Key clinical point: Switching to once every-6-weeks (QW6) dosing of natalizumab from a stable dosing of once every-4-weeks (QW4) was safe without any clinically meaningful loss of efficacy in most patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: The mean number of new or newly enlarging T2 hyperintense lesions at 72 weeks was 0.20 (95% CI 0.07-0.63) vs 0.05 (95% CI 0.01-0.22) with natalizumab QW6 vs QW4 dosing regimen, with two patients developing ≥25 lesions contributing to most of the excess lesions in the QW6 dosing regimen. The safety profile was similar for both the regimens.

Study details: Findings are from a phase 3b NOVA trial including 499 patients with RRMS on stable intravenous natalizumab QW4 dosing who were randomly assigned to continue QW4 (n  = 248) or switch to QW6 (n = 251) natalizumab dosing.

Disclosures: This study was funded by Biogen. Five authors reported being current or former employees or holding stocks in Biogen, and some authors reported receiving consulting or speakers’ fees, personal compensation, or serving as a steering committee or advisory board member for various sources.

Source: Foley JF et al. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): A randomised, controlled, open-label, phase 3b trial. Lancet Neurol. 2022 (Apr 25). Doi: 10.1016/ S1474-4422(22)00143-0

Key clinical point: Switching to once every-6-weeks (QW6) dosing of natalizumab from a stable dosing of once every-4-weeks (QW4) was safe without any clinically meaningful loss of efficacy in most patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: The mean number of new or newly enlarging T2 hyperintense lesions at 72 weeks was 0.20 (95% CI 0.07-0.63) vs 0.05 (95% CI 0.01-0.22) with natalizumab QW6 vs QW4 dosing regimen, with two patients developing ≥25 lesions contributing to most of the excess lesions in the QW6 dosing regimen. The safety profile was similar for both the regimens.

Study details: Findings are from a phase 3b NOVA trial including 499 patients with RRMS on stable intravenous natalizumab QW4 dosing who were randomly assigned to continue QW4 (n  = 248) or switch to QW6 (n = 251) natalizumab dosing.

Disclosures: This study was funded by Biogen. Five authors reported being current or former employees or holding stocks in Biogen, and some authors reported receiving consulting or speakers’ fees, personal compensation, or serving as a steering committee or advisory board member for various sources.

Source: Foley JF et al. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): A randomised, controlled, open-label, phase 3b trial. Lancet Neurol. 2022 (Apr 25). Doi: 10.1016/ S1474-4422(22)00143-0

Key clinical point: Switching to once every-6-weeks (QW6) dosing of natalizumab from a stable dosing of once every-4-weeks (QW4) was safe without any clinically meaningful loss of efficacy in most patients with relapsing-remitting multiple sclerosis (RRMS).

Major finding: The mean number of new or newly enlarging T2 hyperintense lesions at 72 weeks was 0.20 (95% CI 0.07-0.63) vs 0.05 (95% CI 0.01-0.22) with natalizumab QW6 vs QW4 dosing regimen, with two patients developing ≥25 lesions contributing to most of the excess lesions in the QW6 dosing regimen. The safety profile was similar for both the regimens.

Study details: Findings are from a phase 3b NOVA trial including 499 patients with RRMS on stable intravenous natalizumab QW4 dosing who were randomly assigned to continue QW4 (n  = 248) or switch to QW6 (n = 251) natalizumab dosing.

Disclosures: This study was funded by Biogen. Five authors reported being current or former employees or holding stocks in Biogen, and some authors reported receiving consulting or speakers’ fees, personal compensation, or serving as a steering committee or advisory board member for various sources.

Source: Foley JF et al. Comparison of switching to 6-week dosing of natalizumab versus continuing with 4-week dosing in patients with relapsing-remitting multiple sclerosis (NOVA): A randomised, controlled, open-label, phase 3b trial. Lancet Neurol. 2022 (Apr 25). Doi: 10.1016/ S1474-4422(22)00143-0

“Here and now is what counts. So, let’s go to work!” –Walter Orthmann, 100 years old
 

How long before you retire? If you know the answer in exact years, months, and days, you aren’t alone. For many good reasons, we doctors are more likely to be counting down the years until we retire rather than counting up the years since we started working. For me, if I’m to break the Guinness World Record, I have 69 more years, 3 months and 6 days left to go. That would surpass the current achievement for the longest career at one company, Mr. Walter Orthmann, who has been sitting at the same desk for 84 years. At 100 years old, Mr. Orthmann still shows up every Monday morning, as bright eyed and bushy tailed as a young squirrel. I’ll be 119 when I break his streak, which would also put me past Anthony Mancinelli, a New York barber who at 107 years of age was still brushing off his chair for the next customer. Unbelievable, I know! I wonder, what’s the one weird trick these guys are doing that keeps them going?

Guinness World Records

Of course, the job itself matters. Some jobs, like being a police officer, aren’t suitable for old people. Or are they? Officer L.C. “Buckshot” Smith was still keeping streets safe from his patrol car at 91 years old. After a bit of searching, I found pretty much any job you can think of has a very long-lasting Energizer Bunny story: A female surgeon who was operating at 90 years old, a 100-year-old rheumatologist who was still teaching at University of California, San Francisco, and a 105-year-old Japanese physician who was still seeing patients. There are plenty of geriatric lawyers, nurses, land surveyors, accountants, judges, you name it. So it seems it’s not the work, but the worker that matters. Why do some older workers recharge daily and carry on while many younger ones say the daily grind is burning them out? What makes the Greatest Generation so great?

We all know colleagues who hung up their white coats early. In my medical group, it’s often financially feasible to retire at 58 and many have chosen that option. Yet, we have loads of Partner Emeritus docs in their 70’s who still log on to EPIC and pitch in everyday.

“So, how do you keep going?” I asked my 105-year-old patient who still walks and manages his affairs. “Just stay healthy,” he advised. A circular argument, yet he’s right. You must both be lucky and also choose to be active mentally and physically. Mr. Mancinelli, who was barbering full time at 107 years old, had no aches and pains and all his teeth. He pruned his own bushes. The data are crystal clear that physical activity adds not only years of life, but also improves cognitive capabilities during those years.

As for beating burnout, it seems the one trick that these ultraworkers do is to focus only on the present. Mr. Orthmann’s pithy advice as quoted by NPR is, “You need to get busy with the present, not the past or the future.” These centenarian employees also frame their work not as stressful but rather as their daily series of problems to be solved.

When I asked my super-geriatric patient how he sleeps so well, he said, “I never worry when I get into bed, I just shut my eyes and sleep. I’ll think about tomorrow when I wake up.” Now if I can do that about 25,000 more times, I’ll have the record.

Dr. Jeff Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

“Here and now is what counts. So, let’s go to work!” –Walter Orthmann, 100 years old
 

How long before you retire? If you know the answer in exact years, months, and days, you aren’t alone. For many good reasons, we doctors are more likely to be counting down the years until we retire rather than counting up the years since we started working. For me, if I’m to break the Guinness World Record, I have 69 more years, 3 months and 6 days left to go. That would surpass the current achievement for the longest career at one company, Mr. Walter Orthmann, who has been sitting at the same desk for 84 years. At 100 years old, Mr. Orthmann still shows up every Monday morning, as bright eyed and bushy tailed as a young squirrel. I’ll be 119 when I break his streak, which would also put me past Anthony Mancinelli, a New York barber who at 107 years of age was still brushing off his chair for the next customer. Unbelievable, I know! I wonder, what’s the one weird trick these guys are doing that keeps them going?

Guinness World Records

Of course, the job itself matters. Some jobs, like being a police officer, aren’t suitable for old people. Or are they? Officer L.C. “Buckshot” Smith was still keeping streets safe from his patrol car at 91 years old. After a bit of searching, I found pretty much any job you can think of has a very long-lasting Energizer Bunny story: A female surgeon who was operating at 90 years old, a 100-year-old rheumatologist who was still teaching at University of California, San Francisco, and a 105-year-old Japanese physician who was still seeing patients. There are plenty of geriatric lawyers, nurses, land surveyors, accountants, judges, you name it. So it seems it’s not the work, but the worker that matters. Why do some older workers recharge daily and carry on while many younger ones say the daily grind is burning them out? What makes the Greatest Generation so great?

We all know colleagues who hung up their white coats early. In my medical group, it’s often financially feasible to retire at 58 and many have chosen that option. Yet, we have loads of Partner Emeritus docs in their 70’s who still log on to EPIC and pitch in everyday.

“So, how do you keep going?” I asked my 105-year-old patient who still walks and manages his affairs. “Just stay healthy,” he advised. A circular argument, yet he’s right. You must both be lucky and also choose to be active mentally and physically. Mr. Mancinelli, who was barbering full time at 107 years old, had no aches and pains and all his teeth. He pruned his own bushes. The data are crystal clear that physical activity adds not only years of life, but also improves cognitive capabilities during those years.

As for beating burnout, it seems the one trick that these ultraworkers do is to focus only on the present. Mr. Orthmann’s pithy advice as quoted by NPR is, “You need to get busy with the present, not the past or the future.” These centenarian employees also frame their work not as stressful but rather as their daily series of problems to be solved.

When I asked my super-geriatric patient how he sleeps so well, he said, “I never worry when I get into bed, I just shut my eyes and sleep. I’ll think about tomorrow when I wake up.” Now if I can do that about 25,000 more times, I’ll have the record.

Dr. Jeff Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

“Here and now is what counts. So, let’s go to work!” –Walter Orthmann, 100 years old
 

How long before you retire? If you know the answer in exact years, months, and days, you aren’t alone. For many good reasons, we doctors are more likely to be counting down the years until we retire rather than counting up the years since we started working. For me, if I’m to break the Guinness World Record, I have 69 more years, 3 months and 6 days left to go. That would surpass the current achievement for the longest career at one company, Mr. Walter Orthmann, who has been sitting at the same desk for 84 years. At 100 years old, Mr. Orthmann still shows up every Monday morning, as bright eyed and bushy tailed as a young squirrel. I’ll be 119 when I break his streak, which would also put me past Anthony Mancinelli, a New York barber who at 107 years of age was still brushing off his chair for the next customer. Unbelievable, I know! I wonder, what’s the one weird trick these guys are doing that keeps them going?

Guinness World Records

Of course, the job itself matters. Some jobs, like being a police officer, aren’t suitable for old people. Or are they? Officer L.C. “Buckshot” Smith was still keeping streets safe from his patrol car at 91 years old. After a bit of searching, I found pretty much any job you can think of has a very long-lasting Energizer Bunny story: A female surgeon who was operating at 90 years old, a 100-year-old rheumatologist who was still teaching at University of California, San Francisco, and a 105-year-old Japanese physician who was still seeing patients. There are plenty of geriatric lawyers, nurses, land surveyors, accountants, judges, you name it. So it seems it’s not the work, but the worker that matters. Why do some older workers recharge daily and carry on while many younger ones say the daily grind is burning them out? What makes the Greatest Generation so great?

We all know colleagues who hung up their white coats early. In my medical group, it’s often financially feasible to retire at 58 and many have chosen that option. Yet, we have loads of Partner Emeritus docs in their 70’s who still log on to EPIC and pitch in everyday.

“So, how do you keep going?” I asked my 105-year-old patient who still walks and manages his affairs. “Just stay healthy,” he advised. A circular argument, yet he’s right. You must both be lucky and also choose to be active mentally and physically. Mr. Mancinelli, who was barbering full time at 107 years old, had no aches and pains and all his teeth. He pruned his own bushes. The data are crystal clear that physical activity adds not only years of life, but also improves cognitive capabilities during those years.

As for beating burnout, it seems the one trick that these ultraworkers do is to focus only on the present. Mr. Orthmann’s pithy advice as quoted by NPR is, “You need to get busy with the present, not the past or the future.” These centenarian employees also frame their work not as stressful but rather as their daily series of problems to be solved.

When I asked my super-geriatric patient how he sleeps so well, he said, “I never worry when I get into bed, I just shut my eyes and sleep. I’ll think about tomorrow when I wake up.” Now if I can do that about 25,000 more times, I’ll have the record.

Dr. Jeff Benabio is director of Healthcare Transformation and chief of dermatology at Kaiser Permanente San Diego. The opinions expressed in this column are his own and do not represent those of Kaiser Permanente. Dr. Benabio is @Dermdoc on Twitter. Write to him at [email protected]

Doctors are advising women who have had bariatric surgery to wait at least 2 years before trying to conceive to reduce the risk of a small-for-gestational-age baby.

In fact, babies conceived less than 2 years post bariatric surgery are 15 times more likely to be small for gestational age as those conceived after this cut-off point, new study findings indicate.

Ana Carreira, MD, Coimbra Hospital and University Centre, Portugal, presented the findings as a poster at the European Congress on Obesity (ECO) 2022.

“The prevalence of small-for-gestational-age babies was similar across the different types of bariatric surgery, and we calculated that the cut-off for the bariatric-surgery-to-conception interval for a lower risk of small for gestational age babies was 24.5 months,” Dr. Carreira reported.

The study also found that for each additional month after the 2-year time point from bariatric surgery to conception, there was a 4.2-g (0.15-oz) increase in birth weight, and there was a 5% lower risk for a small-for-gestational-age neonate. 

“Clinically, this is very significant,” she told this news organization.

“While it may be possible to slightly adjust this on an individual basis, it is important that women who are undergoing bariatric surgery are aware of the risk of early conception and of the benefits of delaying pregnancy,” she added.

Asked to comment, Kari Johansson, PhD, of the Karolinska Institute, Stockholm, who has worked in the field, said: “These increased risks have been hypothesized to potentially be attributed to the inadequate in utero availability of nutrients to the fetus, especially during the first year post bariatric surgery when the rapid and largest weight loss occurs. This is why many clinical guidelines recommend women wait 12-24 months until getting pregnant.”

Indeed, the American College of Obstetricians and Gynecologists recommends women wait 12-24 months post bariatric surgery before trying to conceive.

Dr. Johansson also noted, however, that there were no significant increased risks of adverse outcomes between pregnancies with a surgery-to-conception interval of 12 months or less versus over 12 months in a recent meta-analysis. But those authors also concluded that large cohorts with sufficient power are needed “before any definite conclusions can be made on the optimal surgery-to-conception interval,” she cautioned.
 

All types of bariatric surgery investigated

Bariatric surgery, which is increasingly popular in women of reproductive age, involves rapid weight loss, which can trigger improved fertility, Dr. Carreira explained. Currently, clinics generally advise women to wait at least 1 year before trying for a baby post-surgery.

Dr. Carreira and colleagues conducted the study because “the optimal bariatric-surgery-to-conception interval has yet to be determined,” and they wanted to examine the issue of small-for-gestational-age babies in particular, she noted. They also examined outcomes after a number of different bariatric procedures.

They retrospectively reviewed a cohort of 48 post surgery pregnancies (in 2008-2020) with a minimum follow-up of 30 weeks and determined the proportion of small-for-gestational-age neonates, defined as having a birth weight less than the 10th percentile according to National Center for Health Statistics growth charts.

Mean maternal age was 34.3 years, mean body mass index at conception was 30.9 kg/m², and 70.8% had a bariatric-surgery-to-conception interval of over 24 months, 14.6% of 12-24 months, and 14.6% of less than 12 months.

Bariatric surgeries included adjustable gastric banding (22.9%), sleeve gastrectomy (35.4%), Roux-en-Y gastric bypass (37.5%), and biliopancreatic diversion (4.2%).

Overall, mean birth weight was 2.98 kg (6.6 lb) and the prevalence of small-for-gestational-age babies was 26.3%.

“For an interval of less than 24 months, around 60% of babies were small for gestational age,” Dr. Carreira noted. 

Most babies who were small for gestational age were conceived at 18 months (median), and those who were not were conceived at 59 months (median).

And, after adjustment for maternal comorbidities, the odds ratio for a small-for-gestational-age neonate was 15.1 (95% confidence interval, 2.4-93.1) for a baby conceived less than 24 months after surgery.  

“Some people think the interval can change according to the type of bariatric surgery, but we found no difference in findings according to [surgery] type,” added Dr. Carreira.

She pointed out that after discharge from their endocrinology clinic (after bariatric surgery), the women are cared for by their family doctor, “and we find that when they return to us in pregnancy their nutrient deficiencies have not been properly addressed. They need to be addressed at least 6 months prior to conception.”

“We recommend that women wait at least 2 years after bariatric surgery before trying to conceive, irrespective of the type of surgery,” she reiterated.

Dr. Carreira and Dr. Johansson have reported no relevant financial relationships.

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

Doctors are advising women who have had bariatric surgery to wait at least 2 years before trying to conceive to reduce the risk of a small-for-gestational-age baby.

In fact, babies conceived less than 2 years post bariatric surgery are 15 times more likely to be small for gestational age as those conceived after this cut-off point, new study findings indicate.

Ana Carreira, MD, Coimbra Hospital and University Centre, Portugal, presented the findings as a poster at the European Congress on Obesity (ECO) 2022.

“The prevalence of small-for-gestational-age babies was similar across the different types of bariatric surgery, and we calculated that the cut-off for the bariatric-surgery-to-conception interval for a lower risk of small for gestational age babies was 24.5 months,” Dr. Carreira reported.

The study also found that for each additional month after the 2-year time point from bariatric surgery to conception, there was a 4.2-g (0.15-oz) increase in birth weight, and there was a 5% lower risk for a small-for-gestational-age neonate. 

“Clinically, this is very significant,” she told this news organization.

“While it may be possible to slightly adjust this on an individual basis, it is important that women who are undergoing bariatric surgery are aware of the risk of early conception and of the benefits of delaying pregnancy,” she added.

Asked to comment, Kari Johansson, PhD, of the Karolinska Institute, Stockholm, who has worked in the field, said: “These increased risks have been hypothesized to potentially be attributed to the inadequate in utero availability of nutrients to the fetus, especially during the first year post bariatric surgery when the rapid and largest weight loss occurs. This is why many clinical guidelines recommend women wait 12-24 months until getting pregnant.”

Indeed, the American College of Obstetricians and Gynecologists recommends women wait 12-24 months post bariatric surgery before trying to conceive.

Dr. Johansson also noted, however, that there were no significant increased risks of adverse outcomes between pregnancies with a surgery-to-conception interval of 12 months or less versus over 12 months in a recent meta-analysis. But those authors also concluded that large cohorts with sufficient power are needed “before any definite conclusions can be made on the optimal surgery-to-conception interval,” she cautioned.
 

All types of bariatric surgery investigated

Bariatric surgery, which is increasingly popular in women of reproductive age, involves rapid weight loss, which can trigger improved fertility, Dr. Carreira explained. Currently, clinics generally advise women to wait at least 1 year before trying for a baby post-surgery.

Dr. Carreira and colleagues conducted the study because “the optimal bariatric-surgery-to-conception interval has yet to be determined,” and they wanted to examine the issue of small-for-gestational-age babies in particular, she noted. They also examined outcomes after a number of different bariatric procedures.

They retrospectively reviewed a cohort of 48 post surgery pregnancies (in 2008-2020) with a minimum follow-up of 30 weeks and determined the proportion of small-for-gestational-age neonates, defined as having a birth weight less than the 10th percentile according to National Center for Health Statistics growth charts.

Mean maternal age was 34.3 years, mean body mass index at conception was 30.9 kg/m², and 70.8% had a bariatric-surgery-to-conception interval of over 24 months, 14.6% of 12-24 months, and 14.6% of less than 12 months.

Bariatric surgeries included adjustable gastric banding (22.9%), sleeve gastrectomy (35.4%), Roux-en-Y gastric bypass (37.5%), and biliopancreatic diversion (4.2%).

Overall, mean birth weight was 2.98 kg (6.6 lb) and the prevalence of small-for-gestational-age babies was 26.3%.

“For an interval of less than 24 months, around 60% of babies were small for gestational age,” Dr. Carreira noted. 

Most babies who were small for gestational age were conceived at 18 months (median), and those who were not were conceived at 59 months (median).

And, after adjustment for maternal comorbidities, the odds ratio for a small-for-gestational-age neonate was 15.1 (95% confidence interval, 2.4-93.1) for a baby conceived less than 24 months after surgery.  

“Some people think the interval can change according to the type of bariatric surgery, but we found no difference in findings according to [surgery] type,” added Dr. Carreira.

She pointed out that after discharge from their endocrinology clinic (after bariatric surgery), the women are cared for by their family doctor, “and we find that when they return to us in pregnancy their nutrient deficiencies have not been properly addressed. They need to be addressed at least 6 months prior to conception.”

“We recommend that women wait at least 2 years after bariatric surgery before trying to conceive, irrespective of the type of surgery,” she reiterated.

Dr. Carreira and Dr. Johansson have reported no relevant financial relationships.

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

Doctors are advising women who have had bariatric surgery to wait at least 2 years before trying to conceive to reduce the risk of a small-for-gestational-age baby.

In fact, babies conceived less than 2 years post bariatric surgery are 15 times more likely to be small for gestational age as those conceived after this cut-off point, new study findings indicate.

Ana Carreira, MD, Coimbra Hospital and University Centre, Portugal, presented the findings as a poster at the European Congress on Obesity (ECO) 2022.

“The prevalence of small-for-gestational-age babies was similar across the different types of bariatric surgery, and we calculated that the cut-off for the bariatric-surgery-to-conception interval for a lower risk of small for gestational age babies was 24.5 months,” Dr. Carreira reported.

The study also found that for each additional month after the 2-year time point from bariatric surgery to conception, there was a 4.2-g (0.15-oz) increase in birth weight, and there was a 5% lower risk for a small-for-gestational-age neonate. 

“Clinically, this is very significant,” she told this news organization.

“While it may be possible to slightly adjust this on an individual basis, it is important that women who are undergoing bariatric surgery are aware of the risk of early conception and of the benefits of delaying pregnancy,” she added.

Asked to comment, Kari Johansson, PhD, of the Karolinska Institute, Stockholm, who has worked in the field, said: “These increased risks have been hypothesized to potentially be attributed to the inadequate in utero availability of nutrients to the fetus, especially during the first year post bariatric surgery when the rapid and largest weight loss occurs. This is why many clinical guidelines recommend women wait 12-24 months until getting pregnant.”

Indeed, the American College of Obstetricians and Gynecologists recommends women wait 12-24 months post bariatric surgery before trying to conceive.

Dr. Johansson also noted, however, that there were no significant increased risks of adverse outcomes between pregnancies with a surgery-to-conception interval of 12 months or less versus over 12 months in a recent meta-analysis. But those authors also concluded that large cohorts with sufficient power are needed “before any definite conclusions can be made on the optimal surgery-to-conception interval,” she cautioned.
 

All types of bariatric surgery investigated

Bariatric surgery, which is increasingly popular in women of reproductive age, involves rapid weight loss, which can trigger improved fertility, Dr. Carreira explained. Currently, clinics generally advise women to wait at least 1 year before trying for a baby post-surgery.

Dr. Carreira and colleagues conducted the study because “the optimal bariatric-surgery-to-conception interval has yet to be determined,” and they wanted to examine the issue of small-for-gestational-age babies in particular, she noted. They also examined outcomes after a number of different bariatric procedures.

They retrospectively reviewed a cohort of 48 post surgery pregnancies (in 2008-2020) with a minimum follow-up of 30 weeks and determined the proportion of small-for-gestational-age neonates, defined as having a birth weight less than the 10th percentile according to National Center for Health Statistics growth charts.

Mean maternal age was 34.3 years, mean body mass index at conception was 30.9 kg/m², and 70.8% had a bariatric-surgery-to-conception interval of over 24 months, 14.6% of 12-24 months, and 14.6% of less than 12 months.

Bariatric surgeries included adjustable gastric banding (22.9%), sleeve gastrectomy (35.4%), Roux-en-Y gastric bypass (37.5%), and biliopancreatic diversion (4.2%).

Overall, mean birth weight was 2.98 kg (6.6 lb) and the prevalence of small-for-gestational-age babies was 26.3%.

“For an interval of less than 24 months, around 60% of babies were small for gestational age,” Dr. Carreira noted. 

Most babies who were small for gestational age were conceived at 18 months (median), and those who were not were conceived at 59 months (median).

And, after adjustment for maternal comorbidities, the odds ratio for a small-for-gestational-age neonate was 15.1 (95% confidence interval, 2.4-93.1) for a baby conceived less than 24 months after surgery.  

“Some people think the interval can change according to the type of bariatric surgery, but we found no difference in findings according to [surgery] type,” added Dr. Carreira.

She pointed out that after discharge from their endocrinology clinic (after bariatric surgery), the women are cared for by their family doctor, “and we find that when they return to us in pregnancy their nutrient deficiencies have not been properly addressed. They need to be addressed at least 6 months prior to conception.”

“We recommend that women wait at least 2 years after bariatric surgery before trying to conceive, irrespective of the type of surgery,” she reiterated.

Dr. Carreira and Dr. Johansson have reported no relevant financial relationships.

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

Advanced maternal age and maternal hypertension are a one-two punch that boosts the risk of cesarean births, a new study reports.

While the findings presented at the 2022 annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists aren’t surprising, the insight they provide can be helpful in counseling women at risk about delivery options, lead author and Loma Linda (Calif.) University maternal-fetal medicine physician Sarah D. Smithson, DO, said in an interview.

The prospect of a cesarean birth “can be introduced early and often, which can be important in managing expectations,” she said, especially since women can feel depression and a sense of failure if it turns out they can’t give birth vaginally as they anticipated.

As Dr. Smithson noted, there’s a continuum of maternal hypertension conditions from less severe to more severe. The physicians need to hurry delivery along in the most severe cases. “The clock is clicking when you have preeclampsia, and you do not have time for an induction that could take 2-3 days if you’re having a hard time controlling blood pressure. You may consider cesarean to expedite delivery,” she said.

For the new study, Dr. Smithson and colleagues sought to understand how a combination of maternal hypertension and advanced maternal age affected cesarean delivery rates. They retrospectively tracked 1,625 women with maternal hypertension (chronic hypertension, gestational hypertension, preeclampsia without severe features, and preeclampsia with severe features) who were treated in the Oregon Health & Science University system from 2013 to 2018.

Of the women, 450 were older than 35, and they were more likely than younger women to have cesarean deliveries (46% vs. 34%; P < .001; adjusted OR, 1.7; 95% CI, 1.0-2.7; P = .03).

“We aim to get our cesarean section rates below 20%,” Dr. Smithson said. “These are high rates, and the fact that they’re significantly higher in the advanced maternal age group is compelling.”

The cesarean rates were higher at a statistically significant rate in patients with gestational hypertension (37% in older women vs. 26% in younger women; P = .021) and in those with preeclampsia with severe features (57% vs. 44%, respectively; P = .02). However, the differences were not statistically significant in the groups with chronic hypertension and preeclampsia without severe features.

In an interview, maternal-fetal medicine specialist Alex C. Vidaeff, MD, MPH, of Baylor College of Medicine, Houston, questioned the usefulness of the subgroup analysis, which he thinks may be statistically misleading. “How would one otherwise explain that the rate difference between advanced maternal-age and non–advanced maternal-age subjects is statistically significant for gestational hypertension but not for preeclampsia without severe features?”

He added: “With the very limited information provided by this study, important questions remained unanswered. What is causing the increased rate of cesarean delivery? Provider’s bias or preferences? It would have been useful to know if the cesarean deliveries were elective, without labor, or cesarean deliveries performed during labor or even emergency cesarean deliveries.”

No study funding or disclosures are reported.

Advanced maternal age and maternal hypertension are a one-two punch that boosts the risk of cesarean births, a new study reports.

While the findings presented at the 2022 annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists aren’t surprising, the insight they provide can be helpful in counseling women at risk about delivery options, lead author and Loma Linda (Calif.) University maternal-fetal medicine physician Sarah D. Smithson, DO, said in an interview.

The prospect of a cesarean birth “can be introduced early and often, which can be important in managing expectations,” she said, especially since women can feel depression and a sense of failure if it turns out they can’t give birth vaginally as they anticipated.

As Dr. Smithson noted, there’s a continuum of maternal hypertension conditions from less severe to more severe. The physicians need to hurry delivery along in the most severe cases. “The clock is clicking when you have preeclampsia, and you do not have time for an induction that could take 2-3 days if you’re having a hard time controlling blood pressure. You may consider cesarean to expedite delivery,” she said.

For the new study, Dr. Smithson and colleagues sought to understand how a combination of maternal hypertension and advanced maternal age affected cesarean delivery rates. They retrospectively tracked 1,625 women with maternal hypertension (chronic hypertension, gestational hypertension, preeclampsia without severe features, and preeclampsia with severe features) who were treated in the Oregon Health & Science University system from 2013 to 2018.

Of the women, 450 were older than 35, and they were more likely than younger women to have cesarean deliveries (46% vs. 34%; P < .001; adjusted OR, 1.7; 95% CI, 1.0-2.7; P = .03).

“We aim to get our cesarean section rates below 20%,” Dr. Smithson said. “These are high rates, and the fact that they’re significantly higher in the advanced maternal age group is compelling.”

The cesarean rates were higher at a statistically significant rate in patients with gestational hypertension (37% in older women vs. 26% in younger women; P = .021) and in those with preeclampsia with severe features (57% vs. 44%, respectively; P = .02). However, the differences were not statistically significant in the groups with chronic hypertension and preeclampsia without severe features.

In an interview, maternal-fetal medicine specialist Alex C. Vidaeff, MD, MPH, of Baylor College of Medicine, Houston, questioned the usefulness of the subgroup analysis, which he thinks may be statistically misleading. “How would one otherwise explain that the rate difference between advanced maternal-age and non–advanced maternal-age subjects is statistically significant for gestational hypertension but not for preeclampsia without severe features?”

He added: “With the very limited information provided by this study, important questions remained unanswered. What is causing the increased rate of cesarean delivery? Provider’s bias or preferences? It would have been useful to know if the cesarean deliveries were elective, without labor, or cesarean deliveries performed during labor or even emergency cesarean deliveries.”

No study funding or disclosures are reported.

Advanced maternal age and maternal hypertension are a one-two punch that boosts the risk of cesarean births, a new study reports.

While the findings presented at the 2022 annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists aren’t surprising, the insight they provide can be helpful in counseling women at risk about delivery options, lead author and Loma Linda (Calif.) University maternal-fetal medicine physician Sarah D. Smithson, DO, said in an interview.

The prospect of a cesarean birth “can be introduced early and often, which can be important in managing expectations,” she said, especially since women can feel depression and a sense of failure if it turns out they can’t give birth vaginally as they anticipated.

As Dr. Smithson noted, there’s a continuum of maternal hypertension conditions from less severe to more severe. The physicians need to hurry delivery along in the most severe cases. “The clock is clicking when you have preeclampsia, and you do not have time for an induction that could take 2-3 days if you’re having a hard time controlling blood pressure. You may consider cesarean to expedite delivery,” she said.

For the new study, Dr. Smithson and colleagues sought to understand how a combination of maternal hypertension and advanced maternal age affected cesarean delivery rates. They retrospectively tracked 1,625 women with maternal hypertension (chronic hypertension, gestational hypertension, preeclampsia without severe features, and preeclampsia with severe features) who were treated in the Oregon Health & Science University system from 2013 to 2018.

Of the women, 450 were older than 35, and they were more likely than younger women to have cesarean deliveries (46% vs. 34%; P < .001; adjusted OR, 1.7; 95% CI, 1.0-2.7; P = .03).

“We aim to get our cesarean section rates below 20%,” Dr. Smithson said. “These are high rates, and the fact that they’re significantly higher in the advanced maternal age group is compelling.”

The cesarean rates were higher at a statistically significant rate in patients with gestational hypertension (37% in older women vs. 26% in younger women; P = .021) and in those with preeclampsia with severe features (57% vs. 44%, respectively; P = .02). However, the differences were not statistically significant in the groups with chronic hypertension and preeclampsia without severe features.

In an interview, maternal-fetal medicine specialist Alex C. Vidaeff, MD, MPH, of Baylor College of Medicine, Houston, questioned the usefulness of the subgroup analysis, which he thinks may be statistically misleading. “How would one otherwise explain that the rate difference between advanced maternal-age and non–advanced maternal-age subjects is statistically significant for gestational hypertension but not for preeclampsia without severe features?”

He added: “With the very limited information provided by this study, important questions remained unanswered. What is causing the increased rate of cesarean delivery? Provider’s bias or preferences? It would have been useful to know if the cesarean deliveries were elective, without labor, or cesarean deliveries performed during labor or even emergency cesarean deliveries.”

No study funding or disclosures are reported.

Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These benzophenones are found in various skin care and personal care products, including body washes, exfoliants, fragrances, liquid hand soaps, lip balms, lipsticks, moisturizers, styling gels/creams, and sunscreens, as well as conditioners, hair sprays, and shampoos. Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.

Sunscreens and benzophenones

BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.

mark wragg/iStockphoto.com

In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.¹ Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.^2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
 

Effects of BPs in animals

A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.¹

Effects of BPs in humans and systemic absorption

In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.^4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.⁶

A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.⁷

Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.⁸ Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.³

However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.^3,9

Risks of BPs in sunscreens and other skincare products

In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.¹⁰

In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.¹¹

Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.^3,12

Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.¹³ The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).^13,14

Promising use of nanocapsules

The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.¹⁵

Conclusion

The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.

2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.

3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.

4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.

5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.

6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.

7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.

8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.

9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.

10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.

11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.

12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.

13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.

14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.

15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.

Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These benzophenones are found in various skin care and personal care products, including body washes, exfoliants, fragrances, liquid hand soaps, lip balms, lipsticks, moisturizers, styling gels/creams, and sunscreens, as well as conditioners, hair sprays, and shampoos. Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.

Sunscreens and benzophenones

BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.

mark wragg/iStockphoto.com

In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.¹ Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.^2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
 

Effects of BPs in animals

A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.¹

Effects of BPs in humans and systemic absorption

In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.^4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.⁶

A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.⁷

Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.⁸ Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.³

However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.^3,9

Risks of BPs in sunscreens and other skincare products

In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.¹⁰

In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.¹¹

Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.^3,12

Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.¹³ The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).^13,14

Promising use of nanocapsules

The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.¹⁵

Conclusion

The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.

2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.

3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.

4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.

5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.

6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.

7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.

8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.

9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.

10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.

11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.

12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.

13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.

14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.

15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.

Benzophenones are a family of compounds that include dixoxybenzone, sulisobenzone, and benzophenone-3, or oxybenzone. These benzophenones are found in various skin care and personal care products, including body washes, exfoliants, fragrances, liquid hand soaps, lip balms, lipsticks, moisturizers, styling gels/creams, and sunscreens, as well as conditioners, hair sprays, and shampoos. Benzophenones (BPs) act as penetration enhancers, as they modify the structure of the skin and facilitate the absorption of other chemical ingredients into the body. The best known uses of these compounds are as perfume fixatives and sunscreen agents.

Sunscreens and benzophenones

BP-2, -3 and -4 are used as sunscreens but have many downsides. They are well known photoallergens, are toxic to aquatic animals (especially BP-3), and are found in urine. BP-2 has weak estrogenic effects, and some studies suggest that it decreases fertility in men. BP-4 can increase absorption of pesticides. BP-3 is banned in Hawaii because of the risk to coral and is the most worrisome.

mark wragg/iStockphoto.com

In particular, BP-3 is known to protect skin and hair from UV radiation-induced harm.¹ Unfortunately, BPs are also associated with photocontact allergies, hypersensitivity, hives, contact urticaria, anaphylaxis, hormone disruption, and DNA damage.^2,3 BP-3 has also been implicated as an environmental contaminant. This column will focus on recent studies pertaining to effects on humans, primarily, and on the role of BPs in sunscreen agents.
 

Effects of BPs in animals

A recent study on the cytotoxicity of BP-3 against thymocytes in rats revealed that cell mortality increased significantly after 3 hours of exposure to 300 μM BP-3, but the membrane potential of thymocytes was unchanged by BP-3 exposure. In a concentration-dependent fashion, intracellular Zn2+ levels increased significantly after administration of at least 30 μM BP-3. The investigators concluded that the cytotoxicity engendered by BP-3 could be the result of oxidative stress linked to elevated intracellular Zn2+ levels.¹

Effects of BPs in humans and systemic absorption

In multiple studies, exposure to BP-3, as well as to octinoxate, has been linked to endocrine and hormonal disruptions in humans and animals.^4,5 Motivated by several notable observations (global increase in the use of sunscreens with UV filters; rapid rise in malignant melanoma, against which sunscreens should protect; increase in reported experimental findings of UV filters acting as endocrine disruptors), Krause et al. in 2012 reviewed animal and human data on the UV filters BP-3, 3-benzylidene camphor (3-BC), 3-(4-methyl-benzylidene) camphor (4-MBC), 2-ethylhexyl 4-methoxy cinnamate (OMC), homosalate (HMS), 2-ethylhexyl 4-dimethylaminobenzoate, and 4-aminobenzoic acid (PABA). Importantly, BP-3 was present in 96% of human urine samples in the United States, and various filters were found in 85% of the human breast milk samples in Switzerland.⁶

A 2019 analysis by Wang and Ganley reported that systemic absorption of the active sunscreen ingredient BP-3 can be substantial, justifying the assessment and understanding of systemic exposure to characterize the risks of long-term usage.⁷

Between January and February 2019, Matta et al. conducted a randomized clinical trial with 48 healthy participants to evaluate the systemic absorption and pharmacokinetics of six active ingredients in four sunscreen formulations, including avobenzone and BP-3. The researchers found that all ingredients were systemically absorbed, with plasma concentrations exceeding the Food and Drug Administration threshold for considering the waiving of further safety studies. They concluded that these results did not warrant discontinuing the use of the tested sunscreen ingredients.⁸ Yeager and Lim add that, while BP-3 has been incorporated into sunscreen formulations for sale in the United States since 1978, there have been no reports of adverse systemic reactions in human beings.³

However, topical reactions have elicited a different assessment. That is, in 2014, the American Contact Dermatitis Society labeled BPs the Contact Allergen of the Year, as they were identified as the most common source of photoallergic and contact allergic reactions of all UV filters.^3,9

Risks of BPs in sunscreens and other skincare products

In 2015, Amar et al. investigated the photogenotoxicity and apoptotic effects in human keratinocytes (HaCaT cells) of BP-1, which is used as a UV blocker in sunscreens. They found that BP-1, when exposed to UV radiation, photosensitized cells and yielded intracellular reactive oxygen species. Significant reductions in cell viability were also seen with exposure to sunlight, UVA, and UVB. The researchers also confirmed genotoxic activity, with BP-1 augmenting lipid peroxidation and upregulating apoptotic proteins. They concluded that sunscreen users should be advised to avoid products that contain BP-1.¹⁰

In 2019, Amar et al. evaluated the effects of BPs on the differential expression of proteins in HaCaT cells exposed to UVA. Their findings indicated the expression of novel proteins that helped to initiate or promote apoptosis. They concluded that, because of the predilection to render such effects in human skin keratinocytes, consumers should avoid the use of sunscreens that contain BPs as UV blocking ingredients.¹¹

Still widely used as an effective filter against UVA2 and UVB, BP-3 was believed to be present in two thirds of nonmineral sunscreens in the United States in 2018.^3,12

Notably, BP-1 and BP-3 were found in small proportions (3.7% and 4.9%, respectively) among a total of 283 products culled from various stores in Lecce, Italy, in a survey of the potentially dangerous chemicals found in rinse-off, leave-on, and makeup products in 2019.¹³ The authors added that the International Agency for Research on Cancer, in 2010, classified BP as potentially carcinogenic to humans (2B group).^13,14

Promising use of nanocapsules

The widespread concern about the phototoxicity of BP has prompted some interesting research into workarounds. Specifically, in 2019, Barbosa et al. reported on the creation of a new sunscreen formulation using polymeric nanocapsules loading BP-3. The nanocapsules are made of poly(ε-caprolactone) carrot oil and Pluronic F68 (nonionic surfactant used in suspension cultures), and the BP-3–loaded capsules were found to be noncytotoxic in L929 fibroblast cell lines with a sun protection factor of 8.64. The researchers concluded that this promising nanocapsule may be an effective and safe way to use lipophilic sunscreen ingredients such as BP-3.¹⁵

Conclusion

The body of evidence is weighted against the use of BPs. Luckily, we have safe sunscreen choices that allow us to protect our skin without using these compounds.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Galderma, Revance, Evolus, and Burt’s Bees. She is the CEO of Skin Type Solutions Inc., a company that independently tests skin care products and makes recommendations to physicians on which skin care technologies are best. Write to her at [email protected].

References

1. Utsunomiya H et al. Chem Biol Interact. 2019 Jan 25;298:52-6.

2. Schneider SL and Lim HW. J Am Acad Dermatol. 2019 Jan;80(1):266-71.

3. Yeager DG and Lim HW. Dermatol Clin. 2019 Apr;37(2):149-57.

4. Ramos S et al. Sci Total Environ. 2015 Sep 1;526:278-311.

5. Siller A et al. Plast Surg Nur. 2019 Oct/Dec;39(4):157-60.

6. Krause M et al. Int J Androl. 2012 Jun;35(3):424-36.

7. Wang J and Ganley CJ. Clin Pharmacol Ther. 2019 Jan;105(1):161-7.

8. Matta MK et al. JAMA. 2020 Jan 21;323(3):256-67.

9. Warshaw EM et al. Dermatitis. 2013 Jul-Aug;24(4):176-82.

10. Amar SK et al. Toxicol Lett. 2015 Dec 15;239(3):182-93.

11. Amar SK et al. Toxicol Ind Health. 2019 Jul;35(7):457-65.

12. EWG. The trouble with ingredients in sunscreens. Accessed on 4 April 2020.

13. Panico A et al. J Prev Med Hyg. 2019 Mar 29;60(1):E50-7.

14. International Agency for Research on Cancer (IARC). Benzophenone. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. WHO, IARC Press, Lyon, France. 2010;101:285-304.

15. Barbosa TC et al. Toxics. 2019 Sep 22;7(4):51.

Maybe you know some of these patients: They may come late or not show up at all. They may have little to say and minimize their difficulties, often because they are ashamed of how much effort it takes to meet ordinary obligations. They may struggle to complete assignments, fail classes, or lose jobs. And being in the right place at the right time can feel monumental to them: They forget appointments, double book themselves, or sometimes sleep through important events.

It’s not just appointments. They lose their keys and valuables, forget to pay bills, and may not answer calls, texts, or emails. Their voicemail may be full and people are often frustrated with them. These are all characteristics of executive dysfunction, which together can make the routine responsibilities of life very difficult.

Executive dysfunction is a hallmark symptom cluster often seen in patients with attention deficit hyperactivity disorder (ADD or ADHD). Not everyone with attentional issues struggles with executive dysfunction, but it is quite common.

Treatments include stimulants, and because of their potential for abuse, these medications are more strictly regulated when it comes to prescribing. The FDA does not allow them to be phoned into a pharmacy or refills to be added to prescriptions. Patients must wait until right before they are due to run out to get the next prescription, and this can present a problem if the patient travels or takes long vacations. 

And although it is not the patient’s fault that stimulants can’t be ordered with refills, this adds to the burden of treating patients who take them. It’s hard to imagine that these restrictions on stimulants and opiates (but not on benzodiazepines) do much to deter abuse or diversion.

I trained at a time when ADD and ADHD were disorders of childhood, and as an adult psychiatrist, I was not exposed to patients on these medications. Occasionally, a stimulant was prescribed in a low dose to help activate a very depressed patient, but it was thought that children outgrow issues of attention and focus, and I have never felt fully confident in the more nuanced use of these medications with adults. Most of the patients I now treat with ADD have come to me on stable doses of the medications or at least with a history that directs care.

With others, the tip-off to look for the disorder is their disorganization in the absence of a substance use or active mood disorder. Medications help, sometimes remarkably, yet patients still struggle with organization and planning, and sometimes I find myself frustrated when patients forget their appointments or the issues around prescribing stimulants become time-consuming.

David W. Goodman, MD, director of the Adult Attention Deficit Center of Maryland, Lutherville, currently treats hundreds of patients with ADD and has written and spoken extensively about treating this disorder in adults.

“There are three things that make it difficult to manage patients with ADD,” Dr. Goodman noted, referring specifically to administrative issues. “You can’t write for refills, but with e-prescribing you can write a sequence of prescriptions with ‘fill-after’ dates. Or some patients are able to get a 90-day supply from mail-order pharmacies. Still, it’s a hassle if the patient moves around, as college students often do, and there are inventory shortages when some pharmacies can’t get the medications.”

“The second issue,” he adds, “is that it’s the nature of this disorder that patients struggle with organizational issues. Yelling at someone with ADD to pay attention is like yelling at a blind person not to run into furniture when they are in a new room. They go through life with people being impatient that they can’t do the things an ordinary person can do easily.”

Finally, Dr. Goodman noted that the clinicians who treat patients with ADD may have counter-transference issues. 

“You have to understand that this is a disability and be sympathetic to it. They often have comorbid disorders, including personality disorders, and this can all bleed over to cause frustrations in their care. Psychiatrists who treat patients with ADD need to know they can deal with them compassionately.” 

“I am occasionally contacted by patients who already have an ADHD diagnosis and are on stimulants, and who seem like they just want to get their prescriptions filled and aren’t interested in working on their issues,” says Douglas Beech, MD, a psychiatrist in private practice in Worthington, Ohio. “The doctor in this situation can feel like they are functioning as a sort of drug dealer. There are logistical matters that are structurally inherent in trying to assist these patients, from both a regulatory perspective and from a functional perspective. Dr. Beech feels that it’s helpful to acknowledge these issues when seeing patients with ADHD, so that he is prepared when problems do arise. 

“It can almost feel cruel to charge a patient for a “no-show,” when difficulty keeping appointments may be a symptom of their illness, Dr. Beech adds. But he does believe it’s important to apply any fee policy equitably to all patients. “I don’t apply the ‘missed appointment’ policy differently to a person with an ADHD diagnosis versus any other diagnosis.” Though for their first missed appointment, he does give patients a “mulligan.”

“I don’t charge, but it puts both patient and doctor on notice,” he says.

And when his patients do miss an appointment, he offers to send a reminder for the next time, which is he says is effective. “With electronic messaging, this is a quick and easy way to prevent missed appointments and the complications that arise with prescriptions and rescheduling,” says Dr. Beech.

Dr. Goodman speaks about manging a large caseload of patients, many of whom have organizational issues.  

“I have a full-time office manager who handles a lot of the logistics of scheduling and prescribing. Patients are sent multiple reminders, and I charge a nominal administrative fee if prescriptions need to be sent outside of appointments. This is not to make money, but to encourage patients to consider the administrative time.”

“I charge for appointments that are not canceled 48 hours in advance, and for patients who have missed appointments, a credit card is kept on file,” he says.  

In a practice similar to Dr. Beech, Dr. Goodman notes that he shows some flexibility for new patients when they miss an appointment the first time. “By the second time, they know this is the policy. Having ADHD can be financially costly.” 

He notes that about 10% of his patients, roughly one a day, cancel late or don’t show up for scheduled appointments: “We keep a waitlist, and if someone cancels before the appointment, we can often fill the time with another patient in need on our waitlist.”   

Dr. Goodman noted repeatedly that the clinician needs to be able to empathize with the patient’s condition and how they suffer. “This is not something people choose to have. The trap is that people think that if you’re successful you can’t have ADHD, and that’s not true. Often people with this condition work harder, are brighter, and find ways to compensate.” 

If a practice is set up to accommodate the needs of patients with attention and organizational issues, treating them can be very gratifying. In settings without administrative support, the psychiatrist needs to stay cognizant of this invisible disability and the frustration that may come with this disorder, not just for the patient, but also for the family, friends, and employers, and even for the psychiatrist.

Dr. Dinah Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, Baltimore. Dr. Miller has no conflicts of interest.

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

Maybe you know some of these patients: They may come late or not show up at all. They may have little to say and minimize their difficulties, often because they are ashamed of how much effort it takes to meet ordinary obligations. They may struggle to complete assignments, fail classes, or lose jobs. And being in the right place at the right time can feel monumental to them: They forget appointments, double book themselves, or sometimes sleep through important events.

It’s not just appointments. They lose their keys and valuables, forget to pay bills, and may not answer calls, texts, or emails. Their voicemail may be full and people are often frustrated with them. These are all characteristics of executive dysfunction, which together can make the routine responsibilities of life very difficult.

Executive dysfunction is a hallmark symptom cluster often seen in patients with attention deficit hyperactivity disorder (ADD or ADHD). Not everyone with attentional issues struggles with executive dysfunction, but it is quite common.

Treatments include stimulants, and because of their potential for abuse, these medications are more strictly regulated when it comes to prescribing. The FDA does not allow them to be phoned into a pharmacy or refills to be added to prescriptions. Patients must wait until right before they are due to run out to get the next prescription, and this can present a problem if the patient travels or takes long vacations. 

And although it is not the patient’s fault that stimulants can’t be ordered with refills, this adds to the burden of treating patients who take them. It’s hard to imagine that these restrictions on stimulants and opiates (but not on benzodiazepines) do much to deter abuse or diversion.

I trained at a time when ADD and ADHD were disorders of childhood, and as an adult psychiatrist, I was not exposed to patients on these medications. Occasionally, a stimulant was prescribed in a low dose to help activate a very depressed patient, but it was thought that children outgrow issues of attention and focus, and I have never felt fully confident in the more nuanced use of these medications with adults. Most of the patients I now treat with ADD have come to me on stable doses of the medications or at least with a history that directs care.

With others, the tip-off to look for the disorder is their disorganization in the absence of a substance use or active mood disorder. Medications help, sometimes remarkably, yet patients still struggle with organization and planning, and sometimes I find myself frustrated when patients forget their appointments or the issues around prescribing stimulants become time-consuming.

David W. Goodman, MD, director of the Adult Attention Deficit Center of Maryland, Lutherville, currently treats hundreds of patients with ADD and has written and spoken extensively about treating this disorder in adults.

“There are three things that make it difficult to manage patients with ADD,” Dr. Goodman noted, referring specifically to administrative issues. “You can’t write for refills, but with e-prescribing you can write a sequence of prescriptions with ‘fill-after’ dates. Or some patients are able to get a 90-day supply from mail-order pharmacies. Still, it’s a hassle if the patient moves around, as college students often do, and there are inventory shortages when some pharmacies can’t get the medications.”

“The second issue,” he adds, “is that it’s the nature of this disorder that patients struggle with organizational issues. Yelling at someone with ADD to pay attention is like yelling at a blind person not to run into furniture when they are in a new room. They go through life with people being impatient that they can’t do the things an ordinary person can do easily.”

Finally, Dr. Goodman noted that the clinicians who treat patients with ADD may have counter-transference issues. 

“You have to understand that this is a disability and be sympathetic to it. They often have comorbid disorders, including personality disorders, and this can all bleed over to cause frustrations in their care. Psychiatrists who treat patients with ADD need to know they can deal with them compassionately.” 

“I am occasionally contacted by patients who already have an ADHD diagnosis and are on stimulants, and who seem like they just want to get their prescriptions filled and aren’t interested in working on their issues,” says Douglas Beech, MD, a psychiatrist in private practice in Worthington, Ohio. “The doctor in this situation can feel like they are functioning as a sort of drug dealer. There are logistical matters that are structurally inherent in trying to assist these patients, from both a regulatory perspective and from a functional perspective. Dr. Beech feels that it’s helpful to acknowledge these issues when seeing patients with ADHD, so that he is prepared when problems do arise. 

“It can almost feel cruel to charge a patient for a “no-show,” when difficulty keeping appointments may be a symptom of their illness, Dr. Beech adds. But he does believe it’s important to apply any fee policy equitably to all patients. “I don’t apply the ‘missed appointment’ policy differently to a person with an ADHD diagnosis versus any other diagnosis.” Though for their first missed appointment, he does give patients a “mulligan.”

“I don’t charge, but it puts both patient and doctor on notice,” he says.

And when his patients do miss an appointment, he offers to send a reminder for the next time, which is he says is effective. “With electronic messaging, this is a quick and easy way to prevent missed appointments and the complications that arise with prescriptions and rescheduling,” says Dr. Beech.

Dr. Goodman speaks about manging a large caseload of patients, many of whom have organizational issues.  

“I have a full-time office manager who handles a lot of the logistics of scheduling and prescribing. Patients are sent multiple reminders, and I charge a nominal administrative fee if prescriptions need to be sent outside of appointments. This is not to make money, but to encourage patients to consider the administrative time.”

“I charge for appointments that are not canceled 48 hours in advance, and for patients who have missed appointments, a credit card is kept on file,” he says.  

In a practice similar to Dr. Beech, Dr. Goodman notes that he shows some flexibility for new patients when they miss an appointment the first time. “By the second time, they know this is the policy. Having ADHD can be financially costly.” 

He notes that about 10% of his patients, roughly one a day, cancel late or don’t show up for scheduled appointments: “We keep a waitlist, and if someone cancels before the appointment, we can often fill the time with another patient in need on our waitlist.”   

Dr. Goodman noted repeatedly that the clinician needs to be able to empathize with the patient’s condition and how they suffer. “This is not something people choose to have. The trap is that people think that if you’re successful you can’t have ADHD, and that’s not true. Often people with this condition work harder, are brighter, and find ways to compensate.” 

If a practice is set up to accommodate the needs of patients with attention and organizational issues, treating them can be very gratifying. In settings without administrative support, the psychiatrist needs to stay cognizant of this invisible disability and the frustration that may come with this disorder, not just for the patient, but also for the family, friends, and employers, and even for the psychiatrist.

Dr. Dinah Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, Baltimore. Dr. Miller has no conflicts of interest.

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

Maybe you know some of these patients: They may come late or not show up at all. They may have little to say and minimize their difficulties, often because they are ashamed of how much effort it takes to meet ordinary obligations. They may struggle to complete assignments, fail classes, or lose jobs. And being in the right place at the right time can feel monumental to them: They forget appointments, double book themselves, or sometimes sleep through important events.

It’s not just appointments. They lose their keys and valuables, forget to pay bills, and may not answer calls, texts, or emails. Their voicemail may be full and people are often frustrated with them. These are all characteristics of executive dysfunction, which together can make the routine responsibilities of life very difficult.

Executive dysfunction is a hallmark symptom cluster often seen in patients with attention deficit hyperactivity disorder (ADD or ADHD). Not everyone with attentional issues struggles with executive dysfunction, but it is quite common.

Treatments include stimulants, and because of their potential for abuse, these medications are more strictly regulated when it comes to prescribing. The FDA does not allow them to be phoned into a pharmacy or refills to be added to prescriptions. Patients must wait until right before they are due to run out to get the next prescription, and this can present a problem if the patient travels or takes long vacations. 

And although it is not the patient’s fault that stimulants can’t be ordered with refills, this adds to the burden of treating patients who take them. It’s hard to imagine that these restrictions on stimulants and opiates (but not on benzodiazepines) do much to deter abuse or diversion.

I trained at a time when ADD and ADHD were disorders of childhood, and as an adult psychiatrist, I was not exposed to patients on these medications. Occasionally, a stimulant was prescribed in a low dose to help activate a very depressed patient, but it was thought that children outgrow issues of attention and focus, and I have never felt fully confident in the more nuanced use of these medications with adults. Most of the patients I now treat with ADD have come to me on stable doses of the medications or at least with a history that directs care.

With others, the tip-off to look for the disorder is their disorganization in the absence of a substance use or active mood disorder. Medications help, sometimes remarkably, yet patients still struggle with organization and planning, and sometimes I find myself frustrated when patients forget their appointments or the issues around prescribing stimulants become time-consuming.

David W. Goodman, MD, director of the Adult Attention Deficit Center of Maryland, Lutherville, currently treats hundreds of patients with ADD and has written and spoken extensively about treating this disorder in adults.

“There are three things that make it difficult to manage patients with ADD,” Dr. Goodman noted, referring specifically to administrative issues. “You can’t write for refills, but with e-prescribing you can write a sequence of prescriptions with ‘fill-after’ dates. Or some patients are able to get a 90-day supply from mail-order pharmacies. Still, it’s a hassle if the patient moves around, as college students often do, and there are inventory shortages when some pharmacies can’t get the medications.”

“The second issue,” he adds, “is that it’s the nature of this disorder that patients struggle with organizational issues. Yelling at someone with ADD to pay attention is like yelling at a blind person not to run into furniture when they are in a new room. They go through life with people being impatient that they can’t do the things an ordinary person can do easily.”

Finally, Dr. Goodman noted that the clinicians who treat patients with ADD may have counter-transference issues. 

“You have to understand that this is a disability and be sympathetic to it. They often have comorbid disorders, including personality disorders, and this can all bleed over to cause frustrations in their care. Psychiatrists who treat patients with ADD need to know they can deal with them compassionately.” 

“I am occasionally contacted by patients who already have an ADHD diagnosis and are on stimulants, and who seem like they just want to get their prescriptions filled and aren’t interested in working on their issues,” says Douglas Beech, MD, a psychiatrist in private practice in Worthington, Ohio. “The doctor in this situation can feel like they are functioning as a sort of drug dealer. There are logistical matters that are structurally inherent in trying to assist these patients, from both a regulatory perspective and from a functional perspective. Dr. Beech feels that it’s helpful to acknowledge these issues when seeing patients with ADHD, so that he is prepared when problems do arise. 

“It can almost feel cruel to charge a patient for a “no-show,” when difficulty keeping appointments may be a symptom of their illness, Dr. Beech adds. But he does believe it’s important to apply any fee policy equitably to all patients. “I don’t apply the ‘missed appointment’ policy differently to a person with an ADHD diagnosis versus any other diagnosis.” Though for their first missed appointment, he does give patients a “mulligan.”

“I don’t charge, but it puts both patient and doctor on notice,” he says.

And when his patients do miss an appointment, he offers to send a reminder for the next time, which is he says is effective. “With electronic messaging, this is a quick and easy way to prevent missed appointments and the complications that arise with prescriptions and rescheduling,” says Dr. Beech.

Dr. Goodman speaks about manging a large caseload of patients, many of whom have organizational issues.  

“I have a full-time office manager who handles a lot of the logistics of scheduling and prescribing. Patients are sent multiple reminders, and I charge a nominal administrative fee if prescriptions need to be sent outside of appointments. This is not to make money, but to encourage patients to consider the administrative time.”

“I charge for appointments that are not canceled 48 hours in advance, and for patients who have missed appointments, a credit card is kept on file,” he says.  

In a practice similar to Dr. Beech, Dr. Goodman notes that he shows some flexibility for new patients when they miss an appointment the first time. “By the second time, they know this is the policy. Having ADHD can be financially costly.” 

He notes that about 10% of his patients, roughly one a day, cancel late or don’t show up for scheduled appointments: “We keep a waitlist, and if someone cancels before the appointment, we can often fill the time with another patient in need on our waitlist.”   

Dr. Goodman noted repeatedly that the clinician needs to be able to empathize with the patient’s condition and how they suffer. “This is not something people choose to have. The trap is that people think that if you’re successful you can’t have ADHD, and that’s not true. Often people with this condition work harder, are brighter, and find ways to compensate.” 

If a practice is set up to accommodate the needs of patients with attention and organizational issues, treating them can be very gratifying. In settings without administrative support, the psychiatrist needs to stay cognizant of this invisible disability and the frustration that may come with this disorder, not just for the patient, but also for the family, friends, and employers, and even for the psychiatrist.

Dr. Dinah Miller is a coauthor of “Committed: The Battle Over Involuntary Psychiatric Care” (Baltimore: Johns Hopkins University Press, 2016). She has a private practice and is assistant professor of psychiatry and behavioral sciences at Johns Hopkins, Baltimore. Dr. Miller has no conflicts of interest.

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

SAN FRANCISCO – Children who live in neighborhoods that are at the bottom of the socioeconomic ladder are at significantly greater risk for being admitted to a pediatric intensive care unit (PICU) and of dying there, a study of Medicaid data showed.

Among more than 4 million children and adolescents in 12 U.S. states, those in the most socioeconomically deprived quartile had a significantly higher risk for PICU admission and in-hospital death, compared with patients from the least-deprived areas.

Black children were also at significantly higher risk for death than children of other races, reported Hannah K. Mitchell, BMBS, MSc, from Evelina Children’s Hospital, London.“I think we need to do better work for trying to understand the mechanisms behind these disparities, ... whether they can be intervened over in a hospital setting, and to try to identify targeted interventions,” she said during a presentation at the American Thoracic Society International Conference 2022.
 

Medicaid data

During her residency in pediatrics at Children’s Hospital of Philadelphia, Ms. Mitchell and colleagues conducted a study to determine whether there were disparities in PICU admissions and mortality according to socioeconomic deprivation in specific neighborhoods.

They created a retrospective cohort study of Medicaid patients from birth to age 20 who were covered from 2007 through 2014 in 12 U.S. states, using ZIP codes to identify areas of social deprivation.

They restricted the analysis to children from households with annual incomes below 150% of the federal poverty line and divided the cohort into socioeconomic quartiles.

A total of nearly 4.1 million children and adolescents were included in the sample. Of this group, 274,782 were admitted to a PICU during the study period.

The median age of children admitted to a PICU was 4 years (interquartile range 0-15), and slightly more than two-thirds (68.5%) had a chronic complex condition.

In all, 43.5% were identified as White, and 32.1% were identified as Black. Ms. Mitchell noted that one of the limitations of the study was missing data on patients of Hispanic/Latinx origin.

The mortality rate among all patients admitted to a PICU was 2.5%.

In univariate logistic regression analysis, the odds ratio for PICU admission among children living in the most impoverished circumstances was 1.21 (P < .0001).

Among all patients admitted to a PICU, the OR for death for children in the most deprived quartile, compared with the least deprived was 1.12 (P = .0047).

In addition, Black children were significantly more likely than White children to be admitted to a PICU (OR, 1.14; P < .0001) and to die in hospital (OR, 1.18, P < .0001).

Ms. Mitchell said that clinicians need to move beyond describing disparities and should instead begin to focus on interventions to eliminate or reduce them.

She noted that children in poor neighborhoods may be more likely to receive care in lower-quality hospitals or may be treated differently from other children when hospitalized because of their socioeconomic status.
 

Poor housing, environmental injustice

A pediatric pulmonary specialist who works in a safety net hospital told this news organization that there are multiple factors that contribute to increased risk for PICU admissions and mortality in disadvantaged neighborhoods.

“The overwhelming majority of our patients are not only of low socioeconomic status on an individual level but also live in areas of great socioeconomic deprivation, and all of those social determinants of health are resulting in increased admissions to the PICU,” said Robyn T. Cohen, MD, associate professor of pediatrics at Boston University Medical Center.

“They’re living in poor housing conditions with environmental pollution and experiencing competing priorities that prevent early access to care or the ability to obtain medications. We should be doing better to prevent that from happening” said Dr. Cohen, who co-moderated the session but was not involved with the study.

The study was supported by a grant from the National Institutes of Health. Ms. Mitchell and Dr. Cohen have disclosed no relevant financial relationships.

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

SAN FRANCISCO – Children who live in neighborhoods that are at the bottom of the socioeconomic ladder are at significantly greater risk for being admitted to a pediatric intensive care unit (PICU) and of dying there, a study of Medicaid data showed.

Among more than 4 million children and adolescents in 12 U.S. states, those in the most socioeconomically deprived quartile had a significantly higher risk for PICU admission and in-hospital death, compared with patients from the least-deprived areas.

Black children were also at significantly higher risk for death than children of other races, reported Hannah K. Mitchell, BMBS, MSc, from Evelina Children’s Hospital, London.“I think we need to do better work for trying to understand the mechanisms behind these disparities, ... whether they can be intervened over in a hospital setting, and to try to identify targeted interventions,” she said during a presentation at the American Thoracic Society International Conference 2022.
 

Medicaid data

During her residency in pediatrics at Children’s Hospital of Philadelphia, Ms. Mitchell and colleagues conducted a study to determine whether there were disparities in PICU admissions and mortality according to socioeconomic deprivation in specific neighborhoods.

They created a retrospective cohort study of Medicaid patients from birth to age 20 who were covered from 2007 through 2014 in 12 U.S. states, using ZIP codes to identify areas of social deprivation.

They restricted the analysis to children from households with annual incomes below 150% of the federal poverty line and divided the cohort into socioeconomic quartiles.

A total of nearly 4.1 million children and adolescents were included in the sample. Of this group, 274,782 were admitted to a PICU during the study period.

The median age of children admitted to a PICU was 4 years (interquartile range 0-15), and slightly more than two-thirds (68.5%) had a chronic complex condition.

In all, 43.5% were identified as White, and 32.1% were identified as Black. Ms. Mitchell noted that one of the limitations of the study was missing data on patients of Hispanic/Latinx origin.

The mortality rate among all patients admitted to a PICU was 2.5%.

In univariate logistic regression analysis, the odds ratio for PICU admission among children living in the most impoverished circumstances was 1.21 (P < .0001).

Among all patients admitted to a PICU, the OR for death for children in the most deprived quartile, compared with the least deprived was 1.12 (P = .0047).

In addition, Black children were significantly more likely than White children to be admitted to a PICU (OR, 1.14; P < .0001) and to die in hospital (OR, 1.18, P < .0001).

Ms. Mitchell said that clinicians need to move beyond describing disparities and should instead begin to focus on interventions to eliminate or reduce them.

She noted that children in poor neighborhoods may be more likely to receive care in lower-quality hospitals or may be treated differently from other children when hospitalized because of their socioeconomic status.
 

Poor housing, environmental injustice

A pediatric pulmonary specialist who works in a safety net hospital told this news organization that there are multiple factors that contribute to increased risk for PICU admissions and mortality in disadvantaged neighborhoods.

“The overwhelming majority of our patients are not only of low socioeconomic status on an individual level but also live in areas of great socioeconomic deprivation, and all of those social determinants of health are resulting in increased admissions to the PICU,” said Robyn T. Cohen, MD, associate professor of pediatrics at Boston University Medical Center.

“They’re living in poor housing conditions with environmental pollution and experiencing competing priorities that prevent early access to care or the ability to obtain medications. We should be doing better to prevent that from happening” said Dr. Cohen, who co-moderated the session but was not involved with the study.

The study was supported by a grant from the National Institutes of Health. Ms. Mitchell and Dr. Cohen have disclosed no relevant financial relationships.

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

SAN FRANCISCO – Children who live in neighborhoods that are at the bottom of the socioeconomic ladder are at significantly greater risk for being admitted to a pediatric intensive care unit (PICU) and of dying there, a study of Medicaid data showed.

Among more than 4 million children and adolescents in 12 U.S. states, those in the most socioeconomically deprived quartile had a significantly higher risk for PICU admission and in-hospital death, compared with patients from the least-deprived areas.

Black children were also at significantly higher risk for death than children of other races, reported Hannah K. Mitchell, BMBS, MSc, from Evelina Children’s Hospital, London.“I think we need to do better work for trying to understand the mechanisms behind these disparities, ... whether they can be intervened over in a hospital setting, and to try to identify targeted interventions,” she said during a presentation at the American Thoracic Society International Conference 2022.
 

Medicaid data

During her residency in pediatrics at Children’s Hospital of Philadelphia, Ms. Mitchell and colleagues conducted a study to determine whether there were disparities in PICU admissions and mortality according to socioeconomic deprivation in specific neighborhoods.

They created a retrospective cohort study of Medicaid patients from birth to age 20 who were covered from 2007 through 2014 in 12 U.S. states, using ZIP codes to identify areas of social deprivation.

They restricted the analysis to children from households with annual incomes below 150% of the federal poverty line and divided the cohort into socioeconomic quartiles.

A total of nearly 4.1 million children and adolescents were included in the sample. Of this group, 274,782 were admitted to a PICU during the study period.

The median age of children admitted to a PICU was 4 years (interquartile range 0-15), and slightly more than two-thirds (68.5%) had a chronic complex condition.

In all, 43.5% were identified as White, and 32.1% were identified as Black. Ms. Mitchell noted that one of the limitations of the study was missing data on patients of Hispanic/Latinx origin.

The mortality rate among all patients admitted to a PICU was 2.5%.

In univariate logistic regression analysis, the odds ratio for PICU admission among children living in the most impoverished circumstances was 1.21 (P < .0001).

Among all patients admitted to a PICU, the OR for death for children in the most deprived quartile, compared with the least deprived was 1.12 (P = .0047).

In addition, Black children were significantly more likely than White children to be admitted to a PICU (OR, 1.14; P < .0001) and to die in hospital (OR, 1.18, P < .0001).

Ms. Mitchell said that clinicians need to move beyond describing disparities and should instead begin to focus on interventions to eliminate or reduce them.

She noted that children in poor neighborhoods may be more likely to receive care in lower-quality hospitals or may be treated differently from other children when hospitalized because of their socioeconomic status.
 

Poor housing, environmental injustice

A pediatric pulmonary specialist who works in a safety net hospital told this news organization that there are multiple factors that contribute to increased risk for PICU admissions and mortality in disadvantaged neighborhoods.

“The overwhelming majority of our patients are not only of low socioeconomic status on an individual level but also live in areas of great socioeconomic deprivation, and all of those social determinants of health are resulting in increased admissions to the PICU,” said Robyn T. Cohen, MD, associate professor of pediatrics at Boston University Medical Center.

“They’re living in poor housing conditions with environmental pollution and experiencing competing priorities that prevent early access to care or the ability to obtain medications. We should be doing better to prevent that from happening” said Dr. Cohen, who co-moderated the session but was not involved with the study.

The study was supported by a grant from the National Institutes of Health. Ms. Mitchell and Dr. Cohen have disclosed no relevant financial relationships.

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

A new study highlights the importance of avoiding both exogenous hyperthyroidism and exogenous hypothyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.

“Our findings suggest that clinicians should make every effort to maintain euthyroidism in patients on thyroid hormone treatment, regardless of underlying cardiovascular risk, particularly in vulnerable populations, such as older adults,” senior author Maria Papaleontiou, MD, said in an interview.

Commenting on the study, David S. Cooper, MD, of Johns Hopkins University School of Medicine, Baltimore, agreed that the findings are significant.

“Both undertreatment and overtreatment were associated with adverse cardiovascular outcomes, meaning that patients’ thyroid function needs to be monitored, and levothyroxine adjusted if need be, on an ongoing basis,” he told this news organization.
 

Getting the balance right: a tricky task

Variations in thyroid hormone levels falling above or below target ranges are common with thyroid hormone therapy, as a wide array of factors can prompt the need to regularly adjust dosing to maintain “index” levels. And while guidelines from the American Thyroid Association (ATA) recommend maintaining serum thyroid stimulating hormone (TSH) levels in the normal ranges during treatment, the task is tricky.

“Despite these [ATA] guidelines, prior studies in adults with hypothyroidism have shown that up to 30% are undertreated and up to 48% are overtreated,” said Dr. Papaleontiou, an assistant professor in the Division of Metabolism, Endocrinology at the University of Michigan, Ann Arbor.

In a previous study, Dr. Papaleontiou and colleagues showed that the intensity of thyroid hormone treatment is a modifiable risk factor for incident atrial fibrillation and stroke, however, less is understood about the association with cardiovascular mortality.

For the new study, published in JAMA Network Open, Josh M. Evron, MD, of the University of North Carolina, Chapel Hill, and colleagues further investigated the issue in a large, retrospective cohort of 705,307 adults in the Veterans Health Administration Corporate Data Warehouse treated with thyroid hormone during 2004-2017 who had a median follow-up of 4 years.

They investigated the roles of TSH as well as free thyroxine (FT4) levels among 701,929 adults in the group with data on TSH and 373,981 patients with FT4 measurements.

The mean age of participants was 67 years and 88.7% were male.

Over the course of the study, 10.8% of patients (75,963) died of cardiovascular causes.

Compared with patients with normal thyroid levels, those with exogenous hyperthyroidism related to thyroid hormone treatment had an increased risk of cardiovascular mortality, specifically including when TSH levels were below 0.1 mIU/L (adjusted hazard ratio, 1.39) and when FT4 levels were above 1.9 ng/dL (AHR, 1.29), independent of factors including age, sex, and traditional cardiovascular risk factors, including hypertension, smoking, and previous cardiovascular disease or arrhythmia.

In addition, the increased risk of cardiovascular mortality was observed with exogenous hypothyroidism, specifically among those with TSH levels above 20 mIU/L (AHR, 2.67) and FT4 levels below 0.7 ng/dL (AHR, 1.56), after multivariate adjustment.

Of note, the risk of cardiovascular mortality was dose-dependent, with the risk increasing progressively with the lower and higher TSH levels, compared with normal levels.

The increased mortality risk in relation to TSH levels was more pronounced among older patients, compared with FT4 associations, the authors note.

“From a clinical perspective, older adults, and particularly the oldest old (aged 85 years), appear to be the most vulnerable, with increased risk of cardiovascular mortality with both exogenous hyperthyroidism and hypothyroidism,” they report.

Among key limitations is that women, who make up the majority of patients with thyroid disease, are under-represented in the predominantly male population of the Veterans Health Administration.

Nevertheless, “because the risk of cardiovascular disease is higher for men than for women, and because more than 70,000 women were included in this cohort, the results of this study are highly clinically relevant,” the authors note.

Addressing over- and under-treatment will avoid harm

The results are also important considering the status of levothyroxine (for hypothyroidism) as consistently ranking among the top three prescription medications in the United States.

And with the common occurrence of exogenous hyperthyroidism or hypothyroidism, the findings have important implications.

“Addressing over- and under-treatment of hypothyroidism promptly will help reduce patient harm, particularly in vulnerable populations such as older adults who are at higher risk for adverse effects,” Dr. Papaleontiou said.

Dr. Cooper further commented that the findings underscore the need to be aware of treatment adjustments and targets that may vary according to patient age.

“In older persons, over 65-70, the target TSH may be higher [for example, 2-4 mIU/L] than in younger persons, and in patients above ages 70 or 80, serum TSH levels may be allowed to rise even further into the 4-6 mIU/L range,” he explained.

“The older the patient, the higher the chance for an adverse cardiovascular outcome if the TSH is subnormal due to iatrogenic thyrotoxicosis,” Dr. Cooper explained.

“In contrast, in younger individuals, an elevated TSH, indicating mild [subclinical] hypothyroidism may be associated with increased cardiovascular risk, especially with serum TSH levels greater than 7 mIU/L.”

The authors have reported no relevant financial relationships.

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

A new study highlights the importance of avoiding both exogenous hyperthyroidism and exogenous hypothyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.

“Our findings suggest that clinicians should make every effort to maintain euthyroidism in patients on thyroid hormone treatment, regardless of underlying cardiovascular risk, particularly in vulnerable populations, such as older adults,” senior author Maria Papaleontiou, MD, said in an interview.

Commenting on the study, David S. Cooper, MD, of Johns Hopkins University School of Medicine, Baltimore, agreed that the findings are significant.

“Both undertreatment and overtreatment were associated with adverse cardiovascular outcomes, meaning that patients’ thyroid function needs to be monitored, and levothyroxine adjusted if need be, on an ongoing basis,” he told this news organization.
 

Getting the balance right: a tricky task

Variations in thyroid hormone levels falling above or below target ranges are common with thyroid hormone therapy, as a wide array of factors can prompt the need to regularly adjust dosing to maintain “index” levels. And while guidelines from the American Thyroid Association (ATA) recommend maintaining serum thyroid stimulating hormone (TSH) levels in the normal ranges during treatment, the task is tricky.

“Despite these [ATA] guidelines, prior studies in adults with hypothyroidism have shown that up to 30% are undertreated and up to 48% are overtreated,” said Dr. Papaleontiou, an assistant professor in the Division of Metabolism, Endocrinology at the University of Michigan, Ann Arbor.

In a previous study, Dr. Papaleontiou and colleagues showed that the intensity of thyroid hormone treatment is a modifiable risk factor for incident atrial fibrillation and stroke, however, less is understood about the association with cardiovascular mortality.

For the new study, published in JAMA Network Open, Josh M. Evron, MD, of the University of North Carolina, Chapel Hill, and colleagues further investigated the issue in a large, retrospective cohort of 705,307 adults in the Veterans Health Administration Corporate Data Warehouse treated with thyroid hormone during 2004-2017 who had a median follow-up of 4 years.

They investigated the roles of TSH as well as free thyroxine (FT4) levels among 701,929 adults in the group with data on TSH and 373,981 patients with FT4 measurements.

The mean age of participants was 67 years and 88.7% were male.

Over the course of the study, 10.8% of patients (75,963) died of cardiovascular causes.

Compared with patients with normal thyroid levels, those with exogenous hyperthyroidism related to thyroid hormone treatment had an increased risk of cardiovascular mortality, specifically including when TSH levels were below 0.1 mIU/L (adjusted hazard ratio, 1.39) and when FT4 levels were above 1.9 ng/dL (AHR, 1.29), independent of factors including age, sex, and traditional cardiovascular risk factors, including hypertension, smoking, and previous cardiovascular disease or arrhythmia.

In addition, the increased risk of cardiovascular mortality was observed with exogenous hypothyroidism, specifically among those with TSH levels above 20 mIU/L (AHR, 2.67) and FT4 levels below 0.7 ng/dL (AHR, 1.56), after multivariate adjustment.

Of note, the risk of cardiovascular mortality was dose-dependent, with the risk increasing progressively with the lower and higher TSH levels, compared with normal levels.

The increased mortality risk in relation to TSH levels was more pronounced among older patients, compared with FT4 associations, the authors note.

“From a clinical perspective, older adults, and particularly the oldest old (aged 85 years), appear to be the most vulnerable, with increased risk of cardiovascular mortality with both exogenous hyperthyroidism and hypothyroidism,” they report.

Among key limitations is that women, who make up the majority of patients with thyroid disease, are under-represented in the predominantly male population of the Veterans Health Administration.

Nevertheless, “because the risk of cardiovascular disease is higher for men than for women, and because more than 70,000 women were included in this cohort, the results of this study are highly clinically relevant,” the authors note.

Addressing over- and under-treatment will avoid harm

The results are also important considering the status of levothyroxine (for hypothyroidism) as consistently ranking among the top three prescription medications in the United States.

And with the common occurrence of exogenous hyperthyroidism or hypothyroidism, the findings have important implications.

“Addressing over- and under-treatment of hypothyroidism promptly will help reduce patient harm, particularly in vulnerable populations such as older adults who are at higher risk for adverse effects,” Dr. Papaleontiou said.

Dr. Cooper further commented that the findings underscore the need to be aware of treatment adjustments and targets that may vary according to patient age.

“In older persons, over 65-70, the target TSH may be higher [for example, 2-4 mIU/L] than in younger persons, and in patients above ages 70 or 80, serum TSH levels may be allowed to rise even further into the 4-6 mIU/L range,” he explained.

“The older the patient, the higher the chance for an adverse cardiovascular outcome if the TSH is subnormal due to iatrogenic thyrotoxicosis,” Dr. Cooper explained.

“In contrast, in younger individuals, an elevated TSH, indicating mild [subclinical] hypothyroidism may be associated with increased cardiovascular risk, especially with serum TSH levels greater than 7 mIU/L.”

The authors have reported no relevant financial relationships.

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

A new study highlights the importance of avoiding both exogenous hyperthyroidism and exogenous hypothyroidism to decrease cardiovascular risk and death among patients receiving thyroid hormone treatment.

“Our findings suggest that clinicians should make every effort to maintain euthyroidism in patients on thyroid hormone treatment, regardless of underlying cardiovascular risk, particularly in vulnerable populations, such as older adults,” senior author Maria Papaleontiou, MD, said in an interview.

Commenting on the study, David S. Cooper, MD, of Johns Hopkins University School of Medicine, Baltimore, agreed that the findings are significant.

“Both undertreatment and overtreatment were associated with adverse cardiovascular outcomes, meaning that patients’ thyroid function needs to be monitored, and levothyroxine adjusted if need be, on an ongoing basis,” he told this news organization.
 

Getting the balance right: a tricky task

Variations in thyroid hormone levels falling above or below target ranges are common with thyroid hormone therapy, as a wide array of factors can prompt the need to regularly adjust dosing to maintain “index” levels. And while guidelines from the American Thyroid Association (ATA) recommend maintaining serum thyroid stimulating hormone (TSH) levels in the normal ranges during treatment, the task is tricky.

“Despite these [ATA] guidelines, prior studies in adults with hypothyroidism have shown that up to 30% are undertreated and up to 48% are overtreated,” said Dr. Papaleontiou, an assistant professor in the Division of Metabolism, Endocrinology at the University of Michigan, Ann Arbor.

In a previous study, Dr. Papaleontiou and colleagues showed that the intensity of thyroid hormone treatment is a modifiable risk factor for incident atrial fibrillation and stroke, however, less is understood about the association with cardiovascular mortality.

For the new study, published in JAMA Network Open, Josh M. Evron, MD, of the University of North Carolina, Chapel Hill, and colleagues further investigated the issue in a large, retrospective cohort of 705,307 adults in the Veterans Health Administration Corporate Data Warehouse treated with thyroid hormone during 2004-2017 who had a median follow-up of 4 years.

They investigated the roles of TSH as well as free thyroxine (FT4) levels among 701,929 adults in the group with data on TSH and 373,981 patients with FT4 measurements.

The mean age of participants was 67 years and 88.7% were male.

Over the course of the study, 10.8% of patients (75,963) died of cardiovascular causes.

Compared with patients with normal thyroid levels, those with exogenous hyperthyroidism related to thyroid hormone treatment had an increased risk of cardiovascular mortality, specifically including when TSH levels were below 0.1 mIU/L (adjusted hazard ratio, 1.39) and when FT4 levels were above 1.9 ng/dL (AHR, 1.29), independent of factors including age, sex, and traditional cardiovascular risk factors, including hypertension, smoking, and previous cardiovascular disease or arrhythmia.

In addition, the increased risk of cardiovascular mortality was observed with exogenous hypothyroidism, specifically among those with TSH levels above 20 mIU/L (AHR, 2.67) and FT4 levels below 0.7 ng/dL (AHR, 1.56), after multivariate adjustment.

Of note, the risk of cardiovascular mortality was dose-dependent, with the risk increasing progressively with the lower and higher TSH levels, compared with normal levels.

The increased mortality risk in relation to TSH levels was more pronounced among older patients, compared with FT4 associations, the authors note.

“From a clinical perspective, older adults, and particularly the oldest old (aged 85 years), appear to be the most vulnerable, with increased risk of cardiovascular mortality with both exogenous hyperthyroidism and hypothyroidism,” they report.

Among key limitations is that women, who make up the majority of patients with thyroid disease, are under-represented in the predominantly male population of the Veterans Health Administration.

Nevertheless, “because the risk of cardiovascular disease is higher for men than for women, and because more than 70,000 women were included in this cohort, the results of this study are highly clinically relevant,” the authors note.

Addressing over- and under-treatment will avoid harm

The results are also important considering the status of levothyroxine (for hypothyroidism) as consistently ranking among the top three prescription medications in the United States.

And with the common occurrence of exogenous hyperthyroidism or hypothyroidism, the findings have important implications.

“Addressing over- and under-treatment of hypothyroidism promptly will help reduce patient harm, particularly in vulnerable populations such as older adults who are at higher risk for adverse effects,” Dr. Papaleontiou said.

Dr. Cooper further commented that the findings underscore the need to be aware of treatment adjustments and targets that may vary according to patient age.

“In older persons, over 65-70, the target TSH may be higher [for example, 2-4 mIU/L] than in younger persons, and in patients above ages 70 or 80, serum TSH levels may be allowed to rise even further into the 4-6 mIU/L range,” he explained.

“The older the patient, the higher the chance for an adverse cardiovascular outcome if the TSH is subnormal due to iatrogenic thyrotoxicosis,” Dr. Cooper explained.

“In contrast, in younger individuals, an elevated TSH, indicating mild [subclinical] hypothyroidism may be associated with increased cardiovascular risk, especially with serum TSH levels greater than 7 mIU/L.”

The authors have reported no relevant financial relationships.

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

Vaccinated people who have a breakthrough case of Omicron will have better protection against COVID-19 variants than vaccinated people who receive a booster shot, two preprint studies show.

The University of Washington, Seattle, working with Vir Biotechnology of San Francisco, looked at blood samples of vaccinated people who had breakthrough cases of Delta or Omicron and compared the samples with three other groups: people who caught COVID and were later vaccinated, vaccinated people who were never infected, and people who were infected and never vaccinated.

The vaccinated people who had a breakthrough case of Omicron produced antibodies that helped protect against coronavirus variants, whereas unvaccinated people who caught Omicron didn’t produce as many antibodies, the study showed.

BioNTech, the German biotechnology company, found that people who’d been double and triple vaccinated and then became infected with Omicron had a better B-cell response than people who’d gotten a booster shot but had not been infected.

The University of Washington research team also came up with similar findings about B cells.

The findings don’t mean people should deliberately try to become infected with COVID, said Alexandra Walls, PhD, one of the University of Washington scientists, according to Business Standard.

But the study does indicate “that we are at the point where we may want to consider having a different vaccine to boost people,” said David Veesler, PhD, of the University of Washington team.

“We should think about breakthrough infections as essentially equivalent to another dose of vaccine,” John Wherry, PhD, a professor and director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, told Business Standard. Dr. Wherry was not involved in the studies but reviewed the BioNTech study.

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

Vaccinated people who have a breakthrough case of Omicron will have better protection against COVID-19 variants than vaccinated people who receive a booster shot, two preprint studies show.

The University of Washington, Seattle, working with Vir Biotechnology of San Francisco, looked at blood samples of vaccinated people who had breakthrough cases of Delta or Omicron and compared the samples with three other groups: people who caught COVID and were later vaccinated, vaccinated people who were never infected, and people who were infected and never vaccinated.

The vaccinated people who had a breakthrough case of Omicron produced antibodies that helped protect against coronavirus variants, whereas unvaccinated people who caught Omicron didn’t produce as many antibodies, the study showed.

BioNTech, the German biotechnology company, found that people who’d been double and triple vaccinated and then became infected with Omicron had a better B-cell response than people who’d gotten a booster shot but had not been infected.

The University of Washington research team also came up with similar findings about B cells.

The findings don’t mean people should deliberately try to become infected with COVID, said Alexandra Walls, PhD, one of the University of Washington scientists, according to Business Standard.

But the study does indicate “that we are at the point where we may want to consider having a different vaccine to boost people,” said David Veesler, PhD, of the University of Washington team.

“We should think about breakthrough infections as essentially equivalent to another dose of vaccine,” John Wherry, PhD, a professor and director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, told Business Standard. Dr. Wherry was not involved in the studies but reviewed the BioNTech study.

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

Vaccinated people who have a breakthrough case of Omicron will have better protection against COVID-19 variants than vaccinated people who receive a booster shot, two preprint studies show.

The University of Washington, Seattle, working with Vir Biotechnology of San Francisco, looked at blood samples of vaccinated people who had breakthrough cases of Delta or Omicron and compared the samples with three other groups: people who caught COVID and were later vaccinated, vaccinated people who were never infected, and people who were infected and never vaccinated.

The vaccinated people who had a breakthrough case of Omicron produced antibodies that helped protect against coronavirus variants, whereas unvaccinated people who caught Omicron didn’t produce as many antibodies, the study showed.

BioNTech, the German biotechnology company, found that people who’d been double and triple vaccinated and then became infected with Omicron had a better B-cell response than people who’d gotten a booster shot but had not been infected.

The University of Washington research team also came up with similar findings about B cells.

The findings don’t mean people should deliberately try to become infected with COVID, said Alexandra Walls, PhD, one of the University of Washington scientists, according to Business Standard.

But the study does indicate “that we are at the point where we may want to consider having a different vaccine to boost people,” said David Veesler, PhD, of the University of Washington team.

“We should think about breakthrough infections as essentially equivalent to another dose of vaccine,” John Wherry, PhD, a professor and director of the Institute for Immunology at the University of Pennsylvania, Philadelphia, told Business Standard. Dr. Wherry was not involved in the studies but reviewed the BioNTech study.

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

In April, the Iowa Supreme Court dismissed a knotty claim against a local doctor and hospital accused of concealing a woman’s renal cancer, according to a story in the Iowa Capital Dispatch, among other news outlets.

In 2004, Linda Berry visited Mercy Medical Center in Cedar Rapids for an unspecified ailment. At the hospital, Ms. Berry underwent a CT scan, which revealed a benign cyst on her right kidney. According to the suit later filed by her family, she was not informed about the growth during this visit — nor during four successive visits to the same hospital over the next decade.

The first of these four visits occurred in 2006, when Ms. Berry was again seen at Mercy, this time for a urinary tract infection. Despite undergoing a second renal scan, Ms. Berry was not informed of the mass on her right kidney.

Three years later, in October 2009, she arrived with her daughter at the Mercy emergency department (ED) complaining of abdominal pain. She was examined by Paul Grossmann, MD, a general surgeon. Ms. Berry underwent an abdominal scan that showed her renal abnormality. Dr. Grossmann diagnosed her as having constipation and released her from the ED. According to the family, he made no mention of the mass on her right kidney.

En route home, however, Ms. Berry and her daughter received a call from a resident under Dr. Grossmann’s supervision. Returning to the hospital, Ms. Berry learned that her constipation was actually colitis. She was prescribed an antibiotic and was again released from the ED. Her post-release instructions made no mention of the now larger mass on her kidney.

Two days later, still complaining of abdominal pain, Ms. Berry returned to the Mercy ED. Examined by another ED doctor, she underwent a fourth CT scan, which also showed the kidney mass. A radiology report urged Dr. Grossmann, her previous physician, to pursue the matter in order to rule out renal cancer. Dr. Grossmann followed up with Berry’s primary care doctor. In doing so, though, he mentioned only the patient’s ongoing colitis, not her kidney mass, according to the plaintiffs’ claim.

In 2016, following a fall, Ms. Berry returned yet again to the Mercy ED, this time with a broken arm. During her treatment, she underwent a fifth CT scan, which revealed the same kidney mass. This time, though, a discharge nurse mentioned the abnormality to Ms. Berry — allegedly the first time in more than a decade that a medical professional had alerted her to the potential problem.

The alert may have been too late, however. Ms. Berry was diagnosed shortly thereafter with metastatic renal cell carcinoma. She died on May 22, 2019.

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

In April, the Iowa Supreme Court dismissed a knotty claim against a local doctor and hospital accused of concealing a woman’s renal cancer, according to a story in the Iowa Capital Dispatch, among other news outlets.

In 2004, Linda Berry visited Mercy Medical Center in Cedar Rapids for an unspecified ailment. At the hospital, Ms. Berry underwent a CT scan, which revealed a benign cyst on her right kidney. According to the suit later filed by her family, she was not informed about the growth during this visit — nor during four successive visits to the same hospital over the next decade.

The first of these four visits occurred in 2006, when Ms. Berry was again seen at Mercy, this time for a urinary tract infection. Despite undergoing a second renal scan, Ms. Berry was not informed of the mass on her right kidney.

Three years later, in October 2009, she arrived with her daughter at the Mercy emergency department (ED) complaining of abdominal pain. She was examined by Paul Grossmann, MD, a general surgeon. Ms. Berry underwent an abdominal scan that showed her renal abnormality. Dr. Grossmann diagnosed her as having constipation and released her from the ED. According to the family, he made no mention of the mass on her right kidney.

En route home, however, Ms. Berry and her daughter received a call from a resident under Dr. Grossmann’s supervision. Returning to the hospital, Ms. Berry learned that her constipation was actually colitis. She was prescribed an antibiotic and was again released from the ED. Her post-release instructions made no mention of the now larger mass on her kidney.

Two days later, still complaining of abdominal pain, Ms. Berry returned to the Mercy ED. Examined by another ED doctor, she underwent a fourth CT scan, which also showed the kidney mass. A radiology report urged Dr. Grossmann, her previous physician, to pursue the matter in order to rule out renal cancer. Dr. Grossmann followed up with Berry’s primary care doctor. In doing so, though, he mentioned only the patient’s ongoing colitis, not her kidney mass, according to the plaintiffs’ claim.

In 2016, following a fall, Ms. Berry returned yet again to the Mercy ED, this time with a broken arm. During her treatment, she underwent a fifth CT scan, which revealed the same kidney mass. This time, though, a discharge nurse mentioned the abnormality to Ms. Berry — allegedly the first time in more than a decade that a medical professional had alerted her to the potential problem.

The alert may have been too late, however. Ms. Berry was diagnosed shortly thereafter with metastatic renal cell carcinoma. She died on May 22, 2019.

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

In April, the Iowa Supreme Court dismissed a knotty claim against a local doctor and hospital accused of concealing a woman’s renal cancer, according to a story in the Iowa Capital Dispatch, among other news outlets.

In 2004, Linda Berry visited Mercy Medical Center in Cedar Rapids for an unspecified ailment. At the hospital, Ms. Berry underwent a CT scan, which revealed a benign cyst on her right kidney. According to the suit later filed by her family, she was not informed about the growth during this visit — nor during four successive visits to the same hospital over the next decade.

The first of these four visits occurred in 2006, when Ms. Berry was again seen at Mercy, this time for a urinary tract infection. Despite undergoing a second renal scan, Ms. Berry was not informed of the mass on her right kidney.

Three years later, in October 2009, she arrived with her daughter at the Mercy emergency department (ED) complaining of abdominal pain. She was examined by Paul Grossmann, MD, a general surgeon. Ms. Berry underwent an abdominal scan that showed her renal abnormality. Dr. Grossmann diagnosed her as having constipation and released her from the ED. According to the family, he made no mention of the mass on her right kidney.

En route home, however, Ms. Berry and her daughter received a call from a resident under Dr. Grossmann’s supervision. Returning to the hospital, Ms. Berry learned that her constipation was actually colitis. She was prescribed an antibiotic and was again released from the ED. Her post-release instructions made no mention of the now larger mass on her kidney.

Two days later, still complaining of abdominal pain, Ms. Berry returned to the Mercy ED. Examined by another ED doctor, she underwent a fourth CT scan, which also showed the kidney mass. A radiology report urged Dr. Grossmann, her previous physician, to pursue the matter in order to rule out renal cancer. Dr. Grossmann followed up with Berry’s primary care doctor. In doing so, though, he mentioned only the patient’s ongoing colitis, not her kidney mass, according to the plaintiffs’ claim.

In 2016, following a fall, Ms. Berry returned yet again to the Mercy ED, this time with a broken arm. During her treatment, she underwent a fifth CT scan, which revealed the same kidney mass. This time, though, a discharge nurse mentioned the abnormality to Ms. Berry — allegedly the first time in more than a decade that a medical professional had alerted her to the potential problem.

The alert may have been too late, however. Ms. Berry was diagnosed shortly thereafter with metastatic renal cell carcinoma. She died on May 22, 2019.

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