For many patients, sexual function is an important component of a healthy quality of life.¹ However, to many transgender individuals, their sexual organs are often a source of gender dysphoria, which can significantly inhibit sexual activity with their partners. Patients who seek gender-affirming surgery not only hope to have these feelings of dysphoria alleviated but also desire improvement in sexual function after surgery. While the medical and psychiatric criteria for patients seeking vaginoplasty procedures are well established by the World Professional Association for Transgender Health,² there is little guidance surrounding the discourse surgeons should have regarding sexual function pre- and postsurgery.

Setting realistic expectations is one of the major challenges surgeons and patients alike face in preoperative and postoperative encounters. Patients not only are tasked with recovering from a major surgical procedure, but must also now learn their new anatomy, which includes learning how to urinate, maintain proper neovaginal hygiene, and experience sexual pleasure.

Given the permanence of these procedures and the possibility of loss of sexual function, the surgeon must ensure that patients truly comprehend the nature of the procedure and its complications. During the preoperative consultation, the surgeon must inquire about any desire for future fertility, discuss any history of pelvic radiation, epispadias, hypospadias, current erectile dysfunction, libido, comorbid medical conditions (such as diabetes or smoking), current sexual practices, and overall patient goals regarding their surgical outcome.

The vast majority of patients state they will experience a significant decrease in gender dysphoria with the removal of their current natal male genitalia.¹ However, some patients have very specific preferences regarding the cosmetic appearance of vulvar structures. Others have more functional concerns about neovaginal depth and the ability to have receptive penetrative intercourse. It is important to note that not all transgender women have male partners. Furthermore, whether patients have male or female partners, some patients do not desire the ability to have penetrative intercourse and/or do not want to undergo the potential complications of a full-depth vaginoplasty. In these patients, offering a “shallow depth” vaginoplasty may be acceptable.

It is useful in the consultation to discuss a patient’s sexual partners and sexual practices in order to best determine the type of procedure that may be appropriate for a patient. In my practice, I emphasize that full-depth vaginoplasties require a lifelong commitment of dilation to maintain patency. Unlike cisgender women, patients must also douche to ensure appropriate vaginal hygiene. Regarding cosmetic preferences patients may have, it is essential to educate patients on the significant variation in the appearance of vulvar structures among both cisgender and transgender women.

During the surgical consultation, I review which structures from their natal genitalia are removed and which structures are utilized to create the neo–vulvar-vaginal anatomy. The testicles and spermatic cord are excised. The dorsal neurovascular bundle of the penile shaft and portion of the dorsal aspect of the glans penis are used to create the neoclitoris. A combination of penile shaft skin and scrotal skin is used to line the neovaginal canal. The erectile tissue of the penile shaft is also resected and the natal urethra is shortened and spatulated to create the urethral plate and urethral meatus. I also remind patients that the prostate remains intact during vaginoplasty procedures. Unless patients undergo the colonic interposition vaginoplasty and in some cases the peritoneal vaginoplasty, the neovaginal canal is not self-lubricating, nor will patients experience ejaculation after surgery. In the presurgical period, I often remind patients that the location of erogenous sensation after surgery will be altered and the method by which they self-stimulate will also be different. It is also essential to document whether patients can achieve satisfactory orgasms presurgically in order to determine adequate sexual function in the postoperative period.

It cannot be emphasized enough that the best predictor of unsatisfactory sexual function after genital gender-affirming surgery is poor sexual function prior to surgery.^1,3

Retention of sexual function after gender-affirming genital surgery is common, with studies citing a range of 70%-90% of patients reporting their ability to regularly achieve an orgasm after surgery.^1,4 In some cases, patients will report issues with sexual function after surgery despite having no prior history of sexual dysfunction. If patients present with complaints of postsurgical anorgasmia, the provider should rule out insufficient time for wound healing and resolution of surgery-site pain, and determine if there was an intraoperative injury to the neurovascular bundle or significant clitoral necrosis. A thorough genital exam should include a sensory examination of the neoclitoris and the introitus and neovaginal canal for signs of scarring, stenosis, loss of vaginal depth, or high-tone pelvic-floor dysfunction.

Unfortunately, if the neurovascular bundle is injured or if a patient experienced clitoral necrosis, the likelihood of a patient regaining sensation is decreased, although there are currently no studies examining the exact rates. It is also important to reassure patients that wound healing after surgery and relearning sexual function is not linear. I encourage patients to initially self-stimulate without a partner as they learn their new anatomy in order to remove any potential performance anxiety a partner could cause immediately after surgery. Similar to the approach to sexual dysfunction in cisgender patients, referral to a specialist in sexual health and/or pelvic floor physical therapy are useful adjuncts, depending on the findings from the physical exam and patient symptoms.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Garcia MM. Clin Plastic Surg. 2018;45:437-46.

2. Eli Coleman WB et al. “Standards of care for the health of transsexual, transgender, and gender non-conforming people” 7th version. World Professional Association for Transgender Health: 2012.

3. Garcia MM et al. Transl Androl Urol. 2014;3:156.

4. Ferrando CA, Bowers ML. “Genital gender confirmation surgery for patients assigned male at birth” In: Ferrando CA, ed. “Comprehensive care for the transgender patient” Philadelphia: Elsevier, 2020:82-92.

For many patients, sexual function is an important component of a healthy quality of life.¹ However, to many transgender individuals, their sexual organs are often a source of gender dysphoria, which can significantly inhibit sexual activity with their partners. Patients who seek gender-affirming surgery not only hope to have these feelings of dysphoria alleviated but also desire improvement in sexual function after surgery. While the medical and psychiatric criteria for patients seeking vaginoplasty procedures are well established by the World Professional Association for Transgender Health,² there is little guidance surrounding the discourse surgeons should have regarding sexual function pre- and postsurgery.

Setting realistic expectations is one of the major challenges surgeons and patients alike face in preoperative and postoperative encounters. Patients not only are tasked with recovering from a major surgical procedure, but must also now learn their new anatomy, which includes learning how to urinate, maintain proper neovaginal hygiene, and experience sexual pleasure.

Given the permanence of these procedures and the possibility of loss of sexual function, the surgeon must ensure that patients truly comprehend the nature of the procedure and its complications. During the preoperative consultation, the surgeon must inquire about any desire for future fertility, discuss any history of pelvic radiation, epispadias, hypospadias, current erectile dysfunction, libido, comorbid medical conditions (such as diabetes or smoking), current sexual practices, and overall patient goals regarding their surgical outcome.

The vast majority of patients state they will experience a significant decrease in gender dysphoria with the removal of their current natal male genitalia.¹ However, some patients have very specific preferences regarding the cosmetic appearance of vulvar structures. Others have more functional concerns about neovaginal depth and the ability to have receptive penetrative intercourse. It is important to note that not all transgender women have male partners. Furthermore, whether patients have male or female partners, some patients do not desire the ability to have penetrative intercourse and/or do not want to undergo the potential complications of a full-depth vaginoplasty. In these patients, offering a “shallow depth” vaginoplasty may be acceptable.

It is useful in the consultation to discuss a patient’s sexual partners and sexual practices in order to best determine the type of procedure that may be appropriate for a patient. In my practice, I emphasize that full-depth vaginoplasties require a lifelong commitment of dilation to maintain patency. Unlike cisgender women, patients must also douche to ensure appropriate vaginal hygiene. Regarding cosmetic preferences patients may have, it is essential to educate patients on the significant variation in the appearance of vulvar structures among both cisgender and transgender women.

During the surgical consultation, I review which structures from their natal genitalia are removed and which structures are utilized to create the neo–vulvar-vaginal anatomy. The testicles and spermatic cord are excised. The dorsal neurovascular bundle of the penile shaft and portion of the dorsal aspect of the glans penis are used to create the neoclitoris. A combination of penile shaft skin and scrotal skin is used to line the neovaginal canal. The erectile tissue of the penile shaft is also resected and the natal urethra is shortened and spatulated to create the urethral plate and urethral meatus. I also remind patients that the prostate remains intact during vaginoplasty procedures. Unless patients undergo the colonic interposition vaginoplasty and in some cases the peritoneal vaginoplasty, the neovaginal canal is not self-lubricating, nor will patients experience ejaculation after surgery. In the presurgical period, I often remind patients that the location of erogenous sensation after surgery will be altered and the method by which they self-stimulate will also be different. It is also essential to document whether patients can achieve satisfactory orgasms presurgically in order to determine adequate sexual function in the postoperative period.

It cannot be emphasized enough that the best predictor of unsatisfactory sexual function after genital gender-affirming surgery is poor sexual function prior to surgery.^1,3

Retention of sexual function after gender-affirming genital surgery is common, with studies citing a range of 70%-90% of patients reporting their ability to regularly achieve an orgasm after surgery.^1,4 In some cases, patients will report issues with sexual function after surgery despite having no prior history of sexual dysfunction. If patients present with complaints of postsurgical anorgasmia, the provider should rule out insufficient time for wound healing and resolution of surgery-site pain, and determine if there was an intraoperative injury to the neurovascular bundle or significant clitoral necrosis. A thorough genital exam should include a sensory examination of the neoclitoris and the introitus and neovaginal canal for signs of scarring, stenosis, loss of vaginal depth, or high-tone pelvic-floor dysfunction.

Unfortunately, if the neurovascular bundle is injured or if a patient experienced clitoral necrosis, the likelihood of a patient regaining sensation is decreased, although there are currently no studies examining the exact rates. It is also important to reassure patients that wound healing after surgery and relearning sexual function is not linear. I encourage patients to initially self-stimulate without a partner as they learn their new anatomy in order to remove any potential performance anxiety a partner could cause immediately after surgery. Similar to the approach to sexual dysfunction in cisgender patients, referral to a specialist in sexual health and/or pelvic floor physical therapy are useful adjuncts, depending on the findings from the physical exam and patient symptoms.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Garcia MM. Clin Plastic Surg. 2018;45:437-46.

2. Eli Coleman WB et al. “Standards of care for the health of transsexual, transgender, and gender non-conforming people” 7th version. World Professional Association for Transgender Health: 2012.

3. Garcia MM et al. Transl Androl Urol. 2014;3:156.

4. Ferrando CA, Bowers ML. “Genital gender confirmation surgery for patients assigned male at birth” In: Ferrando CA, ed. “Comprehensive care for the transgender patient” Philadelphia: Elsevier, 2020:82-92.

For many patients, sexual function is an important component of a healthy quality of life.¹ However, to many transgender individuals, their sexual organs are often a source of gender dysphoria, which can significantly inhibit sexual activity with their partners. Patients who seek gender-affirming surgery not only hope to have these feelings of dysphoria alleviated but also desire improvement in sexual function after surgery. While the medical and psychiatric criteria for patients seeking vaginoplasty procedures are well established by the World Professional Association for Transgender Health,² there is little guidance surrounding the discourse surgeons should have regarding sexual function pre- and postsurgery.

Setting realistic expectations is one of the major challenges surgeons and patients alike face in preoperative and postoperative encounters. Patients not only are tasked with recovering from a major surgical procedure, but must also now learn their new anatomy, which includes learning how to urinate, maintain proper neovaginal hygiene, and experience sexual pleasure.

Given the permanence of these procedures and the possibility of loss of sexual function, the surgeon must ensure that patients truly comprehend the nature of the procedure and its complications. During the preoperative consultation, the surgeon must inquire about any desire for future fertility, discuss any history of pelvic radiation, epispadias, hypospadias, current erectile dysfunction, libido, comorbid medical conditions (such as diabetes or smoking), current sexual practices, and overall patient goals regarding their surgical outcome.

The vast majority of patients state they will experience a significant decrease in gender dysphoria with the removal of their current natal male genitalia.¹ However, some patients have very specific preferences regarding the cosmetic appearance of vulvar structures. Others have more functional concerns about neovaginal depth and the ability to have receptive penetrative intercourse. It is important to note that not all transgender women have male partners. Furthermore, whether patients have male or female partners, some patients do not desire the ability to have penetrative intercourse and/or do not want to undergo the potential complications of a full-depth vaginoplasty. In these patients, offering a “shallow depth” vaginoplasty may be acceptable.

It is useful in the consultation to discuss a patient’s sexual partners and sexual practices in order to best determine the type of procedure that may be appropriate for a patient. In my practice, I emphasize that full-depth vaginoplasties require a lifelong commitment of dilation to maintain patency. Unlike cisgender women, patients must also douche to ensure appropriate vaginal hygiene. Regarding cosmetic preferences patients may have, it is essential to educate patients on the significant variation in the appearance of vulvar structures among both cisgender and transgender women.

During the surgical consultation, I review which structures from their natal genitalia are removed and which structures are utilized to create the neo–vulvar-vaginal anatomy. The testicles and spermatic cord are excised. The dorsal neurovascular bundle of the penile shaft and portion of the dorsal aspect of the glans penis are used to create the neoclitoris. A combination of penile shaft skin and scrotal skin is used to line the neovaginal canal. The erectile tissue of the penile shaft is also resected and the natal urethra is shortened and spatulated to create the urethral plate and urethral meatus. I also remind patients that the prostate remains intact during vaginoplasty procedures. Unless patients undergo the colonic interposition vaginoplasty and in some cases the peritoneal vaginoplasty, the neovaginal canal is not self-lubricating, nor will patients experience ejaculation after surgery. In the presurgical period, I often remind patients that the location of erogenous sensation after surgery will be altered and the method by which they self-stimulate will also be different. It is also essential to document whether patients can achieve satisfactory orgasms presurgically in order to determine adequate sexual function in the postoperative period.

It cannot be emphasized enough that the best predictor of unsatisfactory sexual function after genital gender-affirming surgery is poor sexual function prior to surgery.^1,3

Retention of sexual function after gender-affirming genital surgery is common, with studies citing a range of 70%-90% of patients reporting their ability to regularly achieve an orgasm after surgery.^1,4 In some cases, patients will report issues with sexual function after surgery despite having no prior history of sexual dysfunction. If patients present with complaints of postsurgical anorgasmia, the provider should rule out insufficient time for wound healing and resolution of surgery-site pain, and determine if there was an intraoperative injury to the neurovascular bundle or significant clitoral necrosis. A thorough genital exam should include a sensory examination of the neoclitoris and the introitus and neovaginal canal for signs of scarring, stenosis, loss of vaginal depth, or high-tone pelvic-floor dysfunction.

Unfortunately, if the neurovascular bundle is injured or if a patient experienced clitoral necrosis, the likelihood of a patient regaining sensation is decreased, although there are currently no studies examining the exact rates. It is also important to reassure patients that wound healing after surgery and relearning sexual function is not linear. I encourage patients to initially self-stimulate without a partner as they learn their new anatomy in order to remove any potential performance anxiety a partner could cause immediately after surgery. Similar to the approach to sexual dysfunction in cisgender patients, referral to a specialist in sexual health and/or pelvic floor physical therapy are useful adjuncts, depending on the findings from the physical exam and patient symptoms.
 

Dr. Brandt is an ob.gyn. and fellowship-trained gender-affirming surgeon in West Reading, Pa.

References

1. Garcia MM. Clin Plastic Surg. 2018;45:437-46.

2. Eli Coleman WB et al. “Standards of care for the health of transsexual, transgender, and gender non-conforming people” 7th version. World Professional Association for Transgender Health: 2012.

3. Garcia MM et al. Transl Androl Urol. 2014;3:156.

4. Ferrando CA, Bowers ML. “Genital gender confirmation surgery for patients assigned male at birth” In: Ferrando CA, ed. “Comprehensive care for the transgender patient” Philadelphia: Elsevier, 2020:82-92.

A new study of educational attainment among U.K. primary and secondary schoolchildren born prematurely now provides some reassurance about the longer-term outcomes for many of these children.

For the study, published in the open-access journal PLOS ONE, researchers from the University of Oxford with colleagues from the University of Leicester and City University, London, used data from 11,695 children in the population-based UK Millennium Cohort Study, which included children born in England from Sept. 1, 2000 to Aug. 31, 2001. They analyzed data on educational attainment in primary school, at age 11, for 6,950 pupils and in secondary school, at age 16, for 7,131 pupils.

Preterm birth is a known risk factor for developmental impairment, lower educational performance and reduced academic attainment, with the impact proportional to the degree of prematurity. Not every child born prematurely will experience learning or developmental challenges, but studies of children born before 34 weeks gestation have shown that they are more likely to have cognitive difficulties, particularly poorer reading and maths skills, at primary school, and to have special educational needs by the end of primary education.
 

Elevated risk of all preterm children in primary school

Until now, few studies have followed these children through secondary school or examined the full spectrum of gestational ages at birth. Yet as neonatal care advances and more premature babies now survive, an average primary class in the United Kingdom now includes two preterm children.

Among the primary school children overall, 17.7% had not achieved their expected level in English and mathematics at age 11. Children born very preterm, before 32 weeks or at 32-33 weeks gestation, were more than twice as likely as full term children to fail to meet these benchmarks, with adjusted relative risks of 2.06 and 2.13, respectively. Those born late preterm, at 34-36 weeks, or early term, at 37-38 weeks, were at lesser risk, with RRs of 1.18 and 1.21, respectively.

By the end of secondary school, 45.2% of pupils had not passed the benchmark of at least five General Certificate of Secondary Education (GCSE) examinations, including English and mathematics. The RR for children born very preterm, compared with full term children, was 1.26, with 60% of students in this group failing to achieve five GCSEs. However, children born at gestations between 32 and 38 weeks were not at elevated risk, compared with children born at full term.
 

Risk persists to secondary level only for very preterm children

A similar pattern was seen with English and mathematics analyzed separately, with no additional risk of not passing among children born at 32 weeks or above, but adjusted RRs of 1.33 for not passing English and 1.42 for not passing maths among pupils who had been born very preterm, compared with full term children.

“All children born before full term are more likely to have poorer attainment during primary school, compared with children born full term (39-41 weeks), but only children born very preterm (before 32 weeks) remain at risk of poor attainment at the end of secondary schooling,” the researchers concluded.

“Further studies are needed in order to confirm this result,” they acknowledge. They suggested their results could be explained by catch-up in academic attainment among children born moderately or late preterm or at early term. However, “very preterm children appear to be a high-risk group with persistent difficulties in terms of educational outcomes,” they said, noting that even this risk was of lower magnitude than the reduced attainment scores they found among pupils eligible for free school meals, meaning those from disadvantaged socioeconomic backgrounds.
 

Extra educational support needed

The researchers concluded: “Children born very preterm may benefit from screening for cognitive and language difficulties prior to school entry to guide the provision of additional support during schooling.” In addition, those born very preterm “may require additional educational support throughout compulsory schooling.”

Commenting on the study, Caroline Lee-Davey, chief executive of premature baby charity Bliss, told this news organization: “Every child who is born premature is unique, and their development and achievements will be individual to them. However, these new findings are significant and add to our understanding of how prematurity is related to longer-term educational attainment, particularly for children who were born very preterm.”

“Most importantly, they highlight the need for all children who were born premature – and particularly those who were born before 32 weeks – to have access to early support. This means ensuring all eligible babies receive a follow-up check at 2 and 4 years as recommended by NICE and for early years and educational professionals to be aware of the relationship between premature birth and development.”

“We know how concerning these findings might be for families with babies and very young children right now. That’s why Bliss has developed a suite of information to support families as they make choices about their child’s education.”

A version of this article first appeared on Medscape UK.

A new study of educational attainment among U.K. primary and secondary schoolchildren born prematurely now provides some reassurance about the longer-term outcomes for many of these children.

For the study, published in the open-access journal PLOS ONE, researchers from the University of Oxford with colleagues from the University of Leicester and City University, London, used data from 11,695 children in the population-based UK Millennium Cohort Study, which included children born in England from Sept. 1, 2000 to Aug. 31, 2001. They analyzed data on educational attainment in primary school, at age 11, for 6,950 pupils and in secondary school, at age 16, for 7,131 pupils.

Preterm birth is a known risk factor for developmental impairment, lower educational performance and reduced academic attainment, with the impact proportional to the degree of prematurity. Not every child born prematurely will experience learning or developmental challenges, but studies of children born before 34 weeks gestation have shown that they are more likely to have cognitive difficulties, particularly poorer reading and maths skills, at primary school, and to have special educational needs by the end of primary education.
 

Elevated risk of all preterm children in primary school

Until now, few studies have followed these children through secondary school or examined the full spectrum of gestational ages at birth. Yet as neonatal care advances and more premature babies now survive, an average primary class in the United Kingdom now includes two preterm children.

Among the primary school children overall, 17.7% had not achieved their expected level in English and mathematics at age 11. Children born very preterm, before 32 weeks or at 32-33 weeks gestation, were more than twice as likely as full term children to fail to meet these benchmarks, with adjusted relative risks of 2.06 and 2.13, respectively. Those born late preterm, at 34-36 weeks, or early term, at 37-38 weeks, were at lesser risk, with RRs of 1.18 and 1.21, respectively.

By the end of secondary school, 45.2% of pupils had not passed the benchmark of at least five General Certificate of Secondary Education (GCSE) examinations, including English and mathematics. The RR for children born very preterm, compared with full term children, was 1.26, with 60% of students in this group failing to achieve five GCSEs. However, children born at gestations between 32 and 38 weeks were not at elevated risk, compared with children born at full term.
 

Risk persists to secondary level only for very preterm children

A similar pattern was seen with English and mathematics analyzed separately, with no additional risk of not passing among children born at 32 weeks or above, but adjusted RRs of 1.33 for not passing English and 1.42 for not passing maths among pupils who had been born very preterm, compared with full term children.

“All children born before full term are more likely to have poorer attainment during primary school, compared with children born full term (39-41 weeks), but only children born very preterm (before 32 weeks) remain at risk of poor attainment at the end of secondary schooling,” the researchers concluded.

“Further studies are needed in order to confirm this result,” they acknowledge. They suggested their results could be explained by catch-up in academic attainment among children born moderately or late preterm or at early term. However, “very preterm children appear to be a high-risk group with persistent difficulties in terms of educational outcomes,” they said, noting that even this risk was of lower magnitude than the reduced attainment scores they found among pupils eligible for free school meals, meaning those from disadvantaged socioeconomic backgrounds.
 

Extra educational support needed

The researchers concluded: “Children born very preterm may benefit from screening for cognitive and language difficulties prior to school entry to guide the provision of additional support during schooling.” In addition, those born very preterm “may require additional educational support throughout compulsory schooling.”

Commenting on the study, Caroline Lee-Davey, chief executive of premature baby charity Bliss, told this news organization: “Every child who is born premature is unique, and their development and achievements will be individual to them. However, these new findings are significant and add to our understanding of how prematurity is related to longer-term educational attainment, particularly for children who were born very preterm.”

“Most importantly, they highlight the need for all children who were born premature – and particularly those who were born before 32 weeks – to have access to early support. This means ensuring all eligible babies receive a follow-up check at 2 and 4 years as recommended by NICE and for early years and educational professionals to be aware of the relationship between premature birth and development.”

“We know how concerning these findings might be for families with babies and very young children right now. That’s why Bliss has developed a suite of information to support families as they make choices about their child’s education.”

A version of this article first appeared on Medscape UK.

A new study of educational attainment among U.K. primary and secondary schoolchildren born prematurely now provides some reassurance about the longer-term outcomes for many of these children.

For the study, published in the open-access journal PLOS ONE, researchers from the University of Oxford with colleagues from the University of Leicester and City University, London, used data from 11,695 children in the population-based UK Millennium Cohort Study, which included children born in England from Sept. 1, 2000 to Aug. 31, 2001. They analyzed data on educational attainment in primary school, at age 11, for 6,950 pupils and in secondary school, at age 16, for 7,131 pupils.

Preterm birth is a known risk factor for developmental impairment, lower educational performance and reduced academic attainment, with the impact proportional to the degree of prematurity. Not every child born prematurely will experience learning or developmental challenges, but studies of children born before 34 weeks gestation have shown that they are more likely to have cognitive difficulties, particularly poorer reading and maths skills, at primary school, and to have special educational needs by the end of primary education.
 

Elevated risk of all preterm children in primary school

Until now, few studies have followed these children through secondary school or examined the full spectrum of gestational ages at birth. Yet as neonatal care advances and more premature babies now survive, an average primary class in the United Kingdom now includes two preterm children.

Among the primary school children overall, 17.7% had not achieved their expected level in English and mathematics at age 11. Children born very preterm, before 32 weeks or at 32-33 weeks gestation, were more than twice as likely as full term children to fail to meet these benchmarks, with adjusted relative risks of 2.06 and 2.13, respectively. Those born late preterm, at 34-36 weeks, or early term, at 37-38 weeks, were at lesser risk, with RRs of 1.18 and 1.21, respectively.

By the end of secondary school, 45.2% of pupils had not passed the benchmark of at least five General Certificate of Secondary Education (GCSE) examinations, including English and mathematics. The RR for children born very preterm, compared with full term children, was 1.26, with 60% of students in this group failing to achieve five GCSEs. However, children born at gestations between 32 and 38 weeks were not at elevated risk, compared with children born at full term.
 

Risk persists to secondary level only for very preterm children

A similar pattern was seen with English and mathematics analyzed separately, with no additional risk of not passing among children born at 32 weeks or above, but adjusted RRs of 1.33 for not passing English and 1.42 for not passing maths among pupils who had been born very preterm, compared with full term children.

“All children born before full term are more likely to have poorer attainment during primary school, compared with children born full term (39-41 weeks), but only children born very preterm (before 32 weeks) remain at risk of poor attainment at the end of secondary schooling,” the researchers concluded.

“Further studies are needed in order to confirm this result,” they acknowledge. They suggested their results could be explained by catch-up in academic attainment among children born moderately or late preterm or at early term. However, “very preterm children appear to be a high-risk group with persistent difficulties in terms of educational outcomes,” they said, noting that even this risk was of lower magnitude than the reduced attainment scores they found among pupils eligible for free school meals, meaning those from disadvantaged socioeconomic backgrounds.
 

Extra educational support needed

The researchers concluded: “Children born very preterm may benefit from screening for cognitive and language difficulties prior to school entry to guide the provision of additional support during schooling.” In addition, those born very preterm “may require additional educational support throughout compulsory schooling.”

Commenting on the study, Caroline Lee-Davey, chief executive of premature baby charity Bliss, told this news organization: “Every child who is born premature is unique, and their development and achievements will be individual to them. However, these new findings are significant and add to our understanding of how prematurity is related to longer-term educational attainment, particularly for children who were born very preterm.”

“Most importantly, they highlight the need for all children who were born premature – and particularly those who were born before 32 weeks – to have access to early support. This means ensuring all eligible babies receive a follow-up check at 2 and 4 years as recommended by NICE and for early years and educational professionals to be aware of the relationship between premature birth and development.”

“We know how concerning these findings might be for families with babies and very young children right now. That’s why Bliss has developed a suite of information to support families as they make choices about their child’s education.”

A version of this article first appeared on Medscape UK.

Mothers who have a family history of any psychiatric disorder have almost two times the risk of postpartum depression as do mothers without such history, according to a new study.

Mette-Marie Zacher Kjeldsen, MSc, with the National Centre for Register-based Research at Aarhus (Denmark) University, led the study, a meta-analysis that included 26 studies with information on 100,877 women.

Findings were published online in JAMA Psychiatry.

When mothers had a family history of psychiatric disorders, the odds ratio for PPD was 2.08 (95% confidence interval, 1.67-2.59). That corresponds to a risk ratio of 1.79 (95% CI, 1.52-2.09), assuming a 15% postpartum depression prevalence in the general population.
 

Not doomed to develop PPD

Polina Teslyar, MD, a perinatal psychiatrist at Brigham and Women’s Hospital in Boston told this news organization it’s important to point out that though the risk is higher, women with a family psychiatric history should not feel as though they are destined to develop PPD.

“You are still more likely to not have postpartum depression, but it is important to be aware of personal risk factors so that if a person is experiencing that, they ask for help quickly rather than suffering and not knowing something is amiss,” she emphasized. Dr. Teslyar says she does see the higher risk for PPD, which is preventable and treatable, in her own practice when women have had a family history of psychiatric disorders.

The association makes sense, but literature on why that is has been varied, she said, and likely involves both genetics and socioeconomic factors. It’s difficult to tease apart how big a part each plays.

In her perinatal practice she sees women even before they are pregnant to discuss risk factors for PPD so she does ask about family history of psychiatric disorders, specifically about history of PPD and anxiety.

The researchers suggest routine perinatal care should include an easy low-cost, two-part question about both personal and family history of psychiatric disorders.

“As the assessment is possible even prior to conception, this would leave time for planning preventive efforts, such as psychosocial and psychological interventions targeting these at-risk women,” the authors write.
 

Asking about family history a challenge

Dr. Teslyar noted though that one of the challenges in asking about family history is that families may not have openly shared psychiatric history details with offspring. Family members may also report conditions they suspect a family member had rather than having a documented diagnosis.

In places where there is universal health care, she noted, finding documented diagnoses is easier, but otherwise “you’re really taking a subjective interpretation.”

The researchers found that subgroup, sensitivity, and meta–regression analyses aligned with the primary findings. The overall certainty of evidence was graded as moderate.

This study was not able to make clear how the specific diagnoses of family members affect the risk of developing PPD because much of the data from the studies came from self-report and questions were not consistent across the studies.

For instance, only 7 studies asked specifically about first-degree family members and 10 asked about specific diagnoses. Diagnoses ranged from mild affective disorders to more intrusive disorders, such as schizophrenia.

And while this study doesn’t seek to determine why the family history and risk of PPD appear to be connected, the authors offer some possible explanations.

“Growing up in an environment with parents struggling with mental health problems potentially influences the social support received from these parents when going into motherhood,” the authors write. “This particular explanation is supported by umbrella reviews concluding that lack of social support is a significant PPD risk factor.”

Screening, extraction, and assessment of studies included was done independently by two reviewers, increasing validity, the authors note.

The authors state that approximately 10%-15% of new mothers experience PPD, but Dr. Teslyar points out the numbers in the United States are typically quoted at up to 20%-30%. PPD ranges from mild to severe episodes and includes symptoms like those for major depression outside the postpartum period.

Study authors received funding from The Lundbeck Foundation and the European Union’s Horizon 2020 Research and Innovation Programme. A coauthor, Vibe G. Frokjaer, MD, PhD, has served as consultant and lecturer for H. Lundbeck and Sage Therapeutics. No other disclosures were reported. Dr. Teslyar reports no relevant financial relationships.

Mothers who have a family history of any psychiatric disorder have almost two times the risk of postpartum depression as do mothers without such history, according to a new study.

Mette-Marie Zacher Kjeldsen, MSc, with the National Centre for Register-based Research at Aarhus (Denmark) University, led the study, a meta-analysis that included 26 studies with information on 100,877 women.

Findings were published online in JAMA Psychiatry.

When mothers had a family history of psychiatric disorders, the odds ratio for PPD was 2.08 (95% confidence interval, 1.67-2.59). That corresponds to a risk ratio of 1.79 (95% CI, 1.52-2.09), assuming a 15% postpartum depression prevalence in the general population.
 

Not doomed to develop PPD

Polina Teslyar, MD, a perinatal psychiatrist at Brigham and Women’s Hospital in Boston told this news organization it’s important to point out that though the risk is higher, women with a family psychiatric history should not feel as though they are destined to develop PPD.

“You are still more likely to not have postpartum depression, but it is important to be aware of personal risk factors so that if a person is experiencing that, they ask for help quickly rather than suffering and not knowing something is amiss,” she emphasized. Dr. Teslyar says she does see the higher risk for PPD, which is preventable and treatable, in her own practice when women have had a family history of psychiatric disorders.

The association makes sense, but literature on why that is has been varied, she said, and likely involves both genetics and socioeconomic factors. It’s difficult to tease apart how big a part each plays.

In her perinatal practice she sees women even before they are pregnant to discuss risk factors for PPD so she does ask about family history of psychiatric disorders, specifically about history of PPD and anxiety.

The researchers suggest routine perinatal care should include an easy low-cost, two-part question about both personal and family history of psychiatric disorders.

“As the assessment is possible even prior to conception, this would leave time for planning preventive efforts, such as psychosocial and psychological interventions targeting these at-risk women,” the authors write.
 

Asking about family history a challenge

Dr. Teslyar noted though that one of the challenges in asking about family history is that families may not have openly shared psychiatric history details with offspring. Family members may also report conditions they suspect a family member had rather than having a documented diagnosis.

In places where there is universal health care, she noted, finding documented diagnoses is easier, but otherwise “you’re really taking a subjective interpretation.”

The researchers found that subgroup, sensitivity, and meta–regression analyses aligned with the primary findings. The overall certainty of evidence was graded as moderate.

This study was not able to make clear how the specific diagnoses of family members affect the risk of developing PPD because much of the data from the studies came from self-report and questions were not consistent across the studies.

For instance, only 7 studies asked specifically about first-degree family members and 10 asked about specific diagnoses. Diagnoses ranged from mild affective disorders to more intrusive disorders, such as schizophrenia.

And while this study doesn’t seek to determine why the family history and risk of PPD appear to be connected, the authors offer some possible explanations.

“Growing up in an environment with parents struggling with mental health problems potentially influences the social support received from these parents when going into motherhood,” the authors write. “This particular explanation is supported by umbrella reviews concluding that lack of social support is a significant PPD risk factor.”

Screening, extraction, and assessment of studies included was done independently by two reviewers, increasing validity, the authors note.

The authors state that approximately 10%-15% of new mothers experience PPD, but Dr. Teslyar points out the numbers in the United States are typically quoted at up to 20%-30%. PPD ranges from mild to severe episodes and includes symptoms like those for major depression outside the postpartum period.

Study authors received funding from The Lundbeck Foundation and the European Union’s Horizon 2020 Research and Innovation Programme. A coauthor, Vibe G. Frokjaer, MD, PhD, has served as consultant and lecturer for H. Lundbeck and Sage Therapeutics. No other disclosures were reported. Dr. Teslyar reports no relevant financial relationships.

Mothers who have a family history of any psychiatric disorder have almost two times the risk of postpartum depression as do mothers without such history, according to a new study.

Mette-Marie Zacher Kjeldsen, MSc, with the National Centre for Register-based Research at Aarhus (Denmark) University, led the study, a meta-analysis that included 26 studies with information on 100,877 women.

Findings were published online in JAMA Psychiatry.

When mothers had a family history of psychiatric disorders, the odds ratio for PPD was 2.08 (95% confidence interval, 1.67-2.59). That corresponds to a risk ratio of 1.79 (95% CI, 1.52-2.09), assuming a 15% postpartum depression prevalence in the general population.
 

Not doomed to develop PPD

Polina Teslyar, MD, a perinatal psychiatrist at Brigham and Women’s Hospital in Boston told this news organization it’s important to point out that though the risk is higher, women with a family psychiatric history should not feel as though they are destined to develop PPD.

“You are still more likely to not have postpartum depression, but it is important to be aware of personal risk factors so that if a person is experiencing that, they ask for help quickly rather than suffering and not knowing something is amiss,” she emphasized. Dr. Teslyar says she does see the higher risk for PPD, which is preventable and treatable, in her own practice when women have had a family history of psychiatric disorders.

The association makes sense, but literature on why that is has been varied, she said, and likely involves both genetics and socioeconomic factors. It’s difficult to tease apart how big a part each plays.

In her perinatal practice she sees women even before they are pregnant to discuss risk factors for PPD so she does ask about family history of psychiatric disorders, specifically about history of PPD and anxiety.

The researchers suggest routine perinatal care should include an easy low-cost, two-part question about both personal and family history of psychiatric disorders.

“As the assessment is possible even prior to conception, this would leave time for planning preventive efforts, such as psychosocial and psychological interventions targeting these at-risk women,” the authors write.
 

Asking about family history a challenge

Dr. Teslyar noted though that one of the challenges in asking about family history is that families may not have openly shared psychiatric history details with offspring. Family members may also report conditions they suspect a family member had rather than having a documented diagnosis.

In places where there is universal health care, she noted, finding documented diagnoses is easier, but otherwise “you’re really taking a subjective interpretation.”

The researchers found that subgroup, sensitivity, and meta–regression analyses aligned with the primary findings. The overall certainty of evidence was graded as moderate.

This study was not able to make clear how the specific diagnoses of family members affect the risk of developing PPD because much of the data from the studies came from self-report and questions were not consistent across the studies.

For instance, only 7 studies asked specifically about first-degree family members and 10 asked about specific diagnoses. Diagnoses ranged from mild affective disorders to more intrusive disorders, such as schizophrenia.

And while this study doesn’t seek to determine why the family history and risk of PPD appear to be connected, the authors offer some possible explanations.

“Growing up in an environment with parents struggling with mental health problems potentially influences the social support received from these parents when going into motherhood,” the authors write. “This particular explanation is supported by umbrella reviews concluding that lack of social support is a significant PPD risk factor.”

Screening, extraction, and assessment of studies included was done independently by two reviewers, increasing validity, the authors note.

The authors state that approximately 10%-15% of new mothers experience PPD, but Dr. Teslyar points out the numbers in the United States are typically quoted at up to 20%-30%. PPD ranges from mild to severe episodes and includes symptoms like those for major depression outside the postpartum period.

Study authors received funding from The Lundbeck Foundation and the European Union’s Horizon 2020 Research and Innovation Programme. A coauthor, Vibe G. Frokjaer, MD, PhD, has served as consultant and lecturer for H. Lundbeck and Sage Therapeutics. No other disclosures were reported. Dr. Teslyar reports no relevant financial relationships.

Vitamin D deficiency has a causative role in the systemic inflammation that commonly accompanies it, with inflammation declining, reflected by reductions in elevated C-reactive protein (CRP), as vitamin D levels increase to normal levels, new research shows.

However, there is no reverse effect between the two: Changes in CRP levels did not appear to affect vitamin D levels.

“This is the first study of its kind, and the first to show that the well-known relationship between vitamin D status and CRP is at least in part driven by vitamin D,” first author Elina Hypponen, PhD, a professor in nutritional and genetic epidemiology and director of the Australian Centre for Precision Health, Adelaide, said in an interview.

“Given that the serum CRP level is a widely used biomarker for chronic inflammation, these results suggest that improving vitamin D status may reduce chronic inflammation, but only for people with vitamin D deficiency,” Dr. Hypponen and coauthors reported in their study, published in the International Journal of Epidemiology.
 

Vitamin D associated with CRP in ‘L-shaped’ manner

Nutritional factors are known to influence systemic inflammation in a variety of ways. However, there has been debate over the association between vitamin D – specifically, serum 25-hydroxyvitamin D (25[OH]D), an indicator of vitamin D status – and CRP, with some reports of observational associations between the two disputed in more robust randomized trials.

To further evaluate the relationship, the authors performed a bidirectional Mendelian randomization analysis, using a cohort of 294,970 unrelated participants of White/British ancestry in the UK Biobank, the largest cohort to date with measured serum 25(OH)D concentrations, they noted.

Overall, the average 25(OH)D concentration was 50.0 nmol/L (range, 10-340 nmol/L), with 11.7% (n = 34,403) of participants having concentrations of less than 25 nmol/L, considered deficient.

The analysis showed that genetically predicted serum 25(OH)D was associated with serum CRP in an L-shaped manner, with CRP levels, and hence inflammation, sharply decreasing in relation to increasing 25(OH)D concentration to normal levels.

However, the relationship was only significant among participants with 25(OH)D levels in the deficiency range (< 25 nmol/L), with the association leveling off at about 50 nmol/L of 25(OH)D, which is generally considered a normal level.

The association was supported in further stratified Mendelian randomization analyses, which confirmed an inverse association between serum 25(OH)D in the deficiency range and CRP, but not with higher concentrations of serum vitamin D.

Conversely, neither linear nor nonlinear Mendelian randomization analyses showed a causal effect of serum CRP level on 25(OH)D concentrations.

The findings suggest that “improving vitamin D status in the deficiency range could reduce systemic low-grade inflammation and potentially mitigate the risk or severity of chronic illnesses with an inflammatory component,” the authors noted.

Dr. Hypponen added that the greatest reductions in CRP are observed with correction of the most severe vitamin D deficiency.

“The strongest benefits of improving concentrations will be seen for people with severe deficiency,” Dr. Hypponen said in an interview.

“In our study, much of the benefit was achieved when people reached the National Academy of Sciences endorsed cutoff of 50 nmol/L [for vitamin D sufficiency].”
 

Prohormone effects?

The anti-inflammatory effects observed with serum vitamin D could be related to its role as a prohormone that can impact vitamin D receptor–expressing immune cells, such as monocytes, B cells, T cells, and antigen-presenting cells, the authors noted.

“Indeed, cell experiments have shown that active vitamin D can inhibit the production of proinflammatory cytokines, including [tumor necrosis factor]–alpha, interleukin-1b, IL-6, IL-8, and IL-12, and promote the production of IL-10, an anti-inflammatory cytokine,” they explained.

In that regard, adequate vitamin D concentrations could be important in preventing inflammation-related complications from obesity and reduce the risk or severity of chronic illnesses with an inflammatory component, such as cardiovascular diseases, diabetes, autoimmune diseases, neurodegenerative conditions, and others, the authors noted.
 

Previous studies unable to assess effect of deficiency

While the current findings contradict other studies that have used Mendelian randomization and showed no causal effect of 25(OH)D on CRP, those previous studies only used a standard linear Mendelian randomization method that could not rule out the possibility of a ‘threshold effect’ restricted to vitamin D deficiency, the authors noted.

“Indeed, it is logical to expect that improving vitamin D status would be relevant only in the presence of vitamin D deficiency, whereas any further additions may be redundant and, in the ... extreme of supplementation, might become toxic,” they wrote.

However, the nonlinear Mendelian randomization approach used in the current study allows for better detection of the association, and the authors point out that the method has also been recently used in research showing an adverse effect of vitamin D deficiency on cardiovascular disease risk and mortality, which would not be visible using the standard linear Mendelian randomization approach.

Meanwhile, the current findings add to broader research showing benefits of increases in vitamin D to be mainly limited to those who are deficient, with limited benefit of supplementation for those who are not, Dr. Hypponen emphasized.

“We have repeatedly seen evidence for health benefits for increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little to no benefit,” Dr. Hypponen said in a press statement. 

“These findings highlight the importance of avoiding clinical vitamin D deficiency and provide further evidence for the wide-ranging effects of hormonal vitamin D,” she added.

The study was financially supported by the National Health and Medical Research Council, Australia. The authors reported no relevant financial relationships.

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

Vitamin D deficiency has a causative role in the systemic inflammation that commonly accompanies it, with inflammation declining, reflected by reductions in elevated C-reactive protein (CRP), as vitamin D levels increase to normal levels, new research shows.

However, there is no reverse effect between the two: Changes in CRP levels did not appear to affect vitamin D levels.

“This is the first study of its kind, and the first to show that the well-known relationship between vitamin D status and CRP is at least in part driven by vitamin D,” first author Elina Hypponen, PhD, a professor in nutritional and genetic epidemiology and director of the Australian Centre for Precision Health, Adelaide, said in an interview.

“Given that the serum CRP level is a widely used biomarker for chronic inflammation, these results suggest that improving vitamin D status may reduce chronic inflammation, but only for people with vitamin D deficiency,” Dr. Hypponen and coauthors reported in their study, published in the International Journal of Epidemiology.
 

Vitamin D associated with CRP in ‘L-shaped’ manner

Nutritional factors are known to influence systemic inflammation in a variety of ways. However, there has been debate over the association between vitamin D – specifically, serum 25-hydroxyvitamin D (25[OH]D), an indicator of vitamin D status – and CRP, with some reports of observational associations between the two disputed in more robust randomized trials.

To further evaluate the relationship, the authors performed a bidirectional Mendelian randomization analysis, using a cohort of 294,970 unrelated participants of White/British ancestry in the UK Biobank, the largest cohort to date with measured serum 25(OH)D concentrations, they noted.

Overall, the average 25(OH)D concentration was 50.0 nmol/L (range, 10-340 nmol/L), with 11.7% (n = 34,403) of participants having concentrations of less than 25 nmol/L, considered deficient.

The analysis showed that genetically predicted serum 25(OH)D was associated with serum CRP in an L-shaped manner, with CRP levels, and hence inflammation, sharply decreasing in relation to increasing 25(OH)D concentration to normal levels.

However, the relationship was only significant among participants with 25(OH)D levels in the deficiency range (< 25 nmol/L), with the association leveling off at about 50 nmol/L of 25(OH)D, which is generally considered a normal level.

The association was supported in further stratified Mendelian randomization analyses, which confirmed an inverse association between serum 25(OH)D in the deficiency range and CRP, but not with higher concentrations of serum vitamin D.

Conversely, neither linear nor nonlinear Mendelian randomization analyses showed a causal effect of serum CRP level on 25(OH)D concentrations.

The findings suggest that “improving vitamin D status in the deficiency range could reduce systemic low-grade inflammation and potentially mitigate the risk or severity of chronic illnesses with an inflammatory component,” the authors noted.

Dr. Hypponen added that the greatest reductions in CRP are observed with correction of the most severe vitamin D deficiency.

“The strongest benefits of improving concentrations will be seen for people with severe deficiency,” Dr. Hypponen said in an interview.

“In our study, much of the benefit was achieved when people reached the National Academy of Sciences endorsed cutoff of 50 nmol/L [for vitamin D sufficiency].”
 

Prohormone effects?

The anti-inflammatory effects observed with serum vitamin D could be related to its role as a prohormone that can impact vitamin D receptor–expressing immune cells, such as monocytes, B cells, T cells, and antigen-presenting cells, the authors noted.

“Indeed, cell experiments have shown that active vitamin D can inhibit the production of proinflammatory cytokines, including [tumor necrosis factor]–alpha, interleukin-1b, IL-6, IL-8, and IL-12, and promote the production of IL-10, an anti-inflammatory cytokine,” they explained.

In that regard, adequate vitamin D concentrations could be important in preventing inflammation-related complications from obesity and reduce the risk or severity of chronic illnesses with an inflammatory component, such as cardiovascular diseases, diabetes, autoimmune diseases, neurodegenerative conditions, and others, the authors noted.
 

Previous studies unable to assess effect of deficiency

While the current findings contradict other studies that have used Mendelian randomization and showed no causal effect of 25(OH)D on CRP, those previous studies only used a standard linear Mendelian randomization method that could not rule out the possibility of a ‘threshold effect’ restricted to vitamin D deficiency, the authors noted.

“Indeed, it is logical to expect that improving vitamin D status would be relevant only in the presence of vitamin D deficiency, whereas any further additions may be redundant and, in the ... extreme of supplementation, might become toxic,” they wrote.

However, the nonlinear Mendelian randomization approach used in the current study allows for better detection of the association, and the authors point out that the method has also been recently used in research showing an adverse effect of vitamin D deficiency on cardiovascular disease risk and mortality, which would not be visible using the standard linear Mendelian randomization approach.

Meanwhile, the current findings add to broader research showing benefits of increases in vitamin D to be mainly limited to those who are deficient, with limited benefit of supplementation for those who are not, Dr. Hypponen emphasized.

“We have repeatedly seen evidence for health benefits for increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little to no benefit,” Dr. Hypponen said in a press statement. 

“These findings highlight the importance of avoiding clinical vitamin D deficiency and provide further evidence for the wide-ranging effects of hormonal vitamin D,” she added.

The study was financially supported by the National Health and Medical Research Council, Australia. The authors reported no relevant financial relationships.

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

Vitamin D deficiency has a causative role in the systemic inflammation that commonly accompanies it, with inflammation declining, reflected by reductions in elevated C-reactive protein (CRP), as vitamin D levels increase to normal levels, new research shows.

However, there is no reverse effect between the two: Changes in CRP levels did not appear to affect vitamin D levels.

“This is the first study of its kind, and the first to show that the well-known relationship between vitamin D status and CRP is at least in part driven by vitamin D,” first author Elina Hypponen, PhD, a professor in nutritional and genetic epidemiology and director of the Australian Centre for Precision Health, Adelaide, said in an interview.

“Given that the serum CRP level is a widely used biomarker for chronic inflammation, these results suggest that improving vitamin D status may reduce chronic inflammation, but only for people with vitamin D deficiency,” Dr. Hypponen and coauthors reported in their study, published in the International Journal of Epidemiology.
 

Vitamin D associated with CRP in ‘L-shaped’ manner

Nutritional factors are known to influence systemic inflammation in a variety of ways. However, there has been debate over the association between vitamin D – specifically, serum 25-hydroxyvitamin D (25[OH]D), an indicator of vitamin D status – and CRP, with some reports of observational associations between the two disputed in more robust randomized trials.

To further evaluate the relationship, the authors performed a bidirectional Mendelian randomization analysis, using a cohort of 294,970 unrelated participants of White/British ancestry in the UK Biobank, the largest cohort to date with measured serum 25(OH)D concentrations, they noted.

Overall, the average 25(OH)D concentration was 50.0 nmol/L (range, 10-340 nmol/L), with 11.7% (n = 34,403) of participants having concentrations of less than 25 nmol/L, considered deficient.

The analysis showed that genetically predicted serum 25(OH)D was associated with serum CRP in an L-shaped manner, with CRP levels, and hence inflammation, sharply decreasing in relation to increasing 25(OH)D concentration to normal levels.

However, the relationship was only significant among participants with 25(OH)D levels in the deficiency range (< 25 nmol/L), with the association leveling off at about 50 nmol/L of 25(OH)D, which is generally considered a normal level.

The association was supported in further stratified Mendelian randomization analyses, which confirmed an inverse association between serum 25(OH)D in the deficiency range and CRP, but not with higher concentrations of serum vitamin D.

Conversely, neither linear nor nonlinear Mendelian randomization analyses showed a causal effect of serum CRP level on 25(OH)D concentrations.

The findings suggest that “improving vitamin D status in the deficiency range could reduce systemic low-grade inflammation and potentially mitigate the risk or severity of chronic illnesses with an inflammatory component,” the authors noted.

Dr. Hypponen added that the greatest reductions in CRP are observed with correction of the most severe vitamin D deficiency.

“The strongest benefits of improving concentrations will be seen for people with severe deficiency,” Dr. Hypponen said in an interview.

“In our study, much of the benefit was achieved when people reached the National Academy of Sciences endorsed cutoff of 50 nmol/L [for vitamin D sufficiency].”
 

Prohormone effects?

The anti-inflammatory effects observed with serum vitamin D could be related to its role as a prohormone that can impact vitamin D receptor–expressing immune cells, such as monocytes, B cells, T cells, and antigen-presenting cells, the authors noted.

“Indeed, cell experiments have shown that active vitamin D can inhibit the production of proinflammatory cytokines, including [tumor necrosis factor]–alpha, interleukin-1b, IL-6, IL-8, and IL-12, and promote the production of IL-10, an anti-inflammatory cytokine,” they explained.

In that regard, adequate vitamin D concentrations could be important in preventing inflammation-related complications from obesity and reduce the risk or severity of chronic illnesses with an inflammatory component, such as cardiovascular diseases, diabetes, autoimmune diseases, neurodegenerative conditions, and others, the authors noted.
 

Previous studies unable to assess effect of deficiency

While the current findings contradict other studies that have used Mendelian randomization and showed no causal effect of 25(OH)D on CRP, those previous studies only used a standard linear Mendelian randomization method that could not rule out the possibility of a ‘threshold effect’ restricted to vitamin D deficiency, the authors noted.

“Indeed, it is logical to expect that improving vitamin D status would be relevant only in the presence of vitamin D deficiency, whereas any further additions may be redundant and, in the ... extreme of supplementation, might become toxic,” they wrote.

However, the nonlinear Mendelian randomization approach used in the current study allows for better detection of the association, and the authors point out that the method has also been recently used in research showing an adverse effect of vitamin D deficiency on cardiovascular disease risk and mortality, which would not be visible using the standard linear Mendelian randomization approach.

Meanwhile, the current findings add to broader research showing benefits of increases in vitamin D to be mainly limited to those who are deficient, with limited benefit of supplementation for those who are not, Dr. Hypponen emphasized.

“We have repeatedly seen evidence for health benefits for increasing vitamin D concentrations in individuals with very low levels, while for others, there appears to be little to no benefit,” Dr. Hypponen said in a press statement. 

“These findings highlight the importance of avoiding clinical vitamin D deficiency and provide further evidence for the wide-ranging effects of hormonal vitamin D,” she added.

The study was financially supported by the National Health and Medical Research Council, Australia. The authors reported no relevant financial relationships.

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

COVID-19 can cause disorders of gut-brain interaction, including postinfection irritable bowel syndrome (IBS), researchers say.

Gastrointestinal symptoms are common with long COVID, also known as post-acute COVID-19 syndrome, according to Walter Chan, MD, MPH, and Madhusudan Grover, MBBS.

Dr. Chan, an assistant professor at Harvard Medical School, Boston, and Dr. Grover, an associate professor of medicine and physiology at Mayo Clinic, Rochester, Minn., conducted a review of the literature on COVID-19’s long-term gastrointestinal effects. Their review was published in Clinical Gastroenterology and Hepatology.

Estimates of the prevalence of gastrointestinal symptoms with COVID-19 have ranged as high as 60%, Dr. Chan and Dr. Grover report, and the symptoms may be present in patients with long COVID, a syndrome that continues 4 weeks or longer.

In one survey of 749 COVID-19 survivors, 29% reported at least one new chronic gastrointestinal symptom. The most common were heartburn, constipation, diarrhea, and abdominal pain. Of those with abdominal pain, 39% had symptoms that met Rome IV criteria for irritable bowel syndrome.

People who have gastrointestinal symptoms after their initial SARS-CoV-2 infection are more likely to have them with long COVID. Psychiatric diagnoses, hospitalization, and the loss of smell and taste are predictors of gastrointestinal symptoms.

Infectious gastroenteritis can increase the risk for disorders of gut-brain interaction, especially postinfection IBS, Dr. Chan and Dr. Grover write.

COVID-19 likely causes gastrointestinal symptoms through multiple mechanisms. It may suppress angiotensin-converting enzyme 2, which protects intestinal cells. It can alter the microbiome. It can cause or worsen weight gain and diabetes. It may disrupt the immune system and trigger an autoimmune reaction. It can cause depression and anxiety, and it can alter dietary habits.

No specific treatments for gastrointestinal symptoms associated with long COVID have emerged, so clinicians should make use of established therapies for disorders of gut-brain interaction, Dr. Chan and Dr. Grover recommend.

Beyond adequate sleep and exercise, these may include high-fiber, low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), gluten-free, low-carbohydrate, or elimination diets.

For diarrhea, they list loperamide, ondansetron, alosetron, eluxadoline, antispasmodics, rifaximin, and bile acid sequestrants.

For constipation, they mention fiber supplements, polyethylene glycol, linaclotide, plecanatide, lubiprostone, tenapanor, tegaserod, and prucalopride.

For modulating intestinal permeability, they recommend glutamine.

Neuromodulation may be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, azaperones, and delta ligands, they write.

For psychological therapy, they recommend cognitive-behavioral therapy and gut-directed hypnotherapy.

A handful of studies have suggested benefits from Lactiplantibacillus plantarum and Pediococcus acidilactici as probiotic therapies. Additionally, one study showed positive results with a high-fiber formula, perhaps by nourishing short-chain fatty acid-producing bacteria, Dr. Chan and Dr. Grover write.

Dr. Chan reported financial relationships with Ironwood, Takeda, and Phathom Pharmaceuticals. Dr. Grover reported financial relationships with Takeda, Donga, Alexza Pharmaceuticals, and Alfasigma.

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

COVID-19 can cause disorders of gut-brain interaction, including postinfection irritable bowel syndrome (IBS), researchers say.

Gastrointestinal symptoms are common with long COVID, also known as post-acute COVID-19 syndrome, according to Walter Chan, MD, MPH, and Madhusudan Grover, MBBS.

Dr. Chan, an assistant professor at Harvard Medical School, Boston, and Dr. Grover, an associate professor of medicine and physiology at Mayo Clinic, Rochester, Minn., conducted a review of the literature on COVID-19’s long-term gastrointestinal effects. Their review was published in Clinical Gastroenterology and Hepatology.

Estimates of the prevalence of gastrointestinal symptoms with COVID-19 have ranged as high as 60%, Dr. Chan and Dr. Grover report, and the symptoms may be present in patients with long COVID, a syndrome that continues 4 weeks or longer.

In one survey of 749 COVID-19 survivors, 29% reported at least one new chronic gastrointestinal symptom. The most common were heartburn, constipation, diarrhea, and abdominal pain. Of those with abdominal pain, 39% had symptoms that met Rome IV criteria for irritable bowel syndrome.

People who have gastrointestinal symptoms after their initial SARS-CoV-2 infection are more likely to have them with long COVID. Psychiatric diagnoses, hospitalization, and the loss of smell and taste are predictors of gastrointestinal symptoms.

Infectious gastroenteritis can increase the risk for disorders of gut-brain interaction, especially postinfection IBS, Dr. Chan and Dr. Grover write.

COVID-19 likely causes gastrointestinal symptoms through multiple mechanisms. It may suppress angiotensin-converting enzyme 2, which protects intestinal cells. It can alter the microbiome. It can cause or worsen weight gain and diabetes. It may disrupt the immune system and trigger an autoimmune reaction. It can cause depression and anxiety, and it can alter dietary habits.

No specific treatments for gastrointestinal symptoms associated with long COVID have emerged, so clinicians should make use of established therapies for disorders of gut-brain interaction, Dr. Chan and Dr. Grover recommend.

Beyond adequate sleep and exercise, these may include high-fiber, low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), gluten-free, low-carbohydrate, or elimination diets.

For diarrhea, they list loperamide, ondansetron, alosetron, eluxadoline, antispasmodics, rifaximin, and bile acid sequestrants.

For constipation, they mention fiber supplements, polyethylene glycol, linaclotide, plecanatide, lubiprostone, tenapanor, tegaserod, and prucalopride.

For modulating intestinal permeability, they recommend glutamine.

Neuromodulation may be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, azaperones, and delta ligands, they write.

For psychological therapy, they recommend cognitive-behavioral therapy and gut-directed hypnotherapy.

A handful of studies have suggested benefits from Lactiplantibacillus plantarum and Pediococcus acidilactici as probiotic therapies. Additionally, one study showed positive results with a high-fiber formula, perhaps by nourishing short-chain fatty acid-producing bacteria, Dr. Chan and Dr. Grover write.

Dr. Chan reported financial relationships with Ironwood, Takeda, and Phathom Pharmaceuticals. Dr. Grover reported financial relationships with Takeda, Donga, Alexza Pharmaceuticals, and Alfasigma.

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

COVID-19 can cause disorders of gut-brain interaction, including postinfection irritable bowel syndrome (IBS), researchers say.

Gastrointestinal symptoms are common with long COVID, also known as post-acute COVID-19 syndrome, according to Walter Chan, MD, MPH, and Madhusudan Grover, MBBS.

Dr. Chan, an assistant professor at Harvard Medical School, Boston, and Dr. Grover, an associate professor of medicine and physiology at Mayo Clinic, Rochester, Minn., conducted a review of the literature on COVID-19’s long-term gastrointestinal effects. Their review was published in Clinical Gastroenterology and Hepatology.

Estimates of the prevalence of gastrointestinal symptoms with COVID-19 have ranged as high as 60%, Dr. Chan and Dr. Grover report, and the symptoms may be present in patients with long COVID, a syndrome that continues 4 weeks or longer.

In one survey of 749 COVID-19 survivors, 29% reported at least one new chronic gastrointestinal symptom. The most common were heartburn, constipation, diarrhea, and abdominal pain. Of those with abdominal pain, 39% had symptoms that met Rome IV criteria for irritable bowel syndrome.

People who have gastrointestinal symptoms after their initial SARS-CoV-2 infection are more likely to have them with long COVID. Psychiatric diagnoses, hospitalization, and the loss of smell and taste are predictors of gastrointestinal symptoms.

Infectious gastroenteritis can increase the risk for disorders of gut-brain interaction, especially postinfection IBS, Dr. Chan and Dr. Grover write.

COVID-19 likely causes gastrointestinal symptoms through multiple mechanisms. It may suppress angiotensin-converting enzyme 2, which protects intestinal cells. It can alter the microbiome. It can cause or worsen weight gain and diabetes. It may disrupt the immune system and trigger an autoimmune reaction. It can cause depression and anxiety, and it can alter dietary habits.

No specific treatments for gastrointestinal symptoms associated with long COVID have emerged, so clinicians should make use of established therapies for disorders of gut-brain interaction, Dr. Chan and Dr. Grover recommend.

Beyond adequate sleep and exercise, these may include high-fiber, low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols), gluten-free, low-carbohydrate, or elimination diets.

For diarrhea, they list loperamide, ondansetron, alosetron, eluxadoline, antispasmodics, rifaximin, and bile acid sequestrants.

For constipation, they mention fiber supplements, polyethylene glycol, linaclotide, plecanatide, lubiprostone, tenapanor, tegaserod, and prucalopride.

For modulating intestinal permeability, they recommend glutamine.

Neuromodulation may be achieved with tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, azaperones, and delta ligands, they write.

For psychological therapy, they recommend cognitive-behavioral therapy and gut-directed hypnotherapy.

A handful of studies have suggested benefits from Lactiplantibacillus plantarum and Pediococcus acidilactici as probiotic therapies. Additionally, one study showed positive results with a high-fiber formula, perhaps by nourishing short-chain fatty acid-producing bacteria, Dr. Chan and Dr. Grover write.

Dr. Chan reported financial relationships with Ironwood, Takeda, and Phathom Pharmaceuticals. Dr. Grover reported financial relationships with Takeda, Donga, Alexza Pharmaceuticals, and Alfasigma.

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

Rural patients with early onset dementia are more likely than urban patients to rely solely on primary care physicians or nurse practitioners for the initial diagnosis and treatment of the disease, a new study has found.

Patients in rural areas are also less likely to see psychologists and undergo neuropsychological testing, according to the study, published in JAMA Network Open.

Patients who forgo such specialist visits and testing may be missing information about their condition that could help them prepare for changes in job responsibilities and future care decisions, said Wendy Yi Xu, PhD, of The Ohio State University, Columbus, who led the research.

“A lot of them are still in the workforce,” Dr. Xu said. Patients in the study were an average age of 56 years, well before the conventional age of retirement.
 

Location, location, location

To examine rural versus urban differences in the use of diagnostic tests and health care visits for early onset Alzheimer’s disease and related dementias, Dr. Xu and colleagues analyzed commercial claims data from 2012-2018. They identified more than 71,000 patients aged 40-64 years with those conditions and focused on health care use by 7,311 patients in urban areas and 1,119 in rural areas within 90 days of a new dementia diagnosis.

The proportion who received neuropsychological testing was 19% among urban patients and 16% among rural patients. Psychological assessments, which are less specialized and detailed than neuropsychological testing, and brain imaging occurred at similar rates in both groups. Similar proportions of rural and urban patients visited neurologists (17.7% and 17.96%, respectively) and psychiatrists (6.02% and 6.47%).

But more urban patients than rural patients visited a psychologist, at 19% versus 15%, according to the researchers.

Approximately 18% of patients in rural areas saw a primary care provider without visiting other specialists, compared with 13% in urban areas.

The researchers found that rural patients were significantly less likely to undergo neuropsychological testing (odds ratio, 0.83; 95% confidence interval, 0.70-0.98) or see a psychologist (OR, 0.72; 95% CI, 0.60-0.85).

Similarly, rural patients had significantly higher odds of having only primary care providers involved in the diagnosis of dementia and symptom management (OR, 1.40; 95% CI, 1.19-1.66).
 

Addressing workforce deficiencies

More primary care training in dementia care and collaboration with specialist colleagues could help address differences in care, Dr. Xu’s group writes. Such efforts are already underway.

In 2018, the Alzheimer’s Association launched telementoring programs focused on dementia care using the Project ECHO (Extension for Community Healthcare Outcomes) model. Researchers originally developed Project ECHO at the University of New Mexico in 2003 to teach primary care clinicians in remote settings how to treat patients infected with the hepatitis C virus.

With the Alzheimer’s and Dementia Care ECHO Program for Clinicians, primary care clinicians can participate in interactive case-based video conferencing sessions to better understand dementia and how to provide high-quality care in community settings, according to the association.

The program covers guidelines for diagnosis, disclosure, and follow-up; the initiation of care planning; managing disease-related challenges; and resources for patients and caregivers.

Since 2018, nearly 100 primary care practices in the United States have completed training in dementia care using Project ECHO, said Morgan Daven, vice president of health systems for the Alzheimer’s Association. Many cases featured in the program are challenging, he added.

“With primary care being on the front lines, it is really important that primary care physicians are equipped to do what they can to detect or diagnose and know when to refer,” Mr. Daven said.

The association has compiled other resources for clinicians as well.

A 2020 report from the association examined the role that primary care physicians play in dementia care. One survey found that 82% of primary care physicians consider themselves on the front lines of providing care for patients with dementia.

Meanwhile, about half say medical professionals are not prepared to meet rising demands associated with Alzheimer’s disease and dementia care.

Mr. Daven said the geographic disparities Dr. Xu and colleagues found are unsurprising. More than half of primary care physicians who care for people with Alzheimer’s disease say dementia specialists in their communities cannot meet demand. The problem is more urgent in rural areas. Roughly half of nonmetropolitan counties in the United States lack a practicing psychologist, according to a 2018 study published in the American Journal of Preventive Medicine.

“We really need to approach this on both sides – build the capacity in primary care, but we also need to address the dementia care specialty shortages,” Mr. Daven said.

The lack of obvious differences in access to neurologists in the new study “was surprising, given the more than fourfold difference between urban and rural areas in the supply of neurologists,” the researchers note. Health plans may maintain more access to neurologists than psychologists because of relatively higher reimbursement for neurologists, they observed.

One of the study coauthors disclosed ties to Aveanna Healthcare, a company that delivers home health and hospice care.

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

Rural patients with early onset dementia are more likely than urban patients to rely solely on primary care physicians or nurse practitioners for the initial diagnosis and treatment of the disease, a new study has found.

Patients in rural areas are also less likely to see psychologists and undergo neuropsychological testing, according to the study, published in JAMA Network Open.

Patients who forgo such specialist visits and testing may be missing information about their condition that could help them prepare for changes in job responsibilities and future care decisions, said Wendy Yi Xu, PhD, of The Ohio State University, Columbus, who led the research.

“A lot of them are still in the workforce,” Dr. Xu said. Patients in the study were an average age of 56 years, well before the conventional age of retirement.
 

Location, location, location

To examine rural versus urban differences in the use of diagnostic tests and health care visits for early onset Alzheimer’s disease and related dementias, Dr. Xu and colleagues analyzed commercial claims data from 2012-2018. They identified more than 71,000 patients aged 40-64 years with those conditions and focused on health care use by 7,311 patients in urban areas and 1,119 in rural areas within 90 days of a new dementia diagnosis.

The proportion who received neuropsychological testing was 19% among urban patients and 16% among rural patients. Psychological assessments, which are less specialized and detailed than neuropsychological testing, and brain imaging occurred at similar rates in both groups. Similar proportions of rural and urban patients visited neurologists (17.7% and 17.96%, respectively) and psychiatrists (6.02% and 6.47%).

But more urban patients than rural patients visited a psychologist, at 19% versus 15%, according to the researchers.

Approximately 18% of patients in rural areas saw a primary care provider without visiting other specialists, compared with 13% in urban areas.

The researchers found that rural patients were significantly less likely to undergo neuropsychological testing (odds ratio, 0.83; 95% confidence interval, 0.70-0.98) or see a psychologist (OR, 0.72; 95% CI, 0.60-0.85).

Similarly, rural patients had significantly higher odds of having only primary care providers involved in the diagnosis of dementia and symptom management (OR, 1.40; 95% CI, 1.19-1.66).
 

Addressing workforce deficiencies

More primary care training in dementia care and collaboration with specialist colleagues could help address differences in care, Dr. Xu’s group writes. Such efforts are already underway.

In 2018, the Alzheimer’s Association launched telementoring programs focused on dementia care using the Project ECHO (Extension for Community Healthcare Outcomes) model. Researchers originally developed Project ECHO at the University of New Mexico in 2003 to teach primary care clinicians in remote settings how to treat patients infected with the hepatitis C virus.

With the Alzheimer’s and Dementia Care ECHO Program for Clinicians, primary care clinicians can participate in interactive case-based video conferencing sessions to better understand dementia and how to provide high-quality care in community settings, according to the association.

The program covers guidelines for diagnosis, disclosure, and follow-up; the initiation of care planning; managing disease-related challenges; and resources for patients and caregivers.

Since 2018, nearly 100 primary care practices in the United States have completed training in dementia care using Project ECHO, said Morgan Daven, vice president of health systems for the Alzheimer’s Association. Many cases featured in the program are challenging, he added.

“With primary care being on the front lines, it is really important that primary care physicians are equipped to do what they can to detect or diagnose and know when to refer,” Mr. Daven said.

The association has compiled other resources for clinicians as well.

A 2020 report from the association examined the role that primary care physicians play in dementia care. One survey found that 82% of primary care physicians consider themselves on the front lines of providing care for patients with dementia.

Meanwhile, about half say medical professionals are not prepared to meet rising demands associated with Alzheimer’s disease and dementia care.

Mr. Daven said the geographic disparities Dr. Xu and colleagues found are unsurprising. More than half of primary care physicians who care for people with Alzheimer’s disease say dementia specialists in their communities cannot meet demand. The problem is more urgent in rural areas. Roughly half of nonmetropolitan counties in the United States lack a practicing psychologist, according to a 2018 study published in the American Journal of Preventive Medicine.

“We really need to approach this on both sides – build the capacity in primary care, but we also need to address the dementia care specialty shortages,” Mr. Daven said.

The lack of obvious differences in access to neurologists in the new study “was surprising, given the more than fourfold difference between urban and rural areas in the supply of neurologists,” the researchers note. Health plans may maintain more access to neurologists than psychologists because of relatively higher reimbursement for neurologists, they observed.

One of the study coauthors disclosed ties to Aveanna Healthcare, a company that delivers home health and hospice care.

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

Rural patients with early onset dementia are more likely than urban patients to rely solely on primary care physicians or nurse practitioners for the initial diagnosis and treatment of the disease, a new study has found.

Patients in rural areas are also less likely to see psychologists and undergo neuropsychological testing, according to the study, published in JAMA Network Open.

Patients who forgo such specialist visits and testing may be missing information about their condition that could help them prepare for changes in job responsibilities and future care decisions, said Wendy Yi Xu, PhD, of The Ohio State University, Columbus, who led the research.

“A lot of them are still in the workforce,” Dr. Xu said. Patients in the study were an average age of 56 years, well before the conventional age of retirement.
 

Location, location, location

To examine rural versus urban differences in the use of diagnostic tests and health care visits for early onset Alzheimer’s disease and related dementias, Dr. Xu and colleagues analyzed commercial claims data from 2012-2018. They identified more than 71,000 patients aged 40-64 years with those conditions and focused on health care use by 7,311 patients in urban areas and 1,119 in rural areas within 90 days of a new dementia diagnosis.

The proportion who received neuropsychological testing was 19% among urban patients and 16% among rural patients. Psychological assessments, which are less specialized and detailed than neuropsychological testing, and brain imaging occurred at similar rates in both groups. Similar proportions of rural and urban patients visited neurologists (17.7% and 17.96%, respectively) and psychiatrists (6.02% and 6.47%).

But more urban patients than rural patients visited a psychologist, at 19% versus 15%, according to the researchers.

Approximately 18% of patients in rural areas saw a primary care provider without visiting other specialists, compared with 13% in urban areas.

The researchers found that rural patients were significantly less likely to undergo neuropsychological testing (odds ratio, 0.83; 95% confidence interval, 0.70-0.98) or see a psychologist (OR, 0.72; 95% CI, 0.60-0.85).

Similarly, rural patients had significantly higher odds of having only primary care providers involved in the diagnosis of dementia and symptom management (OR, 1.40; 95% CI, 1.19-1.66).
 

Addressing workforce deficiencies

More primary care training in dementia care and collaboration with specialist colleagues could help address differences in care, Dr. Xu’s group writes. Such efforts are already underway.

In 2018, the Alzheimer’s Association launched telementoring programs focused on dementia care using the Project ECHO (Extension for Community Healthcare Outcomes) model. Researchers originally developed Project ECHO at the University of New Mexico in 2003 to teach primary care clinicians in remote settings how to treat patients infected with the hepatitis C virus.

With the Alzheimer’s and Dementia Care ECHO Program for Clinicians, primary care clinicians can participate in interactive case-based video conferencing sessions to better understand dementia and how to provide high-quality care in community settings, according to the association.

The program covers guidelines for diagnosis, disclosure, and follow-up; the initiation of care planning; managing disease-related challenges; and resources for patients and caregivers.

Since 2018, nearly 100 primary care practices in the United States have completed training in dementia care using Project ECHO, said Morgan Daven, vice president of health systems for the Alzheimer’s Association. Many cases featured in the program are challenging, he added.

“With primary care being on the front lines, it is really important that primary care physicians are equipped to do what they can to detect or diagnose and know when to refer,” Mr. Daven said.

The association has compiled other resources for clinicians as well.

A 2020 report from the association examined the role that primary care physicians play in dementia care. One survey found that 82% of primary care physicians consider themselves on the front lines of providing care for patients with dementia.

Meanwhile, about half say medical professionals are not prepared to meet rising demands associated with Alzheimer’s disease and dementia care.

Mr. Daven said the geographic disparities Dr. Xu and colleagues found are unsurprising. More than half of primary care physicians who care for people with Alzheimer’s disease say dementia specialists in their communities cannot meet demand. The problem is more urgent in rural areas. Roughly half of nonmetropolitan counties in the United States lack a practicing psychologist, according to a 2018 study published in the American Journal of Preventive Medicine.

“We really need to approach this on both sides – build the capacity in primary care, but we also need to address the dementia care specialty shortages,” Mr. Daven said.

The lack of obvious differences in access to neurologists in the new study “was surprising, given the more than fourfold difference between urban and rural areas in the supply of neurologists,” the researchers note. Health plans may maintain more access to neurologists than psychologists because of relatively higher reimbursement for neurologists, they observed.

One of the study coauthors disclosed ties to Aveanna Healthcare, a company that delivers home health and hospice care.

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

After New York–based yoga instructor Erin Conley’s two sisters gave birth, Ms. Conley suggested a few advanced poses to help strengthen their pelvic floor.

“With one of my sisters, she said, ‘Honestly right now, I just can’t even stand up,’ ” she recalled.

Ms. Conley’s other sister could do slightly more advanced poses – leading Ms. Conley to recognize that after delivery, women’s ability to practice yoga varied widely.

“Post-birth is certainly a progression for each woman,” she said. “You can’t just go into these advance postures.”

Ms. Conley tailored a slow sequence of 30-second poses that each sister could start with, and they eventually reported an improvement of pelvic floor issues. Ms. Conley’s suggestions to her sisters are backed by a small but growing body of research. One study published in August in the journal Urology suggests that yoga may be a way to help treat multiple types of pelvic floor disorders.

More than 1 in 4 women in the United States experience pelvic floor disorders such as bowel or urinary incontinence or pelvic organ prolapse, many as a result of giving birth. But less than 15% of these women seek medical treatment for their symptoms, according to Hari Tunuguntla, MD, associate professor of urologic surgery at Rutgers University’s Robert Wood Johnson Medical School, New Brunswick.

For those who do seek medical help, many patients have trouble complying with initial lifestyle-based recommendations, such as refraining from drinking caffeinated and carbonated beverages, Dr. Tunuguntla said.

“It requires a lot of persistence and knowledge and compliance,” he said.

Medication and physical therapy are routes doctors can order before considering surgery, but some patients find clinical-based interventions to be costly. The cost of the interventions can add up depending on what a person’s insurance policy covers, Dr. Tunuguntla said.

With those struggles in mind, he and his colleagues set out to study the efficacy of the mobile app Yoga of Immortals, which offers a holistic form of yoga that includes postures, breathing exercises, sound therapy, and meditation.

“It includes sound therapy, summative breathing exercise,” Dr. Tunuguntla said. “These are useful not just for the condition but for general well-being.”

For the study, Dr. Tunuguntla and his colleagues emailed surveys to 420 people between ages 18 and 74 years in 23 countries who reported having any type of urinary incontinence, regardless of severity. The participants, most of whom were women, used the yoga app for 30 minutes a day for 8 weeks.

More than three-quarters of participants reported that the frequency and severity of their incontinence improved after 8 weeks of practice, compared with when they started, without having to visit their health care provider. Most participants also said that they felt “very much better” after 8 weeks, compared with when they began the yoga regimen, the researchers found.

The study did not compare the effectiveness of the approach with other standard treatments for incontinence, like physical therapy, medication, or surgery.

Ms. Conley, an instructor since 2010, said that one of the benefits of yoga is building strength and flexibility slowly and simultaneously. She uses yoga poses that focus less on movement and more on holding positions for longer periods of time.

“I’ll do sequences of a mountain pose with a block to activate the core in the most basic ways and really focus on the breathing,” she said.

Another benefit of slower forms of yoga is that they can help participants become more aware of the structures of their pelvic floor, according to Alison Huang, MD, professor of medicine, urology and epidemiology, and biostatistics at University of California, San Francisco.

“In some ways we can think of it as a complementary substitute for rehabilitation therapy,” Dr. Huang said.

Dr. Huang and her colleagues published a short report recently in The Journal of Integrative and Complementary Medicine, showing that even telehealth-based yoga programs for older women with urinary incontinence can offer an accessible way for women of any background to take advantage of yoga’s benefits.

An estimated 93% of 66 participants who practiced yoga through planned telehealth appointments reported feeling “very or moderately satisfied” with their practice. Dr. Huang said that the study is not yet complete but offers a glimpse into some of the advantages of yoga for women with urinary incontinence.

“Any kind of treatment that relies on intensive one-on-one visits with specialists is going to be harder to access for some women,” Dr. Huang told this news organization. “Yoga is typically practiced in a community setting, outside of traditional health care settings.”

The accessibility of yoga and its community-based practice may help eliminate any obstacles to care and compliance that clinicians like she and Dr. Tunuguntla at times experience. Mounting studies have also indicated that yoga may help improve overall wellness, manage stress, promote healthier eating, and benefit a person’s mental and emotional health.

Despite emerging research on the link between yoga and pelvic floor disorders, Dr. Huang said that it’s still early for clinicians to recommend the exercise form for every patient.

“We just don’t have the [solid] evidence to show your pelvic floor will improve,” she said.

“For any woman who is starting out more sedentary, I think there are benefits to practic[ing] yoga for overall health,” Dr. Huang said. “Most clinicians would say there are opportunities to practice yoga regularly in a way that is safe, with a knowledgeable instructor.”

According to Ms. Conley, yoga is only as beneficial as a person’s level of consistency in the practice.

“The dedication to yoga is your willingness to showing up,” she said. “I think depending on your commitment to the practice, if you’re really committed to the practice – just like you show up to physical therapy every day – you will improve,” said Ms. Conley.

“Being gentle and patient with the process is important too,” she said.

Dr. Tunuguntla and coauthors report no relevant financial relationships. 

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

After New York–based yoga instructor Erin Conley’s two sisters gave birth, Ms. Conley suggested a few advanced poses to help strengthen their pelvic floor.

“With one of my sisters, she said, ‘Honestly right now, I just can’t even stand up,’ ” she recalled.

Ms. Conley’s other sister could do slightly more advanced poses – leading Ms. Conley to recognize that after delivery, women’s ability to practice yoga varied widely.

“Post-birth is certainly a progression for each woman,” she said. “You can’t just go into these advance postures.”

Ms. Conley tailored a slow sequence of 30-second poses that each sister could start with, and they eventually reported an improvement of pelvic floor issues. Ms. Conley’s suggestions to her sisters are backed by a small but growing body of research. One study published in August in the journal Urology suggests that yoga may be a way to help treat multiple types of pelvic floor disorders.

More than 1 in 4 women in the United States experience pelvic floor disorders such as bowel or urinary incontinence or pelvic organ prolapse, many as a result of giving birth. But less than 15% of these women seek medical treatment for their symptoms, according to Hari Tunuguntla, MD, associate professor of urologic surgery at Rutgers University’s Robert Wood Johnson Medical School, New Brunswick.

For those who do seek medical help, many patients have trouble complying with initial lifestyle-based recommendations, such as refraining from drinking caffeinated and carbonated beverages, Dr. Tunuguntla said.

“It requires a lot of persistence and knowledge and compliance,” he said.

Medication and physical therapy are routes doctors can order before considering surgery, but some patients find clinical-based interventions to be costly. The cost of the interventions can add up depending on what a person’s insurance policy covers, Dr. Tunuguntla said.

With those struggles in mind, he and his colleagues set out to study the efficacy of the mobile app Yoga of Immortals, which offers a holistic form of yoga that includes postures, breathing exercises, sound therapy, and meditation.

“It includes sound therapy, summative breathing exercise,” Dr. Tunuguntla said. “These are useful not just for the condition but for general well-being.”

For the study, Dr. Tunuguntla and his colleagues emailed surveys to 420 people between ages 18 and 74 years in 23 countries who reported having any type of urinary incontinence, regardless of severity. The participants, most of whom were women, used the yoga app for 30 minutes a day for 8 weeks.

More than three-quarters of participants reported that the frequency and severity of their incontinence improved after 8 weeks of practice, compared with when they started, without having to visit their health care provider. Most participants also said that they felt “very much better” after 8 weeks, compared with when they began the yoga regimen, the researchers found.

The study did not compare the effectiveness of the approach with other standard treatments for incontinence, like physical therapy, medication, or surgery.

Ms. Conley, an instructor since 2010, said that one of the benefits of yoga is building strength and flexibility slowly and simultaneously. She uses yoga poses that focus less on movement and more on holding positions for longer periods of time.

“I’ll do sequences of a mountain pose with a block to activate the core in the most basic ways and really focus on the breathing,” she said.

Another benefit of slower forms of yoga is that they can help participants become more aware of the structures of their pelvic floor, according to Alison Huang, MD, professor of medicine, urology and epidemiology, and biostatistics at University of California, San Francisco.

“In some ways we can think of it as a complementary substitute for rehabilitation therapy,” Dr. Huang said.

Dr. Huang and her colleagues published a short report recently in The Journal of Integrative and Complementary Medicine, showing that even telehealth-based yoga programs for older women with urinary incontinence can offer an accessible way for women of any background to take advantage of yoga’s benefits.

An estimated 93% of 66 participants who practiced yoga through planned telehealth appointments reported feeling “very or moderately satisfied” with their practice. Dr. Huang said that the study is not yet complete but offers a glimpse into some of the advantages of yoga for women with urinary incontinence.

“Any kind of treatment that relies on intensive one-on-one visits with specialists is going to be harder to access for some women,” Dr. Huang told this news organization. “Yoga is typically practiced in a community setting, outside of traditional health care settings.”

The accessibility of yoga and its community-based practice may help eliminate any obstacles to care and compliance that clinicians like she and Dr. Tunuguntla at times experience. Mounting studies have also indicated that yoga may help improve overall wellness, manage stress, promote healthier eating, and benefit a person’s mental and emotional health.

Despite emerging research on the link between yoga and pelvic floor disorders, Dr. Huang said that it’s still early for clinicians to recommend the exercise form for every patient.

“We just don’t have the [solid] evidence to show your pelvic floor will improve,” she said.

“For any woman who is starting out more sedentary, I think there are benefits to practic[ing] yoga for overall health,” Dr. Huang said. “Most clinicians would say there are opportunities to practice yoga regularly in a way that is safe, with a knowledgeable instructor.”

According to Ms. Conley, yoga is only as beneficial as a person’s level of consistency in the practice.

“The dedication to yoga is your willingness to showing up,” she said. “I think depending on your commitment to the practice, if you’re really committed to the practice – just like you show up to physical therapy every day – you will improve,” said Ms. Conley.

“Being gentle and patient with the process is important too,” she said.

Dr. Tunuguntla and coauthors report no relevant financial relationships. 

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

After New York–based yoga instructor Erin Conley’s two sisters gave birth, Ms. Conley suggested a few advanced poses to help strengthen their pelvic floor.

“With one of my sisters, she said, ‘Honestly right now, I just can’t even stand up,’ ” she recalled.

Ms. Conley’s other sister could do slightly more advanced poses – leading Ms. Conley to recognize that after delivery, women’s ability to practice yoga varied widely.

“Post-birth is certainly a progression for each woman,” she said. “You can’t just go into these advance postures.”

Ms. Conley tailored a slow sequence of 30-second poses that each sister could start with, and they eventually reported an improvement of pelvic floor issues. Ms. Conley’s suggestions to her sisters are backed by a small but growing body of research. One study published in August in the journal Urology suggests that yoga may be a way to help treat multiple types of pelvic floor disorders.

More than 1 in 4 women in the United States experience pelvic floor disorders such as bowel or urinary incontinence or pelvic organ prolapse, many as a result of giving birth. But less than 15% of these women seek medical treatment for their symptoms, according to Hari Tunuguntla, MD, associate professor of urologic surgery at Rutgers University’s Robert Wood Johnson Medical School, New Brunswick.

For those who do seek medical help, many patients have trouble complying with initial lifestyle-based recommendations, such as refraining from drinking caffeinated and carbonated beverages, Dr. Tunuguntla said.

“It requires a lot of persistence and knowledge and compliance,” he said.

Medication and physical therapy are routes doctors can order before considering surgery, but some patients find clinical-based interventions to be costly. The cost of the interventions can add up depending on what a person’s insurance policy covers, Dr. Tunuguntla said.

With those struggles in mind, he and his colleagues set out to study the efficacy of the mobile app Yoga of Immortals, which offers a holistic form of yoga that includes postures, breathing exercises, sound therapy, and meditation.

“It includes sound therapy, summative breathing exercise,” Dr. Tunuguntla said. “These are useful not just for the condition but for general well-being.”

For the study, Dr. Tunuguntla and his colleagues emailed surveys to 420 people between ages 18 and 74 years in 23 countries who reported having any type of urinary incontinence, regardless of severity. The participants, most of whom were women, used the yoga app for 30 minutes a day for 8 weeks.

More than three-quarters of participants reported that the frequency and severity of their incontinence improved after 8 weeks of practice, compared with when they started, without having to visit their health care provider. Most participants also said that they felt “very much better” after 8 weeks, compared with when they began the yoga regimen, the researchers found.

The study did not compare the effectiveness of the approach with other standard treatments for incontinence, like physical therapy, medication, or surgery.

Ms. Conley, an instructor since 2010, said that one of the benefits of yoga is building strength and flexibility slowly and simultaneously. She uses yoga poses that focus less on movement and more on holding positions for longer periods of time.

“I’ll do sequences of a mountain pose with a block to activate the core in the most basic ways and really focus on the breathing,” she said.

Another benefit of slower forms of yoga is that they can help participants become more aware of the structures of their pelvic floor, according to Alison Huang, MD, professor of medicine, urology and epidemiology, and biostatistics at University of California, San Francisco.

“In some ways we can think of it as a complementary substitute for rehabilitation therapy,” Dr. Huang said.

Dr. Huang and her colleagues published a short report recently in The Journal of Integrative and Complementary Medicine, showing that even telehealth-based yoga programs for older women with urinary incontinence can offer an accessible way for women of any background to take advantage of yoga’s benefits.

An estimated 93% of 66 participants who practiced yoga through planned telehealth appointments reported feeling “very or moderately satisfied” with their practice. Dr. Huang said that the study is not yet complete but offers a glimpse into some of the advantages of yoga for women with urinary incontinence.

“Any kind of treatment that relies on intensive one-on-one visits with specialists is going to be harder to access for some women,” Dr. Huang told this news organization. “Yoga is typically practiced in a community setting, outside of traditional health care settings.”

The accessibility of yoga and its community-based practice may help eliminate any obstacles to care and compliance that clinicians like she and Dr. Tunuguntla at times experience. Mounting studies have also indicated that yoga may help improve overall wellness, manage stress, promote healthier eating, and benefit a person’s mental and emotional health.

Despite emerging research on the link between yoga and pelvic floor disorders, Dr. Huang said that it’s still early for clinicians to recommend the exercise form for every patient.

“We just don’t have the [solid] evidence to show your pelvic floor will improve,” she said.

“For any woman who is starting out more sedentary, I think there are benefits to practic[ing] yoga for overall health,” Dr. Huang said. “Most clinicians would say there are opportunities to practice yoga regularly in a way that is safe, with a knowledgeable instructor.”

According to Ms. Conley, yoga is only as beneficial as a person’s level of consistency in the practice.

“The dedication to yoga is your willingness to showing up,” she said. “I think depending on your commitment to the practice, if you’re really committed to the practice – just like you show up to physical therapy every day – you will improve,” said Ms. Conley.

“Being gentle and patient with the process is important too,” she said.

Dr. Tunuguntla and coauthors report no relevant financial relationships. 

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

A case study of a 65-year-old man in Japan with long COVID describes how he recovered from certain impaired hormone deficiencies that persisted for more than a year.

Days after the patient recovered from respiratory failure and came off a ventilator, he had a sudden drop in blood pressure, which responded to hydrocortisone.

The patient was found to have low levels of growth hormone and adrenocorticotropic hormone (ACTH), hypopituitarism, that persisted for more than a year. He also had low levels of testosterone that remained low at 15 months (the study end).

“An important finding in the present case is the eventual recovery from hypopituitarism over time but not from hypogonadism,” the researchers write in their study published in Endocrine Journal.

This is the first published case of secondary adrenal insufficiency after recovery from COVID-19, which was confirmed using an insulin tolerance test, Kai Yoshimura, Kakogawa Medical Center, Japan, and colleagues report.

The findings show that “pituitary insufficiency should be considered in patients with prolonged symptoms of COVID-19,” they report, since it can be treated with hormone supplements that markedly improve symptoms and quality of life.

“It might be worthwhile to screen for endocrine dysfunction in patients with such persistent symptoms after their recovery from the acute disease,” the researchers conclude.
 

Case study timeline

The patient in this study was healthy without obesity, previous endocrine disease, or steroid use. He was admitted to hospital because he had dyspnea and fever for 8 days and a reverse transcription-polymerase chain reaction (RT-PCR) test that was positive for COVID-19.

He received ciclesonide 200 mcg/day for 2 days. Then he was put on a ventilator and the drug was discontinued and “favipiravir, ritonavir, and lopinavir, a standard regimen during the early phase of the COVID-19 pandemic, were initiated;” the researchers explain.

On day 25 of his hospital stay the patient had recovered from respiratory failure and was extubated.

On day 31, he had a negative PCR test for COVID-19.

On day 36, the patient’s blood pressure suddenly dropped from 120/80 mmHg to 80/50 mmHg. His plasma ACTH and serum cortisol levels were low, suggesting secondary adrenal insufficiency. The low blood pressure responded to hydrocortisone 100 mg, which was gradually tapered.

At day 96, the patient was discharged from hospital with a dose of 15 mg/day hydrocortisone.

At 3 months after discharge, an insulin tolerance test revealed that the patient’s ACTH and cortisol responses were blunted, suggestive of adrenal insufficiency. The patient also had moderate growth hormone deficiency and symptoms of hypogonadism.

At 6 months after discharge, the patient started testosterone therapy because his dysspermatism had worsened.

At 12 months after discharge, a repeat insulin tolerance test showed that both ACTH and cortisol responses were low but improved. The patient was no longer deficient in growth hormone.

At 15 months after discharge, early morning levels of ACTH and cortisol were now in the normal range. The patient discontinued testosterone treatment, but the symptoms returned, so he resumed it.
 

Long COVID symptoms, possible biological mechanism

The present case shows how certain COVID-19–associated conditions develop after the onset of, or the recovery from, respiratory disorders, the authors note.

Symptoms of long COVID-19 include fatigue, weakness, hair loss, diarrhea, arthralgia, and depression, and these symptoms are associated with pituitary insufficiency, especially secondary adrenocortical insufficiency.

In addition, an estimated 25% of sexually active men who recover from COVID have semen disorders such as azoospermia and oligospermia.

The underlying mechanism by which COVID-19 might trigger pituitary insufficiency is unknown, but other viral infections such as influenza-A and herpes simplex are also associated with transient hypopituitarism. An exaggerated immune response triggered by SARS-CoV-2 may explain the dysfunction of multiple endocrine organs, the researchers write.  

The researchers have declared no conflicts of interest.

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

A case study of a 65-year-old man in Japan with long COVID describes how he recovered from certain impaired hormone deficiencies that persisted for more than a year.

Days after the patient recovered from respiratory failure and came off a ventilator, he had a sudden drop in blood pressure, which responded to hydrocortisone.

The patient was found to have low levels of growth hormone and adrenocorticotropic hormone (ACTH), hypopituitarism, that persisted for more than a year. He also had low levels of testosterone that remained low at 15 months (the study end).

“An important finding in the present case is the eventual recovery from hypopituitarism over time but not from hypogonadism,” the researchers write in their study published in Endocrine Journal.

This is the first published case of secondary adrenal insufficiency after recovery from COVID-19, which was confirmed using an insulin tolerance test, Kai Yoshimura, Kakogawa Medical Center, Japan, and colleagues report.

The findings show that “pituitary insufficiency should be considered in patients with prolonged symptoms of COVID-19,” they report, since it can be treated with hormone supplements that markedly improve symptoms and quality of life.

“It might be worthwhile to screen for endocrine dysfunction in patients with such persistent symptoms after their recovery from the acute disease,” the researchers conclude.
 

Case study timeline

The patient in this study was healthy without obesity, previous endocrine disease, or steroid use. He was admitted to hospital because he had dyspnea and fever for 8 days and a reverse transcription-polymerase chain reaction (RT-PCR) test that was positive for COVID-19.

He received ciclesonide 200 mcg/day for 2 days. Then he was put on a ventilator and the drug was discontinued and “favipiravir, ritonavir, and lopinavir, a standard regimen during the early phase of the COVID-19 pandemic, were initiated;” the researchers explain.

On day 25 of his hospital stay the patient had recovered from respiratory failure and was extubated.

On day 31, he had a negative PCR test for COVID-19.

On day 36, the patient’s blood pressure suddenly dropped from 120/80 mmHg to 80/50 mmHg. His plasma ACTH and serum cortisol levels were low, suggesting secondary adrenal insufficiency. The low blood pressure responded to hydrocortisone 100 mg, which was gradually tapered.

At day 96, the patient was discharged from hospital with a dose of 15 mg/day hydrocortisone.

At 3 months after discharge, an insulin tolerance test revealed that the patient’s ACTH and cortisol responses were blunted, suggestive of adrenal insufficiency. The patient also had moderate growth hormone deficiency and symptoms of hypogonadism.

At 6 months after discharge, the patient started testosterone therapy because his dysspermatism had worsened.

At 12 months after discharge, a repeat insulin tolerance test showed that both ACTH and cortisol responses were low but improved. The patient was no longer deficient in growth hormone.

At 15 months after discharge, early morning levels of ACTH and cortisol were now in the normal range. The patient discontinued testosterone treatment, but the symptoms returned, so he resumed it.
 

Long COVID symptoms, possible biological mechanism

The present case shows how certain COVID-19–associated conditions develop after the onset of, or the recovery from, respiratory disorders, the authors note.

Symptoms of long COVID-19 include fatigue, weakness, hair loss, diarrhea, arthralgia, and depression, and these symptoms are associated with pituitary insufficiency, especially secondary adrenocortical insufficiency.

In addition, an estimated 25% of sexually active men who recover from COVID have semen disorders such as azoospermia and oligospermia.

The underlying mechanism by which COVID-19 might trigger pituitary insufficiency is unknown, but other viral infections such as influenza-A and herpes simplex are also associated with transient hypopituitarism. An exaggerated immune response triggered by SARS-CoV-2 may explain the dysfunction of multiple endocrine organs, the researchers write.  

The researchers have declared no conflicts of interest.

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

A case study of a 65-year-old man in Japan with long COVID describes how he recovered from certain impaired hormone deficiencies that persisted for more than a year.

Days after the patient recovered from respiratory failure and came off a ventilator, he had a sudden drop in blood pressure, which responded to hydrocortisone.

The patient was found to have low levels of growth hormone and adrenocorticotropic hormone (ACTH), hypopituitarism, that persisted for more than a year. He also had low levels of testosterone that remained low at 15 months (the study end).

“An important finding in the present case is the eventual recovery from hypopituitarism over time but not from hypogonadism,” the researchers write in their study published in Endocrine Journal.

This is the first published case of secondary adrenal insufficiency after recovery from COVID-19, which was confirmed using an insulin tolerance test, Kai Yoshimura, Kakogawa Medical Center, Japan, and colleagues report.

The findings show that “pituitary insufficiency should be considered in patients with prolonged symptoms of COVID-19,” they report, since it can be treated with hormone supplements that markedly improve symptoms and quality of life.

“It might be worthwhile to screen for endocrine dysfunction in patients with such persistent symptoms after their recovery from the acute disease,” the researchers conclude.
 

Case study timeline

The patient in this study was healthy without obesity, previous endocrine disease, or steroid use. He was admitted to hospital because he had dyspnea and fever for 8 days and a reverse transcription-polymerase chain reaction (RT-PCR) test that was positive for COVID-19.

He received ciclesonide 200 mcg/day for 2 days. Then he was put on a ventilator and the drug was discontinued and “favipiravir, ritonavir, and lopinavir, a standard regimen during the early phase of the COVID-19 pandemic, were initiated;” the researchers explain.

On day 25 of his hospital stay the patient had recovered from respiratory failure and was extubated.

On day 31, he had a negative PCR test for COVID-19.

On day 36, the patient’s blood pressure suddenly dropped from 120/80 mmHg to 80/50 mmHg. His plasma ACTH and serum cortisol levels were low, suggesting secondary adrenal insufficiency. The low blood pressure responded to hydrocortisone 100 mg, which was gradually tapered.

At day 96, the patient was discharged from hospital with a dose of 15 mg/day hydrocortisone.

At 3 months after discharge, an insulin tolerance test revealed that the patient’s ACTH and cortisol responses were blunted, suggestive of adrenal insufficiency. The patient also had moderate growth hormone deficiency and symptoms of hypogonadism.

At 6 months after discharge, the patient started testosterone therapy because his dysspermatism had worsened.

At 12 months after discharge, a repeat insulin tolerance test showed that both ACTH and cortisol responses were low but improved. The patient was no longer deficient in growth hormone.

At 15 months after discharge, early morning levels of ACTH and cortisol were now in the normal range. The patient discontinued testosterone treatment, but the symptoms returned, so he resumed it.
 

Long COVID symptoms, possible biological mechanism

The present case shows how certain COVID-19–associated conditions develop after the onset of, or the recovery from, respiratory disorders, the authors note.

Symptoms of long COVID-19 include fatigue, weakness, hair loss, diarrhea, arthralgia, and depression, and these symptoms are associated with pituitary insufficiency, especially secondary adrenocortical insufficiency.

In addition, an estimated 25% of sexually active men who recover from COVID have semen disorders such as azoospermia and oligospermia.

The underlying mechanism by which COVID-19 might trigger pituitary insufficiency is unknown, but other viral infections such as influenza-A and herpes simplex are also associated with transient hypopituitarism. An exaggerated immune response triggered by SARS-CoV-2 may explain the dysfunction of multiple endocrine organs, the researchers write.  

The researchers have declared no conflicts of interest.

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

Lower limits on serum urate levels applied in gout management may be based on a misreading of data on mortality risks, researchers say.

Low urate levels may not in themselves pose a risk of death but may be a sign of some other illness, said Joshua F. Baker, MD, MSCE, associate professor of rheumatology and epidemiology at the University of Pennsylvania in Philadelphia.

jarun011/Thinkstock

“It points us towards being more reassured that we can be aggressive in treating gout without a concern about long-term effects for our patients,” he said in an interview. He and colleagues published their findings online in Arthritis & Rheumatology.

Previous research has linked high levels of urate with excessive fat and low levels of urate with loss of skeletal muscle mass. And epidemiologic studies have shown a U-shaped relationship between urate levels and mortality, suggesting that very high and very low levels of urate could be harmful.

Based on this correlation, and the theory that urate could have antioxidant benefits, some professional societies have recommended not lowering urate levels below a defined threshold when treating gout. The European Alliance of Associations for Rheumatology has recommended a lower limit of 3 mg/dL.

But the evidence doesn’t entirely support this caution. For example, in a clinical trial of pegloticase (Krystexxa) in patients with refractory gout, patients whose mean serum urate dropped below 2 mg/dL did not die in higher proportions than patients with higher urate levels.

To better understand the risk of low urate, Dr. Baker and colleagues analyzed data on 13,979 participants in the National Health and Nutrition Examination Survey (NHANES) during 1999-2006. The dataset included whole-body dual-energy x-ray absorptiometry (DXA) body composition measures as well as urate levels.

The researchers argue this measurement reveals more about a person’s overall health than body mass index (BMI), which doesn’t distinguish between mass from fat and mass from muscle.

They defined low lean body mass, or sarcopenia, as an appendicular lean mass index relative to fat mass index z score of –1. And they defined low urate as less than 2.5 mg/dL in women and less than 3.5 mg/dL in men.

They found that 29% of people with low urate had low lean body mass, compared with 16% of people with normal urate levels. The difference was statistically significant (P = .001).

They found an association between low urate and increased mortality (hazard ratio, 1.61; 95% confidence interval, 1.14-2.28; P = .008). But that association lost its statistical significance when the researchers adjusted for body composition and weight loss (HR, 1.30; 95% CI, 0.92-1.85; P = .13).

Dr. Baker thinks the association between elevated mortality and low urate can be explained by conditions such as cancer or lung inflammation that might on one hand increase the risk of death and on the other hand lower urate levels by lowering muscle mass. “Low uric acid levels are observed in people who have lost weight for unhealthy reasons, and that can explain relationships with long-term outcomes,” he said.

Proportions of muscle and fat could not account for the risk of mortality associated with high levels of urate, the researchers found. Those participants with urate levels above 5.7 mg/dL had a higher risk of death with higher levels of urate, and this persisted even after statistical adjustment for body composition.

The study sheds light on an important area of controversy, said Mehdi Fini, MD, of the department of medicine at the University of Colorado at Denver, Aurora, who was not involved in the research.

But body composition does not entirely explain the relationship between urate and mortality, he told this news organization. Medications used to lower urate can cause side effects that might increase mortality, he said.

Also, he said, it’s important to understand the role of comorbidities. He cited evidence that low urate is associated with renal, cardiovascular, and pulmonary conditions. Safe levels of urate might differ depending on these factors. So rather than applying the same target serum level to all patients, perhaps researchers should investigate whether lowering urate by a percentage of the patient’s current level is safer and more effective, he suggested.

He agreed with an editorial that also appeared in Arthritis & Rheumatology saying that there is no evidence for a benefit in lowering urate much below 5 mg/dL. “No matter what, I think we should just be careful,” Dr. Fini said.

Dr. Fini and Dr. Baker report no relevant financial relationships. Dr. Baker acknowledged support from a VA Clinical Science Research & Development Merit Award and a Rehabilitation R&D Merit Award.

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

Lower limits on serum urate levels applied in gout management may be based on a misreading of data on mortality risks, researchers say.

Low urate levels may not in themselves pose a risk of death but may be a sign of some other illness, said Joshua F. Baker, MD, MSCE, associate professor of rheumatology and epidemiology at the University of Pennsylvania in Philadelphia.

jarun011/Thinkstock

“It points us towards being more reassured that we can be aggressive in treating gout without a concern about long-term effects for our patients,” he said in an interview. He and colleagues published their findings online in Arthritis & Rheumatology.

Previous research has linked high levels of urate with excessive fat and low levels of urate with loss of skeletal muscle mass. And epidemiologic studies have shown a U-shaped relationship between urate levels and mortality, suggesting that very high and very low levels of urate could be harmful.

Based on this correlation, and the theory that urate could have antioxidant benefits, some professional societies have recommended not lowering urate levels below a defined threshold when treating gout. The European Alliance of Associations for Rheumatology has recommended a lower limit of 3 mg/dL.

But the evidence doesn’t entirely support this caution. For example, in a clinical trial of pegloticase (Krystexxa) in patients with refractory gout, patients whose mean serum urate dropped below 2 mg/dL did not die in higher proportions than patients with higher urate levels.

To better understand the risk of low urate, Dr. Baker and colleagues analyzed data on 13,979 participants in the National Health and Nutrition Examination Survey (NHANES) during 1999-2006. The dataset included whole-body dual-energy x-ray absorptiometry (DXA) body composition measures as well as urate levels.

The researchers argue this measurement reveals more about a person’s overall health than body mass index (BMI), which doesn’t distinguish between mass from fat and mass from muscle.

They defined low lean body mass, or sarcopenia, as an appendicular lean mass index relative to fat mass index z score of –1. And they defined low urate as less than 2.5 mg/dL in women and less than 3.5 mg/dL in men.

They found that 29% of people with low urate had low lean body mass, compared with 16% of people with normal urate levels. The difference was statistically significant (P = .001).

They found an association between low urate and increased mortality (hazard ratio, 1.61; 95% confidence interval, 1.14-2.28; P = .008). But that association lost its statistical significance when the researchers adjusted for body composition and weight loss (HR, 1.30; 95% CI, 0.92-1.85; P = .13).

Dr. Baker thinks the association between elevated mortality and low urate can be explained by conditions such as cancer or lung inflammation that might on one hand increase the risk of death and on the other hand lower urate levels by lowering muscle mass. “Low uric acid levels are observed in people who have lost weight for unhealthy reasons, and that can explain relationships with long-term outcomes,” he said.

Proportions of muscle and fat could not account for the risk of mortality associated with high levels of urate, the researchers found. Those participants with urate levels above 5.7 mg/dL had a higher risk of death with higher levels of urate, and this persisted even after statistical adjustment for body composition.

The study sheds light on an important area of controversy, said Mehdi Fini, MD, of the department of medicine at the University of Colorado at Denver, Aurora, who was not involved in the research.

But body composition does not entirely explain the relationship between urate and mortality, he told this news organization. Medications used to lower urate can cause side effects that might increase mortality, he said.

Also, he said, it’s important to understand the role of comorbidities. He cited evidence that low urate is associated with renal, cardiovascular, and pulmonary conditions. Safe levels of urate might differ depending on these factors. So rather than applying the same target serum level to all patients, perhaps researchers should investigate whether lowering urate by a percentage of the patient’s current level is safer and more effective, he suggested.

He agreed with an editorial that also appeared in Arthritis & Rheumatology saying that there is no evidence for a benefit in lowering urate much below 5 mg/dL. “No matter what, I think we should just be careful,” Dr. Fini said.

Dr. Fini and Dr. Baker report no relevant financial relationships. Dr. Baker acknowledged support from a VA Clinical Science Research & Development Merit Award and a Rehabilitation R&D Merit Award.

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

Lower limits on serum urate levels applied in gout management may be based on a misreading of data on mortality risks, researchers say.

Low urate levels may not in themselves pose a risk of death but may be a sign of some other illness, said Joshua F. Baker, MD, MSCE, associate professor of rheumatology and epidemiology at the University of Pennsylvania in Philadelphia.

jarun011/Thinkstock

“It points us towards being more reassured that we can be aggressive in treating gout without a concern about long-term effects for our patients,” he said in an interview. He and colleagues published their findings online in Arthritis & Rheumatology.

Previous research has linked high levels of urate with excessive fat and low levels of urate with loss of skeletal muscle mass. And epidemiologic studies have shown a U-shaped relationship between urate levels and mortality, suggesting that very high and very low levels of urate could be harmful.

Based on this correlation, and the theory that urate could have antioxidant benefits, some professional societies have recommended not lowering urate levels below a defined threshold when treating gout. The European Alliance of Associations for Rheumatology has recommended a lower limit of 3 mg/dL.

But the evidence doesn’t entirely support this caution. For example, in a clinical trial of pegloticase (Krystexxa) in patients with refractory gout, patients whose mean serum urate dropped below 2 mg/dL did not die in higher proportions than patients with higher urate levels.

To better understand the risk of low urate, Dr. Baker and colleagues analyzed data on 13,979 participants in the National Health and Nutrition Examination Survey (NHANES) during 1999-2006. The dataset included whole-body dual-energy x-ray absorptiometry (DXA) body composition measures as well as urate levels.

The researchers argue this measurement reveals more about a person’s overall health than body mass index (BMI), which doesn’t distinguish between mass from fat and mass from muscle.

They defined low lean body mass, or sarcopenia, as an appendicular lean mass index relative to fat mass index z score of –1. And they defined low urate as less than 2.5 mg/dL in women and less than 3.5 mg/dL in men.

They found that 29% of people with low urate had low lean body mass, compared with 16% of people with normal urate levels. The difference was statistically significant (P = .001).

They found an association between low urate and increased mortality (hazard ratio, 1.61; 95% confidence interval, 1.14-2.28; P = .008). But that association lost its statistical significance when the researchers adjusted for body composition and weight loss (HR, 1.30; 95% CI, 0.92-1.85; P = .13).

Dr. Baker thinks the association between elevated mortality and low urate can be explained by conditions such as cancer or lung inflammation that might on one hand increase the risk of death and on the other hand lower urate levels by lowering muscle mass. “Low uric acid levels are observed in people who have lost weight for unhealthy reasons, and that can explain relationships with long-term outcomes,” he said.

Proportions of muscle and fat could not account for the risk of mortality associated with high levels of urate, the researchers found. Those participants with urate levels above 5.7 mg/dL had a higher risk of death with higher levels of urate, and this persisted even after statistical adjustment for body composition.

The study sheds light on an important area of controversy, said Mehdi Fini, MD, of the department of medicine at the University of Colorado at Denver, Aurora, who was not involved in the research.

But body composition does not entirely explain the relationship between urate and mortality, he told this news organization. Medications used to lower urate can cause side effects that might increase mortality, he said.

Also, he said, it’s important to understand the role of comorbidities. He cited evidence that low urate is associated with renal, cardiovascular, and pulmonary conditions. Safe levels of urate might differ depending on these factors. So rather than applying the same target serum level to all patients, perhaps researchers should investigate whether lowering urate by a percentage of the patient’s current level is safer and more effective, he suggested.

He agreed with an editorial that also appeared in Arthritis & Rheumatology saying that there is no evidence for a benefit in lowering urate much below 5 mg/dL. “No matter what, I think we should just be careful,” Dr. Fini said.

Dr. Fini and Dr. Baker report no relevant financial relationships. Dr. Baker acknowledged support from a VA Clinical Science Research & Development Merit Award and a Rehabilitation R&D Merit Award.

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

A sweeping study of 85,000 infants found no link between mRNA COVID vaccination in pregnancy and greater risk of preterm birth, babies being born small for their gestational age, or stillbirth.

The research team wrote in the BMJ that their reassuring findings – drawn from a registry of all births in Ontario over an 8-month period – “can inform evidence-based decision-making” about COVID vaccination during pregnancy.

Previous research has found that pregnant patients are at higher risk of severe complications and death if they become infected with COVID and that vaccination before or during pregnancy prevents such outcomes and reduces the risk of newborn infection, noted Jeffrey Ecker, chief of obstetrics and gynecology at Massachusetts General Hospital, Boston.

This new study “adds to a growing body of information arguing clearly and reassuringly that vaccination during pregnancy is not associated with complications during pregnancy,” said Dr. Ecker, who was not involved in the new study.

He added that it “should help obstetric providers further reassure those who are hesitant that vaccination is safe and best both for the pregnant patient and their pregnancy.”
 

Methods and results

For the new study, researchers tapped a provincial registry of all live and stillborn infants with a gestational age of at least 20 weeks or birth weight of at least 500 g. Unique health card numbers were used to link birth records to a database of COVID vaccinations.

Of 85,162 infants born from May through December of 2021, 43,099 (50.6%) were born to individuals who received at least one vaccine dose during pregnancy. Among those, 99.7% received an mRNA vaccine such as Pfizer-BioNTech or Moderna.

Vaccination during pregnancy was not associated with greater risk of overall preterm birth (6.5% among vaccinated individuals versus 6.9% among unvaccinated; hazard ratio, 1.02; 95% confidence interval, 0.96-1.08), spontaneous preterm birth (3.7% versus 4.4%; hazard ratio, 0.96; 95% CI, 0.90-1.03) or very preterm birth (0.59% versus 0.89%; hazard ratio, 0.80; 95% CI, 0.67-0.95).

Likewise, no increase was observed in the risk of an infant being small for gestational age at birth (9.1% versus 9.2%; hazard ratio, 0.98; 95% CI, 0.93-1.03).

The researchers observed a reduction in the risk of stillbirth, even after adjusting for potential confounders. Stillbirths occurred in 0.25% of vaccinated individuals, compared with 0.44% of unvaccinated individuals (hazard ratio, 0.65; 95% CI, 0.51-0.84).

A reduced risk of stillbirth – albeit to a smaller degree – was also found in a Scandinavian registry study that included 28,506 babies born to individuals who were vaccinated during pregnancy.

“Collectively, the findings from these two studies are reassuring and are consistent with no increased risk of stillbirth after COVID-19 vaccination during pregnancy. In contrast, COVID-19 disease during pregnancy has been associated with an increased risk of stillbirth,” the researchers wrote.

Findings did not vary by which mRNA vaccine a mother received, the number of doses she received, or the trimester in which a vaccine was given, the researchers reported.
 

Stillbirth findings will be ‘very reassuring’ for patients

The lead investigator, Deshayne Fell, PhD, said in an interview, the fact that the study comprised the entire population of pregnant people in Ontario during the study period “increases our confidence” about the validity and relevance of the findings for other geographic settings.

Dr. Fell, an associate professor in epidemiology and public health at the University of Ottawa and a scientist at the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, said the evaluation of stillbirth in particular, “a rare but devastating outcome,” will be “very reassuring and useful for clinical counseling.”

A limitation cited by the research team included a lack of data on vaccination prior to pregnancy.

In the new study, Dr, Ecker said, “Though the investigators were able to adjust for many variables they cannot be certain that some unmeasured variable that, accordingly, was not adjusted for does not hide a small risk. This seems very unlikely, however.”

The Canadian research team said similar studies of non-mRNA COVID vaccines “should be a research priority.” However, such studies are not underway in Canada, where only mRNA vaccines are used in pregnancy, Dr. Fell said.

This study was supported by the Public Health Agency of Canada.

Dr. Fell and Dr. Ecker reported no competing financial interests.

A sweeping study of 85,000 infants found no link between mRNA COVID vaccination in pregnancy and greater risk of preterm birth, babies being born small for their gestational age, or stillbirth.

The research team wrote in the BMJ that their reassuring findings – drawn from a registry of all births in Ontario over an 8-month period – “can inform evidence-based decision-making” about COVID vaccination during pregnancy.

Previous research has found that pregnant patients are at higher risk of severe complications and death if they become infected with COVID and that vaccination before or during pregnancy prevents such outcomes and reduces the risk of newborn infection, noted Jeffrey Ecker, chief of obstetrics and gynecology at Massachusetts General Hospital, Boston.

This new study “adds to a growing body of information arguing clearly and reassuringly that vaccination during pregnancy is not associated with complications during pregnancy,” said Dr. Ecker, who was not involved in the new study.

He added that it “should help obstetric providers further reassure those who are hesitant that vaccination is safe and best both for the pregnant patient and their pregnancy.”
 

Methods and results

For the new study, researchers tapped a provincial registry of all live and stillborn infants with a gestational age of at least 20 weeks or birth weight of at least 500 g. Unique health card numbers were used to link birth records to a database of COVID vaccinations.

Of 85,162 infants born from May through December of 2021, 43,099 (50.6%) were born to individuals who received at least one vaccine dose during pregnancy. Among those, 99.7% received an mRNA vaccine such as Pfizer-BioNTech or Moderna.

Vaccination during pregnancy was not associated with greater risk of overall preterm birth (6.5% among vaccinated individuals versus 6.9% among unvaccinated; hazard ratio, 1.02; 95% confidence interval, 0.96-1.08), spontaneous preterm birth (3.7% versus 4.4%; hazard ratio, 0.96; 95% CI, 0.90-1.03) or very preterm birth (0.59% versus 0.89%; hazard ratio, 0.80; 95% CI, 0.67-0.95).

Likewise, no increase was observed in the risk of an infant being small for gestational age at birth (9.1% versus 9.2%; hazard ratio, 0.98; 95% CI, 0.93-1.03).

The researchers observed a reduction in the risk of stillbirth, even after adjusting for potential confounders. Stillbirths occurred in 0.25% of vaccinated individuals, compared with 0.44% of unvaccinated individuals (hazard ratio, 0.65; 95% CI, 0.51-0.84).

A reduced risk of stillbirth – albeit to a smaller degree – was also found in a Scandinavian registry study that included 28,506 babies born to individuals who were vaccinated during pregnancy.

“Collectively, the findings from these two studies are reassuring and are consistent with no increased risk of stillbirth after COVID-19 vaccination during pregnancy. In contrast, COVID-19 disease during pregnancy has been associated with an increased risk of stillbirth,” the researchers wrote.

Findings did not vary by which mRNA vaccine a mother received, the number of doses she received, or the trimester in which a vaccine was given, the researchers reported.
 

Stillbirth findings will be ‘very reassuring’ for patients

The lead investigator, Deshayne Fell, PhD, said in an interview, the fact that the study comprised the entire population of pregnant people in Ontario during the study period “increases our confidence” about the validity and relevance of the findings for other geographic settings.

Dr. Fell, an associate professor in epidemiology and public health at the University of Ottawa and a scientist at the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, said the evaluation of stillbirth in particular, “a rare but devastating outcome,” will be “very reassuring and useful for clinical counseling.”

A limitation cited by the research team included a lack of data on vaccination prior to pregnancy.

In the new study, Dr, Ecker said, “Though the investigators were able to adjust for many variables they cannot be certain that some unmeasured variable that, accordingly, was not adjusted for does not hide a small risk. This seems very unlikely, however.”

The Canadian research team said similar studies of non-mRNA COVID vaccines “should be a research priority.” However, such studies are not underway in Canada, where only mRNA vaccines are used in pregnancy, Dr. Fell said.

This study was supported by the Public Health Agency of Canada.

Dr. Fell and Dr. Ecker reported no competing financial interests.

A sweeping study of 85,000 infants found no link between mRNA COVID vaccination in pregnancy and greater risk of preterm birth, babies being born small for their gestational age, or stillbirth.

The research team wrote in the BMJ that their reassuring findings – drawn from a registry of all births in Ontario over an 8-month period – “can inform evidence-based decision-making” about COVID vaccination during pregnancy.

Previous research has found that pregnant patients are at higher risk of severe complications and death if they become infected with COVID and that vaccination before or during pregnancy prevents such outcomes and reduces the risk of newborn infection, noted Jeffrey Ecker, chief of obstetrics and gynecology at Massachusetts General Hospital, Boston.

This new study “adds to a growing body of information arguing clearly and reassuringly that vaccination during pregnancy is not associated with complications during pregnancy,” said Dr. Ecker, who was not involved in the new study.

He added that it “should help obstetric providers further reassure those who are hesitant that vaccination is safe and best both for the pregnant patient and their pregnancy.”
 

Methods and results

For the new study, researchers tapped a provincial registry of all live and stillborn infants with a gestational age of at least 20 weeks or birth weight of at least 500 g. Unique health card numbers were used to link birth records to a database of COVID vaccinations.

Of 85,162 infants born from May through December of 2021, 43,099 (50.6%) were born to individuals who received at least one vaccine dose during pregnancy. Among those, 99.7% received an mRNA vaccine such as Pfizer-BioNTech or Moderna.

Vaccination during pregnancy was not associated with greater risk of overall preterm birth (6.5% among vaccinated individuals versus 6.9% among unvaccinated; hazard ratio, 1.02; 95% confidence interval, 0.96-1.08), spontaneous preterm birth (3.7% versus 4.4%; hazard ratio, 0.96; 95% CI, 0.90-1.03) or very preterm birth (0.59% versus 0.89%; hazard ratio, 0.80; 95% CI, 0.67-0.95).

Likewise, no increase was observed in the risk of an infant being small for gestational age at birth (9.1% versus 9.2%; hazard ratio, 0.98; 95% CI, 0.93-1.03).

The researchers observed a reduction in the risk of stillbirth, even after adjusting for potential confounders. Stillbirths occurred in 0.25% of vaccinated individuals, compared with 0.44% of unvaccinated individuals (hazard ratio, 0.65; 95% CI, 0.51-0.84).

A reduced risk of stillbirth – albeit to a smaller degree – was also found in a Scandinavian registry study that included 28,506 babies born to individuals who were vaccinated during pregnancy.

“Collectively, the findings from these two studies are reassuring and are consistent with no increased risk of stillbirth after COVID-19 vaccination during pregnancy. In contrast, COVID-19 disease during pregnancy has been associated with an increased risk of stillbirth,” the researchers wrote.

Findings did not vary by which mRNA vaccine a mother received, the number of doses she received, or the trimester in which a vaccine was given, the researchers reported.
 

Stillbirth findings will be ‘very reassuring’ for patients

The lead investigator, Deshayne Fell, PhD, said in an interview, the fact that the study comprised the entire population of pregnant people in Ontario during the study period “increases our confidence” about the validity and relevance of the findings for other geographic settings.

Dr. Fell, an associate professor in epidemiology and public health at the University of Ottawa and a scientist at the Children’s Hospital of Eastern Ontario Research Institute, Ottawa, said the evaluation of stillbirth in particular, “a rare but devastating outcome,” will be “very reassuring and useful for clinical counseling.”

A limitation cited by the research team included a lack of data on vaccination prior to pregnancy.

In the new study, Dr, Ecker said, “Though the investigators were able to adjust for many variables they cannot be certain that some unmeasured variable that, accordingly, was not adjusted for does not hide a small risk. This seems very unlikely, however.”

The Canadian research team said similar studies of non-mRNA COVID vaccines “should be a research priority.” However, such studies are not underway in Canada, where only mRNA vaccines are used in pregnancy, Dr. Fell said.

This study was supported by the Public Health Agency of Canada.

Dr. Fell and Dr. Ecker reported no competing financial interests.