years,” corresponding author Angela K. Talley, MD, said in an interview. The new research was published in the New England Journal of Medicine.

Courtesy Spero Therapeutics

Patients with complicated urinary tract infection (cUTI), including acute pyelonephritis (AP), are often hospitalized and treated with intravenous therapy because of the lack of oral options, especially in cases of antibiotic-resistant pathogens, explained Dr. Talley, of Spero Therapeutics.

In their new phase 3, double-blind randomized trial, the researchers evaluated the safety and effectiveness of oral TBP-PI-HBr, compared with intravenous ertapenem in hospitalized patients with cUTIs or AP. Oral tebipenem is an investigational carbapenem with demonstrated activity against uropathogenic Enterobacterales, and it has shown effectiveness in animal models, the researchers noted in their paper.
 

Methods and results

The researchers randomized 1,372 adult patients. The microbiologic intent-to-treat population included 449 patients who received TBP-PI-HBr (600 mg every 8 hours) and 419 who received ertapenem (1 g every 24 hours) for 7-10 days or up to 14 days for patients with bacteremia.

The primary endpoint was a composite of clinical cure and favorable microbiologic response, assessed at a test-of-cure visit on day 19. Clinical cure was defined as “complete resolution or clinically significant alleviation of baseline signs and symptoms of complicated urinary tract infection or acute pyelonephritis and no new symptoms, such that no further antimicrobial therapy was warranted,” the researchers wrote. Microbiologic response was defined as a reduction to less than 103 CFU per milliliter in uropathogen levels from baseline at day 19.

Overall, the clinical response occurred in 58.8% of patients who received TBP-PI-HBr and 61.6% of those who received ertapenem at the test-of-cure visit.

Clinical cure rates were similar in the TBP-PI-HBr and ertapenem groups (93.1% vs. 93.6%) at the test-of-cure visit.

Both treatment groups showed similar responses to Enterobacterales pathogens at the test-of-cure visit (62.7% for TBP-PI-HBr and 65.2% for ertapenem).

Among patients with bacteremia at baseline, overall response rates were 72.3% and 66.0% for TBP-PI-HBr and ertapenem, respectively, at the test-of-cure visit, and 93.6% and 96.2%, respectively, at the end-of-treatment visit on or around day 25.

The overall incidence of adverse events was approximately 26% in both treatment groups. Most adverse events were mild or moderate in severity and did not limit treatment, the researchers wrote.

The mean age of the patients was 58.1 years; 46.1% were aged 65 and older, and 11.5% had bacteremia at baseline.

The study findings were limited by several factors, including the mandated 7- to 10-day course of antibiotics, which may not reflect the standard of care in other settings in the United States. The study’s trial sites were located in the United States, South Africa, and Europe. The study population was primarily White and from Central and Eastern Europe. Other limitations included the randomization of patients before confirming the baseline pathogen, although this was done to limit potential confounding from previous antibiotics, the researchers noted.
 

Safety and efficacy support application for approval

“To our knowledge, this is the first head-to-head evaluation of an IV vs. an oral drug for the treatment of cUTI and acute pyelonephritis,” Dr. Talley said in an interview.  

“The findings demonstrate that almost all patients in the study achieved complete resolution of the signs and symptoms of their infection,” she said.

TBP-PI-HBr has not been approved by the Food and Drug Administration, but a new drug application that included data from the current study was submitted to the FDA and is currently under review, Dr. Talley noted.

As for additional research, the current study was conducted in hospitalized patients, and the use of TBP-PI-HBr in the outpatient setting has not yet been evaluated, she said.
 

Approval and use of oral carbapenem will change practice

The current study is very important because it provides a viable and effective alternative form of antibiotic delivery for the patients with complicated UTI, Noel N. Deep, MD, emphasized in an interview.

“Currently these patients have to be treated with IV carbapenem antibiotics either in a hospital or through a home health nurse,” Dr. Deep, a general internist in group practice in Antigo, Wisc., explained.

Current IV strategies also carry the inherent risk associated with the insertion of an IV catheter that is left in place for several days or replaced periodically. “The oral antibiotic eliminates these risks and higher health care costs and provides a safer and equally efficacious option,” Dr. Deep said.

In the current study, “I was definitely surprised at the effectiveness of the oral carbapenem,” Dr. Deep said. “I am absolutely delighted with this new treatment option that physicians can now add to their armamentarium [assuming FDA approval] as we provide care to our patients,” he said.

If approved, TBP-PI-HBr will definitely change the treatment spectrum for the multidrug-resistant bacterial UTIs, said Dr. Deep. “Carbapenems have continued to be effective and low antibiotic resistance to carbapenems has been recorded.”

As for additional research, “I would like to see studies done in other ethnicities and different countries to ascertain the effectiveness of this antibiotic in those populations and against other bacterial strains with potentially different resistance mechanisms,” Dr. Deep said.

The study was supported by Spero Therapeutics and the Department of Health and Human Services. Lead author Paul B. Eckburg, MD, of Stanford (Calif.) University, and Dr. Talley are employees of Spero Therapeutics. Dr. Deep had no financial conflicts to disclose, but serves on the editorial advisory board of Internal Medicine News.

Oral tebipenem pivoxil hydrobromide (TBP-PI-HBr) offers a safe and effective strategy for treating patients with complicated urinary tract infections, according to a new study.

“No new oral antibiotic alternative has emerged to treat these conditions in more than 25 years,” corresponding author Angela K. Talley, MD, said in an interview. The new research was published in the New England Journal of Medicine.

Courtesy Spero Therapeutics

Patients with complicated urinary tract infection (cUTI), including acute pyelonephritis (AP), are often hospitalized and treated with intravenous therapy because of the lack of oral options, especially in cases of antibiotic-resistant pathogens, explained Dr. Talley, of Spero Therapeutics.

In their new phase 3, double-blind randomized trial, the researchers evaluated the safety and effectiveness of oral TBP-PI-HBr, compared with intravenous ertapenem in hospitalized patients with cUTIs or AP. Oral tebipenem is an investigational carbapenem with demonstrated activity against uropathogenic Enterobacterales, and it has shown effectiveness in animal models, the researchers noted in their paper.
 

Methods and results

The researchers randomized 1,372 adult patients. The microbiologic intent-to-treat population included 449 patients who received TBP-PI-HBr (600 mg every 8 hours) and 419 who received ertapenem (1 g every 24 hours) for 7-10 days or up to 14 days for patients with bacteremia.

The primary endpoint was a composite of clinical cure and favorable microbiologic response, assessed at a test-of-cure visit on day 19. Clinical cure was defined as “complete resolution or clinically significant alleviation of baseline signs and symptoms of complicated urinary tract infection or acute pyelonephritis and no new symptoms, such that no further antimicrobial therapy was warranted,” the researchers wrote. Microbiologic response was defined as a reduction to less than 103 CFU per milliliter in uropathogen levels from baseline at day 19.

Overall, the clinical response occurred in 58.8% of patients who received TBP-PI-HBr and 61.6% of those who received ertapenem at the test-of-cure visit.

Clinical cure rates were similar in the TBP-PI-HBr and ertapenem groups (93.1% vs. 93.6%) at the test-of-cure visit.

Both treatment groups showed similar responses to Enterobacterales pathogens at the test-of-cure visit (62.7% for TBP-PI-HBr and 65.2% for ertapenem).

Among patients with bacteremia at baseline, overall response rates were 72.3% and 66.0% for TBP-PI-HBr and ertapenem, respectively, at the test-of-cure visit, and 93.6% and 96.2%, respectively, at the end-of-treatment visit on or around day 25.

The overall incidence of adverse events was approximately 26% in both treatment groups. Most adverse events were mild or moderate in severity and did not limit treatment, the researchers wrote.

The mean age of the patients was 58.1 years; 46.1% were aged 65 and older, and 11.5% had bacteremia at baseline.

The study findings were limited by several factors, including the mandated 7- to 10-day course of antibiotics, which may not reflect the standard of care in other settings in the United States. The study’s trial sites were located in the United States, South Africa, and Europe. The study population was primarily White and from Central and Eastern Europe. Other limitations included the randomization of patients before confirming the baseline pathogen, although this was done to limit potential confounding from previous antibiotics, the researchers noted.
 

Safety and efficacy support application for approval

“To our knowledge, this is the first head-to-head evaluation of an IV vs. an oral drug for the treatment of cUTI and acute pyelonephritis,” Dr. Talley said in an interview.  

“The findings demonstrate that almost all patients in the study achieved complete resolution of the signs and symptoms of their infection,” she said.

TBP-PI-HBr has not been approved by the Food and Drug Administration, but a new drug application that included data from the current study was submitted to the FDA and is currently under review, Dr. Talley noted.

As for additional research, the current study was conducted in hospitalized patients, and the use of TBP-PI-HBr in the outpatient setting has not yet been evaluated, she said.
 

Approval and use of oral carbapenem will change practice

The current study is very important because it provides a viable and effective alternative form of antibiotic delivery for the patients with complicated UTI, Noel N. Deep, MD, emphasized in an interview.

“Currently these patients have to be treated with IV carbapenem antibiotics either in a hospital or through a home health nurse,” Dr. Deep, a general internist in group practice in Antigo, Wisc., explained.

Current IV strategies also carry the inherent risk associated with the insertion of an IV catheter that is left in place for several days or replaced periodically. “The oral antibiotic eliminates these risks and higher health care costs and provides a safer and equally efficacious option,” Dr. Deep said.

In the current study, “I was definitely surprised at the effectiveness of the oral carbapenem,” Dr. Deep said. “I am absolutely delighted with this new treatment option that physicians can now add to their armamentarium [assuming FDA approval] as we provide care to our patients,” he said.

If approved, TBP-PI-HBr will definitely change the treatment spectrum for the multidrug-resistant bacterial UTIs, said Dr. Deep. “Carbapenems have continued to be effective and low antibiotic resistance to carbapenems has been recorded.”

As for additional research, “I would like to see studies done in other ethnicities and different countries to ascertain the effectiveness of this antibiotic in those populations and against other bacterial strains with potentially different resistance mechanisms,” Dr. Deep said.

The study was supported by Spero Therapeutics and the Department of Health and Human Services. Lead author Paul B. Eckburg, MD, of Stanford (Calif.) University, and Dr. Talley are employees of Spero Therapeutics. Dr. Deep had no financial conflicts to disclose, but serves on the editorial advisory board of Internal Medicine News.

Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.

“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.

“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.

In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.

“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.

The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.

The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).

After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).

In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.

The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.

Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.

Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).

Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.

“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.

“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.

The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.

“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.

However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
 

Estradiol may have limited clinical impact

“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.

Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”

For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.

“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.

The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.

“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.

“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.

In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.

“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.

The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.

The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).

After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).

In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.

The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.

Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.

Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).

Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.

“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.

“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.

The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.

“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.

However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
 

Estradiol may have limited clinical impact

“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.

Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”

For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.

“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.

The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Vaginal estradiol tablets promoted significant changes in the vaginal microbiota in postmenopausal women compared with vaginal moisturizer or placebo, but reduction in bothersome symptoms were similar, based on data from 144 individuals.

“In the Menopause Strategies–Finding Lasting Answers and Health (MsFLASH) trial network’s Vaginal Health Trial of treatment for moderate to severe vaginal symptoms of menopause, there were no significant differences in reduction of vaginal symptoms among women using the estradiol vaginal tablet or vaginal moisturizer compared to women using the placebo regimen; all three groups had a reduction in vaginal symptoms,” lead author Sujatha Srinivasan, PhD, of the Fred Hutchinson Cancer Center, Seattle, said in an interview.

“However, the impact of these treatments on the vaginal microenvironment are poorly understood,” she said.

In a study published in JAMA Network Open, Dr. Srinivasan and colleagues conducted a secondary analysis to examine the effects of estradiol or a low-pH vaginal moisturizer on the vaginal microbiota, metabolome, and pH after 12 weeks of treatment vs. a low-pH placebo.

“Changes, or lack thereof, in the vaginal microenvironment might have implications beyond symptoms, and might be linked to risk for cervical cancer, genital infections, or other outcomes, though our study did not evaluate those associations,” Dr. Srinivasan said in an interview. Dr. Srinivasan’s comments were corroborated by coauthor Caroline M. Mitchell, MD, of Massachusetts General Hospital, Boston.

The study population included postmenopausal women with moderate to severe genitourinary symptoms who were enrolled in a randomized, controlled trial between April 2016 and February 2017. The average age of the women was 61 years, and 90% were White. The women were randomized to 10 mcg vaginal estradiol plus placebo gel, placebo tablet plus vaginal moisturizer, or a dual placebo.

The primary outcome in the original study was a change in the reported most bothersome symptoms (MBS) selected by the participants at the time of study enrollment; these included pain with penetration, vaginal dryness, and vulvovaginal irritation, itching, and pain. The main outcomes in the secondary analysis were changes in the diversity and composition of the vaginal microbiota, changes in the metabolome, and pH. Microbiota diversity was calculated via the Shannon Diversity Index (SDI).

After 12 weeks, the bacterial microbiota were dominated by Lactobacillus and Bifidobacterium in 80% of the estradiol group, 36% of the moisturizer group, and 26% of the placebo group (P < .001).

In addition, diversity analysis showed significant changes in bacterial composition in women in the estradiol group compared with the placebo group, but no significant differences between the moisturizer and placebo groups.

The composition of vaginal fluid small molecule metabolites changed significantly in 90 of 171 metabolites measured in the estradiol group from baseline to 12 weeks. Changes in the moisturizer and placebo groups were not significant.

Vaginal pH among women in the estradiol group was significantly lower than placebo at 12 weeks, with a median of 5 vs. 6 (P = .005). No significant difference in pH occurred for women in the moisturizer group. “However, pH significantly decreased over 12 weeks within each treatment group, reflecting the low-pH formulations of both the moisturizer and the placebo,” the researchers wrote.

Overall, women with high-diversity bacterial communities at baseline showed a greater median change in pH compared with women with low-diversity communities (median change of −1 vs. −0.3, P = .007).

Improvement in MBS symptoms by at least 2 points occurred in 53% of the estradiol group, 44% of the moisturizer group, and 49% of the placebo group. The similarity in severe symptom improvement among the groups confirms the lack of a causal association between microbiota and postmenopausal vaginal symptom severity, the researchers wrote.

“This study demonstrated that a decrease in vaginal pH alone was insufficient to change the vaginal microbiota,” Dr. Srinivasan said. “While the changes with estrogen were somewhat expected, the observation that low-pH vaginal products don’t change the vaginal microbiota is contrary to some expectations, and suggests that “low-pH” products may not be as helpful as their marketing claims,” she added. “A vaginal microbiota with an abundance of lactobacilli, a vaginal microenvironment with high concentrations of lactate, and a low vaginal pH is associated with health in premenopausal women. We also know that such a microenvironment is typically associated with low inflammation,” said Dr. Srinivasan. “At this time, we don’t have specific information as to how this is beneficial to postmenopausal women,” she noted. However, “If we extrapolate from the data on premenopausal women, the data from this secondary analysis suggests that vaginal estradiol may have positive impacts on the vaginal microenvironment regardless of impact on symptoms,” she said.

“Future areas of investigation should focus on understanding potential benefits of a Lactobacillus-dominant microbiota in postmenopausal women,” Dr. Srinivasan said.

The study findings were limited by several factors including the relatively small number of participants, and collection of data samples at only three time periods, as well as the lack of data on whether the observed changes are durable over longer treatment times, the researchers noted.

“The need to increase participant diversity in studies of postmenopausal women is highlighted by our finding that the 6 Black women in our analysis were all categorized in the low-diversity subgroup; data from premenopausal women suggest that Black women have diverse bacterial communities,” they added.

However, the results suggest that “a significant decrease in pH over the course of a trial may not reflect the same underlying biological processes among different interventions, and thus, lowering pH should not be a primary goal,” they concluded.
 

Estradiol may have limited clinical impact

“For postmenopausal women with dyspareunia, vaginal dryness, and/or burning/itching/irritation, the question of appropriate treatment is common,” Constance Bohon, MD, a gynecologist in private practice in Washington, said in an interview. “It is helpful to have a study that focuses on the benefit of a moisturizer as compared with vaginal estrogen for these women,” she said.

Dr. Bohon said she was not surprised with the benefits of the moisturizer for dyspareunia and vaginal dryness. “What did surprise me was that the complaint of vaginal itch, burn, or irritation was not significantly improved in the vaginal estrogen group compared with the moisturizer group. I assumed that estrogen would have been more beneficial in this group because these symptoms are more likely to be caused by a vaginal infection that would not be improved with moisturizer alone,” she said. “I expected that the change in the vaginal flora to increase Lactobacillus would have had a greater impact on an infection than the moisturizer, which did not significantly change the flora.”

For clinicians, the take-home message is that, for these patients, use of a moisturizer may be sufficient, Dr. Bohon said.

“Additional research should be done to assess each issue,” she noted. “For example, in the women who have pain with sex, what is the frequency of intercourse?” she asked. Other research should address the questions of whether women who have intercourse at least once a week have less dyspareunia than those who have less frequent sex, and whether a lubricant decreases dyspareunia as well as a moisturizer or vaginal estrogen, she added.

The study was supported by the National Institutes of Health. Dr. Srinivasan disclosed personal fees from Lupin unrelated to the current study. Dr. Bohon had no financial conflicts to disclose and serves on the editorial advisory board of Ob.Gyn. News.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Outcomes for patients with bacteremic Streptococcus pneumoniae were significantly worse than those for patients with Legionnaires disease (LD), based on data from 106 individuals.

Reported cases of LD in the United States have increased in recent decades, but they are likely under-reported, wrote Sima Salahie, MD, of Wayne State University School of Medicine, Detroit, and Central Michigan University College of Medicine, Grosse Pointe Woods, and colleagues.

Clinical presentations may be similar for both conditions, but different antimicrobial therapies are needed; therefore, identifying distinguishing factors can promote better management of hospitalized patients, they reported.

In a retrospective case companion study published in the American Journal of the Medical Sciences, the researchers reviewed data from 51 adults with LD and 55 with bacteremic S. pneumoniae pneumonia (SP) who were hospitalized at a single center between 2013 and 2018. Diagnoses were confirmed by laboratory and radiology results. In addition, data were collected on clinical features including body mass index, systolic and diastolic blood pressure, pulse, respiratory rate, and temperature.

Overall, patients with SP were significantly more likely than those with LD to require mechanical ventilation (P = .04), intensive care unit stay (P = .004), and to die (P = .002). Patients with SP also had higher rates of septic shock compared to LD patients, although this difference fell short of statistical significance (49.1% vs. 30.4%; P = .06).

In a multivariate analysis, male sex, diarrhea, higher body mass index, hyponatremia, and lower Charleston Weighted Index of Comorbidity (CWIC) score were significant independent predictors of LD, with odds ratios of 21.6, 4.5, 1.13, 5.6, and 0.61, respectively.

The incidence of LD peaked in summer, while the incidence of SP peaked in the winter, the researchers noted. “Seasonality is a variable that has not always been included in previous scoring systems but should be considered in future modeling,” they said.

“Noteworthy is that LD represented almost as many cases as documented bacteremic pneumococcal pneumonia,” the researchers wrote in their discussion. “This occurred at a time when there was no outbreak of L. pneumophila in our community, and as these were all community acquired, there was no evidence of a nosocomial outbreak in our institution,” they said.

The study findings were limited by several factors, including the possible underestimation of SP because of the requirement for positive blood cultures and the lack of other methods of diagnosing SP, the researchers noted.

“However, the data suggest variables to distinguish LD from SP,” they said. “Establishing reliable clinical and laboratory parameters embedded in a simple diagnostic score that can accurately identify patients with LD may be helpful in aiding physicians’ early diagnosis in distinguishing LD from SP but will need to be defined.”

The study received no outside funding. The researchers disclosed no financial conflicts.

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

Outcomes for patients with bacteremic Streptococcus pneumoniae were significantly worse than those for patients with Legionnaires disease (LD), based on data from 106 individuals.

Reported cases of LD in the United States have increased in recent decades, but they are likely under-reported, wrote Sima Salahie, MD, of Wayne State University School of Medicine, Detroit, and Central Michigan University College of Medicine, Grosse Pointe Woods, and colleagues.

Clinical presentations may be similar for both conditions, but different antimicrobial therapies are needed; therefore, identifying distinguishing factors can promote better management of hospitalized patients, they reported.

In a retrospective case companion study published in the American Journal of the Medical Sciences, the researchers reviewed data from 51 adults with LD and 55 with bacteremic S. pneumoniae pneumonia (SP) who were hospitalized at a single center between 2013 and 2018. Diagnoses were confirmed by laboratory and radiology results. In addition, data were collected on clinical features including body mass index, systolic and diastolic blood pressure, pulse, respiratory rate, and temperature.

Overall, patients with SP were significantly more likely than those with LD to require mechanical ventilation (P = .04), intensive care unit stay (P = .004), and to die (P = .002). Patients with SP also had higher rates of septic shock compared to LD patients, although this difference fell short of statistical significance (49.1% vs. 30.4%; P = .06).

In a multivariate analysis, male sex, diarrhea, higher body mass index, hyponatremia, and lower Charleston Weighted Index of Comorbidity (CWIC) score were significant independent predictors of LD, with odds ratios of 21.6, 4.5, 1.13, 5.6, and 0.61, respectively.

The incidence of LD peaked in summer, while the incidence of SP peaked in the winter, the researchers noted. “Seasonality is a variable that has not always been included in previous scoring systems but should be considered in future modeling,” they said.

“Noteworthy is that LD represented almost as many cases as documented bacteremic pneumococcal pneumonia,” the researchers wrote in their discussion. “This occurred at a time when there was no outbreak of L. pneumophila in our community, and as these were all community acquired, there was no evidence of a nosocomial outbreak in our institution,” they said.

The study findings were limited by several factors, including the possible underestimation of SP because of the requirement for positive blood cultures and the lack of other methods of diagnosing SP, the researchers noted.

“However, the data suggest variables to distinguish LD from SP,” they said. “Establishing reliable clinical and laboratory parameters embedded in a simple diagnostic score that can accurately identify patients with LD may be helpful in aiding physicians’ early diagnosis in distinguishing LD from SP but will need to be defined.”

The study received no outside funding. The researchers disclosed no financial conflicts.

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

Outcomes for patients with bacteremic Streptococcus pneumoniae were significantly worse than those for patients with Legionnaires disease (LD), based on data from 106 individuals.

Reported cases of LD in the United States have increased in recent decades, but they are likely under-reported, wrote Sima Salahie, MD, of Wayne State University School of Medicine, Detroit, and Central Michigan University College of Medicine, Grosse Pointe Woods, and colleagues.

Clinical presentations may be similar for both conditions, but different antimicrobial therapies are needed; therefore, identifying distinguishing factors can promote better management of hospitalized patients, they reported.

In a retrospective case companion study published in the American Journal of the Medical Sciences, the researchers reviewed data from 51 adults with LD and 55 with bacteremic S. pneumoniae pneumonia (SP) who were hospitalized at a single center between 2013 and 2018. Diagnoses were confirmed by laboratory and radiology results. In addition, data were collected on clinical features including body mass index, systolic and diastolic blood pressure, pulse, respiratory rate, and temperature.

Overall, patients with SP were significantly more likely than those with LD to require mechanical ventilation (P = .04), intensive care unit stay (P = .004), and to die (P = .002). Patients with SP also had higher rates of septic shock compared to LD patients, although this difference fell short of statistical significance (49.1% vs. 30.4%; P = .06).

In a multivariate analysis, male sex, diarrhea, higher body mass index, hyponatremia, and lower Charleston Weighted Index of Comorbidity (CWIC) score were significant independent predictors of LD, with odds ratios of 21.6, 4.5, 1.13, 5.6, and 0.61, respectively.

The incidence of LD peaked in summer, while the incidence of SP peaked in the winter, the researchers noted. “Seasonality is a variable that has not always been included in previous scoring systems but should be considered in future modeling,” they said.

“Noteworthy is that LD represented almost as many cases as documented bacteremic pneumococcal pneumonia,” the researchers wrote in their discussion. “This occurred at a time when there was no outbreak of L. pneumophila in our community, and as these were all community acquired, there was no evidence of a nosocomial outbreak in our institution,” they said.

The study findings were limited by several factors, including the possible underestimation of SP because of the requirement for positive blood cultures and the lack of other methods of diagnosing SP, the researchers noted.

“However, the data suggest variables to distinguish LD from SP,” they said. “Establishing reliable clinical and laboratory parameters embedded in a simple diagnostic score that can accurately identify patients with LD may be helpful in aiding physicians’ early diagnosis in distinguishing LD from SP but will need to be defined.”

The study received no outside funding. The researchers disclosed no financial conflicts.

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

Histologic remission using the Nancy Histologic Index (NHI) was superior to endoscopic mucosal healing in predicting relapse-free survival in ulcerative colitis (UC), based on data from 74 patients.

A growing body of evidence suggests that UC patients in both histologic and endoscopic remission experience longer relapse-free survival and improved outcomes, but data on specific histologic assessments are limited, wrote Hunter Wang, MBBS, of Canberra Hospital, Australia, and colleagues. The NHI is a validated score drawing interest as an option for predicting survival, they said.

In a retrospective cohort study published Feb. 28 in the Journal of Clinical Gastroenterology, the researchers identified 74 adults aged 18 years and older with UC who were treated at a single center between 2009 and 2017. All patients were in clinical and endoscopic remission without concurrent corticosteroid use. Mucosal healing was defined as Mayo endoscopic subscore (MES) of 1 or less, and clinical remission was defined as partial Mayo score (MSp) less than 2. The median age of the participants was 41 years, and the median disease duration was 8 years at the time of surveillance colonoscopy.

Over a median follow-up of 42 months, patients with an MES of 0 and histologic remission had significantly longer relapse-free survival compared to those with MES 1 and NHI 2 to 4, respectively.

Thirty-three patients relapsed during the study period. Clinical relapse rates were similar for patients with MES 0 and MES 1 (40% and 52%, respectively), but only 29% of patients in histologic remission at baseline relapsed vs. 64% of those with histologic activity at baseline (P = 0.0064).

Risk factors for earlier relapse on univariate analysis included MES 1 and NHI 2 to 4. Only histologic activity predicted future relapse in a multivariate analysis (hazard ratio, 4.36, P = 0.002).

The study findings reflect data from previous research supporting the prognostic value of histologic remission using NHI, the researchers noted in their discussion. Barriers to adoption of histologic indices include “their multiplicity, complexity, lack of validation, and inconsistent incorporation in randomized controlled trials,” which create challenges in interpreting and comparing research outcomes, they wrote.

The study findings were limited by several factors, including the retrospective design, collection of clinical and endoscopic variables from electronic medical records without objective measures of relapse, lack of standardization of colonic biopsies, and lack of power to detect differences in dysplasia and colectomy, the researchers noted.

The results suggest that histologic remission using the NHI serves as an effective predictor of longer relapse-free survival in UC patients with clinical and endoscopic remission, they said.

“Further prospective trials are needed to clarify whether histologic remission as a therapeutic endpoint in addition to endoscopic remission will alter disease course and patient outcomes,” while helping guide treatment management decisions for patients and clinicians, the researchers concluded.

Not the ultimate endpoint?

“There is ongoing interest in whether histological findings (biopsies) of the mucosa are a clinically important and reachable treatment goal in ulcerative colitis,” David T. Rubin, MD, of the University of Chicago, who was not involved in the study, said in an interview.

Questions about this approach remain, such as how findings should be incorporated into clinical care and whether histology offers advantages over patient-reported symptoms, endoscopic findings, or other surrogates of inflammation like calprotectin, a protein related to histology detected in stool, Dr. Rubin explained.

“A number of retrospective studies have demonstrated the clinical importance of achieving histological remission, but the details of how to get there are not yet clearly defined. In this study, using one of the established indices of histological activity, the Nancy Histological Index, those patients who achieved histological remission had better clinical outcomes (stable remission) than symptoms alone or endoscopy alone.”

According to Dr. Rubin, clinicians can inform patients that histological remission supports that the therapy is working and they have a very good likelihood of staying in remission over the next year.

“Importantly, this is not the same as saying we should treat to get to this endpoint,” Dr. Rubin emphasized. “If a patient is in clinical remission with normalized labs and endoscopy (or calprotectin) that show healing, we do not yet recommend adjusting therapy for histological endpoints. This was edified in the consensus paper called STRIDE 2, published in Gastroenterology in 2021.”

As for additional research, the ongoing prospective randomized VERDICT trial is exploring different endpoints of treatment, “one of which is the combination of symptoms, endoscopy, and histology to assess whether this is better than symptoms or endoscopy alone,” said Dr. Rubin. “We also need more work to understand the timing of this finding, the number of biopsies that may be required to get an adequate assessment of the bowel, how pathologists should read and interpret our findings, when we should relook if we adjust therapy, and whether some therapies are more or less likely to achieve this endpoint,” he said.

The study received no outside funding. Neither the researchers nor Dr. Rubin reported any financial disclosures.

Histologic remission using the Nancy Histologic Index (NHI) was superior to endoscopic mucosal healing in predicting relapse-free survival in ulcerative colitis (UC), based on data from 74 patients.

A growing body of evidence suggests that UC patients in both histologic and endoscopic remission experience longer relapse-free survival and improved outcomes, but data on specific histologic assessments are limited, wrote Hunter Wang, MBBS, of Canberra Hospital, Australia, and colleagues. The NHI is a validated score drawing interest as an option for predicting survival, they said.

In a retrospective cohort study published Feb. 28 in the Journal of Clinical Gastroenterology, the researchers identified 74 adults aged 18 years and older with UC who were treated at a single center between 2009 and 2017. All patients were in clinical and endoscopic remission without concurrent corticosteroid use. Mucosal healing was defined as Mayo endoscopic subscore (MES) of 1 or less, and clinical remission was defined as partial Mayo score (MSp) less than 2. The median age of the participants was 41 years, and the median disease duration was 8 years at the time of surveillance colonoscopy.

Over a median follow-up of 42 months, patients with an MES of 0 and histologic remission had significantly longer relapse-free survival compared to those with MES 1 and NHI 2 to 4, respectively.

Thirty-three patients relapsed during the study period. Clinical relapse rates were similar for patients with MES 0 and MES 1 (40% and 52%, respectively), but only 29% of patients in histologic remission at baseline relapsed vs. 64% of those with histologic activity at baseline (P = 0.0064).

Risk factors for earlier relapse on univariate analysis included MES 1 and NHI 2 to 4. Only histologic activity predicted future relapse in a multivariate analysis (hazard ratio, 4.36, P = 0.002).

The study findings reflect data from previous research supporting the prognostic value of histologic remission using NHI, the researchers noted in their discussion. Barriers to adoption of histologic indices include “their multiplicity, complexity, lack of validation, and inconsistent incorporation in randomized controlled trials,” which create challenges in interpreting and comparing research outcomes, they wrote.

The study findings were limited by several factors, including the retrospective design, collection of clinical and endoscopic variables from electronic medical records without objective measures of relapse, lack of standardization of colonic biopsies, and lack of power to detect differences in dysplasia and colectomy, the researchers noted.

The results suggest that histologic remission using the NHI serves as an effective predictor of longer relapse-free survival in UC patients with clinical and endoscopic remission, they said.

“Further prospective trials are needed to clarify whether histologic remission as a therapeutic endpoint in addition to endoscopic remission will alter disease course and patient outcomes,” while helping guide treatment management decisions for patients and clinicians, the researchers concluded.

Not the ultimate endpoint?

“There is ongoing interest in whether histological findings (biopsies) of the mucosa are a clinically important and reachable treatment goal in ulcerative colitis,” David T. Rubin, MD, of the University of Chicago, who was not involved in the study, said in an interview.

Questions about this approach remain, such as how findings should be incorporated into clinical care and whether histology offers advantages over patient-reported symptoms, endoscopic findings, or other surrogates of inflammation like calprotectin, a protein related to histology detected in stool, Dr. Rubin explained.

“A number of retrospective studies have demonstrated the clinical importance of achieving histological remission, but the details of how to get there are not yet clearly defined. In this study, using one of the established indices of histological activity, the Nancy Histological Index, those patients who achieved histological remission had better clinical outcomes (stable remission) than symptoms alone or endoscopy alone.”

According to Dr. Rubin, clinicians can inform patients that histological remission supports that the therapy is working and they have a very good likelihood of staying in remission over the next year.

“Importantly, this is not the same as saying we should treat to get to this endpoint,” Dr. Rubin emphasized. “If a patient is in clinical remission with normalized labs and endoscopy (or calprotectin) that show healing, we do not yet recommend adjusting therapy for histological endpoints. This was edified in the consensus paper called STRIDE 2, published in Gastroenterology in 2021.”

As for additional research, the ongoing prospective randomized VERDICT trial is exploring different endpoints of treatment, “one of which is the combination of symptoms, endoscopy, and histology to assess whether this is better than symptoms or endoscopy alone,” said Dr. Rubin. “We also need more work to understand the timing of this finding, the number of biopsies that may be required to get an adequate assessment of the bowel, how pathologists should read and interpret our findings, when we should relook if we adjust therapy, and whether some therapies are more or less likely to achieve this endpoint,” he said.

The study received no outside funding. Neither the researchers nor Dr. Rubin reported any financial disclosures.

Histologic remission using the Nancy Histologic Index (NHI) was superior to endoscopic mucosal healing in predicting relapse-free survival in ulcerative colitis (UC), based on data from 74 patients.

A growing body of evidence suggests that UC patients in both histologic and endoscopic remission experience longer relapse-free survival and improved outcomes, but data on specific histologic assessments are limited, wrote Hunter Wang, MBBS, of Canberra Hospital, Australia, and colleagues. The NHI is a validated score drawing interest as an option for predicting survival, they said.

In a retrospective cohort study published Feb. 28 in the Journal of Clinical Gastroenterology, the researchers identified 74 adults aged 18 years and older with UC who were treated at a single center between 2009 and 2017. All patients were in clinical and endoscopic remission without concurrent corticosteroid use. Mucosal healing was defined as Mayo endoscopic subscore (MES) of 1 or less, and clinical remission was defined as partial Mayo score (MSp) less than 2. The median age of the participants was 41 years, and the median disease duration was 8 years at the time of surveillance colonoscopy.

Over a median follow-up of 42 months, patients with an MES of 0 and histologic remission had significantly longer relapse-free survival compared to those with MES 1 and NHI 2 to 4, respectively.

Thirty-three patients relapsed during the study period. Clinical relapse rates were similar for patients with MES 0 and MES 1 (40% and 52%, respectively), but only 29% of patients in histologic remission at baseline relapsed vs. 64% of those with histologic activity at baseline (P = 0.0064).

Risk factors for earlier relapse on univariate analysis included MES 1 and NHI 2 to 4. Only histologic activity predicted future relapse in a multivariate analysis (hazard ratio, 4.36, P = 0.002).

The study findings reflect data from previous research supporting the prognostic value of histologic remission using NHI, the researchers noted in their discussion. Barriers to adoption of histologic indices include “their multiplicity, complexity, lack of validation, and inconsistent incorporation in randomized controlled trials,” which create challenges in interpreting and comparing research outcomes, they wrote.

The study findings were limited by several factors, including the retrospective design, collection of clinical and endoscopic variables from electronic medical records without objective measures of relapse, lack of standardization of colonic biopsies, and lack of power to detect differences in dysplasia and colectomy, the researchers noted.

The results suggest that histologic remission using the NHI serves as an effective predictor of longer relapse-free survival in UC patients with clinical and endoscopic remission, they said.

“Further prospective trials are needed to clarify whether histologic remission as a therapeutic endpoint in addition to endoscopic remission will alter disease course and patient outcomes,” while helping guide treatment management decisions for patients and clinicians, the researchers concluded.

Not the ultimate endpoint?

“There is ongoing interest in whether histological findings (biopsies) of the mucosa are a clinically important and reachable treatment goal in ulcerative colitis,” David T. Rubin, MD, of the University of Chicago, who was not involved in the study, said in an interview.

Questions about this approach remain, such as how findings should be incorporated into clinical care and whether histology offers advantages over patient-reported symptoms, endoscopic findings, or other surrogates of inflammation like calprotectin, a protein related to histology detected in stool, Dr. Rubin explained.

“A number of retrospective studies have demonstrated the clinical importance of achieving histological remission, but the details of how to get there are not yet clearly defined. In this study, using one of the established indices of histological activity, the Nancy Histological Index, those patients who achieved histological remission had better clinical outcomes (stable remission) than symptoms alone or endoscopy alone.”

According to Dr. Rubin, clinicians can inform patients that histological remission supports that the therapy is working and they have a very good likelihood of staying in remission over the next year.

“Importantly, this is not the same as saying we should treat to get to this endpoint,” Dr. Rubin emphasized. “If a patient is in clinical remission with normalized labs and endoscopy (or calprotectin) that show healing, we do not yet recommend adjusting therapy for histological endpoints. This was edified in the consensus paper called STRIDE 2, published in Gastroenterology in 2021.”

As for additional research, the ongoing prospective randomized VERDICT trial is exploring different endpoints of treatment, “one of which is the combination of symptoms, endoscopy, and histology to assess whether this is better than symptoms or endoscopy alone,” said Dr. Rubin. “We also need more work to understand the timing of this finding, the number of biopsies that may be required to get an adequate assessment of the bowel, how pathologists should read and interpret our findings, when we should relook if we adjust therapy, and whether some therapies are more or less likely to achieve this endpoint,” he said.

The study received no outside funding. Neither the researchers nor Dr. Rubin reported any financial disclosures.

The Food and Drug Administration has recommended thyroid monitoring for newborns and children through 3 years of age within 3 weeks of receiving injections of iodine-containing contrast media as part of imaging procedures.

A recent FDA review showed that “underactive thyroid or a temporary decrease in thyroid hormone levels were uncommon,” according to an updated Drug Safety Communication issued on March 30, 2022.

However, early monitoring will help identify and treat any thyroid abnormalities as a result of the injections to help prevent potential complications in the future, according to the FDA, as babies and children do not generally show visible signs of thyroid problems and may not do so after an iodinated contrast media (ICM) injection.

ICM have been approved and used for decades to enhance images on x-rays or computed tomography (CT) scans, according to the communication.

The new FDA warning and recommendation for monitoring applies to the prescribing information for the entire class of ICM products. The new communication is an update to the 2015 Drug Safety Communication that advised medical professionals of the potential for underactive thyroid in response to ICM injections in newborns and young children. The update reflects new studies since that time.

The recent research showed that most reported cases of adverse effects were transient subclinical hypothyroidism and did not require treatment, according to the FDA. “The reported rate ranged from 1 percent to 15 percent and tended to be higher in neonates, particularly preterm neonates,” they said. Others at increased risk are those with underlying medical conditions, especially those with cardiac conditions who often require higher doses of contrast during invasive procedures.

In the recent studies, the time from ICM exposure to a diagnosis of thyroid dysfunction ranged from 8.5 to 138 days, but most occurred within 3 weeks, according to the update.

Patients and clinicians can report any adverse events from ICM or other medications to the FDA via FDA MedWatch program.

For more information, read the complete Drug Safety Communication.

The Food and Drug Administration has recommended thyroid monitoring for newborns and children through 3 years of age within 3 weeks of receiving injections of iodine-containing contrast media as part of imaging procedures.

A recent FDA review showed that “underactive thyroid or a temporary decrease in thyroid hormone levels were uncommon,” according to an updated Drug Safety Communication issued on March 30, 2022.

However, early monitoring will help identify and treat any thyroid abnormalities as a result of the injections to help prevent potential complications in the future, according to the FDA, as babies and children do not generally show visible signs of thyroid problems and may not do so after an iodinated contrast media (ICM) injection.

ICM have been approved and used for decades to enhance images on x-rays or computed tomography (CT) scans, according to the communication.

The new FDA warning and recommendation for monitoring applies to the prescribing information for the entire class of ICM products. The new communication is an update to the 2015 Drug Safety Communication that advised medical professionals of the potential for underactive thyroid in response to ICM injections in newborns and young children. The update reflects new studies since that time.

The recent research showed that most reported cases of adverse effects were transient subclinical hypothyroidism and did not require treatment, according to the FDA. “The reported rate ranged from 1 percent to 15 percent and tended to be higher in neonates, particularly preterm neonates,” they said. Others at increased risk are those with underlying medical conditions, especially those with cardiac conditions who often require higher doses of contrast during invasive procedures.

In the recent studies, the time from ICM exposure to a diagnosis of thyroid dysfunction ranged from 8.5 to 138 days, but most occurred within 3 weeks, according to the update.

Patients and clinicians can report any adverse events from ICM or other medications to the FDA via FDA MedWatch program.

For more information, read the complete Drug Safety Communication.

The Food and Drug Administration has recommended thyroid monitoring for newborns and children through 3 years of age within 3 weeks of receiving injections of iodine-containing contrast media as part of imaging procedures.

A recent FDA review showed that “underactive thyroid or a temporary decrease in thyroid hormone levels were uncommon,” according to an updated Drug Safety Communication issued on March 30, 2022.

However, early monitoring will help identify and treat any thyroid abnormalities as a result of the injections to help prevent potential complications in the future, according to the FDA, as babies and children do not generally show visible signs of thyroid problems and may not do so after an iodinated contrast media (ICM) injection.

ICM have been approved and used for decades to enhance images on x-rays or computed tomography (CT) scans, according to the communication.

The new FDA warning and recommendation for monitoring applies to the prescribing information for the entire class of ICM products. The new communication is an update to the 2015 Drug Safety Communication that advised medical professionals of the potential for underactive thyroid in response to ICM injections in newborns and young children. The update reflects new studies since that time.

The recent research showed that most reported cases of adverse effects were transient subclinical hypothyroidism and did not require treatment, according to the FDA. “The reported rate ranged from 1 percent to 15 percent and tended to be higher in neonates, particularly preterm neonates,” they said. Others at increased risk are those with underlying medical conditions, especially those with cardiac conditions who often require higher doses of contrast during invasive procedures.

In the recent studies, the time from ICM exposure to a diagnosis of thyroid dysfunction ranged from 8.5 to 138 days, but most occurred within 3 weeks, according to the update.

Patients and clinicians can report any adverse events from ICM or other medications to the FDA via FDA MedWatch program.

For more information, read the complete Drug Safety Communication.

Children at risk of neonatal hypoglycemia who were screened and treated if needed showed no difference in educational achievement from controls at age 9-10 years, based on data from 480 children.

Previous studies have shown an increased risk of poor executive and visual-motor function in children with neonatal hypoglycemia, but the effect on later childhood academic performance remains unclear, wrote Rajesh Shah, PhD, of the University of Auckland, New Zealand, and colleagues.

In a prospective cohort study published in JAMA, the researchers enrolled moderate to late preterm and term infants born at increased risk for hypoglycemia; those with episodes of hypoglycemia were treated to maintain a blood glucose concentration of at least 47 mg/dL.

The study population was enrolled between 2006 and 2010 at a regional perinatal center in New Zealand, and their educational achievement was assessed 9-10 years later. The primary outcome of low educational achievement was defined as performing below the normal curriculum level in standardized tests of reading comprehension or math. The researchers also identified 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.

Rates of low educational achievement were not significantly different for children with and without neonatal hypoglycemia (47% vs. 48%, adjusted risk ratio 0.95).

No significant differences appeared between the two groups for any secondary outcomes, including reading comprehension, math, behavior manifestations of executive function, fine motor function, autism traits, and overall well-being, the researchers noted.

However, children with neonatal hypoglycemia were significantly less likely to be rated as below or well below reading curriculum level by teachers compared to those without neonatal hypoglycemia (24% vs. 31%).

The researchers cited a previous study of the same patient cohort at age 4.5 years, which suggested an association between adverse neurodevelopmental outcomes and infant hypoglycemia. However, the reason this association did not persist at age 9-10 years remains unclear, the researchers wrote in their discussion. “Early disturbances in brain development may have diminishing effects over time due to neuroplasticity, that is, reorganization of neural networks, or delayed maturation with mid-childhood catch-up in neurocognitive function,” they said.

The study findings were limited by several factors including the lack of data on several measures of cognition, notably processing speed, and a lack of adjustment for intelligence quotient at age 4.5 years, the lack of data on any treatment for developmental impairment, and the inclusion of a population with well-managed hypoglycemia, the researchers said.

However, the results were strengthened by having a sample size large enough to detect associations, the prospective design, and the accurate measure of neonatal glycemic exposure, they said. Although the results suggest that at-risk children reach similar endpoints by the end of primary school, “efforts to prevent and optimize adverse pregnancy conditions remain important, and developmental surveillance after birth should be considered for at-risk infants,” they concluded.

In a related study published in JAMA, Taygen Edwards and colleagues found that prophylactic oral dextrose gel had no significant effect on neurosensory function.

The study, a prospective follow-up of a multicenter randomized trial, included 1,197 later preterm or term infants deemed at risk for neonatal hypoglycemia. The infants (49% of whom were female) were randomized to prophylactic 40% dextrose gel or a placebo, massaged into the buccal mucosa at 1 hour after birth.

The primary outcome was neurosensory impairment at 2 years of age, which was assessed by neurologic examination, parent-reported medical questionnaires, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), performance-based executive function, Behavior Rating Inventory of Executive Function–Preschool Version, motion coherence thresholds, growth, and body composition.

At 2 years of age, the prevalence of neurosensory impairment was 21% and 19%, respectively, in infants randomized to prophylactic oral dextrose gel and placebo, a nonsignificant difference. No differences between the two groups were noted for cognitive and language delays, or low performance-based overall executive function. However, infants randomized to dextrose gel had significantly higher risk of motor delay compared to placebo (2.5% vs. 0.7%) and significantly lower Bayley-III composite scores for cognitive, language, and motor performance.

No significant differences were noted between the groups in the areas of moderate or severe neurosensory impairment, hearing impairment, cerebral palsy, developmental delay, above-average development, socioemotional and adaptive behavior, questionnaire-based executive function, low visual processing, history of seizures, allergic and infectious diseases, growth, and body composition.

The results are consistent with previous studies on the safety of dextrose gel, the researchers wrote in their discussion. However, the absolute difference of 7% in the primary outcome may be clinically important, they noted. “Caution is warranted before using prophylactic dextrose gel,” they said.

The researchers noted the results of a dose-finding trial that suggested improved scores on language, executive function, and motor skills in unadjusted analysis with higher doses of dextrose gel, but the reason for these findings remains unknown, they said.

The study findings were limited by the potential underpowering to detect small, but significant differences, and possible lack of generalizability because the majority of the participants were children of mothers with diabetes.

The results were strengthened by the high follow-up rate and comprehensive assessments, and highlight the need for additional research with longer follow-up, the researchers said.
 

Findings fuel further exploration

Although hypoglycemia is common in newborns, its management and potential outcomes remain subjects for debate, Paul J. Rozance, MD, of the University of Colorado, Aurora, wrote in an editorial accompanying both studies.

“Often, the same features that increase the risk of hypoglycemia in newborns also increase the risk for poor outcomes independent of hypoglycemia,” he said.

The study by Shah and colleagues was not a randomized trial of a specific management strategy, Dr. Rozance noted. However, the high rate of low educational attainment in children not exposed to dextrose gel emphasizes the need for more effective management of infant hypoglycemia, he said. “The findings also suggest that antenatal conditions that are associated with increased risk of hypoglycemia among newborns are associated with increased risk for impaired neurodevelopment and educational achievement, independent of neonatal hypoglycemia,” he said. The study findings contrast with those of an earlier study showing low academic achievement association with early transient hypoglycemia, which could argue for earlier intervention, he noted.

The study by Edwards and colleagues addressed the potential value of dextrose gel as an early intervention to prevent neonatal hypoglycemia, said Dr. Rozance.

“The 95% CI for the primary outcome of neurosensory impairment included up to a 7% increased risk for neurosensory impairment in the prophylactic dextrose gel group. The 7% increased risk was defined by the investigators as potentially clinically important, and the study may have been underpowered to detect small differences in the primary outcome,” he wrote.

Although the reasons for adverse outcomes in children given prophylactic dextrose gel remain unclear, “incorporation of prophylactic dextrose gel into clinical practice should await further research,” he said.

Regarding such research, Dr. Rozance proposed an “ideal study,” that would “randomize newborns with hypoglycemia to treatment or no treatment, although equipoise and ethical support for such a study are lacking. Another strategy would be to randomize newborns with hypoglycemia to receive low- or high-treatment glucose concentration goals,” he noted.

The relationship between hypoglycemia and impaired neurodevelopment is yet to be determined, but the two studies provide new evidence for the clinical importance and need for management of neonatal hypoglycemia and subsequent neurodevelopmental outcomes, he concluded.

The study by Shah and colleagues was supported by the Health Research Council of New Zealand and the Maurice and Phyllis Paykel Trust. Dr. Shah disclosed a doctoral fellowship from the University of Auckland. The study by Edwards and colleagues was supported by the Health Research Council of New Zealand and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Ms. Edwards had no financial conflicts to disclose. Dr. Rozance disclosed receiving a StatStrip from Nova Biomedical for use in his laboratory.

Children at risk of neonatal hypoglycemia who were screened and treated if needed showed no difference in educational achievement from controls at age 9-10 years, based on data from 480 children.

Previous studies have shown an increased risk of poor executive and visual-motor function in children with neonatal hypoglycemia, but the effect on later childhood academic performance remains unclear, wrote Rajesh Shah, PhD, of the University of Auckland, New Zealand, and colleagues.

In a prospective cohort study published in JAMA, the researchers enrolled moderate to late preterm and term infants born at increased risk for hypoglycemia; those with episodes of hypoglycemia were treated to maintain a blood glucose concentration of at least 47 mg/dL.

The study population was enrolled between 2006 and 2010 at a regional perinatal center in New Zealand, and their educational achievement was assessed 9-10 years later. The primary outcome of low educational achievement was defined as performing below the normal curriculum level in standardized tests of reading comprehension or math. The researchers also identified 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.

Rates of low educational achievement were not significantly different for children with and without neonatal hypoglycemia (47% vs. 48%, adjusted risk ratio 0.95).

No significant differences appeared between the two groups for any secondary outcomes, including reading comprehension, math, behavior manifestations of executive function, fine motor function, autism traits, and overall well-being, the researchers noted.

However, children with neonatal hypoglycemia were significantly less likely to be rated as below or well below reading curriculum level by teachers compared to those without neonatal hypoglycemia (24% vs. 31%).

The researchers cited a previous study of the same patient cohort at age 4.5 years, which suggested an association between adverse neurodevelopmental outcomes and infant hypoglycemia. However, the reason this association did not persist at age 9-10 years remains unclear, the researchers wrote in their discussion. “Early disturbances in brain development may have diminishing effects over time due to neuroplasticity, that is, reorganization of neural networks, or delayed maturation with mid-childhood catch-up in neurocognitive function,” they said.

The study findings were limited by several factors including the lack of data on several measures of cognition, notably processing speed, and a lack of adjustment for intelligence quotient at age 4.5 years, the lack of data on any treatment for developmental impairment, and the inclusion of a population with well-managed hypoglycemia, the researchers said.

However, the results were strengthened by having a sample size large enough to detect associations, the prospective design, and the accurate measure of neonatal glycemic exposure, they said. Although the results suggest that at-risk children reach similar endpoints by the end of primary school, “efforts to prevent and optimize adverse pregnancy conditions remain important, and developmental surveillance after birth should be considered for at-risk infants,” they concluded.

In a related study published in JAMA, Taygen Edwards and colleagues found that prophylactic oral dextrose gel had no significant effect on neurosensory function.

The study, a prospective follow-up of a multicenter randomized trial, included 1,197 later preterm or term infants deemed at risk for neonatal hypoglycemia. The infants (49% of whom were female) were randomized to prophylactic 40% dextrose gel or a placebo, massaged into the buccal mucosa at 1 hour after birth.

The primary outcome was neurosensory impairment at 2 years of age, which was assessed by neurologic examination, parent-reported medical questionnaires, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), performance-based executive function, Behavior Rating Inventory of Executive Function–Preschool Version, motion coherence thresholds, growth, and body composition.

At 2 years of age, the prevalence of neurosensory impairment was 21% and 19%, respectively, in infants randomized to prophylactic oral dextrose gel and placebo, a nonsignificant difference. No differences between the two groups were noted for cognitive and language delays, or low performance-based overall executive function. However, infants randomized to dextrose gel had significantly higher risk of motor delay compared to placebo (2.5% vs. 0.7%) and significantly lower Bayley-III composite scores for cognitive, language, and motor performance.

No significant differences were noted between the groups in the areas of moderate or severe neurosensory impairment, hearing impairment, cerebral palsy, developmental delay, above-average development, socioemotional and adaptive behavior, questionnaire-based executive function, low visual processing, history of seizures, allergic and infectious diseases, growth, and body composition.

The results are consistent with previous studies on the safety of dextrose gel, the researchers wrote in their discussion. However, the absolute difference of 7% in the primary outcome may be clinically important, they noted. “Caution is warranted before using prophylactic dextrose gel,” they said.

The researchers noted the results of a dose-finding trial that suggested improved scores on language, executive function, and motor skills in unadjusted analysis with higher doses of dextrose gel, but the reason for these findings remains unknown, they said.

The study findings were limited by the potential underpowering to detect small, but significant differences, and possible lack of generalizability because the majority of the participants were children of mothers with diabetes.

The results were strengthened by the high follow-up rate and comprehensive assessments, and highlight the need for additional research with longer follow-up, the researchers said.
 

Findings fuel further exploration

Although hypoglycemia is common in newborns, its management and potential outcomes remain subjects for debate, Paul J. Rozance, MD, of the University of Colorado, Aurora, wrote in an editorial accompanying both studies.

“Often, the same features that increase the risk of hypoglycemia in newborns also increase the risk for poor outcomes independent of hypoglycemia,” he said.

The study by Shah and colleagues was not a randomized trial of a specific management strategy, Dr. Rozance noted. However, the high rate of low educational attainment in children not exposed to dextrose gel emphasizes the need for more effective management of infant hypoglycemia, he said. “The findings also suggest that antenatal conditions that are associated with increased risk of hypoglycemia among newborns are associated with increased risk for impaired neurodevelopment and educational achievement, independent of neonatal hypoglycemia,” he said. The study findings contrast with those of an earlier study showing low academic achievement association with early transient hypoglycemia, which could argue for earlier intervention, he noted.

The study by Edwards and colleagues addressed the potential value of dextrose gel as an early intervention to prevent neonatal hypoglycemia, said Dr. Rozance.

“The 95% CI for the primary outcome of neurosensory impairment included up to a 7% increased risk for neurosensory impairment in the prophylactic dextrose gel group. The 7% increased risk was defined by the investigators as potentially clinically important, and the study may have been underpowered to detect small differences in the primary outcome,” he wrote.

Although the reasons for adverse outcomes in children given prophylactic dextrose gel remain unclear, “incorporation of prophylactic dextrose gel into clinical practice should await further research,” he said.

Regarding such research, Dr. Rozance proposed an “ideal study,” that would “randomize newborns with hypoglycemia to treatment or no treatment, although equipoise and ethical support for such a study are lacking. Another strategy would be to randomize newborns with hypoglycemia to receive low- or high-treatment glucose concentration goals,” he noted.

The relationship between hypoglycemia and impaired neurodevelopment is yet to be determined, but the two studies provide new evidence for the clinical importance and need for management of neonatal hypoglycemia and subsequent neurodevelopmental outcomes, he concluded.

The study by Shah and colleagues was supported by the Health Research Council of New Zealand and the Maurice and Phyllis Paykel Trust. Dr. Shah disclosed a doctoral fellowship from the University of Auckland. The study by Edwards and colleagues was supported by the Health Research Council of New Zealand and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Ms. Edwards had no financial conflicts to disclose. Dr. Rozance disclosed receiving a StatStrip from Nova Biomedical for use in his laboratory.

Children at risk of neonatal hypoglycemia who were screened and treated if needed showed no difference in educational achievement from controls at age 9-10 years, based on data from 480 children.

Previous studies have shown an increased risk of poor executive and visual-motor function in children with neonatal hypoglycemia, but the effect on later childhood academic performance remains unclear, wrote Rajesh Shah, PhD, of the University of Auckland, New Zealand, and colleagues.

In a prospective cohort study published in JAMA, the researchers enrolled moderate to late preterm and term infants born at increased risk for hypoglycemia; those with episodes of hypoglycemia were treated to maintain a blood glucose concentration of at least 47 mg/dL.

The study population was enrolled between 2006 and 2010 at a regional perinatal center in New Zealand, and their educational achievement was assessed 9-10 years later. The primary outcome of low educational achievement was defined as performing below the normal curriculum level in standardized tests of reading comprehension or math. The researchers also identified 47 secondary outcomes related to executive function, visual-motor function, psychosocial adaptation, and general health.

Rates of low educational achievement were not significantly different for children with and without neonatal hypoglycemia (47% vs. 48%, adjusted risk ratio 0.95).

No significant differences appeared between the two groups for any secondary outcomes, including reading comprehension, math, behavior manifestations of executive function, fine motor function, autism traits, and overall well-being, the researchers noted.

However, children with neonatal hypoglycemia were significantly less likely to be rated as below or well below reading curriculum level by teachers compared to those without neonatal hypoglycemia (24% vs. 31%).

The researchers cited a previous study of the same patient cohort at age 4.5 years, which suggested an association between adverse neurodevelopmental outcomes and infant hypoglycemia. However, the reason this association did not persist at age 9-10 years remains unclear, the researchers wrote in their discussion. “Early disturbances in brain development may have diminishing effects over time due to neuroplasticity, that is, reorganization of neural networks, or delayed maturation with mid-childhood catch-up in neurocognitive function,” they said.

The study findings were limited by several factors including the lack of data on several measures of cognition, notably processing speed, and a lack of adjustment for intelligence quotient at age 4.5 years, the lack of data on any treatment for developmental impairment, and the inclusion of a population with well-managed hypoglycemia, the researchers said.

However, the results were strengthened by having a sample size large enough to detect associations, the prospective design, and the accurate measure of neonatal glycemic exposure, they said. Although the results suggest that at-risk children reach similar endpoints by the end of primary school, “efforts to prevent and optimize adverse pregnancy conditions remain important, and developmental surveillance after birth should be considered for at-risk infants,” they concluded.

In a related study published in JAMA, Taygen Edwards and colleagues found that prophylactic oral dextrose gel had no significant effect on neurosensory function.

The study, a prospective follow-up of a multicenter randomized trial, included 1,197 later preterm or term infants deemed at risk for neonatal hypoglycemia. The infants (49% of whom were female) were randomized to prophylactic 40% dextrose gel or a placebo, massaged into the buccal mucosa at 1 hour after birth.

The primary outcome was neurosensory impairment at 2 years of age, which was assessed by neurologic examination, parent-reported medical questionnaires, Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), performance-based executive function, Behavior Rating Inventory of Executive Function–Preschool Version, motion coherence thresholds, growth, and body composition.

At 2 years of age, the prevalence of neurosensory impairment was 21% and 19%, respectively, in infants randomized to prophylactic oral dextrose gel and placebo, a nonsignificant difference. No differences between the two groups were noted for cognitive and language delays, or low performance-based overall executive function. However, infants randomized to dextrose gel had significantly higher risk of motor delay compared to placebo (2.5% vs. 0.7%) and significantly lower Bayley-III composite scores for cognitive, language, and motor performance.

No significant differences were noted between the groups in the areas of moderate or severe neurosensory impairment, hearing impairment, cerebral palsy, developmental delay, above-average development, socioemotional and adaptive behavior, questionnaire-based executive function, low visual processing, history of seizures, allergic and infectious diseases, growth, and body composition.

The results are consistent with previous studies on the safety of dextrose gel, the researchers wrote in their discussion. However, the absolute difference of 7% in the primary outcome may be clinically important, they noted. “Caution is warranted before using prophylactic dextrose gel,” they said.

The researchers noted the results of a dose-finding trial that suggested improved scores on language, executive function, and motor skills in unadjusted analysis with higher doses of dextrose gel, but the reason for these findings remains unknown, they said.

The study findings were limited by the potential underpowering to detect small, but significant differences, and possible lack of generalizability because the majority of the participants were children of mothers with diabetes.

The results were strengthened by the high follow-up rate and comprehensive assessments, and highlight the need for additional research with longer follow-up, the researchers said.
 

Findings fuel further exploration

Although hypoglycemia is common in newborns, its management and potential outcomes remain subjects for debate, Paul J. Rozance, MD, of the University of Colorado, Aurora, wrote in an editorial accompanying both studies.

“Often, the same features that increase the risk of hypoglycemia in newborns also increase the risk for poor outcomes independent of hypoglycemia,” he said.

The study by Shah and colleagues was not a randomized trial of a specific management strategy, Dr. Rozance noted. However, the high rate of low educational attainment in children not exposed to dextrose gel emphasizes the need for more effective management of infant hypoglycemia, he said. “The findings also suggest that antenatal conditions that are associated with increased risk of hypoglycemia among newborns are associated with increased risk for impaired neurodevelopment and educational achievement, independent of neonatal hypoglycemia,” he said. The study findings contrast with those of an earlier study showing low academic achievement association with early transient hypoglycemia, which could argue for earlier intervention, he noted.

The study by Edwards and colleagues addressed the potential value of dextrose gel as an early intervention to prevent neonatal hypoglycemia, said Dr. Rozance.

“The 95% CI for the primary outcome of neurosensory impairment included up to a 7% increased risk for neurosensory impairment in the prophylactic dextrose gel group. The 7% increased risk was defined by the investigators as potentially clinically important, and the study may have been underpowered to detect small differences in the primary outcome,” he wrote.

Although the reasons for adverse outcomes in children given prophylactic dextrose gel remain unclear, “incorporation of prophylactic dextrose gel into clinical practice should await further research,” he said.

Regarding such research, Dr. Rozance proposed an “ideal study,” that would “randomize newborns with hypoglycemia to treatment or no treatment, although equipoise and ethical support for such a study are lacking. Another strategy would be to randomize newborns with hypoglycemia to receive low- or high-treatment glucose concentration goals,” he noted.

The relationship between hypoglycemia and impaired neurodevelopment is yet to be determined, but the two studies provide new evidence for the clinical importance and need for management of neonatal hypoglycemia and subsequent neurodevelopmental outcomes, he concluded.

The study by Shah and colleagues was supported by the Health Research Council of New Zealand and the Maurice and Phyllis Paykel Trust. Dr. Shah disclosed a doctoral fellowship from the University of Auckland. The study by Edwards and colleagues was supported by the Health Research Council of New Zealand and the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health. Ms. Edwards had no financial conflicts to disclose. Dr. Rozance disclosed receiving a StatStrip from Nova Biomedical for use in his laboratory.