Plasma exchange successfully improved symptoms of immunoglobulin A vasculitis in an adult female patient who developed the condition after infection with COVID-19, according to a case report published in Cureus.

Immunoglobulin A (IgA) vasculitis can affect all ages, but is relatively rare in adults, and the etiology remains unclear, wrote Hassan Alwafi, MD, of Umm Al-Qura University, Makkah, Saudi Arabia, and colleagues.

COVID-19 has been associated with pulmonary and extrapulmonary complications, but COVID-19–induced IgA vasculitis has previously been described mainly in pediatric and older adult populations, the authors wrote.

The authors described a case of a 41-year-old otherwise healthy Saudi Arabian woman who presented with an ascending rash on both lower extremities, along with arthralgia. Blood tests showed high blood urea nitrogen, creatinine, and inflammatory markers, and a negative immune panel. The patient had been infected with COVID-19 approximately 2 weeks before the onset of symptoms, but she was treated with supportive care and required no antiviral therapy of dexamethasone.

In addition, the patient’s urinalysis showed proteinuria and hematuria. After a kidney biopsy revealed additional abnormalities, the patient was started on intravenous methylprednisolone pulse therapy.

A few days after the initiation of therapy, the patient experienced nosebleeds and coughing up blood. After a chest x-ray showed bilateral pleural effusion, the patient was transferred to the ICU. The patient was started on intravenous piperacillin-tazobactam, and received two doses of intravenous immunoglobulin and plasma exchange after consultation with a nephrologist. Ultimately, the initial rash and other clinical symptoms improved, and the patient was discharged with a tapering schedule of oral prednisolone.

In this case, COVID-19 may have played a role in the development of IgA vasculitis, the authors said.

The authors also listed 21 cases of IgA vasculitis following COVID-19 infection, including 14 children and 7 adults. Of these, three cases had combined kidney and lung involvement, the two pediatric cases died from respiratory failure, while the adult case was successfully treated with steroid monotherapy.

“As COVID-19 is a novel disease and its pathogenic mechanism of causing IgA vasculitis is not well understood, every patient who is infected with or recently recovered from COVID-19 and presents with a skin rash or arthralgia should have baseline blood and urine tests done and should be treated promptly to avoid the emergence of irreversible consequences,” the authors wrote in their discussion.

Although case reports cannot prove a cause-and-effect link, the data from the cases in the current review suggest that COVID-19 infection may be an indirect trigger for IgA vasculitis, including cases associated with pulmonary renal syndrome, they said. However, more research is needed, especially on the efficacy of treatments in adults, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Plasma exchange successfully improved symptoms of immunoglobulin A vasculitis in an adult female patient who developed the condition after infection with COVID-19, according to a case report published in Cureus.

Immunoglobulin A (IgA) vasculitis can affect all ages, but is relatively rare in adults, and the etiology remains unclear, wrote Hassan Alwafi, MD, of Umm Al-Qura University, Makkah, Saudi Arabia, and colleagues.

COVID-19 has been associated with pulmonary and extrapulmonary complications, but COVID-19–induced IgA vasculitis has previously been described mainly in pediatric and older adult populations, the authors wrote.

The authors described a case of a 41-year-old otherwise healthy Saudi Arabian woman who presented with an ascending rash on both lower extremities, along with arthralgia. Blood tests showed high blood urea nitrogen, creatinine, and inflammatory markers, and a negative immune panel. The patient had been infected with COVID-19 approximately 2 weeks before the onset of symptoms, but she was treated with supportive care and required no antiviral therapy of dexamethasone.

In addition, the patient’s urinalysis showed proteinuria and hematuria. After a kidney biopsy revealed additional abnormalities, the patient was started on intravenous methylprednisolone pulse therapy.

A few days after the initiation of therapy, the patient experienced nosebleeds and coughing up blood. After a chest x-ray showed bilateral pleural effusion, the patient was transferred to the ICU. The patient was started on intravenous piperacillin-tazobactam, and received two doses of intravenous immunoglobulin and plasma exchange after consultation with a nephrologist. Ultimately, the initial rash and other clinical symptoms improved, and the patient was discharged with a tapering schedule of oral prednisolone.

In this case, COVID-19 may have played a role in the development of IgA vasculitis, the authors said.

The authors also listed 21 cases of IgA vasculitis following COVID-19 infection, including 14 children and 7 adults. Of these, three cases had combined kidney and lung involvement, the two pediatric cases died from respiratory failure, while the adult case was successfully treated with steroid monotherapy.

“As COVID-19 is a novel disease and its pathogenic mechanism of causing IgA vasculitis is not well understood, every patient who is infected with or recently recovered from COVID-19 and presents with a skin rash or arthralgia should have baseline blood and urine tests done and should be treated promptly to avoid the emergence of irreversible consequences,” the authors wrote in their discussion.

Although case reports cannot prove a cause-and-effect link, the data from the cases in the current review suggest that COVID-19 infection may be an indirect trigger for IgA vasculitis, including cases associated with pulmonary renal syndrome, they said. However, more research is needed, especially on the efficacy of treatments in adults, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

Plasma exchange successfully improved symptoms of immunoglobulin A vasculitis in an adult female patient who developed the condition after infection with COVID-19, according to a case report published in Cureus.

Immunoglobulin A (IgA) vasculitis can affect all ages, but is relatively rare in adults, and the etiology remains unclear, wrote Hassan Alwafi, MD, of Umm Al-Qura University, Makkah, Saudi Arabia, and colleagues.

COVID-19 has been associated with pulmonary and extrapulmonary complications, but COVID-19–induced IgA vasculitis has previously been described mainly in pediatric and older adult populations, the authors wrote.

The authors described a case of a 41-year-old otherwise healthy Saudi Arabian woman who presented with an ascending rash on both lower extremities, along with arthralgia. Blood tests showed high blood urea nitrogen, creatinine, and inflammatory markers, and a negative immune panel. The patient had been infected with COVID-19 approximately 2 weeks before the onset of symptoms, but she was treated with supportive care and required no antiviral therapy of dexamethasone.

In addition, the patient’s urinalysis showed proteinuria and hematuria. After a kidney biopsy revealed additional abnormalities, the patient was started on intravenous methylprednisolone pulse therapy.

A few days after the initiation of therapy, the patient experienced nosebleeds and coughing up blood. After a chest x-ray showed bilateral pleural effusion, the patient was transferred to the ICU. The patient was started on intravenous piperacillin-tazobactam, and received two doses of intravenous immunoglobulin and plasma exchange after consultation with a nephrologist. Ultimately, the initial rash and other clinical symptoms improved, and the patient was discharged with a tapering schedule of oral prednisolone.

In this case, COVID-19 may have played a role in the development of IgA vasculitis, the authors said.

The authors also listed 21 cases of IgA vasculitis following COVID-19 infection, including 14 children and 7 adults. Of these, three cases had combined kidney and lung involvement, the two pediatric cases died from respiratory failure, while the adult case was successfully treated with steroid monotherapy.

“As COVID-19 is a novel disease and its pathogenic mechanism of causing IgA vasculitis is not well understood, every patient who is infected with or recently recovered from COVID-19 and presents with a skin rash or arthralgia should have baseline blood and urine tests done and should be treated promptly to avoid the emergence of irreversible consequences,” the authors wrote in their discussion.

Although case reports cannot prove a cause-and-effect link, the data from the cases in the current review suggest that COVID-19 infection may be an indirect trigger for IgA vasculitis, including cases associated with pulmonary renal syndrome, they said. However, more research is needed, especially on the efficacy of treatments in adults, they concluded.

The study received no outside funding. The researchers had no financial conflicts to disclose.

The US Preventive Services Task Force (USPSTF) recently published a draft recommendation on the use of folic acid before and during pregnancy to prevent fetal neural tube defects.¹ This reaffirmation of the 2017 recommendation states that all persons planning to or who could become pregnant should take a daily supplement of folic acid.^1,2 This is an “A” recommendation.

Neural tube defects are caused by a failure of the embryonic neural tube to close completely, which should occur in the first 28 days following fertilization. This is why folic acid is most effective if started at least 1 month before conception and continued for the first 2 to 3 months of pregnancy.

An estimated 3000 neural tube defects occur each year in the United States. Spina bifida, anencephaly, and encephalocele occur at respective rates of 3.9, 2.5, and 1.0 in 10,000 live births in the United States, which totals 7.4/10,000.³

Folic acid, if taken before and during pregnancy, can prevent about half of neural tube defects; if taken only during pregnancy, it prevents about one-third. If 50% of neural tube defects could be prevented with folic acid supplements, the number needed to treat (NNT) to prevent 1 case is about 3000.⁴

The case for supplementation. The recommended daily dose of folic acid is between 0.4 mg (400 μg) and 0.8 mg (800 μg), which is contained in many multivitamin products. Certain enriched cereal grain products in the United States have been fortified with folic acid for more than 2 decades, but it is unknown whether women in the United States are ingesting enough of these fortified foods to provide maximum prevention of neural tube defects. There are no known harms to mother or fetus from folic acid supplementation at recommended levels.

Room for improvement. Only 20% to 40% of people who are pregnant or trying to get pregnant, and 5% to 10% of people with an unplanned pregnancy, take folic acid supplements. Half of all pregnancies in the United States are unplanned.⁴ This leaves a lot of room for improvement in the prevention of neural tube defects.

An important recommendation, even if you don’t see the results. The NNT to prevent a case of neural tube defect is high; most family physicians providing perinatal care will not prevent a case during their career. And, as with most preventive interventions, we do not see the cases prevented. However, on a population-wide basis, if all women took folic acid as recommended, the number of severe birth defects prevented would be significant—making this simple recommendation worth mentioning to those of reproductive age.

The US Preventive Services Task Force (USPSTF) recently published a draft recommendation on the use of folic acid before and during pregnancy to prevent fetal neural tube defects.¹ This reaffirmation of the 2017 recommendation states that all persons planning to or who could become pregnant should take a daily supplement of folic acid.^1,2 This is an “A” recommendation.

Neural tube defects are caused by a failure of the embryonic neural tube to close completely, which should occur in the first 28 days following fertilization. This is why folic acid is most effective if started at least 1 month before conception and continued for the first 2 to 3 months of pregnancy.

An estimated 3000 neural tube defects occur each year in the United States. Spina bifida, anencephaly, and encephalocele occur at respective rates of 3.9, 2.5, and 1.0 in 10,000 live births in the United States, which totals 7.4/10,000.³

Folic acid, if taken before and during pregnancy, can prevent about half of neural tube defects; if taken only during pregnancy, it prevents about one-third. If 50% of neural tube defects could be prevented with folic acid supplements, the number needed to treat (NNT) to prevent 1 case is about 3000.⁴

The case for supplementation. The recommended daily dose of folic acid is between 0.4 mg (400 μg) and 0.8 mg (800 μg), which is contained in many multivitamin products. Certain enriched cereal grain products in the United States have been fortified with folic acid for more than 2 decades, but it is unknown whether women in the United States are ingesting enough of these fortified foods to provide maximum prevention of neural tube defects. There are no known harms to mother or fetus from folic acid supplementation at recommended levels.

Room for improvement. Only 20% to 40% of people who are pregnant or trying to get pregnant, and 5% to 10% of people with an unplanned pregnancy, take folic acid supplements. Half of all pregnancies in the United States are unplanned.⁴ This leaves a lot of room for improvement in the prevention of neural tube defects.

An important recommendation, even if you don’t see the results. The NNT to prevent a case of neural tube defect is high; most family physicians providing perinatal care will not prevent a case during their career. And, as with most preventive interventions, we do not see the cases prevented. However, on a population-wide basis, if all women took folic acid as recommended, the number of severe birth defects prevented would be significant—making this simple recommendation worth mentioning to those of reproductive age.

The US Preventive Services Task Force (USPSTF) recently published a draft recommendation on the use of folic acid before and during pregnancy to prevent fetal neural tube defects.¹ This reaffirmation of the 2017 recommendation states that all persons planning to or who could become pregnant should take a daily supplement of folic acid.^1,2 This is an “A” recommendation.

Neural tube defects are caused by a failure of the embryonic neural tube to close completely, which should occur in the first 28 days following fertilization. This is why folic acid is most effective if started at least 1 month before conception and continued for the first 2 to 3 months of pregnancy.

An estimated 3000 neural tube defects occur each year in the United States. Spina bifida, anencephaly, and encephalocele occur at respective rates of 3.9, 2.5, and 1.0 in 10,000 live births in the United States, which totals 7.4/10,000.³

Folic acid, if taken before and during pregnancy, can prevent about half of neural tube defects; if taken only during pregnancy, it prevents about one-third. If 50% of neural tube defects could be prevented with folic acid supplements, the number needed to treat (NNT) to prevent 1 case is about 3000.⁴

The case for supplementation. The recommended daily dose of folic acid is between 0.4 mg (400 μg) and 0.8 mg (800 μg), which is contained in many multivitamin products. Certain enriched cereal grain products in the United States have been fortified with folic acid for more than 2 decades, but it is unknown whether women in the United States are ingesting enough of these fortified foods to provide maximum prevention of neural tube defects. There are no known harms to mother or fetus from folic acid supplementation at recommended levels.

Room for improvement. Only 20% to 40% of people who are pregnant or trying to get pregnant, and 5% to 10% of people with an unplanned pregnancy, take folic acid supplements. Half of all pregnancies in the United States are unplanned.⁴ This leaves a lot of room for improvement in the prevention of neural tube defects.

An important recommendation, even if you don’t see the results. The NNT to prevent a case of neural tube defect is high; most family physicians providing perinatal care will not prevent a case during their career. And, as with most preventive interventions, we do not see the cases prevented. However, on a population-wide basis, if all women took folic acid as recommended, the number of severe birth defects prevented would be significant—making this simple recommendation worth mentioning to those of reproductive age.

Clinical care for fetal demise is complex and multidimensional, including empathic emotional support for the patient and family members who are experiencing a tragedy, investigation of the cause of the demise, and a plan for emptying the uterus. This editorial narrowly focuses on the options for treatment of fetal demise with the goal of emptying the uterus while minimizing complications.

When planning treatment of fetal demise, focus on fetal size and gestational age

Most guidelines for the treatment of fetal demise use gestational age to guide selection of a treatment.^1,2 I believe that fetal size is as important as gestational age for selecting a treatment plan. When considering treatment, there are 2 reasons why fetal size is as important as gestational age:

• The physiologic processes that caused fetal demise may have caused fetal growth restriction, resulting in a fetal size that is 2 or more weeks below expected fetal size for gestational age.
• Fetal demise may have occurred weeks before the diagnosis was made, resulting in gestational age being greater than fetal size. This editorial will use ultrasonography estimate of fetal size in gestational weeks to guide treatment recommendations. When discussing fetal size, we will use the convention of weeks-days (w-d). Twenty-five weeks and zero days gestation is represented as 25w0d.

Treatment in the second and third trimester is a 2-step process

Step 1: Cervical preparation

In most cases of first trimester fetal demise, no cervical preparation is necessary. Cervical dilation with metal dilators followed by uterine evacuation with an appropriately sized vacuum catheter is a highly successful treatment.³ However for second and third trimester fetal demise, it is best to use a 2-step process, beginning with cervical preparation followed by emptying the uterus. For example, at a fetal size of 13w0d to 16w0d, cervical preparation can be achieved by administering a single buccal dose of misoprostol 400 µg 3 to 4 hours prior to uterine evacuation or by inserting a Dilapan-S (Medicem Inc) osmotic cervical dilator 3 to 6 hours prior to uterine evacuation.^4-7 At a fetal size of 16w0d to 19w6d, cervical preparation can be achieved by placing osmotic cervical dilators 4 to 6 hours before surgical evacuation and administering buccal misoprostol 400 µg 3 hours before surgical evacuation.⁸

Alternatively, from 16w0d to 25w0d osmotic cervical dilators can be placed on day 1 of a 2-day process, and the patient can return on day 2 to have the cervical dilators removed followed by surgical evacuation of the uterus. Mifepristone 200 mg oral dose can be administered on day 1 to facilitate cervical preparation. In my practice, I use mifepristone 200 mg on day 1 when the fetal size is ≥20w0d gestation. Options for cervical preparation include use of osmotic dilators, cervical balloons, misoprostol, and/or mifepristone. These options are discussed below. With fetal demise, natural physiologic processes often have caused sufficient cervical softening and dilation that no cervical preparation is necessary and immediate uterine surgical evacuation or induction of labor can be initiated.

Step 2: Emptying the uterus

In the second and third trimesters, the approach to uterine evacuation is based on fetal size. At fetal sizes <25w0d, options for emptying the uterus include surgical evacuation with a vacuum catheter and grasping forceps or induction of labor with misoprostol followed by vaginal birth and expulsion of the placenta. At fetal sizes ˃25w0d gestation, following completion of cervical preparation, the most common approaches to uterine evacuation are induction of labor with misoprostol or oxytocin. Rarely, with a stillbirth at term, some clinicians will select hysterotomy to empty the uterus, avoiding uterine rupture during labor induction for patients at the highest risk, including those with a prior classical cesarean birth or more than 2 prior cesarean births with a low-transverse uterine incision.

Osmotic cervical dilators

The 2 most used cervical dilators are Dilapan-S, a polyacrylate-based hydrogel rod, and laminaria, dried compressed seaweed stipe (stalk) from Laminaria japonica or Laminaria digitata. Dilapan-S rods are available in diameters of 3 mm and 4 mm and rod lengths of 55 mm and 65 mm. Laminaria dilators are available in diameters of 2, 3, 4, 5, 6, 8 and 10 mm and rod length of 60 and 70 mm. Dilapan-S dilators reach near-maximal dilation in approximately 4 to 6 hours but continue to expand over the following 18 hours to achieve a maximum dilation of 3.3 to 3.6 times their dry diameter.⁹ Laminaria dilators expand to 2.7 to 2.9 times their dry diameter over 24 hours.⁹

A general rule is that as many dilators as possible should be placed until significant resistance to the placement of additional dilators is encountered.¹⁰ In my practice, for fetal size ≥20 weeks’ gestation, I place 2 Dilapan-S rods, 4 mm in diameter, 55 mm in length, and then encircle the Dilapan-S with laminaria rods that are 4 mm in diameter and 60 mm in length. Once cervical resistance to the placement of the 4 mm laminaria rods is observed, I encircle those laminaria with laminaria 2 mm in diameter, filling in the interstices between the 4 mm laminaria. The next day, cervical dilation is routinely ≥3 cm.

In a retrospective study of 491 patients undergoing pregnancy termination after 14 weeks’ gestation, with a mean gestational age of 24 weeks, compared with no osmotic cervical dilators, inserting osmotic cervical dilators the day before initiating misoprostol for induction of labor resulted in a decrease in time to delivery (428 min vs 640 min; P<.001) and a decrease in total misoprostol dose (990 µg vs 1,449 µg; P<.0001).¹¹

Cervical balloons

All clinicians know that a Foley catheter or a Cook cervical ripening balloon can be used for cervical preparation in the third trimester.^12,13 The Foley catheter also has been reported to be useful for cervical preparation in the second trimester. In one study of 43 patients 17 to 24 weeks’ gestation scheduled for a second-trimester dilation and evacuation, an intracervical Foley catheter was placed the evening before evacuation, and the balloon was inflated with 30 mL to 50 mL of saline. At the same time, mifepristone 200 mg was administered to the patients.¹⁴ The following day, dilation and evacuation was performed. In 72% of cases no additional cervical dilation was required on the day of evacuation. The investigators concluded that if osmotic cervical dilators are not available, the placement of an intracervical Foley catheter plus administration of mifepristone facilitates performance of an evacuation on the following day. If the patient prefers a 1-day procedure, the Foley can be inserted in the morning to facilitate cervical preparation, and the uterus can be evacuated in the afternoon.

Continue to: Misoprostol...

Misoprostol

Misoprostol, a derivative of prostaglandin E1, is useful for both cervical preparation and induction of labor. The dose of misoprostol and the route of administration are major determinants of uterine response.^15-19 When administered by an oral route, misoprostol has fast onset and offset of action and often does not cause sustained uterine contractions. Hence, oral misoprostol, at a low dose is useful for cervical ripening, but not as useful for stimulation of sustained uterine contractions for induction of labor. When administered by a buccal or vaginal route, misoprostol has prolonged activity and often results in sustained uterine contractions. At any given dose of misoprostol, buccal and vaginal misoprostol administration are more effective than oral administration in inducing sustained uterine contractions sufficient to empty the uterus.^15-19

Mifepristone

Mifepristone, an anti-progestin, is useful for cervical preparation and sensitizing myocytes to the action of uterotonics. Progesterone reduces cell-to-cell communication among uterine myocytes, facilitating uterine quiescence by suppressing connexin 43 and other proteins. Mifepristone blocks the effect of progesterone, inducing the production of myocyte connexin 43, enhancing efficient cell-to-cell communication, permitting uterine myoctes to contract in unison, creating the potential for powerful and sustained contractions.^20-23 Randomized clinical trials report that administration of mifepristone 200 mg prior to misoprostol induced labor results in more rapid emptying of the uterus.^24-27

It takes time for mifepristone to have its full effect on uterine myocytes. Hence, most protocols recommend waiting 24 hours following mifepristone administration before initiating treatment with an agent to stimulate uterine contractions such as misoprostol or oxytocin. However, preliminary data suggest that partial benefit of mifepristone can be obtained when initiating misoprostol 3 to 5 hours after mifepristone administration.²⁸ In a study of 481 patients undergoing induction of labor in the second or third trimester, the time from initiation of misoprostol to vaginal birth was 15 hours with no mifepristone pretreatment, 13.2 hours if mifepristone was administered 3 to 5 hours before initiating misoprostol, 9.3 hours if mifepristone was administered 24 hours before initiating misoprostol, and 10.5 hours if mifepristone was administered 48 hours before initiating misoprostol.²⁸

Fetal size <25w0d gestation: Cervical preparation and surgical evacuation

For fetal demise at a fetal size less than 25w0d, if clinical experts are available, the best treatment option is cervical preparation followed by surgical evacuation of the uterus using a vacuum catheter and grasping forceps to empty the uterus.^29,30 A disadvantage of surgical evacuation of the uterus is that an intact fetus is not available for the patient to hold and mourn, and pathologic examination of an intact fetus is not possible. An alternative approach is cervical preparation followed by induction of labor using misoprostol with the goal of delivering an intact fetus. Although no prospective clinical trials are available comparing these 2 options, retrospective studies have reported that, at fetal size <25w0d gestation, compared with induction of labor, surgical evacuation of the uterus results in fewer complications,³⁰ including fewer cases of retained placenta requiring an unplanned procedure and fewer presumed uterine infections.²⁹

For surgical evacuation of fetal demise with a fetal size of <25w0d gestation, the first step on day 1 is placement of osmotic cervical dilators. In addition to osmotic cervical dilators, if the gestational age or fetal size is ≥19 weeks’ gestation an oral dose of mifepristone 200 mg to facilitate cervical preparation may be considered. On day 2, the osmotic dilators are removed and surgical evacuation is performed. In one randomized study, for pregnancies at 19 to 24 weeks’ gestation, compared with osmotic dilators alone, administration of mifepristone 200 mg at the time of placement of osmotic dilators resulted in fewer procedures that were difficult to complete.³¹ In some cases, 2 consecutive days of cervical preparation with osmotic dilators may be needed to properly prepare the cervix for uterine evacuation. For example, the cervix of a nulliparous teenage patient may require 2 days of cervical preparation with osmotic dilators to facilitate uterine evacuation. In some cases of fetal demise, the cervix is already dilated to ≥3 cm and surgical evacuation of the uterus or induction of labor can be initiated without the need for cervical preparation.

Continue to: Fetal size 14w0d to 28w6d gestation: Cervical preparation and induction of labor...

Treatment of fetal demise at 14w0d to 28w6d gestation with the goal of the vaginal birth of an intact fetus is optimized by the administration of mifepristone for cervical preparation followed by induction of labor with misoprostol.^26,27

In one clinical trial, 66 patients with fetal demise between 14w0d and 28w6d gestation were randomly assigned to receive mifepristone 200 mg or placebo followed 24 to 48 hours later with initiation of misoprostol induction of labor.²⁶ Among the patients from 14w0d to 24 weeks’ gestation, the misoprostol dose was 400 µg vaginally every 6 hours. For patients from 24w0d to 28 weeks’ gestation, the misoprostol dose was 200 µg vaginally every 4 hours. At 24 hours, a consultant obstetrician determined if additional misoprostol should be given. The median time from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups was 6.8 hours and 10.5 hours (P=.002).

Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required fewer doses of misoprostol (2.1 vs 3.4; P= .002) and a lower total dose of misoprostol (768 µg vs 1,182 µg; P=.003). All patients in the mifepristone group delivered within 24 hours. By contrast, 13% of the patients in the placebo group delivered more than 24 hours after the initiation of misoprostol treatment. Five patients were readmitted with retained products of conception needing suction curettage, 4 in the placebo group and 1 in the mifepristone group.²⁶

In a second clinical trial, 105 patients with fetal demise after 20 weeks of gestation were randomly assigned to receive mifepristone 200 mg or placebo.²⁷ In this study, 86% of the patients were ≥26w0d gestation, with a mean gestational age of approximately 32w2d. Thirty-six to 48 hours later, misoprostol induction of labor was initiated. Among the patients from 20 to 25 completed weeks of gestation, the misoprostoldose was 100 µg vaginally every 6 hours for a maximum of 4 doses. For patients from ≥26 weeks’ gestation, the misoprostol dose was 50 µg vaginally every 4 hours for a maximum of 6 doses. The median times from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups were 9.8 hours and 16.3 hours, respectively (P=.001). Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required a lower total dose of misoprostol (110 µg vs 198 µg; P<.001). Delivery within 24 hours following initiation of misoprostol occurred in 93% and 73% of the patients in the mifepristone and placebo groups, respectively (P<.001). Compared with patients in the mifepristone group, shivering occurred more frequently among patients in the placebo group (7.5% vs 19.2%; P=.09), likely because they received greater doses of misoprostol.²⁷

Fetal size ≥29w0d gestation

At a fetal size ≥29w0d gestation, if the cervix is ripe with a Bishop score of ≥7, oxytocin induction of labor is often used as a first-line treatment. If the cervix is not ripe, misoprostol induction of labor may be considered at doses less than those used in the second trimester of pregnancy.³²TABLES 1,^{1, 26, 33–36}2,³⁷ and 3³⁷ summarize regimens proposed for fetal size ≥29w0d. One regimen begins with an initial misoprostol dose of 50 µg. If adequate uterine contractions occur, the 50 µg dose is repeated every 4 hours up to 6 total doses. If contractions are inadequate, the dose can be increased to 100 µg every 4 hours for 5 additional doses.

For fetal demise after 28w0d gestation, the American College of Obstetricians and Gynecologists (ACOG)¹ recommends standard obstetric protocols for induction of labor, including standard protocols for induction of labor following a previous cesarean birth. For a patient with a history of a prior cesarean birth or major uterine surgery, ACOG recommends that management of fetal demise should prioritize the use of mechanical cervical ripening, for example with a balloon catheter, and induction of uterine contractions with oxytocin.³⁸ ACOG recommends against the use of misoprostol for cervical ripening or labor induction for patients with a stillbirth at term with a history of a cesarean birth.³⁸ Preliminary experience suggests that stillbirth protocols using misoprostol doses modestly greater than those used in the management of a pregnancy with a viable fetus may be safe.⁹ See TABLES 2 and 3.

A multidisciplinary approach can optimize compassionate care

There are many gaps in the holistic care of patients and partners experiencing fetal demise. Patients with fetal demise often report that they did not receive sufficient information about the cause of the demise and wanted more opportunity to be involved in decision making about their care.³⁹ The patient’s partner often reports feeling unacknowledged as a grieving parent.⁴⁰ Fetal demise is experienced by many patients as a tragedy, triggering feelings of grief, anger, denial, anxiety and depression, sometimes resulting in isolation and substance misuse.

Using a 5-round Delphi process, experts identified 8 core goals in the care of patients with fetal demise:

1. reduce stigma
2. provide respectful care
3. involve patients in care planning
4. attempt to provide an explanation for the demise¹
5. acknowledge the depth of the grief response and provide emotional support
6. offer information about ongoing psychological support
7. provide information about future pregnancy planning
8. provide opportunities for specialized training and support for care providers.⁴¹

Management of stillbirth is optimized by a multidisciplinary approach that includes the expert care of obstetrician-gynecologists, obstetric nurses, anesthesiologists, and expert consultation from social work, chaplaincy, and pathology. A heart-to-heart connection between clinician and patient is a key component of stillbirth care. ●

Clinical care for fetal demise is complex and multidimensional, including empathic emotional support for the patient and family members who are experiencing a tragedy, investigation of the cause of the demise, and a plan for emptying the uterus. This editorial narrowly focuses on the options for treatment of fetal demise with the goal of emptying the uterus while minimizing complications.

When planning treatment of fetal demise, focus on fetal size and gestational age

Most guidelines for the treatment of fetal demise use gestational age to guide selection of a treatment.^1,2 I believe that fetal size is as important as gestational age for selecting a treatment plan. When considering treatment, there are 2 reasons why fetal size is as important as gestational age:

• The physiologic processes that caused fetal demise may have caused fetal growth restriction, resulting in a fetal size that is 2 or more weeks below expected fetal size for gestational age.
• Fetal demise may have occurred weeks before the diagnosis was made, resulting in gestational age being greater than fetal size. This editorial will use ultrasonography estimate of fetal size in gestational weeks to guide treatment recommendations. When discussing fetal size, we will use the convention of weeks-days (w-d). Twenty-five weeks and zero days gestation is represented as 25w0d.

Treatment in the second and third trimester is a 2-step process

Step 1: Cervical preparation

In most cases of first trimester fetal demise, no cervical preparation is necessary. Cervical dilation with metal dilators followed by uterine evacuation with an appropriately sized vacuum catheter is a highly successful treatment.³ However for second and third trimester fetal demise, it is best to use a 2-step process, beginning with cervical preparation followed by emptying the uterus. For example, at a fetal size of 13w0d to 16w0d, cervical preparation can be achieved by administering a single buccal dose of misoprostol 400 µg 3 to 4 hours prior to uterine evacuation or by inserting a Dilapan-S (Medicem Inc) osmotic cervical dilator 3 to 6 hours prior to uterine evacuation.^4-7 At a fetal size of 16w0d to 19w6d, cervical preparation can be achieved by placing osmotic cervical dilators 4 to 6 hours before surgical evacuation and administering buccal misoprostol 400 µg 3 hours before surgical evacuation.⁸

Alternatively, from 16w0d to 25w0d osmotic cervical dilators can be placed on day 1 of a 2-day process, and the patient can return on day 2 to have the cervical dilators removed followed by surgical evacuation of the uterus. Mifepristone 200 mg oral dose can be administered on day 1 to facilitate cervical preparation. In my practice, I use mifepristone 200 mg on day 1 when the fetal size is ≥20w0d gestation. Options for cervical preparation include use of osmotic dilators, cervical balloons, misoprostol, and/or mifepristone. These options are discussed below. With fetal demise, natural physiologic processes often have caused sufficient cervical softening and dilation that no cervical preparation is necessary and immediate uterine surgical evacuation or induction of labor can be initiated.

Step 2: Emptying the uterus

In the second and third trimesters, the approach to uterine evacuation is based on fetal size. At fetal sizes <25w0d, options for emptying the uterus include surgical evacuation with a vacuum catheter and grasping forceps or induction of labor with misoprostol followed by vaginal birth and expulsion of the placenta. At fetal sizes ˃25w0d gestation, following completion of cervical preparation, the most common approaches to uterine evacuation are induction of labor with misoprostol or oxytocin. Rarely, with a stillbirth at term, some clinicians will select hysterotomy to empty the uterus, avoiding uterine rupture during labor induction for patients at the highest risk, including those with a prior classical cesarean birth or more than 2 prior cesarean births with a low-transverse uterine incision.

Osmotic cervical dilators

The 2 most used cervical dilators are Dilapan-S, a polyacrylate-based hydrogel rod, and laminaria, dried compressed seaweed stipe (stalk) from Laminaria japonica or Laminaria digitata. Dilapan-S rods are available in diameters of 3 mm and 4 mm and rod lengths of 55 mm and 65 mm. Laminaria dilators are available in diameters of 2, 3, 4, 5, 6, 8 and 10 mm and rod length of 60 and 70 mm. Dilapan-S dilators reach near-maximal dilation in approximately 4 to 6 hours but continue to expand over the following 18 hours to achieve a maximum dilation of 3.3 to 3.6 times their dry diameter.⁹ Laminaria dilators expand to 2.7 to 2.9 times their dry diameter over 24 hours.⁹

A general rule is that as many dilators as possible should be placed until significant resistance to the placement of additional dilators is encountered.¹⁰ In my practice, for fetal size ≥20 weeks’ gestation, I place 2 Dilapan-S rods, 4 mm in diameter, 55 mm in length, and then encircle the Dilapan-S with laminaria rods that are 4 mm in diameter and 60 mm in length. Once cervical resistance to the placement of the 4 mm laminaria rods is observed, I encircle those laminaria with laminaria 2 mm in diameter, filling in the interstices between the 4 mm laminaria. The next day, cervical dilation is routinely ≥3 cm.

In a retrospective study of 491 patients undergoing pregnancy termination after 14 weeks’ gestation, with a mean gestational age of 24 weeks, compared with no osmotic cervical dilators, inserting osmotic cervical dilators the day before initiating misoprostol for induction of labor resulted in a decrease in time to delivery (428 min vs 640 min; P<.001) and a decrease in total misoprostol dose (990 µg vs 1,449 µg; P<.0001).¹¹

Cervical balloons

All clinicians know that a Foley catheter or a Cook cervical ripening balloon can be used for cervical preparation in the third trimester.^12,13 The Foley catheter also has been reported to be useful for cervical preparation in the second trimester. In one study of 43 patients 17 to 24 weeks’ gestation scheduled for a second-trimester dilation and evacuation, an intracervical Foley catheter was placed the evening before evacuation, and the balloon was inflated with 30 mL to 50 mL of saline. At the same time, mifepristone 200 mg was administered to the patients.¹⁴ The following day, dilation and evacuation was performed. In 72% of cases no additional cervical dilation was required on the day of evacuation. The investigators concluded that if osmotic cervical dilators are not available, the placement of an intracervical Foley catheter plus administration of mifepristone facilitates performance of an evacuation on the following day. If the patient prefers a 1-day procedure, the Foley can be inserted in the morning to facilitate cervical preparation, and the uterus can be evacuated in the afternoon.

Continue to: Misoprostol...

Misoprostol

Misoprostol, a derivative of prostaglandin E1, is useful for both cervical preparation and induction of labor. The dose of misoprostol and the route of administration are major determinants of uterine response.^15-19 When administered by an oral route, misoprostol has fast onset and offset of action and often does not cause sustained uterine contractions. Hence, oral misoprostol, at a low dose is useful for cervical ripening, but not as useful for stimulation of sustained uterine contractions for induction of labor. When administered by a buccal or vaginal route, misoprostol has prolonged activity and often results in sustained uterine contractions. At any given dose of misoprostol, buccal and vaginal misoprostol administration are more effective than oral administration in inducing sustained uterine contractions sufficient to empty the uterus.^15-19

Mifepristone

Mifepristone, an anti-progestin, is useful for cervical preparation and sensitizing myocytes to the action of uterotonics. Progesterone reduces cell-to-cell communication among uterine myocytes, facilitating uterine quiescence by suppressing connexin 43 and other proteins. Mifepristone blocks the effect of progesterone, inducing the production of myocyte connexin 43, enhancing efficient cell-to-cell communication, permitting uterine myoctes to contract in unison, creating the potential for powerful and sustained contractions.^20-23 Randomized clinical trials report that administration of mifepristone 200 mg prior to misoprostol induced labor results in more rapid emptying of the uterus.^24-27

It takes time for mifepristone to have its full effect on uterine myocytes. Hence, most protocols recommend waiting 24 hours following mifepristone administration before initiating treatment with an agent to stimulate uterine contractions such as misoprostol or oxytocin. However, preliminary data suggest that partial benefit of mifepristone can be obtained when initiating misoprostol 3 to 5 hours after mifepristone administration.²⁸ In a study of 481 patients undergoing induction of labor in the second or third trimester, the time from initiation of misoprostol to vaginal birth was 15 hours with no mifepristone pretreatment, 13.2 hours if mifepristone was administered 3 to 5 hours before initiating misoprostol, 9.3 hours if mifepristone was administered 24 hours before initiating misoprostol, and 10.5 hours if mifepristone was administered 48 hours before initiating misoprostol.²⁸

Fetal size <25w0d gestation: Cervical preparation and surgical evacuation

For fetal demise at a fetal size less than 25w0d, if clinical experts are available, the best treatment option is cervical preparation followed by surgical evacuation of the uterus using a vacuum catheter and grasping forceps to empty the uterus.^29,30 A disadvantage of surgical evacuation of the uterus is that an intact fetus is not available for the patient to hold and mourn, and pathologic examination of an intact fetus is not possible. An alternative approach is cervical preparation followed by induction of labor using misoprostol with the goal of delivering an intact fetus. Although no prospective clinical trials are available comparing these 2 options, retrospective studies have reported that, at fetal size <25w0d gestation, compared with induction of labor, surgical evacuation of the uterus results in fewer complications,³⁰ including fewer cases of retained placenta requiring an unplanned procedure and fewer presumed uterine infections.²⁹

For surgical evacuation of fetal demise with a fetal size of <25w0d gestation, the first step on day 1 is placement of osmotic cervical dilators. In addition to osmotic cervical dilators, if the gestational age or fetal size is ≥19 weeks’ gestation an oral dose of mifepristone 200 mg to facilitate cervical preparation may be considered. On day 2, the osmotic dilators are removed and surgical evacuation is performed. In one randomized study, for pregnancies at 19 to 24 weeks’ gestation, compared with osmotic dilators alone, administration of mifepristone 200 mg at the time of placement of osmotic dilators resulted in fewer procedures that were difficult to complete.³¹ In some cases, 2 consecutive days of cervical preparation with osmotic dilators may be needed to properly prepare the cervix for uterine evacuation. For example, the cervix of a nulliparous teenage patient may require 2 days of cervical preparation with osmotic dilators to facilitate uterine evacuation. In some cases of fetal demise, the cervix is already dilated to ≥3 cm and surgical evacuation of the uterus or induction of labor can be initiated without the need for cervical preparation.

Continue to: Fetal size 14w0d to 28w6d gestation: Cervical preparation and induction of labor...

Treatment of fetal demise at 14w0d to 28w6d gestation with the goal of the vaginal birth of an intact fetus is optimized by the administration of mifepristone for cervical preparation followed by induction of labor with misoprostol.^26,27

In one clinical trial, 66 patients with fetal demise between 14w0d and 28w6d gestation were randomly assigned to receive mifepristone 200 mg or placebo followed 24 to 48 hours later with initiation of misoprostol induction of labor.²⁶ Among the patients from 14w0d to 24 weeks’ gestation, the misoprostol dose was 400 µg vaginally every 6 hours. For patients from 24w0d to 28 weeks’ gestation, the misoprostol dose was 200 µg vaginally every 4 hours. At 24 hours, a consultant obstetrician determined if additional misoprostol should be given. The median time from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups was 6.8 hours and 10.5 hours (P=.002).

Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required fewer doses of misoprostol (2.1 vs 3.4; P= .002) and a lower total dose of misoprostol (768 µg vs 1,182 µg; P=.003). All patients in the mifepristone group delivered within 24 hours. By contrast, 13% of the patients in the placebo group delivered more than 24 hours after the initiation of misoprostol treatment. Five patients were readmitted with retained products of conception needing suction curettage, 4 in the placebo group and 1 in the mifepristone group.²⁶

In a second clinical trial, 105 patients with fetal demise after 20 weeks of gestation were randomly assigned to receive mifepristone 200 mg or placebo.²⁷ In this study, 86% of the patients were ≥26w0d gestation, with a mean gestational age of approximately 32w2d. Thirty-six to 48 hours later, misoprostol induction of labor was initiated. Among the patients from 20 to 25 completed weeks of gestation, the misoprostoldose was 100 µg vaginally every 6 hours for a maximum of 4 doses. For patients from ≥26 weeks’ gestation, the misoprostol dose was 50 µg vaginally every 4 hours for a maximum of 6 doses. The median times from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups were 9.8 hours and 16.3 hours, respectively (P=.001). Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required a lower total dose of misoprostol (110 µg vs 198 µg; P<.001). Delivery within 24 hours following initiation of misoprostol occurred in 93% and 73% of the patients in the mifepristone and placebo groups, respectively (P<.001). Compared with patients in the mifepristone group, shivering occurred more frequently among patients in the placebo group (7.5% vs 19.2%; P=.09), likely because they received greater doses of misoprostol.²⁷

Fetal size ≥29w0d gestation

At a fetal size ≥29w0d gestation, if the cervix is ripe with a Bishop score of ≥7, oxytocin induction of labor is often used as a first-line treatment. If the cervix is not ripe, misoprostol induction of labor may be considered at doses less than those used in the second trimester of pregnancy.³²TABLES 1,^{1, 26, 33–36}2,³⁷ and 3³⁷ summarize regimens proposed for fetal size ≥29w0d. One regimen begins with an initial misoprostol dose of 50 µg. If adequate uterine contractions occur, the 50 µg dose is repeated every 4 hours up to 6 total doses. If contractions are inadequate, the dose can be increased to 100 µg every 4 hours for 5 additional doses.

For fetal demise after 28w0d gestation, the American College of Obstetricians and Gynecologists (ACOG)¹ recommends standard obstetric protocols for induction of labor, including standard protocols for induction of labor following a previous cesarean birth. For a patient with a history of a prior cesarean birth or major uterine surgery, ACOG recommends that management of fetal demise should prioritize the use of mechanical cervical ripening, for example with a balloon catheter, and induction of uterine contractions with oxytocin.³⁸ ACOG recommends against the use of misoprostol for cervical ripening or labor induction for patients with a stillbirth at term with a history of a cesarean birth.³⁸ Preliminary experience suggests that stillbirth protocols using misoprostol doses modestly greater than those used in the management of a pregnancy with a viable fetus may be safe.⁹ See TABLES 2 and 3.

A multidisciplinary approach can optimize compassionate care

There are many gaps in the holistic care of patients and partners experiencing fetal demise. Patients with fetal demise often report that they did not receive sufficient information about the cause of the demise and wanted more opportunity to be involved in decision making about their care.³⁹ The patient’s partner often reports feeling unacknowledged as a grieving parent.⁴⁰ Fetal demise is experienced by many patients as a tragedy, triggering feelings of grief, anger, denial, anxiety and depression, sometimes resulting in isolation and substance misuse.

Using a 5-round Delphi process, experts identified 8 core goals in the care of patients with fetal demise:

1. reduce stigma
2. provide respectful care
3. involve patients in care planning
4. attempt to provide an explanation for the demise¹
5. acknowledge the depth of the grief response and provide emotional support
6. offer information about ongoing psychological support
7. provide information about future pregnancy planning
8. provide opportunities for specialized training and support for care providers.⁴¹

Management of stillbirth is optimized by a multidisciplinary approach that includes the expert care of obstetrician-gynecologists, obstetric nurses, anesthesiologists, and expert consultation from social work, chaplaincy, and pathology. A heart-to-heart connection between clinician and patient is a key component of stillbirth care. ●

Clinical care for fetal demise is complex and multidimensional, including empathic emotional support for the patient and family members who are experiencing a tragedy, investigation of the cause of the demise, and a plan for emptying the uterus. This editorial narrowly focuses on the options for treatment of fetal demise with the goal of emptying the uterus while minimizing complications.

When planning treatment of fetal demise, focus on fetal size and gestational age

Most guidelines for the treatment of fetal demise use gestational age to guide selection of a treatment.^1,2 I believe that fetal size is as important as gestational age for selecting a treatment plan. When considering treatment, there are 2 reasons why fetal size is as important as gestational age:

• The physiologic processes that caused fetal demise may have caused fetal growth restriction, resulting in a fetal size that is 2 or more weeks below expected fetal size for gestational age.
• Fetal demise may have occurred weeks before the diagnosis was made, resulting in gestational age being greater than fetal size. This editorial will use ultrasonography estimate of fetal size in gestational weeks to guide treatment recommendations. When discussing fetal size, we will use the convention of weeks-days (w-d). Twenty-five weeks and zero days gestation is represented as 25w0d.

Treatment in the second and third trimester is a 2-step process

Step 1: Cervical preparation

In most cases of first trimester fetal demise, no cervical preparation is necessary. Cervical dilation with metal dilators followed by uterine evacuation with an appropriately sized vacuum catheter is a highly successful treatment.³ However for second and third trimester fetal demise, it is best to use a 2-step process, beginning with cervical preparation followed by emptying the uterus. For example, at a fetal size of 13w0d to 16w0d, cervical preparation can be achieved by administering a single buccal dose of misoprostol 400 µg 3 to 4 hours prior to uterine evacuation or by inserting a Dilapan-S (Medicem Inc) osmotic cervical dilator 3 to 6 hours prior to uterine evacuation.^4-7 At a fetal size of 16w0d to 19w6d, cervical preparation can be achieved by placing osmotic cervical dilators 4 to 6 hours before surgical evacuation and administering buccal misoprostol 400 µg 3 hours before surgical evacuation.⁸

Alternatively, from 16w0d to 25w0d osmotic cervical dilators can be placed on day 1 of a 2-day process, and the patient can return on day 2 to have the cervical dilators removed followed by surgical evacuation of the uterus. Mifepristone 200 mg oral dose can be administered on day 1 to facilitate cervical preparation. In my practice, I use mifepristone 200 mg on day 1 when the fetal size is ≥20w0d gestation. Options for cervical preparation include use of osmotic dilators, cervical balloons, misoprostol, and/or mifepristone. These options are discussed below. With fetal demise, natural physiologic processes often have caused sufficient cervical softening and dilation that no cervical preparation is necessary and immediate uterine surgical evacuation or induction of labor can be initiated.

Step 2: Emptying the uterus

In the second and third trimesters, the approach to uterine evacuation is based on fetal size. At fetal sizes <25w0d, options for emptying the uterus include surgical evacuation with a vacuum catheter and grasping forceps or induction of labor with misoprostol followed by vaginal birth and expulsion of the placenta. At fetal sizes ˃25w0d gestation, following completion of cervical preparation, the most common approaches to uterine evacuation are induction of labor with misoprostol or oxytocin. Rarely, with a stillbirth at term, some clinicians will select hysterotomy to empty the uterus, avoiding uterine rupture during labor induction for patients at the highest risk, including those with a prior classical cesarean birth or more than 2 prior cesarean births with a low-transverse uterine incision.

Osmotic cervical dilators

The 2 most used cervical dilators are Dilapan-S, a polyacrylate-based hydrogel rod, and laminaria, dried compressed seaweed stipe (stalk) from Laminaria japonica or Laminaria digitata. Dilapan-S rods are available in diameters of 3 mm and 4 mm and rod lengths of 55 mm and 65 mm. Laminaria dilators are available in diameters of 2, 3, 4, 5, 6, 8 and 10 mm and rod length of 60 and 70 mm. Dilapan-S dilators reach near-maximal dilation in approximately 4 to 6 hours but continue to expand over the following 18 hours to achieve a maximum dilation of 3.3 to 3.6 times their dry diameter.⁹ Laminaria dilators expand to 2.7 to 2.9 times their dry diameter over 24 hours.⁹

A general rule is that as many dilators as possible should be placed until significant resistance to the placement of additional dilators is encountered.¹⁰ In my practice, for fetal size ≥20 weeks’ gestation, I place 2 Dilapan-S rods, 4 mm in diameter, 55 mm in length, and then encircle the Dilapan-S with laminaria rods that are 4 mm in diameter and 60 mm in length. Once cervical resistance to the placement of the 4 mm laminaria rods is observed, I encircle those laminaria with laminaria 2 mm in diameter, filling in the interstices between the 4 mm laminaria. The next day, cervical dilation is routinely ≥3 cm.

In a retrospective study of 491 patients undergoing pregnancy termination after 14 weeks’ gestation, with a mean gestational age of 24 weeks, compared with no osmotic cervical dilators, inserting osmotic cervical dilators the day before initiating misoprostol for induction of labor resulted in a decrease in time to delivery (428 min vs 640 min; P<.001) and a decrease in total misoprostol dose (990 µg vs 1,449 µg; P<.0001).¹¹

Cervical balloons

All clinicians know that a Foley catheter or a Cook cervical ripening balloon can be used for cervical preparation in the third trimester.^12,13 The Foley catheter also has been reported to be useful for cervical preparation in the second trimester. In one study of 43 patients 17 to 24 weeks’ gestation scheduled for a second-trimester dilation and evacuation, an intracervical Foley catheter was placed the evening before evacuation, and the balloon was inflated with 30 mL to 50 mL of saline. At the same time, mifepristone 200 mg was administered to the patients.¹⁴ The following day, dilation and evacuation was performed. In 72% of cases no additional cervical dilation was required on the day of evacuation. The investigators concluded that if osmotic cervical dilators are not available, the placement of an intracervical Foley catheter plus administration of mifepristone facilitates performance of an evacuation on the following day. If the patient prefers a 1-day procedure, the Foley can be inserted in the morning to facilitate cervical preparation, and the uterus can be evacuated in the afternoon.

Continue to: Misoprostol...

Misoprostol

Misoprostol, a derivative of prostaglandin E1, is useful for both cervical preparation and induction of labor. The dose of misoprostol and the route of administration are major determinants of uterine response.^15-19 When administered by an oral route, misoprostol has fast onset and offset of action and often does not cause sustained uterine contractions. Hence, oral misoprostol, at a low dose is useful for cervical ripening, but not as useful for stimulation of sustained uterine contractions for induction of labor. When administered by a buccal or vaginal route, misoprostol has prolonged activity and often results in sustained uterine contractions. At any given dose of misoprostol, buccal and vaginal misoprostol administration are more effective than oral administration in inducing sustained uterine contractions sufficient to empty the uterus.^15-19

Mifepristone

Mifepristone, an anti-progestin, is useful for cervical preparation and sensitizing myocytes to the action of uterotonics. Progesterone reduces cell-to-cell communication among uterine myocytes, facilitating uterine quiescence by suppressing connexin 43 and other proteins. Mifepristone blocks the effect of progesterone, inducing the production of myocyte connexin 43, enhancing efficient cell-to-cell communication, permitting uterine myoctes to contract in unison, creating the potential for powerful and sustained contractions.^20-23 Randomized clinical trials report that administration of mifepristone 200 mg prior to misoprostol induced labor results in more rapid emptying of the uterus.^24-27

It takes time for mifepristone to have its full effect on uterine myocytes. Hence, most protocols recommend waiting 24 hours following mifepristone administration before initiating treatment with an agent to stimulate uterine contractions such as misoprostol or oxytocin. However, preliminary data suggest that partial benefit of mifepristone can be obtained when initiating misoprostol 3 to 5 hours after mifepristone administration.²⁸ In a study of 481 patients undergoing induction of labor in the second or third trimester, the time from initiation of misoprostol to vaginal birth was 15 hours with no mifepristone pretreatment, 13.2 hours if mifepristone was administered 3 to 5 hours before initiating misoprostol, 9.3 hours if mifepristone was administered 24 hours before initiating misoprostol, and 10.5 hours if mifepristone was administered 48 hours before initiating misoprostol.²⁸

Fetal size <25w0d gestation: Cervical preparation and surgical evacuation

For fetal demise at a fetal size less than 25w0d, if clinical experts are available, the best treatment option is cervical preparation followed by surgical evacuation of the uterus using a vacuum catheter and grasping forceps to empty the uterus.^29,30 A disadvantage of surgical evacuation of the uterus is that an intact fetus is not available for the patient to hold and mourn, and pathologic examination of an intact fetus is not possible. An alternative approach is cervical preparation followed by induction of labor using misoprostol with the goal of delivering an intact fetus. Although no prospective clinical trials are available comparing these 2 options, retrospective studies have reported that, at fetal size <25w0d gestation, compared with induction of labor, surgical evacuation of the uterus results in fewer complications,³⁰ including fewer cases of retained placenta requiring an unplanned procedure and fewer presumed uterine infections.²⁹

For surgical evacuation of fetal demise with a fetal size of <25w0d gestation, the first step on day 1 is placement of osmotic cervical dilators. In addition to osmotic cervical dilators, if the gestational age or fetal size is ≥19 weeks’ gestation an oral dose of mifepristone 200 mg to facilitate cervical preparation may be considered. On day 2, the osmotic dilators are removed and surgical evacuation is performed. In one randomized study, for pregnancies at 19 to 24 weeks’ gestation, compared with osmotic dilators alone, administration of mifepristone 200 mg at the time of placement of osmotic dilators resulted in fewer procedures that were difficult to complete.³¹ In some cases, 2 consecutive days of cervical preparation with osmotic dilators may be needed to properly prepare the cervix for uterine evacuation. For example, the cervix of a nulliparous teenage patient may require 2 days of cervical preparation with osmotic dilators to facilitate uterine evacuation. In some cases of fetal demise, the cervix is already dilated to ≥3 cm and surgical evacuation of the uterus or induction of labor can be initiated without the need for cervical preparation.

Continue to: Fetal size 14w0d to 28w6d gestation: Cervical preparation and induction of labor...

Treatment of fetal demise at 14w0d to 28w6d gestation with the goal of the vaginal birth of an intact fetus is optimized by the administration of mifepristone for cervical preparation followed by induction of labor with misoprostol.^26,27

In one clinical trial, 66 patients with fetal demise between 14w0d and 28w6d gestation were randomly assigned to receive mifepristone 200 mg or placebo followed 24 to 48 hours later with initiation of misoprostol induction of labor.²⁶ Among the patients from 14w0d to 24 weeks’ gestation, the misoprostol dose was 400 µg vaginally every 6 hours. For patients from 24w0d to 28 weeks’ gestation, the misoprostol dose was 200 µg vaginally every 4 hours. At 24 hours, a consultant obstetrician determined if additional misoprostol should be given. The median time from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups was 6.8 hours and 10.5 hours (P=.002).

Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required fewer doses of misoprostol (2.1 vs 3.4; P= .002) and a lower total dose of misoprostol (768 µg vs 1,182 µg; P=.003). All patients in the mifepristone group delivered within 24 hours. By contrast, 13% of the patients in the placebo group delivered more than 24 hours after the initiation of misoprostol treatment. Five patients were readmitted with retained products of conception needing suction curettage, 4 in the placebo group and 1 in the mifepristone group.²⁶

In a second clinical trial, 105 patients with fetal demise after 20 weeks of gestation were randomly assigned to receive mifepristone 200 mg or placebo.²⁷ In this study, 86% of the patients were ≥26w0d gestation, with a mean gestational age of approximately 32w2d. Thirty-six to 48 hours later, misoprostol induction of labor was initiated. Among the patients from 20 to 25 completed weeks of gestation, the misoprostoldose was 100 µg vaginally every 6 hours for a maximum of 4 doses. For patients from ≥26 weeks’ gestation, the misoprostol dose was 50 µg vaginally every 4 hours for a maximum of 6 doses. The median times from initiation of misoprostol to birth for the patients in the mifepristone and placebo groups were 9.8 hours and 16.3 hours, respectively (P=.001). Compared with the patients in the placebo-misoprostol group, the patients in the mifepristone-misoprostol group required a lower total dose of misoprostol (110 µg vs 198 µg; P<.001). Delivery within 24 hours following initiation of misoprostol occurred in 93% and 73% of the patients in the mifepristone and placebo groups, respectively (P<.001). Compared with patients in the mifepristone group, shivering occurred more frequently among patients in the placebo group (7.5% vs 19.2%; P=.09), likely because they received greater doses of misoprostol.²⁷

Fetal size ≥29w0d gestation

At a fetal size ≥29w0d gestation, if the cervix is ripe with a Bishop score of ≥7, oxytocin induction of labor is often used as a first-line treatment. If the cervix is not ripe, misoprostol induction of labor may be considered at doses less than those used in the second trimester of pregnancy.³²TABLES 1,^{1, 26, 33–36}2,³⁷ and 3³⁷ summarize regimens proposed for fetal size ≥29w0d. One regimen begins with an initial misoprostol dose of 50 µg. If adequate uterine contractions occur, the 50 µg dose is repeated every 4 hours up to 6 total doses. If contractions are inadequate, the dose can be increased to 100 µg every 4 hours for 5 additional doses.

For fetal demise after 28w0d gestation, the American College of Obstetricians and Gynecologists (ACOG)¹ recommends standard obstetric protocols for induction of labor, including standard protocols for induction of labor following a previous cesarean birth. For a patient with a history of a prior cesarean birth or major uterine surgery, ACOG recommends that management of fetal demise should prioritize the use of mechanical cervical ripening, for example with a balloon catheter, and induction of uterine contractions with oxytocin.³⁸ ACOG recommends against the use of misoprostol for cervical ripening or labor induction for patients with a stillbirth at term with a history of a cesarean birth.³⁸ Preliminary experience suggests that stillbirth protocols using misoprostol doses modestly greater than those used in the management of a pregnancy with a viable fetus may be safe.⁹ See TABLES 2 and 3.

A multidisciplinary approach can optimize compassionate care

There are many gaps in the holistic care of patients and partners experiencing fetal demise. Patients with fetal demise often report that they did not receive sufficient information about the cause of the demise and wanted more opportunity to be involved in decision making about their care.³⁹ The patient’s partner often reports feeling unacknowledged as a grieving parent.⁴⁰ Fetal demise is experienced by many patients as a tragedy, triggering feelings of grief, anger, denial, anxiety and depression, sometimes resulting in isolation and substance misuse.

Using a 5-round Delphi process, experts identified 8 core goals in the care of patients with fetal demise:

1. reduce stigma
2. provide respectful care
3. involve patients in care planning
4. attempt to provide an explanation for the demise¹
5. acknowledge the depth of the grief response and provide emotional support
6. offer information about ongoing psychological support
7. provide information about future pregnancy planning
8. provide opportunities for specialized training and support for care providers.⁴¹

Management of stillbirth is optimized by a multidisciplinary approach that includes the expert care of obstetrician-gynecologists, obstetric nurses, anesthesiologists, and expert consultation from social work, chaplaincy, and pathology. A heart-to-heart connection between clinician and patient is a key component of stillbirth care. ●

The sleep aid melatonin is associated with a reduced risk of self-harm in adolescents with psychiatric disorders, new research suggests. However, at least one expert has some concerns about the strength of the evidence.

The results suggest improving sleep hygiene in this population may reduce self-injury, study investigator Sarah E. Bergen, PhD, associate professor, department of medical epidemiology and biostatistics, Karolinska Institute, Stockholm, said in an interview.

In addition, she noted, for “pediatric patients who are experiencing sleep problems, melatonin is a safe and effective way to help them.”

Dr. Bergen believes clinicians should recommend melatonin to all teens because “there’s little harm that could come from it and possibly a lot of benefit.”

The findings were published online in the Journal of Child Psychology and Psychiatry.
 

Few treatments available

Research shows sleep disorders like insomnia are common in youth, particularly among those with psychiatric disorders. Sleep disorders can significantly affect daytime functioning, cognition, emotional regulation, and behavior, and can be a risk factor for unintentional injuries such as falls and vehicular accidents, as well as for intentional self-harm.

The lifetime prevalence of self-harm in youth is estimated to be 17%, but this varies across study designs. There are few treatments for self-harm in youth, although psychosocial treatments appear promising.

Melatonin is a naturally occurring hormone secreted primarily by the pineal gland in response to darkness. It helps promote and maintain the normal sleep-wake cycle and is involved in other biological functions.

In Sweden, melatonin is the most commonly prescribed drug for sleep disturbances in children and adolescents. Prior to 2020, during the course of the study, it was only available by prescription.

The study, which used linked national databases, included 25,575 children and adolescents, 58.2% of them male, who initiated a melatonin treatment between the ages of 6 and 18 years.

Researchers estimated the risks of self-harm, including poisoning (57%) and cutting (34%). The fact that poisoning was more common than cutting was somewhat surprising, said Dr. Bergen. “I would have thought the opposite would be true; that cutting was more prevalent.”

The study examined the risk of self-harm in individual participants by comparing the last unmedicated month with the 12 months after initiating melatonin treatment. In this way, they accounted for potential confounders such as genetics, sleep disorder severity, and psychiatric disorders.

The median age at first melatonin prescription was 13 years for males and 15 years for females.

While there were no statistically significant changes in relative risk for body injuries, falls, and transport accidents, the relative risk for self-injury was statistically significantly lower during the months following melatonin treatment initiation.

The incidence rate ratio in the month following treatment was 0.58 (95% confidence interval, 0.46-0.73) for self-harm and 0.59 (95% CI, 0.45-0.78) for poisoning.
 

Higher risks in females

The relative risk of self-harm was higher in females than males. This, said Dr. Bergen, is possibly because self-harm is more common in adolescence than in childhood. Female study participants were older than their male counterparts.

Melatonin may help male teens, too, she said. “It’s just that the problem is not that great in males to begin with, so a decrease is not very dramatic after melatonin initiation.”

About 87.2% of participants treated with melatonin were diagnosed with at least one psychiatric disorder. Attention-deficit hyperactivity disorder, the most common comorbidity, was diagnosed in more than 50% of new melatonin users. This isn’t surprising, because sleep disturbances are associated with this psychiatric condition and are frequent side effects of ADHD medications.

After ADHD, anxiety and depression were the next most common psychiatric disorders among study subjects. The analysis found risks for self-harm and poisoning were largely driven by patients suffering from one or both of these disorders, particularly among females.

The IRR in the month following melatonin treatment initiation was 0.46 (95% CI, 0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.

Melatonin may reduce the risk of self-harm by treating sleep problems related to psychiatric comorbidities, especially anxiety and depression. It could also decrease pain sensitivity experienced by adolescents who self-harm.

Other factors could play a role in treating sleep problems and/or preventing self-harm in these patients. For example, increased clinician awareness and monitoring, behavioral interventions, a placebo effect, and concurrent use of other medications.

When researchers ran an analysis that excluded individuals taking an antidepressant, “surprisingly, there wasn’t much difference,” said Dr. Bergen. “We thought antidepressants might be causing some of the effect we observed, but when we removed antidepressant users, we saw a very similar pattern of intentional self-harm rates following melatonin use, which suggests melatonin is causal, but we can’t prove that.”

Other sleep medications such as sedatives could also affect self-harm rates by improving sleep. However, these are not typically prescribed to children because of their side effects and overdose potential, said Dr. Bergen.

“Melatonin is extremely safe and side effects are rare; it’s impossible to overdose, and people really can’t hurt themselves with it.”
 

More research needed

Adrian Jacques Ambrose, MD, medical director, Columbia University Irving Medical Center, and assistant professor of psychiatry, Columbia University, New York, pointed out some evidence in the study is relatively weak.

“When the authors separated out the on- and off-melatonin groups, it looks like there wasn’t a statistically significant difference [in IRRs] between the two groups – for example, in any injury, self-harm, or poisoning – and this weakens their argument that melatonin is associated with self-harm and poisoning.”

Given the current youth mental health crisis, more research “would absolutely be indicated” to better explore possible additional variables, said Dr. Ambrose.

“For example, some additional follow-up studies may add on covariates in conjunction with melatonin usage, such as the number of medical appointments, the presence of psychotherapeutic interventions, dosage of melatonin, or even the sleepiness scale, to evaluate whether the symptoms of sleep disturbances are more directly correlated with the self-harm behaviors.”

The study was supported by the European Union’s Horizon 2020 Research and Innovation Programme. Dr. Bergen and Dr. Ambrose report no relevant financial relationships.

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

The sleep aid melatonin is associated with a reduced risk of self-harm in adolescents with psychiatric disorders, new research suggests. However, at least one expert has some concerns about the strength of the evidence.

The results suggest improving sleep hygiene in this population may reduce self-injury, study investigator Sarah E. Bergen, PhD, associate professor, department of medical epidemiology and biostatistics, Karolinska Institute, Stockholm, said in an interview.

In addition, she noted, for “pediatric patients who are experiencing sleep problems, melatonin is a safe and effective way to help them.”

Dr. Bergen believes clinicians should recommend melatonin to all teens because “there’s little harm that could come from it and possibly a lot of benefit.”

The findings were published online in the Journal of Child Psychology and Psychiatry.
 

Few treatments available

Research shows sleep disorders like insomnia are common in youth, particularly among those with psychiatric disorders. Sleep disorders can significantly affect daytime functioning, cognition, emotional regulation, and behavior, and can be a risk factor for unintentional injuries such as falls and vehicular accidents, as well as for intentional self-harm.

The lifetime prevalence of self-harm in youth is estimated to be 17%, but this varies across study designs. There are few treatments for self-harm in youth, although psychosocial treatments appear promising.

Melatonin is a naturally occurring hormone secreted primarily by the pineal gland in response to darkness. It helps promote and maintain the normal sleep-wake cycle and is involved in other biological functions.

In Sweden, melatonin is the most commonly prescribed drug for sleep disturbances in children and adolescents. Prior to 2020, during the course of the study, it was only available by prescription.

The study, which used linked national databases, included 25,575 children and adolescents, 58.2% of them male, who initiated a melatonin treatment between the ages of 6 and 18 years.

Researchers estimated the risks of self-harm, including poisoning (57%) and cutting (34%). The fact that poisoning was more common than cutting was somewhat surprising, said Dr. Bergen. “I would have thought the opposite would be true; that cutting was more prevalent.”

The study examined the risk of self-harm in individual participants by comparing the last unmedicated month with the 12 months after initiating melatonin treatment. In this way, they accounted for potential confounders such as genetics, sleep disorder severity, and psychiatric disorders.

The median age at first melatonin prescription was 13 years for males and 15 years for females.

While there were no statistically significant changes in relative risk for body injuries, falls, and transport accidents, the relative risk for self-injury was statistically significantly lower during the months following melatonin treatment initiation.

The incidence rate ratio in the month following treatment was 0.58 (95% confidence interval, 0.46-0.73) for self-harm and 0.59 (95% CI, 0.45-0.78) for poisoning.
 

Higher risks in females

The relative risk of self-harm was higher in females than males. This, said Dr. Bergen, is possibly because self-harm is more common in adolescence than in childhood. Female study participants were older than their male counterparts.

Melatonin may help male teens, too, she said. “It’s just that the problem is not that great in males to begin with, so a decrease is not very dramatic after melatonin initiation.”

About 87.2% of participants treated with melatonin were diagnosed with at least one psychiatric disorder. Attention-deficit hyperactivity disorder, the most common comorbidity, was diagnosed in more than 50% of new melatonin users. This isn’t surprising, because sleep disturbances are associated with this psychiatric condition and are frequent side effects of ADHD medications.

After ADHD, anxiety and depression were the next most common psychiatric disorders among study subjects. The analysis found risks for self-harm and poisoning were largely driven by patients suffering from one or both of these disorders, particularly among females.

The IRR in the month following melatonin treatment initiation was 0.46 (95% CI, 0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.

Melatonin may reduce the risk of self-harm by treating sleep problems related to psychiatric comorbidities, especially anxiety and depression. It could also decrease pain sensitivity experienced by adolescents who self-harm.

Other factors could play a role in treating sleep problems and/or preventing self-harm in these patients. For example, increased clinician awareness and monitoring, behavioral interventions, a placebo effect, and concurrent use of other medications.

When researchers ran an analysis that excluded individuals taking an antidepressant, “surprisingly, there wasn’t much difference,” said Dr. Bergen. “We thought antidepressants might be causing some of the effect we observed, but when we removed antidepressant users, we saw a very similar pattern of intentional self-harm rates following melatonin use, which suggests melatonin is causal, but we can’t prove that.”

Other sleep medications such as sedatives could also affect self-harm rates by improving sleep. However, these are not typically prescribed to children because of their side effects and overdose potential, said Dr. Bergen.

“Melatonin is extremely safe and side effects are rare; it’s impossible to overdose, and people really can’t hurt themselves with it.”
 

More research needed

Adrian Jacques Ambrose, MD, medical director, Columbia University Irving Medical Center, and assistant professor of psychiatry, Columbia University, New York, pointed out some evidence in the study is relatively weak.

“When the authors separated out the on- and off-melatonin groups, it looks like there wasn’t a statistically significant difference [in IRRs] between the two groups – for example, in any injury, self-harm, or poisoning – and this weakens their argument that melatonin is associated with self-harm and poisoning.”

Given the current youth mental health crisis, more research “would absolutely be indicated” to better explore possible additional variables, said Dr. Ambrose.

“For example, some additional follow-up studies may add on covariates in conjunction with melatonin usage, such as the number of medical appointments, the presence of psychotherapeutic interventions, dosage of melatonin, or even the sleepiness scale, to evaluate whether the symptoms of sleep disturbances are more directly correlated with the self-harm behaviors.”

The study was supported by the European Union’s Horizon 2020 Research and Innovation Programme. Dr. Bergen and Dr. Ambrose report no relevant financial relationships.

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

The sleep aid melatonin is associated with a reduced risk of self-harm in adolescents with psychiatric disorders, new research suggests. However, at least one expert has some concerns about the strength of the evidence.

The results suggest improving sleep hygiene in this population may reduce self-injury, study investigator Sarah E. Bergen, PhD, associate professor, department of medical epidemiology and biostatistics, Karolinska Institute, Stockholm, said in an interview.

In addition, she noted, for “pediatric patients who are experiencing sleep problems, melatonin is a safe and effective way to help them.”

Dr. Bergen believes clinicians should recommend melatonin to all teens because “there’s little harm that could come from it and possibly a lot of benefit.”

The findings were published online in the Journal of Child Psychology and Psychiatry.
 

Few treatments available

Research shows sleep disorders like insomnia are common in youth, particularly among those with psychiatric disorders. Sleep disorders can significantly affect daytime functioning, cognition, emotional regulation, and behavior, and can be a risk factor for unintentional injuries such as falls and vehicular accidents, as well as for intentional self-harm.

The lifetime prevalence of self-harm in youth is estimated to be 17%, but this varies across study designs. There are few treatments for self-harm in youth, although psychosocial treatments appear promising.

Melatonin is a naturally occurring hormone secreted primarily by the pineal gland in response to darkness. It helps promote and maintain the normal sleep-wake cycle and is involved in other biological functions.

In Sweden, melatonin is the most commonly prescribed drug for sleep disturbances in children and adolescents. Prior to 2020, during the course of the study, it was only available by prescription.

The study, which used linked national databases, included 25,575 children and adolescents, 58.2% of them male, who initiated a melatonin treatment between the ages of 6 and 18 years.

Researchers estimated the risks of self-harm, including poisoning (57%) and cutting (34%). The fact that poisoning was more common than cutting was somewhat surprising, said Dr. Bergen. “I would have thought the opposite would be true; that cutting was more prevalent.”

The study examined the risk of self-harm in individual participants by comparing the last unmedicated month with the 12 months after initiating melatonin treatment. In this way, they accounted for potential confounders such as genetics, sleep disorder severity, and psychiatric disorders.

The median age at first melatonin prescription was 13 years for males and 15 years for females.

While there were no statistically significant changes in relative risk for body injuries, falls, and transport accidents, the relative risk for self-injury was statistically significantly lower during the months following melatonin treatment initiation.

The incidence rate ratio in the month following treatment was 0.58 (95% confidence interval, 0.46-0.73) for self-harm and 0.59 (95% CI, 0.45-0.78) for poisoning.
 

Higher risks in females

The relative risk of self-harm was higher in females than males. This, said Dr. Bergen, is possibly because self-harm is more common in adolescence than in childhood. Female study participants were older than their male counterparts.

Melatonin may help male teens, too, she said. “It’s just that the problem is not that great in males to begin with, so a decrease is not very dramatic after melatonin initiation.”

About 87.2% of participants treated with melatonin were diagnosed with at least one psychiatric disorder. Attention-deficit hyperactivity disorder, the most common comorbidity, was diagnosed in more than 50% of new melatonin users. This isn’t surprising, because sleep disturbances are associated with this psychiatric condition and are frequent side effects of ADHD medications.

After ADHD, anxiety and depression were the next most common psychiatric disorders among study subjects. The analysis found risks for self-harm and poisoning were largely driven by patients suffering from one or both of these disorders, particularly among females.

The IRR in the month following melatonin treatment initiation was 0.46 (95% CI, 0.27-0.76] among adolescent females with psychiatric disorders, after excluding antidepressant users.

Melatonin may reduce the risk of self-harm by treating sleep problems related to psychiatric comorbidities, especially anxiety and depression. It could also decrease pain sensitivity experienced by adolescents who self-harm.

Other factors could play a role in treating sleep problems and/or preventing self-harm in these patients. For example, increased clinician awareness and monitoring, behavioral interventions, a placebo effect, and concurrent use of other medications.

When researchers ran an analysis that excluded individuals taking an antidepressant, “surprisingly, there wasn’t much difference,” said Dr. Bergen. “We thought antidepressants might be causing some of the effect we observed, but when we removed antidepressant users, we saw a very similar pattern of intentional self-harm rates following melatonin use, which suggests melatonin is causal, but we can’t prove that.”

Other sleep medications such as sedatives could also affect self-harm rates by improving sleep. However, these are not typically prescribed to children because of their side effects and overdose potential, said Dr. Bergen.

“Melatonin is extremely safe and side effects are rare; it’s impossible to overdose, and people really can’t hurt themselves with it.”
 

More research needed

Adrian Jacques Ambrose, MD, medical director, Columbia University Irving Medical Center, and assistant professor of psychiatry, Columbia University, New York, pointed out some evidence in the study is relatively weak.

“When the authors separated out the on- and off-melatonin groups, it looks like there wasn’t a statistically significant difference [in IRRs] between the two groups – for example, in any injury, self-harm, or poisoning – and this weakens their argument that melatonin is associated with self-harm and poisoning.”

Given the current youth mental health crisis, more research “would absolutely be indicated” to better explore possible additional variables, said Dr. Ambrose.

“For example, some additional follow-up studies may add on covariates in conjunction with melatonin usage, such as the number of medical appointments, the presence of psychotherapeutic interventions, dosage of melatonin, or even the sleepiness scale, to evaluate whether the symptoms of sleep disturbances are more directly correlated with the self-harm behaviors.”

The study was supported by the European Union’s Horizon 2020 Research and Innovation Programme. Dr. Bergen and Dr. Ambrose report no relevant financial relationships.

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

Season 2 of Small Talk, Big Topics is here!

AGA’s podcast for trainees and early career GIs, Small Talk, Big Topics, is back for season two. To kick off the new season, hosts Drs. Matthew Whitson, Nina Nandy, and CS Tse sit down with AGA President Dr. John Carethers in a two-part special to chat about his career and how his involvement with AGA has impacted him.

In episode one, Drs. Whitson, Nandy and Tse take a deep dive with Dr. Carethers to reflect on how he first got involved with AGA, his experience with different committees, and how those roles paved the way to leadership positions.

Now, as president, he says, “I am having so much fun. AGA has been with me for my entire GI career. It’s really the voice of the science and practice of gastroenterology.”

In episode two, Dr. Carethers examines the career advice he’s received, how it shaped his leadership style and provides guidance to early career GIs.

“What’s important about some of these higher-level [decisions] is to set a vision. You can’t be a leader if you have no followers, and people have to believe in something, that they’re moving toward something.”

Listen to more of Dr. Carethers’ insight in the first two episodes of Small Talk, Big Topics wherever you listen to podcasts and subscribe to stay up to date on new episodes.
 

Maximize your first day at DDW^® 2023

Held during the first day of Digestive Disease Week^®, this year’s AGA Postgraduate Course will be held live on Saturday, May 6, from 8:30 a.m. to 5 p.m. CT. This year’s theme – Advances in Gastroenterology: News You Can Use – will help you cut through the noise surrounding best practices for GI physicians.

Pricing is the same for both in-person and virtual attendees, giving you the flexibility to experience the course in-person or from the comfort of your home. All registrants will have on-demand access to the course for three months and the opportunity to earn up to 17.5 total credits when you complete all on-demand content.
 

What’s new this year?

General session format
Presentations will be given in an engaging format that will feel less didactic and more akin to a discussion among faculty, or a conversation with the experts! It’s also an exciting opportunity to mix junior and senior lecturers on the same platform.

Recent clinical practices
Session panelists will work together to select the key papers in their topic areas for discussion. Only the newest — within one year — and most important papers, clinical guidelines and pathways in the field will be selected.

Register to attend DDW and the Postgraduate Course today.

And the winner of this year’s Shark Tank is …

The 13th annual AGA Tech Summit took place in San Francisco, Calif., recently, bringing together GI entrepreneurs, clinicians, medical technology companies, venture capitalists, and regulatory agencies working to improve patient care in the field. A highlight of the event is the annual Shark Tank competition, where forward-thinking companies showcase and pitch their innovations to a panel of expert judges. 

Congratulations to this year’s winner – Endiatx!
From devices providing rapid cancer detection to technology that makes endoscopy safer, the five companies selected for the 2023 AGA Shark Tank represented a glimpse of the future of GI patient care. 

While each team offered a creative solution to modern-day GI challenges, only one could be declared the winner. Congratulations to our 2023 winner, Endiatx! Endiatx will represent AGA in the upcoming Shark Tank competition at DDW^®. 
 

Endiatx has developed a vitamin-sized intrabody robot
PillBot is a miniature robotic capsule endoscopy. Shipped to a patient’s home or picked up from a pharmacy, the standard size capsule is swallowed and then controlled by an external joystick-like device or a phone app by a physician in a physically separate location. Using real-time video transmissions visible to both operator and patient, the capsule navigates the entire stomach in a few minutes without anesthesia and ultimately is excreted outside the body without the need for recapture.

Future GI physician innovators

This year the AGA Center for GI Innovation and Technology (CGIT) welcomed 22 first-year to advanced endoscopy fellows to the AGA Innovation Fellows Program. The program provides a unique opportunity for the fellows to learn from GI clinicians, innovators, entrepreneurs, and medical technology executives on how new technologies are developed and brought to market.

American Gastroenterological Association

The fellows received an exclusive behind-the-scenes tour of Medtronic’s R&D facility in Santa Clara, Calif., and got to experience hands-on demonstrations of GI Genius^TM, PillCam^TM, Endoflip^TM, Nexpowder^TM, Bravo^TM, Barrx^TM and ProdiGI^TM technologies. The group was also hosted by Boston Scientific Corporation, Castle Biosciences and PENTAX Medical at a dinner that included an innovators panel discussion. The program will continue throughout the year with monthly educational sessions moderated by members of the AGA CGIT committee. 

• Mohd Amer Alsamman, MD, Georgetown University
• Mohammad Arfeen, MD, Franciscan Health Olympia Fields
• Alexis Bayudan, MD, University of California, San Francisco
• Aileen Bui, MD, University of Southern California
• Divya Chalikonda, MD, Thomas Jefferson University Hospital
• Alec Faggen, MD, University of California, San Francisco
• Sweta Ghosh, PhD, University of Louisville School of Medicine
• Hemant Goyal, MD, University of Texas Houston
• Averill Guo, MD, Brown University
• Omar Jamil, MD, University of Chicago
• Christina Kratschmer, MD, Washington University in St. Louis
• Thi Khuc, MD, University of Maryland School of Medicine
• Anand Kumar, MD, Northwell Health – Lenox Hill Hospital
• Xing Li, MD, Massachusetts General Hospital
• Alana Persaud, MD, SUNY Downstate Medical Center
• Itegbemie Obaitan, MD, Indiana University School of Medicine
• Chethan Ramprasad, MD, University of Pennsylvania
• Abhishek Satishchandran, MD, University of Michigan
• Kevin Shah, MD, Emory University School of Medicine
• Shifa Umar, MD, University of Chicago
• Kornpong Vantanasiri, MD, Mayo Clinic Rochester
• Shaleen Vasavada, MD, Baylor College of Medicine

Highlights from social media

See what else attendees shared with #AGATech on Twitter.

The 2023 AGA Tech Summit was made possible by support from Castle Biosciences and Medtronic (Diamond Sponsors), AI Medical Services, Boston Scientific, Exact Sciences Corporation, FUJIFILM Medical Systems and Olympus Corporation (Gold Sponsors), Cook Medical Inc., and STERIS Endoscopy (Silver Sponsors), and Apollo Endosurgery and EvoEndo (Bronze Sponsors).
 

AGA takes CRC month to Capitol Hill

Participating in Colorectal Cancer Awareness Month in Washington, D.C., means one thing – taking the fight to save lives from CRC to Capitol Hill and advocating for increased access to screening and research to improve outcomes.

Austin Chiang, MD, MPH

In March, AGA joined the national advocacy organization Fight Colorectal Cancer (Fight CRC) and partners in the colorectal cancer community for events in our nation’s capital. The goal was to destigmatize talking about gut health and CRC and to collaboratively develop solutions that will improve and increase access to CRC screening.

Austin Chiang, MD, MPH

Fight CRC working lunch
Former AGA president Dr. David Lieberman and fellow AGA member and FORWARD graduate Dr. Fola May served as facilitators for the coalition of public and private leaders assembled by Fight CRC. The group is working to develop an action plan to further equitable CRC screening and lower the number of lives impacted by CRC. Among the participants were insurers, industry, federal agencies, healthcare providers, retail businesses, and patients.

White House Cancer Moonshot colorectal cancer forum
In partnership with President Biden’s reignited Cancer Moonshot initiative, we joined Fight CRC and other advocacy and industry leaders in the colorectal cancer community for the Cancer Moonshot Colorectal Cancer Forum, hosted by the White House.

Dr. May participated as a panelist during the forum and discussed how we should address disparities in CRC. “Research dollars are essential in [combating CRC inequity]. We do not know how to effectively deliver care and preventive services to these populations unless we do deep dives into these particular settings to understand how to best deliver that care. This is not a “pick a model and apply broadly” approach. We need to go to the people, and we need to go to the people with the methods that work for that particular setting, and that’s going to be different in every community.”

American Gastroenterological Association

Fight CRC United in Blue rally on the National Mall
It’s become an annual tradition for us to join Fight CRC’s United in Blue rally and blue flag installation on the National Mall, and this year was no different. We joined industry and patient advocacy groups in the CRC community to raise our voices about the need for screening, research, and advocacy to improve colon cancer outcomes.

The rally included inspiring calls to action and CRC testimonials from individuals who have been personally impacted by the disease, including Rep. Donald Payne Jr. (D-NJ), who lost his father to CRC and who personally underwent screening, which led to the discovery of 13 polyps.

Dr. Manish Singla from Capital Digestive Care spoke on behalf of AGA and provided encouragement and a reminder for patients and providers.

“What I keep hearing here is patients feel like they’re not being heard – so we’re listening. We’re trying and we’re here to fight the disease with you all. Everyone here knows somebody who is due for a colonoscopy and isn’t getting it, so use your persuasion – talk about it, convince, cajole, shame – use whatever you need so that everyone gets the screenings they need,” Dr. Singla said.

Our work is just beginning: Let’s work together to encourage screenings for colorectal cancer and save lives. Join us as we remind everyone that 45 is the new 50.

Season 2 of Small Talk, Big Topics is here!

AGA’s podcast for trainees and early career GIs, Small Talk, Big Topics, is back for season two. To kick off the new season, hosts Drs. Matthew Whitson, Nina Nandy, and CS Tse sit down with AGA President Dr. John Carethers in a two-part special to chat about his career and how his involvement with AGA has impacted him.

In episode one, Drs. Whitson, Nandy and Tse take a deep dive with Dr. Carethers to reflect on how he first got involved with AGA, his experience with different committees, and how those roles paved the way to leadership positions.

Now, as president, he says, “I am having so much fun. AGA has been with me for my entire GI career. It’s really the voice of the science and practice of gastroenterology.”

In episode two, Dr. Carethers examines the career advice he’s received, how it shaped his leadership style and provides guidance to early career GIs.

“What’s important about some of these higher-level [decisions] is to set a vision. You can’t be a leader if you have no followers, and people have to believe in something, that they’re moving toward something.”

Listen to more of Dr. Carethers’ insight in the first two episodes of Small Talk, Big Topics wherever you listen to podcasts and subscribe to stay up to date on new episodes.
 

Maximize your first day at DDW^® 2023

Held during the first day of Digestive Disease Week^®, this year’s AGA Postgraduate Course will be held live on Saturday, May 6, from 8:30 a.m. to 5 p.m. CT. This year’s theme – Advances in Gastroenterology: News You Can Use – will help you cut through the noise surrounding best practices for GI physicians.

Pricing is the same for both in-person and virtual attendees, giving you the flexibility to experience the course in-person or from the comfort of your home. All registrants will have on-demand access to the course for three months and the opportunity to earn up to 17.5 total credits when you complete all on-demand content.
 

What’s new this year?

General session format
Presentations will be given in an engaging format that will feel less didactic and more akin to a discussion among faculty, or a conversation with the experts! It’s also an exciting opportunity to mix junior and senior lecturers on the same platform.

Recent clinical practices
Session panelists will work together to select the key papers in their topic areas for discussion. Only the newest — within one year — and most important papers, clinical guidelines and pathways in the field will be selected.

Register to attend DDW and the Postgraduate Course today.

And the winner of this year’s Shark Tank is …

The 13th annual AGA Tech Summit took place in San Francisco, Calif., recently, bringing together GI entrepreneurs, clinicians, medical technology companies, venture capitalists, and regulatory agencies working to improve patient care in the field. A highlight of the event is the annual Shark Tank competition, where forward-thinking companies showcase and pitch their innovations to a panel of expert judges. 

Congratulations to this year’s winner – Endiatx!
From devices providing rapid cancer detection to technology that makes endoscopy safer, the five companies selected for the 2023 AGA Shark Tank represented a glimpse of the future of GI patient care. 

While each team offered a creative solution to modern-day GI challenges, only one could be declared the winner. Congratulations to our 2023 winner, Endiatx! Endiatx will represent AGA in the upcoming Shark Tank competition at DDW^®. 
 

Endiatx has developed a vitamin-sized intrabody robot
PillBot is a miniature robotic capsule endoscopy. Shipped to a patient’s home or picked up from a pharmacy, the standard size capsule is swallowed and then controlled by an external joystick-like device or a phone app by a physician in a physically separate location. Using real-time video transmissions visible to both operator and patient, the capsule navigates the entire stomach in a few minutes without anesthesia and ultimately is excreted outside the body without the need for recapture.

Future GI physician innovators

This year the AGA Center for GI Innovation and Technology (CGIT) welcomed 22 first-year to advanced endoscopy fellows to the AGA Innovation Fellows Program. The program provides a unique opportunity for the fellows to learn from GI clinicians, innovators, entrepreneurs, and medical technology executives on how new technologies are developed and brought to market.

American Gastroenterological Association

The fellows received an exclusive behind-the-scenes tour of Medtronic’s R&D facility in Santa Clara, Calif., and got to experience hands-on demonstrations of GI Genius^TM, PillCam^TM, Endoflip^TM, Nexpowder^TM, Bravo^TM, Barrx^TM and ProdiGI^TM technologies. The group was also hosted by Boston Scientific Corporation, Castle Biosciences and PENTAX Medical at a dinner that included an innovators panel discussion. The program will continue throughout the year with monthly educational sessions moderated by members of the AGA CGIT committee. 

• Mohd Amer Alsamman, MD, Georgetown University
• Mohammad Arfeen, MD, Franciscan Health Olympia Fields
• Alexis Bayudan, MD, University of California, San Francisco
• Aileen Bui, MD, University of Southern California
• Divya Chalikonda, MD, Thomas Jefferson University Hospital
• Alec Faggen, MD, University of California, San Francisco
• Sweta Ghosh, PhD, University of Louisville School of Medicine
• Hemant Goyal, MD, University of Texas Houston
• Averill Guo, MD, Brown University
• Omar Jamil, MD, University of Chicago
• Christina Kratschmer, MD, Washington University in St. Louis
• Thi Khuc, MD, University of Maryland School of Medicine
• Anand Kumar, MD, Northwell Health – Lenox Hill Hospital
• Xing Li, MD, Massachusetts General Hospital
• Alana Persaud, MD, SUNY Downstate Medical Center
• Itegbemie Obaitan, MD, Indiana University School of Medicine
• Chethan Ramprasad, MD, University of Pennsylvania
• Abhishek Satishchandran, MD, University of Michigan
• Kevin Shah, MD, Emory University School of Medicine
• Shifa Umar, MD, University of Chicago
• Kornpong Vantanasiri, MD, Mayo Clinic Rochester
• Shaleen Vasavada, MD, Baylor College of Medicine

Highlights from social media

See what else attendees shared with #AGATech on Twitter.

The 2023 AGA Tech Summit was made possible by support from Castle Biosciences and Medtronic (Diamond Sponsors), AI Medical Services, Boston Scientific, Exact Sciences Corporation, FUJIFILM Medical Systems and Olympus Corporation (Gold Sponsors), Cook Medical Inc., and STERIS Endoscopy (Silver Sponsors), and Apollo Endosurgery and EvoEndo (Bronze Sponsors).
 

AGA takes CRC month to Capitol Hill

Participating in Colorectal Cancer Awareness Month in Washington, D.C., means one thing – taking the fight to save lives from CRC to Capitol Hill and advocating for increased access to screening and research to improve outcomes.

Austin Chiang, MD, MPH

In March, AGA joined the national advocacy organization Fight Colorectal Cancer (Fight CRC) and partners in the colorectal cancer community for events in our nation’s capital. The goal was to destigmatize talking about gut health and CRC and to collaboratively develop solutions that will improve and increase access to CRC screening.

Austin Chiang, MD, MPH

Fight CRC working lunch
Former AGA president Dr. David Lieberman and fellow AGA member and FORWARD graduate Dr. Fola May served as facilitators for the coalition of public and private leaders assembled by Fight CRC. The group is working to develop an action plan to further equitable CRC screening and lower the number of lives impacted by CRC. Among the participants were insurers, industry, federal agencies, healthcare providers, retail businesses, and patients.

White House Cancer Moonshot colorectal cancer forum
In partnership with President Biden’s reignited Cancer Moonshot initiative, we joined Fight CRC and other advocacy and industry leaders in the colorectal cancer community for the Cancer Moonshot Colorectal Cancer Forum, hosted by the White House.

Dr. May participated as a panelist during the forum and discussed how we should address disparities in CRC. “Research dollars are essential in [combating CRC inequity]. We do not know how to effectively deliver care and preventive services to these populations unless we do deep dives into these particular settings to understand how to best deliver that care. This is not a “pick a model and apply broadly” approach. We need to go to the people, and we need to go to the people with the methods that work for that particular setting, and that’s going to be different in every community.”

American Gastroenterological Association

Fight CRC United in Blue rally on the National Mall
It’s become an annual tradition for us to join Fight CRC’s United in Blue rally and blue flag installation on the National Mall, and this year was no different. We joined industry and patient advocacy groups in the CRC community to raise our voices about the need for screening, research, and advocacy to improve colon cancer outcomes.

The rally included inspiring calls to action and CRC testimonials from individuals who have been personally impacted by the disease, including Rep. Donald Payne Jr. (D-NJ), who lost his father to CRC and who personally underwent screening, which led to the discovery of 13 polyps.

Dr. Manish Singla from Capital Digestive Care spoke on behalf of AGA and provided encouragement and a reminder for patients and providers.

“What I keep hearing here is patients feel like they’re not being heard – so we’re listening. We’re trying and we’re here to fight the disease with you all. Everyone here knows somebody who is due for a colonoscopy and isn’t getting it, so use your persuasion – talk about it, convince, cajole, shame – use whatever you need so that everyone gets the screenings they need,” Dr. Singla said.

Our work is just beginning: Let’s work together to encourage screenings for colorectal cancer and save lives. Join us as we remind everyone that 45 is the new 50.

Season 2 of Small Talk, Big Topics is here!

AGA’s podcast for trainees and early career GIs, Small Talk, Big Topics, is back for season two. To kick off the new season, hosts Drs. Matthew Whitson, Nina Nandy, and CS Tse sit down with AGA President Dr. John Carethers in a two-part special to chat about his career and how his involvement with AGA has impacted him.

In episode one, Drs. Whitson, Nandy and Tse take a deep dive with Dr. Carethers to reflect on how he first got involved with AGA, his experience with different committees, and how those roles paved the way to leadership positions.

Now, as president, he says, “I am having so much fun. AGA has been with me for my entire GI career. It’s really the voice of the science and practice of gastroenterology.”

In episode two, Dr. Carethers examines the career advice he’s received, how it shaped his leadership style and provides guidance to early career GIs.

“What’s important about some of these higher-level [decisions] is to set a vision. You can’t be a leader if you have no followers, and people have to believe in something, that they’re moving toward something.”

Listen to more of Dr. Carethers’ insight in the first two episodes of Small Talk, Big Topics wherever you listen to podcasts and subscribe to stay up to date on new episodes.
 

Maximize your first day at DDW^® 2023

Held during the first day of Digestive Disease Week^®, this year’s AGA Postgraduate Course will be held live on Saturday, May 6, from 8:30 a.m. to 5 p.m. CT. This year’s theme – Advances in Gastroenterology: News You Can Use – will help you cut through the noise surrounding best practices for GI physicians.

Pricing is the same for both in-person and virtual attendees, giving you the flexibility to experience the course in-person or from the comfort of your home. All registrants will have on-demand access to the course for three months and the opportunity to earn up to 17.5 total credits when you complete all on-demand content.
 

What’s new this year?

General session format
Presentations will be given in an engaging format that will feel less didactic and more akin to a discussion among faculty, or a conversation with the experts! It’s also an exciting opportunity to mix junior and senior lecturers on the same platform.

Recent clinical practices
Session panelists will work together to select the key papers in their topic areas for discussion. Only the newest — within one year — and most important papers, clinical guidelines and pathways in the field will be selected.

Register to attend DDW and the Postgraduate Course today.

And the winner of this year’s Shark Tank is …

The 13th annual AGA Tech Summit took place in San Francisco, Calif., recently, bringing together GI entrepreneurs, clinicians, medical technology companies, venture capitalists, and regulatory agencies working to improve patient care in the field. A highlight of the event is the annual Shark Tank competition, where forward-thinking companies showcase and pitch their innovations to a panel of expert judges. 

Congratulations to this year’s winner – Endiatx!
From devices providing rapid cancer detection to technology that makes endoscopy safer, the five companies selected for the 2023 AGA Shark Tank represented a glimpse of the future of GI patient care. 

While each team offered a creative solution to modern-day GI challenges, only one could be declared the winner. Congratulations to our 2023 winner, Endiatx! Endiatx will represent AGA in the upcoming Shark Tank competition at DDW^®. 
 

Endiatx has developed a vitamin-sized intrabody robot
PillBot is a miniature robotic capsule endoscopy. Shipped to a patient’s home or picked up from a pharmacy, the standard size capsule is swallowed and then controlled by an external joystick-like device or a phone app by a physician in a physically separate location. Using real-time video transmissions visible to both operator and patient, the capsule navigates the entire stomach in a few minutes without anesthesia and ultimately is excreted outside the body without the need for recapture.

Future GI physician innovators

This year the AGA Center for GI Innovation and Technology (CGIT) welcomed 22 first-year to advanced endoscopy fellows to the AGA Innovation Fellows Program. The program provides a unique opportunity for the fellows to learn from GI clinicians, innovators, entrepreneurs, and medical technology executives on how new technologies are developed and brought to market.

American Gastroenterological Association

The fellows received an exclusive behind-the-scenes tour of Medtronic’s R&D facility in Santa Clara, Calif., and got to experience hands-on demonstrations of GI Genius^TM, PillCam^TM, Endoflip^TM, Nexpowder^TM, Bravo^TM, Barrx^TM and ProdiGI^TM technologies. The group was also hosted by Boston Scientific Corporation, Castle Biosciences and PENTAX Medical at a dinner that included an innovators panel discussion. The program will continue throughout the year with monthly educational sessions moderated by members of the AGA CGIT committee. 

• Mohd Amer Alsamman, MD, Georgetown University
• Mohammad Arfeen, MD, Franciscan Health Olympia Fields
• Alexis Bayudan, MD, University of California, San Francisco
• Aileen Bui, MD, University of Southern California
• Divya Chalikonda, MD, Thomas Jefferson University Hospital
• Alec Faggen, MD, University of California, San Francisco
• Sweta Ghosh, PhD, University of Louisville School of Medicine
• Hemant Goyal, MD, University of Texas Houston
• Averill Guo, MD, Brown University
• Omar Jamil, MD, University of Chicago
• Christina Kratschmer, MD, Washington University in St. Louis
• Thi Khuc, MD, University of Maryland School of Medicine
• Anand Kumar, MD, Northwell Health – Lenox Hill Hospital
• Xing Li, MD, Massachusetts General Hospital
• Alana Persaud, MD, SUNY Downstate Medical Center
• Itegbemie Obaitan, MD, Indiana University School of Medicine
• Chethan Ramprasad, MD, University of Pennsylvania
• Abhishek Satishchandran, MD, University of Michigan
• Kevin Shah, MD, Emory University School of Medicine
• Shifa Umar, MD, University of Chicago
• Kornpong Vantanasiri, MD, Mayo Clinic Rochester
• Shaleen Vasavada, MD, Baylor College of Medicine

Highlights from social media

See what else attendees shared with #AGATech on Twitter.

The 2023 AGA Tech Summit was made possible by support from Castle Biosciences and Medtronic (Diamond Sponsors), AI Medical Services, Boston Scientific, Exact Sciences Corporation, FUJIFILM Medical Systems and Olympus Corporation (Gold Sponsors), Cook Medical Inc., and STERIS Endoscopy (Silver Sponsors), and Apollo Endosurgery and EvoEndo (Bronze Sponsors).
 

AGA takes CRC month to Capitol Hill

Participating in Colorectal Cancer Awareness Month in Washington, D.C., means one thing – taking the fight to save lives from CRC to Capitol Hill and advocating for increased access to screening and research to improve outcomes.

Austin Chiang, MD, MPH

In March, AGA joined the national advocacy organization Fight Colorectal Cancer (Fight CRC) and partners in the colorectal cancer community for events in our nation’s capital. The goal was to destigmatize talking about gut health and CRC and to collaboratively develop solutions that will improve and increase access to CRC screening.

Austin Chiang, MD, MPH

Fight CRC working lunch
Former AGA president Dr. David Lieberman and fellow AGA member and FORWARD graduate Dr. Fola May served as facilitators for the coalition of public and private leaders assembled by Fight CRC. The group is working to develop an action plan to further equitable CRC screening and lower the number of lives impacted by CRC. Among the participants were insurers, industry, federal agencies, healthcare providers, retail businesses, and patients.

White House Cancer Moonshot colorectal cancer forum
In partnership with President Biden’s reignited Cancer Moonshot initiative, we joined Fight CRC and other advocacy and industry leaders in the colorectal cancer community for the Cancer Moonshot Colorectal Cancer Forum, hosted by the White House.

Dr. May participated as a panelist during the forum and discussed how we should address disparities in CRC. “Research dollars are essential in [combating CRC inequity]. We do not know how to effectively deliver care and preventive services to these populations unless we do deep dives into these particular settings to understand how to best deliver that care. This is not a “pick a model and apply broadly” approach. We need to go to the people, and we need to go to the people with the methods that work for that particular setting, and that’s going to be different in every community.”

American Gastroenterological Association

Fight CRC United in Blue rally on the National Mall
It’s become an annual tradition for us to join Fight CRC’s United in Blue rally and blue flag installation on the National Mall, and this year was no different. We joined industry and patient advocacy groups in the CRC community to raise our voices about the need for screening, research, and advocacy to improve colon cancer outcomes.

The rally included inspiring calls to action and CRC testimonials from individuals who have been personally impacted by the disease, including Rep. Donald Payne Jr. (D-NJ), who lost his father to CRC and who personally underwent screening, which led to the discovery of 13 polyps.

Dr. Manish Singla from Capital Digestive Care spoke on behalf of AGA and provided encouragement and a reminder for patients and providers.

“What I keep hearing here is patients feel like they’re not being heard – so we’re listening. We’re trying and we’re here to fight the disease with you all. Everyone here knows somebody who is due for a colonoscopy and isn’t getting it, so use your persuasion – talk about it, convince, cajole, shame – use whatever you need so that everyone gets the screenings they need,” Dr. Singla said.

Our work is just beginning: Let’s work together to encourage screenings for colorectal cancer and save lives. Join us as we remind everyone that 45 is the new 50.

Pregnancy-related deaths have surged as much as 40% during the pandemic, with the increase entirely linked to COVID-19, according to a pair of recent reports. The rise in deaths was most pronounced among Black mothers.

In 2021, 1,205 women died from pregnancy-related causes, making the year one of the worst for maternal mortality in U.S. history, according to newly released data from the Centers for Disease Control and Prevention. Maternal mortality is defined as occurring during pregnancy, at delivery, or soon after delivery.

COVID was the driver of the increased death rate, according to a study published in the journal Obstetrics & Gynecology. The researchers noted that unvaccinated pregnant people are more likely to get severe COVID, and that prenatal and postnatal care were disrupted during the early part of the pandemic. From July 2021 to March 2023, the rate of women being vaccinated before pregnancy has risen from 22% to 70%, CDC data show.

Maternal mortality rates jumped the most among Black women, who in 2021 had a maternal mortality rate of nearly 70 deaths per 100,000 live births, which was 2.6 times the rate for White women. 

Existing risks based on a mother’s age also increased from 2020 to 2021. The maternal mortality rates by age in 2021 per 100,000 live births were:

• 20.4 for women under age 25.
• 31.3 for women ages 25 to 39.
• 138.5 for women ages 40 and older.

Iffath Abbasi Hoskins, MD, FACOG, president of the American College of Obstetricians and Gynecologists, called the situation “stunning” and “preventable.”

The findings “send a resounding message that maternal health and evidence-based efforts to eliminate racial health inequities need to be, and remain, a top public health priority,” Dr. Hoskins said in a statement.

“The COVID-19 pandemic had a dramatic and tragic effect on maternal death rates, but we cannot let that fact obscure that there was – and still is – already a maternal mortality crisis to compound,” she said.

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

Pregnancy-related deaths have surged as much as 40% during the pandemic, with the increase entirely linked to COVID-19, according to a pair of recent reports. The rise in deaths was most pronounced among Black mothers.

In 2021, 1,205 women died from pregnancy-related causes, making the year one of the worst for maternal mortality in U.S. history, according to newly released data from the Centers for Disease Control and Prevention. Maternal mortality is defined as occurring during pregnancy, at delivery, or soon after delivery.

COVID was the driver of the increased death rate, according to a study published in the journal Obstetrics & Gynecology. The researchers noted that unvaccinated pregnant people are more likely to get severe COVID, and that prenatal and postnatal care were disrupted during the early part of the pandemic. From July 2021 to March 2023, the rate of women being vaccinated before pregnancy has risen from 22% to 70%, CDC data show.

Maternal mortality rates jumped the most among Black women, who in 2021 had a maternal mortality rate of nearly 70 deaths per 100,000 live births, which was 2.6 times the rate for White women. 

Existing risks based on a mother’s age also increased from 2020 to 2021. The maternal mortality rates by age in 2021 per 100,000 live births were:

• 20.4 for women under age 25.
• 31.3 for women ages 25 to 39.
• 138.5 for women ages 40 and older.

Iffath Abbasi Hoskins, MD, FACOG, president of the American College of Obstetricians and Gynecologists, called the situation “stunning” and “preventable.”

The findings “send a resounding message that maternal health and evidence-based efforts to eliminate racial health inequities need to be, and remain, a top public health priority,” Dr. Hoskins said in a statement.

“The COVID-19 pandemic had a dramatic and tragic effect on maternal death rates, but we cannot let that fact obscure that there was – and still is – already a maternal mortality crisis to compound,” she said.

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

Pregnancy-related deaths have surged as much as 40% during the pandemic, with the increase entirely linked to COVID-19, according to a pair of recent reports. The rise in deaths was most pronounced among Black mothers.

In 2021, 1,205 women died from pregnancy-related causes, making the year one of the worst for maternal mortality in U.S. history, according to newly released data from the Centers for Disease Control and Prevention. Maternal mortality is defined as occurring during pregnancy, at delivery, or soon after delivery.

COVID was the driver of the increased death rate, according to a study published in the journal Obstetrics & Gynecology. The researchers noted that unvaccinated pregnant people are more likely to get severe COVID, and that prenatal and postnatal care were disrupted during the early part of the pandemic. From July 2021 to March 2023, the rate of women being vaccinated before pregnancy has risen from 22% to 70%, CDC data show.

Maternal mortality rates jumped the most among Black women, who in 2021 had a maternal mortality rate of nearly 70 deaths per 100,000 live births, which was 2.6 times the rate for White women. 

Existing risks based on a mother’s age also increased from 2020 to 2021. The maternal mortality rates by age in 2021 per 100,000 live births were:

• 20.4 for women under age 25.
• 31.3 for women ages 25 to 39.
• 138.5 for women ages 40 and older.

Iffath Abbasi Hoskins, MD, FACOG, president of the American College of Obstetricians and Gynecologists, called the situation “stunning” and “preventable.”

The findings “send a resounding message that maternal health and evidence-based efforts to eliminate racial health inequities need to be, and remain, a top public health priority,” Dr. Hoskins said in a statement.

“The COVID-19 pandemic had a dramatic and tragic effect on maternal death rates, but we cannot let that fact obscure that there was – and still is – already a maternal mortality crisis to compound,” she said.

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

Nearly one in four children diagnosed with type 2 diabetes for 5 years or more develop diabetic retinopathy, according to a new report.

The global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes is about 7%, which appears to increase with age.

“In our clinical practice, we have seen an increase in children presenting with type 2 diabetes over the past few years. These patients present with multiple simultaneous comorbidities and complications like hypertension, fatty liver, and other conditions,” senior author M. Constantine Samaan, MD, told this news organization.

“The exact scale of diabetes-related eye disease was not clear, and we decided to quantify it,” said Dr. Samaan, associate professor of pediatrics at McMaster University and pediatric endocrinologist at McMaster Children’s Hospital in Hamilton, Ont.

“What we found was that in pediatric patients with type 2 diabetes, diabetic retinopathy is present in 1 in 14 youth. The risk of retinopathy increased significantly 5 years after diagnosis to almost one in four,” he noted.

“While we acknowledged that the number of diabetic retinopathy cases was relatively small and there was heterogeneity in studies, we were surprised that retinopathy rates rose so fast in the first few years after diabetes diagnosis,” Dr. Samaan indicated.

The findings signal that the increase in the prevalence of diabetic retinopathy is emerging decades earlier among children compared with adults with type 2 diabetes, the authors wrote in their article published online in JAMA Network Open.

“While the guidelines for eye care in children with type 2 diabetes recommend screening at diagnosis and annually afterward, these recommendations are not followed in almost half of these patients,” Dr. Samaan said. “There is a need to ensure that patients get screened to try and prevent or delay retinopathy onset and progression.”
 

Analyzing prevalence rates

Diabetic retinopathy is the leading cause of blindness in patients with type 2 diabetes. Between 21% and 39% of adults have diabetic retinopathy at diagnosis, with rates subsequently increasing, the authors wrote.

Dr. Samaan and colleagues conducted a systematic review and meta-analysis to estimate the global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes. They included studies that had a study population of at least 10 participants diagnosed at age 21 and younger, an observational study design, and prevalence data on diabetic retinopathy.

Among the 29 studies included, 6 were cross-sectional, 13 had a retrospective cohort design, and 10 had a prospective cohort design. Patients were diagnosed between age 6.5 and 21 years, and the diabetes duration ranged from 0 to 15 years after diagnosis.

The overall global prevalence of diabetic retinopathy in 5,924 pediatric patients was 7.0%. Prevalence varied by study design, ranging from 1.1% in cross-sectional studies to 6.5% in prospective cohort studies and 11.3% in retrospective cohort studies.

In the nine studies that reported diabetic retinopathy classification based on criteria, the prevalence of minimal-to-moderate nonproliferative diabetic retinopathy was 11.2%, the prevalence of severe nonproliferative diabetic retinopathy was 2.6%, the prevalence of proliferative diabetic retinopathy was 2.4%, and the prevalence of macular edema was 3.1%.

In the five studies that reported diabetic retinopathy diagnosis using fundoscopy, the prevalence was 0.5%. In the four studies that used 7-field stereoscopic fundus photography, the prevalence was 13.6%.

In the pooled analysis of 27 studies, the prevalence of diabetic retinopathy was 1.8% less than 2.5 years after diabetes diagnosis but more than doubled to 5.1% in years 2.5 to 5 and jumped to 28.8% more than 5 years after diagnosis.
 

Differences by sex, ethnicity

“We were also surprised that there was very limited evidence to understand the sex and race differences in retinopathy risk,” said Dr. Samaan. “Further research is warranted, considering that more girls develop type 2 diabetes than boys, and the risk of type 2 diabetes is higher in some racial groups.”

In addition, older age, longer diabetes duration, and higher hypertension prevalence were associated with diabetic retinopathy prevalence. There were no associations with obesity prevalence or mean age at diabetes diagnosis. However, patients who developed diabetic retinopathy had a higher mean A1c level of 1.4% compared to those without retinopathy.

Dr. Samaan and colleagues are continuing to research the comorbidities and complications that children with type 2 diabetes face as well as mechanisms that drive diabetes outcomes among children and adolescents.

For now, the findings highlight the importance of retinopathy screening and personalized diabetes treatment to protect vision, Dr. Samaan reiterated.

No funding source for the study was reported. The authors have reported no relevant financial relationships.
 

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

Nearly one in four children diagnosed with type 2 diabetes for 5 years or more develop diabetic retinopathy, according to a new report.

The global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes is about 7%, which appears to increase with age.

“In our clinical practice, we have seen an increase in children presenting with type 2 diabetes over the past few years. These patients present with multiple simultaneous comorbidities and complications like hypertension, fatty liver, and other conditions,” senior author M. Constantine Samaan, MD, told this news organization.

“The exact scale of diabetes-related eye disease was not clear, and we decided to quantify it,” said Dr. Samaan, associate professor of pediatrics at McMaster University and pediatric endocrinologist at McMaster Children’s Hospital in Hamilton, Ont.

“What we found was that in pediatric patients with type 2 diabetes, diabetic retinopathy is present in 1 in 14 youth. The risk of retinopathy increased significantly 5 years after diagnosis to almost one in four,” he noted.

“While we acknowledged that the number of diabetic retinopathy cases was relatively small and there was heterogeneity in studies, we were surprised that retinopathy rates rose so fast in the first few years after diabetes diagnosis,” Dr. Samaan indicated.

The findings signal that the increase in the prevalence of diabetic retinopathy is emerging decades earlier among children compared with adults with type 2 diabetes, the authors wrote in their article published online in JAMA Network Open.

“While the guidelines for eye care in children with type 2 diabetes recommend screening at diagnosis and annually afterward, these recommendations are not followed in almost half of these patients,” Dr. Samaan said. “There is a need to ensure that patients get screened to try and prevent or delay retinopathy onset and progression.”
 

Analyzing prevalence rates

Diabetic retinopathy is the leading cause of blindness in patients with type 2 diabetes. Between 21% and 39% of adults have diabetic retinopathy at diagnosis, with rates subsequently increasing, the authors wrote.

Dr. Samaan and colleagues conducted a systematic review and meta-analysis to estimate the global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes. They included studies that had a study population of at least 10 participants diagnosed at age 21 and younger, an observational study design, and prevalence data on diabetic retinopathy.

Among the 29 studies included, 6 were cross-sectional, 13 had a retrospective cohort design, and 10 had a prospective cohort design. Patients were diagnosed between age 6.5 and 21 years, and the diabetes duration ranged from 0 to 15 years after diagnosis.

The overall global prevalence of diabetic retinopathy in 5,924 pediatric patients was 7.0%. Prevalence varied by study design, ranging from 1.1% in cross-sectional studies to 6.5% in prospective cohort studies and 11.3% in retrospective cohort studies.

In the nine studies that reported diabetic retinopathy classification based on criteria, the prevalence of minimal-to-moderate nonproliferative diabetic retinopathy was 11.2%, the prevalence of severe nonproliferative diabetic retinopathy was 2.6%, the prevalence of proliferative diabetic retinopathy was 2.4%, and the prevalence of macular edema was 3.1%.

In the five studies that reported diabetic retinopathy diagnosis using fundoscopy, the prevalence was 0.5%. In the four studies that used 7-field stereoscopic fundus photography, the prevalence was 13.6%.

In the pooled analysis of 27 studies, the prevalence of diabetic retinopathy was 1.8% less than 2.5 years after diabetes diagnosis but more than doubled to 5.1% in years 2.5 to 5 and jumped to 28.8% more than 5 years after diagnosis.
 

Differences by sex, ethnicity

“We were also surprised that there was very limited evidence to understand the sex and race differences in retinopathy risk,” said Dr. Samaan. “Further research is warranted, considering that more girls develop type 2 diabetes than boys, and the risk of type 2 diabetes is higher in some racial groups.”

In addition, older age, longer diabetes duration, and higher hypertension prevalence were associated with diabetic retinopathy prevalence. There were no associations with obesity prevalence or mean age at diabetes diagnosis. However, patients who developed diabetic retinopathy had a higher mean A1c level of 1.4% compared to those without retinopathy.

Dr. Samaan and colleagues are continuing to research the comorbidities and complications that children with type 2 diabetes face as well as mechanisms that drive diabetes outcomes among children and adolescents.

For now, the findings highlight the importance of retinopathy screening and personalized diabetes treatment to protect vision, Dr. Samaan reiterated.

No funding source for the study was reported. The authors have reported no relevant financial relationships.
 

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

Nearly one in four children diagnosed with type 2 diabetes for 5 years or more develop diabetic retinopathy, according to a new report.

The global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes is about 7%, which appears to increase with age.

“In our clinical practice, we have seen an increase in children presenting with type 2 diabetes over the past few years. These patients present with multiple simultaneous comorbidities and complications like hypertension, fatty liver, and other conditions,” senior author M. Constantine Samaan, MD, told this news organization.

“The exact scale of diabetes-related eye disease was not clear, and we decided to quantify it,” said Dr. Samaan, associate professor of pediatrics at McMaster University and pediatric endocrinologist at McMaster Children’s Hospital in Hamilton, Ont.

“What we found was that in pediatric patients with type 2 diabetes, diabetic retinopathy is present in 1 in 14 youth. The risk of retinopathy increased significantly 5 years after diagnosis to almost one in four,” he noted.

“While we acknowledged that the number of diabetic retinopathy cases was relatively small and there was heterogeneity in studies, we were surprised that retinopathy rates rose so fast in the first few years after diabetes diagnosis,” Dr. Samaan indicated.

The findings signal that the increase in the prevalence of diabetic retinopathy is emerging decades earlier among children compared with adults with type 2 diabetes, the authors wrote in their article published online in JAMA Network Open.

“While the guidelines for eye care in children with type 2 diabetes recommend screening at diagnosis and annually afterward, these recommendations are not followed in almost half of these patients,” Dr. Samaan said. “There is a need to ensure that patients get screened to try and prevent or delay retinopathy onset and progression.”
 

Analyzing prevalence rates

Diabetic retinopathy is the leading cause of blindness in patients with type 2 diabetes. Between 21% and 39% of adults have diabetic retinopathy at diagnosis, with rates subsequently increasing, the authors wrote.

Dr. Samaan and colleagues conducted a systematic review and meta-analysis to estimate the global prevalence of diabetic retinopathy in pediatric patients with type 2 diabetes. They included studies that had a study population of at least 10 participants diagnosed at age 21 and younger, an observational study design, and prevalence data on diabetic retinopathy.

Among the 29 studies included, 6 were cross-sectional, 13 had a retrospective cohort design, and 10 had a prospective cohort design. Patients were diagnosed between age 6.5 and 21 years, and the diabetes duration ranged from 0 to 15 years after diagnosis.

The overall global prevalence of diabetic retinopathy in 5,924 pediatric patients was 7.0%. Prevalence varied by study design, ranging from 1.1% in cross-sectional studies to 6.5% in prospective cohort studies and 11.3% in retrospective cohort studies.

In the nine studies that reported diabetic retinopathy classification based on criteria, the prevalence of minimal-to-moderate nonproliferative diabetic retinopathy was 11.2%, the prevalence of severe nonproliferative diabetic retinopathy was 2.6%, the prevalence of proliferative diabetic retinopathy was 2.4%, and the prevalence of macular edema was 3.1%.

In the five studies that reported diabetic retinopathy diagnosis using fundoscopy, the prevalence was 0.5%. In the four studies that used 7-field stereoscopic fundus photography, the prevalence was 13.6%.

In the pooled analysis of 27 studies, the prevalence of diabetic retinopathy was 1.8% less than 2.5 years after diabetes diagnosis but more than doubled to 5.1% in years 2.5 to 5 and jumped to 28.8% more than 5 years after diagnosis.
 

Differences by sex, ethnicity

“We were also surprised that there was very limited evidence to understand the sex and race differences in retinopathy risk,” said Dr. Samaan. “Further research is warranted, considering that more girls develop type 2 diabetes than boys, and the risk of type 2 diabetes is higher in some racial groups.”

In addition, older age, longer diabetes duration, and higher hypertension prevalence were associated with diabetic retinopathy prevalence. There were no associations with obesity prevalence or mean age at diabetes diagnosis. However, patients who developed diabetic retinopathy had a higher mean A1c level of 1.4% compared to those without retinopathy.

Dr. Samaan and colleagues are continuing to research the comorbidities and complications that children with type 2 diabetes face as well as mechanisms that drive diabetes outcomes among children and adolescents.

For now, the findings highlight the importance of retinopathy screening and personalized diabetes treatment to protect vision, Dr. Samaan reiterated.

No funding source for the study was reported. The authors have reported no relevant financial relationships.
 

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

California lawmakers are considering legislation to protect California physicians and pharmacists who prescribe abortion pills to out-of-state patients. The proposed law would shield health care providers who are legally performing their jobs in California from facing prosecution in another state or being extradited.

State Sen. Nancy Skinner, who introduced the bill, said the legislation is necessary in a fractured, post-Roe legal landscape where doctors in some states can face felony charges or civil penalties for providing reproductive health care. It’s part of a package of 17 new bills aiming to “strengthen California’s standing as a safe haven for abortion, contraception, and pregnancy care,” according to a press release.

“I’m trying to protect our healthcare practitioners so they can do their jobs, without fear,” Ms. Skinner said in a statement on March 24.

Most abortions are banned in 14 states after the Supreme Court overturned Roe v. Wade. Lawmakers in those states have established a variety of penalties for doctors, pharmacists, and other clinicians to provide abortion care or assist patients in obtaining abortions, including jail time, fines, and loss of professional licenses.

As a result, doctors in restrictive states have anguished over having to delay treatment for patients experiencing miscarriages, ectopic pregnancies, and other conditions until their lives are enough at risk to satisfy exceptions to state abortion laws.

“As a physician, I believe everyone deserves the care they need, regardless of where they live,” said Daniel Grossman, MD, a University of California, San Francisco, ob.gyn. professor who directs the university’s Advancing New Standards in Reproductive Health program.

“Since the fall of Roe v. Wade, patients are being forced to travel long distances – often over 500 miles – to access abortion care in a clinic. People should be able to access this essential care closer to home, including by telemedicine, which has been shown to be safe and effective. I am hopeful that SB 345 will provide additional legal protections that would allow California clinicians to help patients in other states,” he stated.

Other states, including New York, Vermont, New Jersey, Massachusetts, and Connecticut, have passed or are considering similar legislation to protect doctors using telemedicine to prescribe abortion medication to out-of-state patients. These laws come amid a growing push by some states and anti-abortion groups to severely restrict access to abortion pills.

Wyoming is the first state to explicitly ban the pills, although a judge on March 22 blocked that ban. And, in a closely watched case, a conservative federal judge could soon rule to ban sales of mifepristone, one of the medications in a two-pill regimen approved for abortions early in pregnancy.

California’s legislation protects clinicians from losing their California professional licenses if an out-of-state medical board takes action against them. It also allows clinicians to sue anyone who tries to legally interfere with the care they are providing.

It also covers California physicians prescribing contraceptives or gender-affirming care to out-of-state patients. At least 21 states are considering restrictions on gender-affirming care for minors and another 9 states have passed them, according to the advocacy group Human Rights Campaign. Courts have blocked the restrictions in some states.

“It’s understandable that states like California want to reassure their doctors ... that, if one of their patients is caught in one of those states and can’t get help locally, they can step up to help and feel safe in doing so,” said Matthew Wynia, MD, MPH, FACP, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora.

“This is also a crazy development in terms of the law. It’s just one part of the legal mayhem that was predicted when the Supreme Court overturned Roe,” Dr. Wynia said of the growing number of bills protecting in-state doctors. These bills “will almost certainly end up being litigated over issues of interstate commerce, cross-state licensure and practice compacts, FDA regulations and authorities, and maybe more. It’s a huge mess, in which both doctors and patients are being hurt.”

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

California lawmakers are considering legislation to protect California physicians and pharmacists who prescribe abortion pills to out-of-state patients. The proposed law would shield health care providers who are legally performing their jobs in California from facing prosecution in another state or being extradited.

State Sen. Nancy Skinner, who introduced the bill, said the legislation is necessary in a fractured, post-Roe legal landscape where doctors in some states can face felony charges or civil penalties for providing reproductive health care. It’s part of a package of 17 new bills aiming to “strengthen California’s standing as a safe haven for abortion, contraception, and pregnancy care,” according to a press release.

“I’m trying to protect our healthcare practitioners so they can do their jobs, without fear,” Ms. Skinner said in a statement on March 24.

Most abortions are banned in 14 states after the Supreme Court overturned Roe v. Wade. Lawmakers in those states have established a variety of penalties for doctors, pharmacists, and other clinicians to provide abortion care or assist patients in obtaining abortions, including jail time, fines, and loss of professional licenses.

As a result, doctors in restrictive states have anguished over having to delay treatment for patients experiencing miscarriages, ectopic pregnancies, and other conditions until their lives are enough at risk to satisfy exceptions to state abortion laws.

“As a physician, I believe everyone deserves the care they need, regardless of where they live,” said Daniel Grossman, MD, a University of California, San Francisco, ob.gyn. professor who directs the university’s Advancing New Standards in Reproductive Health program.

“Since the fall of Roe v. Wade, patients are being forced to travel long distances – often over 500 miles – to access abortion care in a clinic. People should be able to access this essential care closer to home, including by telemedicine, which has been shown to be safe and effective. I am hopeful that SB 345 will provide additional legal protections that would allow California clinicians to help patients in other states,” he stated.

Other states, including New York, Vermont, New Jersey, Massachusetts, and Connecticut, have passed or are considering similar legislation to protect doctors using telemedicine to prescribe abortion medication to out-of-state patients. These laws come amid a growing push by some states and anti-abortion groups to severely restrict access to abortion pills.

Wyoming is the first state to explicitly ban the pills, although a judge on March 22 blocked that ban. And, in a closely watched case, a conservative federal judge could soon rule to ban sales of mifepristone, one of the medications in a two-pill regimen approved for abortions early in pregnancy.

California’s legislation protects clinicians from losing their California professional licenses if an out-of-state medical board takes action against them. It also allows clinicians to sue anyone who tries to legally interfere with the care they are providing.

It also covers California physicians prescribing contraceptives or gender-affirming care to out-of-state patients. At least 21 states are considering restrictions on gender-affirming care for minors and another 9 states have passed them, according to the advocacy group Human Rights Campaign. Courts have blocked the restrictions in some states.

“It’s understandable that states like California want to reassure their doctors ... that, if one of their patients is caught in one of those states and can’t get help locally, they can step up to help and feel safe in doing so,” said Matthew Wynia, MD, MPH, FACP, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora.

“This is also a crazy development in terms of the law. It’s just one part of the legal mayhem that was predicted when the Supreme Court overturned Roe,” Dr. Wynia said of the growing number of bills protecting in-state doctors. These bills “will almost certainly end up being litigated over issues of interstate commerce, cross-state licensure and practice compacts, FDA regulations and authorities, and maybe more. It’s a huge mess, in which both doctors and patients are being hurt.”

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

California lawmakers are considering legislation to protect California physicians and pharmacists who prescribe abortion pills to out-of-state patients. The proposed law would shield health care providers who are legally performing their jobs in California from facing prosecution in another state or being extradited.

State Sen. Nancy Skinner, who introduced the bill, said the legislation is necessary in a fractured, post-Roe legal landscape where doctors in some states can face felony charges or civil penalties for providing reproductive health care. It’s part of a package of 17 new bills aiming to “strengthen California’s standing as a safe haven for abortion, contraception, and pregnancy care,” according to a press release.

“I’m trying to protect our healthcare practitioners so they can do their jobs, without fear,” Ms. Skinner said in a statement on March 24.

Most abortions are banned in 14 states after the Supreme Court overturned Roe v. Wade. Lawmakers in those states have established a variety of penalties for doctors, pharmacists, and other clinicians to provide abortion care or assist patients in obtaining abortions, including jail time, fines, and loss of professional licenses.

As a result, doctors in restrictive states have anguished over having to delay treatment for patients experiencing miscarriages, ectopic pregnancies, and other conditions until their lives are enough at risk to satisfy exceptions to state abortion laws.

“As a physician, I believe everyone deserves the care they need, regardless of where they live,” said Daniel Grossman, MD, a University of California, San Francisco, ob.gyn. professor who directs the university’s Advancing New Standards in Reproductive Health program.

“Since the fall of Roe v. Wade, patients are being forced to travel long distances – often over 500 miles – to access abortion care in a clinic. People should be able to access this essential care closer to home, including by telemedicine, which has been shown to be safe and effective. I am hopeful that SB 345 will provide additional legal protections that would allow California clinicians to help patients in other states,” he stated.

Other states, including New York, Vermont, New Jersey, Massachusetts, and Connecticut, have passed or are considering similar legislation to protect doctors using telemedicine to prescribe abortion medication to out-of-state patients. These laws come amid a growing push by some states and anti-abortion groups to severely restrict access to abortion pills.

Wyoming is the first state to explicitly ban the pills, although a judge on March 22 blocked that ban. And, in a closely watched case, a conservative federal judge could soon rule to ban sales of mifepristone, one of the medications in a two-pill regimen approved for abortions early in pregnancy.

California’s legislation protects clinicians from losing their California professional licenses if an out-of-state medical board takes action against them. It also allows clinicians to sue anyone who tries to legally interfere with the care they are providing.

It also covers California physicians prescribing contraceptives or gender-affirming care to out-of-state patients. At least 21 states are considering restrictions on gender-affirming care for minors and another 9 states have passed them, according to the advocacy group Human Rights Campaign. Courts have blocked the restrictions in some states.

“It’s understandable that states like California want to reassure their doctors ... that, if one of their patients is caught in one of those states and can’t get help locally, they can step up to help and feel safe in doing so,” said Matthew Wynia, MD, MPH, FACP, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora.

“This is also a crazy development in terms of the law. It’s just one part of the legal mayhem that was predicted when the Supreme Court overturned Roe,” Dr. Wynia said of the growing number of bills protecting in-state doctors. These bills “will almost certainly end up being litigated over issues of interstate commerce, cross-state licensure and practice compacts, FDA regulations and authorities, and maybe more. It’s a huge mess, in which both doctors and patients are being hurt.”

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

As a member of CHEST leadership for years, Bob De Marco, MD, FCCP, ruminated over new, exciting ways to increase support of the philanthropic efforts of the American College of Chest Physicians.

Dr. De Marco knows all too well that the percentage of CHEST members who donate to support CHEST’s philanthropic initiatives is – in a word - underwhelming. For those who are involved, they do so greatly and with their whole selves, but Dr. De Marco believed more could be done.

In the months leading up to the CHEST Annual Meeting 2022 in Nashville, Dr. De Marco discussed fundraising with CHEST staff and was already thinking ahead to CHEST 2023 in Hawai’i.

“That’s when it hit me – we could leverage Hawai’i to get donations and to expose people to CHEST philanthropy,” said Dr. De Marco. “Hawai’i is a dream destination, and that might be the exact motivation it would take to get that first donation from someone.”

Having a good idea is one thing, but making sure it happens requires individual commitment. Dr. DeMarco personally pledged to cover the cost of first-class airfare for two to Hawai’i, hotel accommodations, and registration to CHEST 2023 in Honolulu. For a minimum donation of $250 to CHEST between September and the end of 2022, each donor would be entered into a drawing for a chance to win this dream trip.

“I thought to myself, who wouldn’t want this prize?” said Dr. De Marco.

“You get to go to paradise for free – with a guest – and attend a top tier educational conference. Knowing your entry supported an organization as deserving as CHEST is the cherry on top,” he added.

In launching the Hawai’i trip fundraiser before and during CHEST 2022, attendees from around the world were introduced to CHEST’s philanthropic efforts and its mission to champion lung health. Over $180,000 was donated during this time period, in no small part because of the Hawai’i travel reward.

“I’m happy to say that the fundraiser did a lot better than I expected, and I was elated to see all of the new donors,” said Dr. De Marco.

“It’s my hope that those first-time donors continue their support for all that we do to provide grants – community, research, and diversity – and support CHEST initiatives that impact patient care and change lives.”

During CHEST 2022, Dr. De Marco and other donors reflected on the organization’s philanthropic accomplishments and impact over the past decades.

Former grant recipients were invited to celebrate with donors and speak to what they were able to accomplish because of the support they received.

The celebration also introduced new CHEST initiatives, the First 5 Minutes® program and Bridging Specialties™: Timely Diagnosis for ILD. The former improves patient care through strengthened patient/clinician relationships, and the latter aims to eliminate gaps in diagnosing complex lung diseases like pulmonary fibrosis.

To all who donated to CHEST in 2022, Dr. De Marco said, “A sincere thank you to each and every one of you for helping us fulfill our mission. To the first-time donors, hopefully this will inspire you and your friends to be an active part of the CHEST family.”

And, to the winner of the trip, Dr. De Marco said, “A sincere congratulations and I hope you enjoy beautiful Hawai’i and your time at the meeting.”

Those who are interested in getting involved and supporting the philanthropic work of CHEST can contact [email protected].

Out of the 150+ donors who gave $250 or more to CHEST between September 2022 and the end of 2022, longtime friend of CHEST, Noah Dorsky, was the recipient of two first-class tickets to Hawai’i, hotel accommodations, and registration to CHEST 2023 in Honolulu.

Noah donated specifically to the Mark J. Rosen, MD, Master FCCP Endowment in honor of his late friend, Dr. Mark J. Rosen, who served as CHEST President from 2006 to 2007 and died in 2019.

"Mark was a remarkable doctor and valued life-long friend,” Noah said. “My continued support for CHEST is my way of honoring his memory and how much he meant to me and others."

Dr. Rosen’s distinguished career in pulmonary and critical care medicine spanned more than 4 decades, marked by his deep commitments to medical education and patient care. Before serving as President, Dr. Rosen served on the CHEST Board of Regents for many years. He held positions as Chair or member on numerous CHEST committees, including Education, Nominations, Membership, Marketing, and Finance.

Following his passing, Dr. Rosen’s wife, Ilene, stayed engaged with CHEST by creating the endowment in his name and attending the CHEST Annual Meeting every year to award the Rosen Cup to the winners of the annual CHEST Challenge.

Congratulations, Noah, and thank you for your faithful giving to support the work of CHEST.

As a member of CHEST leadership for years, Bob De Marco, MD, FCCP, ruminated over new, exciting ways to increase support of the philanthropic efforts of the American College of Chest Physicians.

Dr. De Marco knows all too well that the percentage of CHEST members who donate to support CHEST’s philanthropic initiatives is – in a word - underwhelming. For those who are involved, they do so greatly and with their whole selves, but Dr. De Marco believed more could be done.

In the months leading up to the CHEST Annual Meeting 2022 in Nashville, Dr. De Marco discussed fundraising with CHEST staff and was already thinking ahead to CHEST 2023 in Hawai’i.

“That’s when it hit me – we could leverage Hawai’i to get donations and to expose people to CHEST philanthropy,” said Dr. De Marco. “Hawai’i is a dream destination, and that might be the exact motivation it would take to get that first donation from someone.”

Having a good idea is one thing, but making sure it happens requires individual commitment. Dr. DeMarco personally pledged to cover the cost of first-class airfare for two to Hawai’i, hotel accommodations, and registration to CHEST 2023 in Honolulu. For a minimum donation of $250 to CHEST between September and the end of 2022, each donor would be entered into a drawing for a chance to win this dream trip.

“I thought to myself, who wouldn’t want this prize?” said Dr. De Marco.

“You get to go to paradise for free – with a guest – and attend a top tier educational conference. Knowing your entry supported an organization as deserving as CHEST is the cherry on top,” he added.

In launching the Hawai’i trip fundraiser before and during CHEST 2022, attendees from around the world were introduced to CHEST’s philanthropic efforts and its mission to champion lung health. Over $180,000 was donated during this time period, in no small part because of the Hawai’i travel reward.

“I’m happy to say that the fundraiser did a lot better than I expected, and I was elated to see all of the new donors,” said Dr. De Marco.

“It’s my hope that those first-time donors continue their support for all that we do to provide grants – community, research, and diversity – and support CHEST initiatives that impact patient care and change lives.”

During CHEST 2022, Dr. De Marco and other donors reflected on the organization’s philanthropic accomplishments and impact over the past decades.

Former grant recipients were invited to celebrate with donors and speak to what they were able to accomplish because of the support they received.

The celebration also introduced new CHEST initiatives, the First 5 Minutes® program and Bridging Specialties™: Timely Diagnosis for ILD. The former improves patient care through strengthened patient/clinician relationships, and the latter aims to eliminate gaps in diagnosing complex lung diseases like pulmonary fibrosis.

To all who donated to CHEST in 2022, Dr. De Marco said, “A sincere thank you to each and every one of you for helping us fulfill our mission. To the first-time donors, hopefully this will inspire you and your friends to be an active part of the CHEST family.”

And, to the winner of the trip, Dr. De Marco said, “A sincere congratulations and I hope you enjoy beautiful Hawai’i and your time at the meeting.”

Those who are interested in getting involved and supporting the philanthropic work of CHEST can contact [email protected].

Out of the 150+ donors who gave $250 or more to CHEST between September 2022 and the end of 2022, longtime friend of CHEST, Noah Dorsky, was the recipient of two first-class tickets to Hawai’i, hotel accommodations, and registration to CHEST 2023 in Honolulu.

Noah donated specifically to the Mark J. Rosen, MD, Master FCCP Endowment in honor of his late friend, Dr. Mark J. Rosen, who served as CHEST President from 2006 to 2007 and died in 2019.

"Mark was a remarkable doctor and valued life-long friend,” Noah said. “My continued support for CHEST is my way of honoring his memory and how much he meant to me and others."

Dr. Rosen’s distinguished career in pulmonary and critical care medicine spanned more than 4 decades, marked by his deep commitments to medical education and patient care. Before serving as President, Dr. Rosen served on the CHEST Board of Regents for many years. He held positions as Chair or member on numerous CHEST committees, including Education, Nominations, Membership, Marketing, and Finance.

Following his passing, Dr. Rosen’s wife, Ilene, stayed engaged with CHEST by creating the endowment in his name and attending the CHEST Annual Meeting every year to award the Rosen Cup to the winners of the annual CHEST Challenge.

Congratulations, Noah, and thank you for your faithful giving to support the work of CHEST.

As a member of CHEST leadership for years, Bob De Marco, MD, FCCP, ruminated over new, exciting ways to increase support of the philanthropic efforts of the American College of Chest Physicians.

Dr. De Marco knows all too well that the percentage of CHEST members who donate to support CHEST’s philanthropic initiatives is – in a word - underwhelming. For those who are involved, they do so greatly and with their whole selves, but Dr. De Marco believed more could be done.

In the months leading up to the CHEST Annual Meeting 2022 in Nashville, Dr. De Marco discussed fundraising with CHEST staff and was already thinking ahead to CHEST 2023 in Hawai’i.

“That’s when it hit me – we could leverage Hawai’i to get donations and to expose people to CHEST philanthropy,” said Dr. De Marco. “Hawai’i is a dream destination, and that might be the exact motivation it would take to get that first donation from someone.”

Having a good idea is one thing, but making sure it happens requires individual commitment. Dr. DeMarco personally pledged to cover the cost of first-class airfare for two to Hawai’i, hotel accommodations, and registration to CHEST 2023 in Honolulu. For a minimum donation of $250 to CHEST between September and the end of 2022, each donor would be entered into a drawing for a chance to win this dream trip.

“I thought to myself, who wouldn’t want this prize?” said Dr. De Marco.

“You get to go to paradise for free – with a guest – and attend a top tier educational conference. Knowing your entry supported an organization as deserving as CHEST is the cherry on top,” he added.

In launching the Hawai’i trip fundraiser before and during CHEST 2022, attendees from around the world were introduced to CHEST’s philanthropic efforts and its mission to champion lung health. Over $180,000 was donated during this time period, in no small part because of the Hawai’i travel reward.

“I’m happy to say that the fundraiser did a lot better than I expected, and I was elated to see all of the new donors,” said Dr. De Marco.

“It’s my hope that those first-time donors continue their support for all that we do to provide grants – community, research, and diversity – and support CHEST initiatives that impact patient care and change lives.”

During CHEST 2022, Dr. De Marco and other donors reflected on the organization’s philanthropic accomplishments and impact over the past decades.

Former grant recipients were invited to celebrate with donors and speak to what they were able to accomplish because of the support they received.

The celebration also introduced new CHEST initiatives, the First 5 Minutes® program and Bridging Specialties™: Timely Diagnosis for ILD. The former improves patient care through strengthened patient/clinician relationships, and the latter aims to eliminate gaps in diagnosing complex lung diseases like pulmonary fibrosis.

To all who donated to CHEST in 2022, Dr. De Marco said, “A sincere thank you to each and every one of you for helping us fulfill our mission. To the first-time donors, hopefully this will inspire you and your friends to be an active part of the CHEST family.”

And, to the winner of the trip, Dr. De Marco said, “A sincere congratulations and I hope you enjoy beautiful Hawai’i and your time at the meeting.”

Those who are interested in getting involved and supporting the philanthropic work of CHEST can contact [email protected].

Out of the 150+ donors who gave $250 or more to CHEST between September 2022 and the end of 2022, longtime friend of CHEST, Noah Dorsky, was the recipient of two first-class tickets to Hawai’i, hotel accommodations, and registration to CHEST 2023 in Honolulu.

Noah donated specifically to the Mark J. Rosen, MD, Master FCCP Endowment in honor of his late friend, Dr. Mark J. Rosen, who served as CHEST President from 2006 to 2007 and died in 2019.

"Mark was a remarkable doctor and valued life-long friend,” Noah said. “My continued support for CHEST is my way of honoring his memory and how much he meant to me and others."

Dr. Rosen’s distinguished career in pulmonary and critical care medicine spanned more than 4 decades, marked by his deep commitments to medical education and patient care. Before serving as President, Dr. Rosen served on the CHEST Board of Regents for many years. He held positions as Chair or member on numerous CHEST committees, including Education, Nominations, Membership, Marketing, and Finance.

Following his passing, Dr. Rosen’s wife, Ilene, stayed engaged with CHEST by creating the endowment in his name and attending the CHEST Annual Meeting every year to award the Rosen Cup to the winners of the annual CHEST Challenge.

Congratulations, Noah, and thank you for your faithful giving to support the work of CHEST.

Renal impairment in severe falciparum malaria independently predicts a poor outcome in both adults and children.¹ Prompt recognition of malaria-associated renal failure and immediate management with renal replacement therapy reduces mortality and can support the recovery of renal function.^2-4 In addition, adjunctive treatment with acetaminophen has demonstrated improvement in the level of creatinine and reduced progression of kidney injury in a randomized, controlled trial of patients with severe falciparum malaria, particularly in patients with notable intravascular hemolysis.⁵ In this open-label, randomized controlled trial, 62 patients were randomly assigned to receive acetaminophen (n = 31) or no acetaminophen (n = 31).⁵ Antimalarial treatment was with IV artesunate, followed by artemether/lumefantrine. Median (IQR) reduction in creatinine after 72 hours was 23% (37, 18) in patients assigned to acetaminophen vs 14% (29, 0) in patients assigned to no acetaminophen (P = .04).⁵ Acetaminophen showed renoprotection without evidence of safety concerns in patients with severe falciparum malaria, especially those with prominent intravascular hemolysis.

Another study showed consistent findings in other malarial infections with prominent hemolysis, namely, Plasmodium knowlesi malaria. In the PACKNOW open-label, randomized controlled trial, 396 patients aged 12 to 96 years with knowlesi malaria of any severity were randomized to acetaminophen (500 mg or 1000 mg every 6 hours for 72 hours) vs no acetaminophen.⁶ All patients received artesunate and/or oral artemether-lumefantrine for malaria.⁶ No difference was seen overall in patients with acute kidney injury (AKI); however, in those with AKI and hemolysis, creatinine fell by a mean (SD) 34.5% (20.7) in the acetaminophen arm vs 25.9% (15.8) in the control arm (P = .04).⁶ Mixed-effects modeling demonstrated a benefit of acetaminophen at 72 hours (P = .04) and 1 week (P = .002) in patients with severe malaria and with AKI and hemolysis (P = .03 and P = .002, respectively).⁶

Earlier models suggest that the redox cycling of hemoproteins between ferric and ferryl states generates the radical species responsible for severe oxidative damage to the kidneys and subsequent renal impairment.⁷ Reduction of heme-ferryl radicals with therapeutic plasma concentrations of acetaminophen can inhibit this oxidative process.⁷ Rhabdomyolysis models treated with acetaminophen have shown reduced oxidative damage to the kidneys and improved renal functioning, supporting acetaminophen as a potential therapeutic option for disease processes involving hemoprotein-mediated oxidative injury.⁷ In this case report, we discuss the use of acetaminophen as a renoprotective treatment in a patient with renal impairment associated with severe falciparum malaria.

Case Presentation

A 50-year-old man with comorbidities, including hypertension, hyperlipidemia, and chronic kidney disease stage 2, with a baseline creatinine level of 1.4 mg/dL presented with severe falciparum malaria with renal impairment. About 7 months prior, the patient received treatment for his first known case of Plasmodium falciparum (P falciparum) infection. He again contracted P falciparum for a second time after traveling to a malaria-endemic country without taking prophylactic medication before travel.

The patient reported fevers, chills, night sweats, and progressive fatigue. His vital signs recorded a fever of 38.9 ºC with tachycardia and relative hypotension. A thin blood smear revealed P falciparum with approximately 8.5% parasitemia. Laboratory tests confirmed hemolytic anemia and thrombocytopenia reflected by consistently decreased hemoglobin, hematocrit, haptoglobin, and platelets with elevated lactate dehydrogenase and hyperbilirubinemia. Initial renal function testing included an elevated creatinine level of 3.4 mg/dL and an elevated blood urea nitrogen (BUN) level of 45 mg/dL.

The patient received multiple boluses of IV isotonic fluids and a single maximum dose of atovaquone and proguanil before procurement of IV artesunate to manage the malaria. Good response with IV artesunate lowered parasitemia from a high at admission of 10.5% to 0.1% before transitioning to oral artemether and lumefantrine. Concomitantly, the patient’s oliguric renal failure continued to progress early during the hospital stay, and he consented to anticipated dialysis.

To halt progression of his renal injury, salvage renal function, and avoid dialysis, the nephrology team considered acetaminophen 975 mg tablets every 6 hours for 72 hours per the Plewes and colleagues randomized trial.⁵ The patient met the criteria for severe falciparum malaria per the inclusion criteria in the Plewes and colleagues study and was deemed eligible for acetaminophen-based adjunctive treatment. The patient discussed and considered both dialysis and a trial of acetaminophen with the nephrology team, and he understood all the associated risks and benefits, including liver failure. The patient agreed to a trial of acetaminophen with close monitoring of his liver function.

Before starting acetaminophen, the patient’s aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels both measured 53 IU/L or 1.3 times the upper limit of normal (Figure 2).

Discussion

AKI in malaria predominantly occurs with P falciparum infection and represents a significant independent factor in determining morbidity and mortality in adults with severe malaria.⁸ In severe malaria, any hemodynamic compromise likely contributes to the development of acute tubular necrosis (ATN) with insensible losses and poor intake decreasing renal perfusion.⁸ Direct tubular injury from hemoglobinuria or less commonly myoglobinuria from concomitant rhabdomyolysis may also drive malarial AKI.⁸ In addition, proposed mechanisms explaining the pathogenesis of malarial AKI include ATN secondary to disruptions in renal microvasculature, immune dysregulation with proinflammatory reactions within the kidneys, and metabolic disturbances.⁸ Oxidate tubular damage caused by the release of cell-free hemoglobin during red blood cell hemolysis represents 1 form of metabolic derangement possibly responsible for renal impairment.⁸ Acetaminophen administration may help mitigate this oxidative stress, especially in cases of significant hemolysis.⁵

In this case of severe falciparum malaria, the patient demonstrated renal impairment with measured falciparum parasitemia. His creatinine level and BUN appeared to stabilize and improve after 72 hours of acetaminophen administration. A recovery of urine output and improvement in cystatin C occurred during the 72 hours of acetaminophen usage. Despite the patient’s underlying chronic kidney disease, measured proteinuria, and significant changes in renal architecture revealed by ultrasound, he never showed signs of uremia, fluid overload, electrolyte derangements, or acidosis requiring urgent renal replacement therapy.

The patient’s treatment for severe falciparum malaria, including a combination of supportive management, acetaminophen, and IV antimalarials, resulted in the resolution of parasitemia and symptoms with some recovery of renal function without necessitating renal replacement therapy. Maximum daily doses of acetaminophen compared with the control in the Plewes and colleagues acetaminophen trial resulted in moderate increases in aminotransferases not rising to the criteria of hepatotoxicity described in Hy’s law.⁵ Following acetaminophen administration, in this case, AST and ALT levels peaked at 130 and 168 IU/L, 2.8 and 3.8 times the upper limits of normal, respectively. These mild, asymptomatic elevations in aminotransferases recovered to within normal limits, measuring 24 and 13 IU/L at the follow-up.

Conclusions

The demonstrated recovery in renal function, with only a transient, moderate increase in aminotransferases, supports the value of adjunctive acetaminophen as a renoprotective treatment in severe malaria. This simple, readily available treatment may significantly alter the morbidity and mortality associated with severe malaria.

Renal impairment in severe falciparum malaria independently predicts a poor outcome in both adults and children.¹ Prompt recognition of malaria-associated renal failure and immediate management with renal replacement therapy reduces mortality and can support the recovery of renal function.^2-4 In addition, adjunctive treatment with acetaminophen has demonstrated improvement in the level of creatinine and reduced progression of kidney injury in a randomized, controlled trial of patients with severe falciparum malaria, particularly in patients with notable intravascular hemolysis.⁵ In this open-label, randomized controlled trial, 62 patients were randomly assigned to receive acetaminophen (n = 31) or no acetaminophen (n = 31).⁵ Antimalarial treatment was with IV artesunate, followed by artemether/lumefantrine. Median (IQR) reduction in creatinine after 72 hours was 23% (37, 18) in patients assigned to acetaminophen vs 14% (29, 0) in patients assigned to no acetaminophen (P = .04).⁵ Acetaminophen showed renoprotection without evidence of safety concerns in patients with severe falciparum malaria, especially those with prominent intravascular hemolysis.

Another study showed consistent findings in other malarial infections with prominent hemolysis, namely, Plasmodium knowlesi malaria. In the PACKNOW open-label, randomized controlled trial, 396 patients aged 12 to 96 years with knowlesi malaria of any severity were randomized to acetaminophen (500 mg or 1000 mg every 6 hours for 72 hours) vs no acetaminophen.⁶ All patients received artesunate and/or oral artemether-lumefantrine for malaria.⁶ No difference was seen overall in patients with acute kidney injury (AKI); however, in those with AKI and hemolysis, creatinine fell by a mean (SD) 34.5% (20.7) in the acetaminophen arm vs 25.9% (15.8) in the control arm (P = .04).⁶ Mixed-effects modeling demonstrated a benefit of acetaminophen at 72 hours (P = .04) and 1 week (P = .002) in patients with severe malaria and with AKI and hemolysis (P = .03 and P = .002, respectively).⁶

Earlier models suggest that the redox cycling of hemoproteins between ferric and ferryl states generates the radical species responsible for severe oxidative damage to the kidneys and subsequent renal impairment.⁷ Reduction of heme-ferryl radicals with therapeutic plasma concentrations of acetaminophen can inhibit this oxidative process.⁷ Rhabdomyolysis models treated with acetaminophen have shown reduced oxidative damage to the kidneys and improved renal functioning, supporting acetaminophen as a potential therapeutic option for disease processes involving hemoprotein-mediated oxidative injury.⁷ In this case report, we discuss the use of acetaminophen as a renoprotective treatment in a patient with renal impairment associated with severe falciparum malaria.

Case Presentation

A 50-year-old man with comorbidities, including hypertension, hyperlipidemia, and chronic kidney disease stage 2, with a baseline creatinine level of 1.4 mg/dL presented with severe falciparum malaria with renal impairment. About 7 months prior, the patient received treatment for his first known case of Plasmodium falciparum (P falciparum) infection. He again contracted P falciparum for a second time after traveling to a malaria-endemic country without taking prophylactic medication before travel.

The patient reported fevers, chills, night sweats, and progressive fatigue. His vital signs recorded a fever of 38.9 ºC with tachycardia and relative hypotension. A thin blood smear revealed P falciparum with approximately 8.5% parasitemia. Laboratory tests confirmed hemolytic anemia and thrombocytopenia reflected by consistently decreased hemoglobin, hematocrit, haptoglobin, and platelets with elevated lactate dehydrogenase and hyperbilirubinemia. Initial renal function testing included an elevated creatinine level of 3.4 mg/dL and an elevated blood urea nitrogen (BUN) level of 45 mg/dL.

The patient received multiple boluses of IV isotonic fluids and a single maximum dose of atovaquone and proguanil before procurement of IV artesunate to manage the malaria. Good response with IV artesunate lowered parasitemia from a high at admission of 10.5% to 0.1% before transitioning to oral artemether and lumefantrine. Concomitantly, the patient’s oliguric renal failure continued to progress early during the hospital stay, and he consented to anticipated dialysis.

To halt progression of his renal injury, salvage renal function, and avoid dialysis, the nephrology team considered acetaminophen 975 mg tablets every 6 hours for 72 hours per the Plewes and colleagues randomized trial.⁵ The patient met the criteria for severe falciparum malaria per the inclusion criteria in the Plewes and colleagues study and was deemed eligible for acetaminophen-based adjunctive treatment. The patient discussed and considered both dialysis and a trial of acetaminophen with the nephrology team, and he understood all the associated risks and benefits, including liver failure. The patient agreed to a trial of acetaminophen with close monitoring of his liver function.

Before starting acetaminophen, the patient’s aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels both measured 53 IU/L or 1.3 times the upper limit of normal (Figure 2).

Discussion

AKI in malaria predominantly occurs with P falciparum infection and represents a significant independent factor in determining morbidity and mortality in adults with severe malaria.⁸ In severe malaria, any hemodynamic compromise likely contributes to the development of acute tubular necrosis (ATN) with insensible losses and poor intake decreasing renal perfusion.⁸ Direct tubular injury from hemoglobinuria or less commonly myoglobinuria from concomitant rhabdomyolysis may also drive malarial AKI.⁸ In addition, proposed mechanisms explaining the pathogenesis of malarial AKI include ATN secondary to disruptions in renal microvasculature, immune dysregulation with proinflammatory reactions within the kidneys, and metabolic disturbances.⁸ Oxidate tubular damage caused by the release of cell-free hemoglobin during red blood cell hemolysis represents 1 form of metabolic derangement possibly responsible for renal impairment.⁸ Acetaminophen administration may help mitigate this oxidative stress, especially in cases of significant hemolysis.⁵

In this case of severe falciparum malaria, the patient demonstrated renal impairment with measured falciparum parasitemia. His creatinine level and BUN appeared to stabilize and improve after 72 hours of acetaminophen administration. A recovery of urine output and improvement in cystatin C occurred during the 72 hours of acetaminophen usage. Despite the patient’s underlying chronic kidney disease, measured proteinuria, and significant changes in renal architecture revealed by ultrasound, he never showed signs of uremia, fluid overload, electrolyte derangements, or acidosis requiring urgent renal replacement therapy.

The patient’s treatment for severe falciparum malaria, including a combination of supportive management, acetaminophen, and IV antimalarials, resulted in the resolution of parasitemia and symptoms with some recovery of renal function without necessitating renal replacement therapy. Maximum daily doses of acetaminophen compared with the control in the Plewes and colleagues acetaminophen trial resulted in moderate increases in aminotransferases not rising to the criteria of hepatotoxicity described in Hy’s law.⁵ Following acetaminophen administration, in this case, AST and ALT levels peaked at 130 and 168 IU/L, 2.8 and 3.8 times the upper limits of normal, respectively. These mild, asymptomatic elevations in aminotransferases recovered to within normal limits, measuring 24 and 13 IU/L at the follow-up.

Conclusions

The demonstrated recovery in renal function, with only a transient, moderate increase in aminotransferases, supports the value of adjunctive acetaminophen as a renoprotective treatment in severe malaria. This simple, readily available treatment may significantly alter the morbidity and mortality associated with severe malaria.

Renal impairment in severe falciparum malaria independently predicts a poor outcome in both adults and children.¹ Prompt recognition of malaria-associated renal failure and immediate management with renal replacement therapy reduces mortality and can support the recovery of renal function.^2-4 In addition, adjunctive treatment with acetaminophen has demonstrated improvement in the level of creatinine and reduced progression of kidney injury in a randomized, controlled trial of patients with severe falciparum malaria, particularly in patients with notable intravascular hemolysis.⁵ In this open-label, randomized controlled trial, 62 patients were randomly assigned to receive acetaminophen (n = 31) or no acetaminophen (n = 31).⁵ Antimalarial treatment was with IV artesunate, followed by artemether/lumefantrine. Median (IQR) reduction in creatinine after 72 hours was 23% (37, 18) in patients assigned to acetaminophen vs 14% (29, 0) in patients assigned to no acetaminophen (P = .04).⁵ Acetaminophen showed renoprotection without evidence of safety concerns in patients with severe falciparum malaria, especially those with prominent intravascular hemolysis.

Another study showed consistent findings in other malarial infections with prominent hemolysis, namely, Plasmodium knowlesi malaria. In the PACKNOW open-label, randomized controlled trial, 396 patients aged 12 to 96 years with knowlesi malaria of any severity were randomized to acetaminophen (500 mg or 1000 mg every 6 hours for 72 hours) vs no acetaminophen.⁶ All patients received artesunate and/or oral artemether-lumefantrine for malaria.⁶ No difference was seen overall in patients with acute kidney injury (AKI); however, in those with AKI and hemolysis, creatinine fell by a mean (SD) 34.5% (20.7) in the acetaminophen arm vs 25.9% (15.8) in the control arm (P = .04).⁶ Mixed-effects modeling demonstrated a benefit of acetaminophen at 72 hours (P = .04) and 1 week (P = .002) in patients with severe malaria and with AKI and hemolysis (P = .03 and P = .002, respectively).⁶

Earlier models suggest that the redox cycling of hemoproteins between ferric and ferryl states generates the radical species responsible for severe oxidative damage to the kidneys and subsequent renal impairment.⁷ Reduction of heme-ferryl radicals with therapeutic plasma concentrations of acetaminophen can inhibit this oxidative process.⁷ Rhabdomyolysis models treated with acetaminophen have shown reduced oxidative damage to the kidneys and improved renal functioning, supporting acetaminophen as a potential therapeutic option for disease processes involving hemoprotein-mediated oxidative injury.⁷ In this case report, we discuss the use of acetaminophen as a renoprotective treatment in a patient with renal impairment associated with severe falciparum malaria.

Case Presentation

A 50-year-old man with comorbidities, including hypertension, hyperlipidemia, and chronic kidney disease stage 2, with a baseline creatinine level of 1.4 mg/dL presented with severe falciparum malaria with renal impairment. About 7 months prior, the patient received treatment for his first known case of Plasmodium falciparum (P falciparum) infection. He again contracted P falciparum for a second time after traveling to a malaria-endemic country without taking prophylactic medication before travel.

The patient reported fevers, chills, night sweats, and progressive fatigue. His vital signs recorded a fever of 38.9 ºC with tachycardia and relative hypotension. A thin blood smear revealed P falciparum with approximately 8.5% parasitemia. Laboratory tests confirmed hemolytic anemia and thrombocytopenia reflected by consistently decreased hemoglobin, hematocrit, haptoglobin, and platelets with elevated lactate dehydrogenase and hyperbilirubinemia. Initial renal function testing included an elevated creatinine level of 3.4 mg/dL and an elevated blood urea nitrogen (BUN) level of 45 mg/dL.

The patient received multiple boluses of IV isotonic fluids and a single maximum dose of atovaquone and proguanil before procurement of IV artesunate to manage the malaria. Good response with IV artesunate lowered parasitemia from a high at admission of 10.5% to 0.1% before transitioning to oral artemether and lumefantrine. Concomitantly, the patient’s oliguric renal failure continued to progress early during the hospital stay, and he consented to anticipated dialysis.

To halt progression of his renal injury, salvage renal function, and avoid dialysis, the nephrology team considered acetaminophen 975 mg tablets every 6 hours for 72 hours per the Plewes and colleagues randomized trial.⁵ The patient met the criteria for severe falciparum malaria per the inclusion criteria in the Plewes and colleagues study and was deemed eligible for acetaminophen-based adjunctive treatment. The patient discussed and considered both dialysis and a trial of acetaminophen with the nephrology team, and he understood all the associated risks and benefits, including liver failure. The patient agreed to a trial of acetaminophen with close monitoring of his liver function.

Before starting acetaminophen, the patient’s aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels both measured 53 IU/L or 1.3 times the upper limit of normal (Figure 2).

Discussion

AKI in malaria predominantly occurs with P falciparum infection and represents a significant independent factor in determining morbidity and mortality in adults with severe malaria.⁸ In severe malaria, any hemodynamic compromise likely contributes to the development of acute tubular necrosis (ATN) with insensible losses and poor intake decreasing renal perfusion.⁸ Direct tubular injury from hemoglobinuria or less commonly myoglobinuria from concomitant rhabdomyolysis may also drive malarial AKI.⁸ In addition, proposed mechanisms explaining the pathogenesis of malarial AKI include ATN secondary to disruptions in renal microvasculature, immune dysregulation with proinflammatory reactions within the kidneys, and metabolic disturbances.⁸ Oxidate tubular damage caused by the release of cell-free hemoglobin during red blood cell hemolysis represents 1 form of metabolic derangement possibly responsible for renal impairment.⁸ Acetaminophen administration may help mitigate this oxidative stress, especially in cases of significant hemolysis.⁵

In this case of severe falciparum malaria, the patient demonstrated renal impairment with measured falciparum parasitemia. His creatinine level and BUN appeared to stabilize and improve after 72 hours of acetaminophen administration. A recovery of urine output and improvement in cystatin C occurred during the 72 hours of acetaminophen usage. Despite the patient’s underlying chronic kidney disease, measured proteinuria, and significant changes in renal architecture revealed by ultrasound, he never showed signs of uremia, fluid overload, electrolyte derangements, or acidosis requiring urgent renal replacement therapy.

The patient’s treatment for severe falciparum malaria, including a combination of supportive management, acetaminophen, and IV antimalarials, resulted in the resolution of parasitemia and symptoms with some recovery of renal function without necessitating renal replacement therapy. Maximum daily doses of acetaminophen compared with the control in the Plewes and colleagues acetaminophen trial resulted in moderate increases in aminotransferases not rising to the criteria of hepatotoxicity described in Hy’s law.⁵ Following acetaminophen administration, in this case, AST and ALT levels peaked at 130 and 168 IU/L, 2.8 and 3.8 times the upper limits of normal, respectively. These mild, asymptomatic elevations in aminotransferases recovered to within normal limits, measuring 24 and 13 IU/L at the follow-up.

Conclusions

The demonstrated recovery in renal function, with only a transient, moderate increase in aminotransferases, supports the value of adjunctive acetaminophen as a renoprotective treatment in severe malaria. This simple, readily available treatment may significantly alter the morbidity and mortality associated with severe malaria.