Delirious mania is a diagnostic term used in variety of settings, including the emergency department and inpatient psychiatry, but it does not have formal criteria established in the DSM-5. Delirious mania was first described in the 1800s and was referred to as “Bell’s Mania.”

As the late Max Fink, MD, wrote in the journal Bipolar Disorders (2002 Feb 23. doi: 10.1034/j.1399-561.1999.10112.x), delirious mania is considered to be a syndrome of the acute onset of the excitement, grandiosity, emotional lability, delusions, and insomnia characteristic of mania, and the disorientation and altered consciousness characteristic of delirium.

Such patients can be considered as having a component of bipolar I disorder, comprising mania with psychotic features. Delirious mania is associated with higher rates of morbidity and mortality, and demonstrates limited response to conventional treatment guidelines. Therefore, early detection and decisive treatment are imperative. The concurrence of delirium and mania is not unusual, yet currently there are no universal accepted treatment guidelines for delirious mania (BMC Psychiatry. 2012 Jun 21. doi: 10.1186/1471-244X-12-65). The purpose of this case report is to inspire and support community psychiatric clinicians in managing such complex cases and to improve behavioral health care outcomes. To protect our patient’s identity, we changed several key identifiers.

The treatment plan emerges

This case is of a middle-aged man with an established diagnosis of bipolar disorder. He was referred to the ED because of worsening manic symptoms marked by mood lability, pressured speech, grandiose delusions, tangential thought processes, poor insight, and impaired sleep.

Laboratory studies in the ED revealed hyponatremia and serum sodium of 126meq/l (ref. range: 135-146). The patient’s toxicology screen was positive for benzodiazepines. He was stabilized on the medical floor and then transitioned to inpatient psychiatry.

Before his admission to psychiatry, the patient’s medications were alprazolam 1 mg at bed time, bupropion 100 mg twice daily, loxapine 25 mg morning and 50 mg at bed time, olanzapine 20 mg at bedtime and 5 mg twice daily, risperidone 2 mg twice daily and oxcarbazepine 900 mg twice daily.

The bupropion was discontinued because of manic behavior, and the patient’s dose of oxcarbazepine was lowered from 900 mg twice daily to 450 mg twice daily because of hyponatremia. Our team continued to administer risperidone, olanzapine, loxapine, and alprazolam to the patient. However, he was agitated and disorganized on the psychiatry floor. In addition, we noticed that the patient exhibited confusion, disorientation, an inability to connect with reality, and periods of profound agitation.

The patient was frequently restrained physically, and medications were administered to him for safety and containment. The use of benzodiazepines and anticholinergics was minimized. However, we noticed that the patient acted paranoid, disinhibited, and combative, and he became difficult to restrain. He seemed to have a high pain tolerance, responded to internal stimuli, and began hallucinating and displaying aggressive behavior toward staff persons.

It became apparent that the patient’s circadian rhythm had been altered. He slept for only a couple of hours during the day. During the course of treatment, in one incidence, the patient became agitated and charged at a nurse. Subsequently, the patient hit his head on a wall and fell – suffering a head strike and lacerations.

The team conducted investigations, including labs and neuroimaging, to make sure that the patient was OK. His CT head scan proved unremarkable. Liver function tests revealed mild transaminitis. His TSH, folate, B₁₂, and B₁ levels were normal.

We then placed the patient in a single room with continuous behavior monitoring. His recovery seemed to take a long time with trials of different antipsychotic medications, including olanzapine, loxapine, risperidone, and paliperidone. Because of his poor response to medications, the team considered using electroconvulsive therapy (ECT).

However, the patient was unable to give informed consent for ECT because of his impaired mental status. At this point, our team submitted a substitute treatment plan that included ECT to the court for approval, and the court approved our plan.

After receiving approximately four bilateral ECT procedures three times a week, the patient’s condition started to improve gradually. He received total of 11 procedures.

Our patient became alert to time, place, and person, and his circadian rhythm normalized. Soon, his delirium cleared, and he demonstrated marked improvement in both insight into his illness and behavioral control. His grandiose delusions were still present, but he was easily redirectable. In addition, our patient demonstrated improved reality testing. He was able to be discharged home following medication adjustments and with community supports within a few short weeks of receiving ECT.

As Bo-Shyan Lee, MD, and associates reported (BMC Psychiatry. 2012 Jun 21;12:65. doi: 10.1186/1471-244X-12-65), delirious mania is closely related to catatonia. Although there are different definitions for delirium and catatonia, even the most lethal form of catatonia meets the criteria for delirium. ECT is a well established first-line treatment for catatonia. This tool has been shown to be highly effective in the treatment of delirious mania. Delirious mania can be life-threatening and should be managed aggressively. The most common causes of death are heart failure from arrhythmias, cardiac arrest, and respiratory failure. ECT is a safe treatment, and, as Dr. Fink argued, the mortality rate is even less than that associated with normal pregnancies (World J Biol Psychiatry. 2001 Jan;2[1]:1-8). In light of the safety and effectiveness of ECT, we think the tool should be considered not only in university hospital settings but as an early intervention in community settings. This case warrants further research in exploring hyperactive delirium and delirious mania.
 

Dr. Lamba is BR-2 unit medical director at BayRidge Hospital in Lynn, Mass. Ms. Kennedy is an attending clinician at BayRidge. Dr. Vu is medical director at BayRidge. He also serves as associate chief of psychiatry at Beverly (Mass.) Hospital and at Addison Gilbert Hospital in Gloucester, Mass. Dr. Lamba, Ms. Kennedy, and Dr. Vu have no disclosures.

Delirious mania is a diagnostic term used in variety of settings, including the emergency department and inpatient psychiatry, but it does not have formal criteria established in the DSM-5. Delirious mania was first described in the 1800s and was referred to as “Bell’s Mania.”

As the late Max Fink, MD, wrote in the journal Bipolar Disorders (2002 Feb 23. doi: 10.1034/j.1399-561.1999.10112.x), delirious mania is considered to be a syndrome of the acute onset of the excitement, grandiosity, emotional lability, delusions, and insomnia characteristic of mania, and the disorientation and altered consciousness characteristic of delirium.

Such patients can be considered as having a component of bipolar I disorder, comprising mania with psychotic features. Delirious mania is associated with higher rates of morbidity and mortality, and demonstrates limited response to conventional treatment guidelines. Therefore, early detection and decisive treatment are imperative. The concurrence of delirium and mania is not unusual, yet currently there are no universal accepted treatment guidelines for delirious mania (BMC Psychiatry. 2012 Jun 21. doi: 10.1186/1471-244X-12-65). The purpose of this case report is to inspire and support community psychiatric clinicians in managing such complex cases and to improve behavioral health care outcomes. To protect our patient’s identity, we changed several key identifiers.

The treatment plan emerges

This case is of a middle-aged man with an established diagnosis of bipolar disorder. He was referred to the ED because of worsening manic symptoms marked by mood lability, pressured speech, grandiose delusions, tangential thought processes, poor insight, and impaired sleep.

Laboratory studies in the ED revealed hyponatremia and serum sodium of 126meq/l (ref. range: 135-146). The patient’s toxicology screen was positive for benzodiazepines. He was stabilized on the medical floor and then transitioned to inpatient psychiatry.

Before his admission to psychiatry, the patient’s medications were alprazolam 1 mg at bed time, bupropion 100 mg twice daily, loxapine 25 mg morning and 50 mg at bed time, olanzapine 20 mg at bedtime and 5 mg twice daily, risperidone 2 mg twice daily and oxcarbazepine 900 mg twice daily.

The bupropion was discontinued because of manic behavior, and the patient’s dose of oxcarbazepine was lowered from 900 mg twice daily to 450 mg twice daily because of hyponatremia. Our team continued to administer risperidone, olanzapine, loxapine, and alprazolam to the patient. However, he was agitated and disorganized on the psychiatry floor. In addition, we noticed that the patient exhibited confusion, disorientation, an inability to connect with reality, and periods of profound agitation.

The patient was frequently restrained physically, and medications were administered to him for safety and containment. The use of benzodiazepines and anticholinergics was minimized. However, we noticed that the patient acted paranoid, disinhibited, and combative, and he became difficult to restrain. He seemed to have a high pain tolerance, responded to internal stimuli, and began hallucinating and displaying aggressive behavior toward staff persons.

It became apparent that the patient’s circadian rhythm had been altered. He slept for only a couple of hours during the day. During the course of treatment, in one incidence, the patient became agitated and charged at a nurse. Subsequently, the patient hit his head on a wall and fell – suffering a head strike and lacerations.

The team conducted investigations, including labs and neuroimaging, to make sure that the patient was OK. His CT head scan proved unremarkable. Liver function tests revealed mild transaminitis. His TSH, folate, B₁₂, and B₁ levels were normal.

We then placed the patient in a single room with continuous behavior monitoring. His recovery seemed to take a long time with trials of different antipsychotic medications, including olanzapine, loxapine, risperidone, and paliperidone. Because of his poor response to medications, the team considered using electroconvulsive therapy (ECT).

However, the patient was unable to give informed consent for ECT because of his impaired mental status. At this point, our team submitted a substitute treatment plan that included ECT to the court for approval, and the court approved our plan.

After receiving approximately four bilateral ECT procedures three times a week, the patient’s condition started to improve gradually. He received total of 11 procedures.

Our patient became alert to time, place, and person, and his circadian rhythm normalized. Soon, his delirium cleared, and he demonstrated marked improvement in both insight into his illness and behavioral control. His grandiose delusions were still present, but he was easily redirectable. In addition, our patient demonstrated improved reality testing. He was able to be discharged home following medication adjustments and with community supports within a few short weeks of receiving ECT.

As Bo-Shyan Lee, MD, and associates reported (BMC Psychiatry. 2012 Jun 21;12:65. doi: 10.1186/1471-244X-12-65), delirious mania is closely related to catatonia. Although there are different definitions for delirium and catatonia, even the most lethal form of catatonia meets the criteria for delirium. ECT is a well established first-line treatment for catatonia. This tool has been shown to be highly effective in the treatment of delirious mania. Delirious mania can be life-threatening and should be managed aggressively. The most common causes of death are heart failure from arrhythmias, cardiac arrest, and respiratory failure. ECT is a safe treatment, and, as Dr. Fink argued, the mortality rate is even less than that associated with normal pregnancies (World J Biol Psychiatry. 2001 Jan;2[1]:1-8). In light of the safety and effectiveness of ECT, we think the tool should be considered not only in university hospital settings but as an early intervention in community settings. This case warrants further research in exploring hyperactive delirium and delirious mania.
 

Dr. Lamba is BR-2 unit medical director at BayRidge Hospital in Lynn, Mass. Ms. Kennedy is an attending clinician at BayRidge. Dr. Vu is medical director at BayRidge. He also serves as associate chief of psychiatry at Beverly (Mass.) Hospital and at Addison Gilbert Hospital in Gloucester, Mass. Dr. Lamba, Ms. Kennedy, and Dr. Vu have no disclosures.

Delirious mania is a diagnostic term used in variety of settings, including the emergency department and inpatient psychiatry, but it does not have formal criteria established in the DSM-5. Delirious mania was first described in the 1800s and was referred to as “Bell’s Mania.”

As the late Max Fink, MD, wrote in the journal Bipolar Disorders (2002 Feb 23. doi: 10.1034/j.1399-561.1999.10112.x), delirious mania is considered to be a syndrome of the acute onset of the excitement, grandiosity, emotional lability, delusions, and insomnia characteristic of mania, and the disorientation and altered consciousness characteristic of delirium.

Such patients can be considered as having a component of bipolar I disorder, comprising mania with psychotic features. Delirious mania is associated with higher rates of morbidity and mortality, and demonstrates limited response to conventional treatment guidelines. Therefore, early detection and decisive treatment are imperative. The concurrence of delirium and mania is not unusual, yet currently there are no universal accepted treatment guidelines for delirious mania (BMC Psychiatry. 2012 Jun 21. doi: 10.1186/1471-244X-12-65). The purpose of this case report is to inspire and support community psychiatric clinicians in managing such complex cases and to improve behavioral health care outcomes. To protect our patient’s identity, we changed several key identifiers.

The treatment plan emerges

This case is of a middle-aged man with an established diagnosis of bipolar disorder. He was referred to the ED because of worsening manic symptoms marked by mood lability, pressured speech, grandiose delusions, tangential thought processes, poor insight, and impaired sleep.

Laboratory studies in the ED revealed hyponatremia and serum sodium of 126meq/l (ref. range: 135-146). The patient’s toxicology screen was positive for benzodiazepines. He was stabilized on the medical floor and then transitioned to inpatient psychiatry.

Before his admission to psychiatry, the patient’s medications were alprazolam 1 mg at bed time, bupropion 100 mg twice daily, loxapine 25 mg morning and 50 mg at bed time, olanzapine 20 mg at bedtime and 5 mg twice daily, risperidone 2 mg twice daily and oxcarbazepine 900 mg twice daily.

The bupropion was discontinued because of manic behavior, and the patient’s dose of oxcarbazepine was lowered from 900 mg twice daily to 450 mg twice daily because of hyponatremia. Our team continued to administer risperidone, olanzapine, loxapine, and alprazolam to the patient. However, he was agitated and disorganized on the psychiatry floor. In addition, we noticed that the patient exhibited confusion, disorientation, an inability to connect with reality, and periods of profound agitation.

The patient was frequently restrained physically, and medications were administered to him for safety and containment. The use of benzodiazepines and anticholinergics was minimized. However, we noticed that the patient acted paranoid, disinhibited, and combative, and he became difficult to restrain. He seemed to have a high pain tolerance, responded to internal stimuli, and began hallucinating and displaying aggressive behavior toward staff persons.

It became apparent that the patient’s circadian rhythm had been altered. He slept for only a couple of hours during the day. During the course of treatment, in one incidence, the patient became agitated and charged at a nurse. Subsequently, the patient hit his head on a wall and fell – suffering a head strike and lacerations.

The team conducted investigations, including labs and neuroimaging, to make sure that the patient was OK. His CT head scan proved unremarkable. Liver function tests revealed mild transaminitis. His TSH, folate, B₁₂, and B₁ levels were normal.

We then placed the patient in a single room with continuous behavior monitoring. His recovery seemed to take a long time with trials of different antipsychotic medications, including olanzapine, loxapine, risperidone, and paliperidone. Because of his poor response to medications, the team considered using electroconvulsive therapy (ECT).

However, the patient was unable to give informed consent for ECT because of his impaired mental status. At this point, our team submitted a substitute treatment plan that included ECT to the court for approval, and the court approved our plan.

After receiving approximately four bilateral ECT procedures three times a week, the patient’s condition started to improve gradually. He received total of 11 procedures.

Our patient became alert to time, place, and person, and his circadian rhythm normalized. Soon, his delirium cleared, and he demonstrated marked improvement in both insight into his illness and behavioral control. His grandiose delusions were still present, but he was easily redirectable. In addition, our patient demonstrated improved reality testing. He was able to be discharged home following medication adjustments and with community supports within a few short weeks of receiving ECT.

As Bo-Shyan Lee, MD, and associates reported (BMC Psychiatry. 2012 Jun 21;12:65. doi: 10.1186/1471-244X-12-65), delirious mania is closely related to catatonia. Although there are different definitions for delirium and catatonia, even the most lethal form of catatonia meets the criteria for delirium. ECT is a well established first-line treatment for catatonia. This tool has been shown to be highly effective in the treatment of delirious mania. Delirious mania can be life-threatening and should be managed aggressively. The most common causes of death are heart failure from arrhythmias, cardiac arrest, and respiratory failure. ECT is a safe treatment, and, as Dr. Fink argued, the mortality rate is even less than that associated with normal pregnancies (World J Biol Psychiatry. 2001 Jan;2[1]:1-8). In light of the safety and effectiveness of ECT, we think the tool should be considered not only in university hospital settings but as an early intervention in community settings. This case warrants further research in exploring hyperactive delirium and delirious mania.
 

Dr. Lamba is BR-2 unit medical director at BayRidge Hospital in Lynn, Mass. Ms. Kennedy is an attending clinician at BayRidge. Dr. Vu is medical director at BayRidge. He also serves as associate chief of psychiatry at Beverly (Mass.) Hospital and at Addison Gilbert Hospital in Gloucester, Mass. Dr. Lamba, Ms. Kennedy, and Dr. Vu have no disclosures.

They say you are what you eat, but scientists have long wondered whether breastfeeding babies are what their mothers eat, too. Their question: How much of a nursing mother’s diet eventually plays a role in a child’s food preferences later in life?

The aroma, taste, and makeup of breast milk change from day to day, based mostly on the mother’s diet. But previous research has already shown that the foods a mother eats do not directly translate into the same smells and tastes of that food in breast milk. Some substances from the mother’s diet enter her breast milk, some don’t, and even ones that do may have a different scent or flavor than what the mother experiences.

But a new study suggests that the active ingredient in black pepper makes its way into breast milk and may help the infant develop a tolerance to pepper later. The researchers published their findings in the journal Molecular Nutrition & Food Research.
 

Pinch of pepper

The study authors thought that maybe some food preferences could result from sensory programming that occurs through breast milk in the first few months of life. Though past studies have looked at which odor-producing substances transfer into breast milk, not many have explored specific substances that give food its distinctive flavor, or even what makes up the taste of breast milk. So they decided to investigate what happens when a mother consumes a meal containing three specific compounds: those that give pepper, chili, and ginger their particularly pungent flavors.

The researchers recruited 18 healthy, nonsmoking, nursing mothers who were producing more than enough milk for their baby’s needs. Their breastfeeding children ranged in age from 8 weeks to 1 year old. The women all ate a curry dish after having spent 2 days avoiding onion, garlic, and the spices in the curry. Then they provided pumped breast milk samples at 1, 2, and 3 hours after eating the curry.

Within an hour of the women eating the curry, the scientists were able to detect piperine, the compound that gives black pepper its bite, in the mothers’ breast milk. They did not find the compounds from ginger, chili, or curcumin – the main active ingredient in turmeric – in the breast milk. The piperine remained there for several hours, but there wasn’t enough for an adult to be able to taste it. It wasn’t possible to reliably tell whether the infants could consciously detect the flavor, but the researchers don’t think it’s likely they did.

But the scientists do suggest it’s possible that the piperine in breast milk could regularly activate a protein that detects pungent or potentially harmful substances. This is the same protein that produces the sensation of heat when eating a spicy food. If the piperine frequently activates that protein in a nursing baby at levels too low for the baby to notice, it may increase the baby’s tolerance for similar spicy substances later in life.

Ultimately, the findings suggest that some compounds in a mother’s diet have the potential to influence a child’s taste preferences later.

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

They say you are what you eat, but scientists have long wondered whether breastfeeding babies are what their mothers eat, too. Their question: How much of a nursing mother’s diet eventually plays a role in a child’s food preferences later in life?

The aroma, taste, and makeup of breast milk change from day to day, based mostly on the mother’s diet. But previous research has already shown that the foods a mother eats do not directly translate into the same smells and tastes of that food in breast milk. Some substances from the mother’s diet enter her breast milk, some don’t, and even ones that do may have a different scent or flavor than what the mother experiences.

But a new study suggests that the active ingredient in black pepper makes its way into breast milk and may help the infant develop a tolerance to pepper later. The researchers published their findings in the journal Molecular Nutrition & Food Research.
 

Pinch of pepper

The study authors thought that maybe some food preferences could result from sensory programming that occurs through breast milk in the first few months of life. Though past studies have looked at which odor-producing substances transfer into breast milk, not many have explored specific substances that give food its distinctive flavor, or even what makes up the taste of breast milk. So they decided to investigate what happens when a mother consumes a meal containing three specific compounds: those that give pepper, chili, and ginger their particularly pungent flavors.

The researchers recruited 18 healthy, nonsmoking, nursing mothers who were producing more than enough milk for their baby’s needs. Their breastfeeding children ranged in age from 8 weeks to 1 year old. The women all ate a curry dish after having spent 2 days avoiding onion, garlic, and the spices in the curry. Then they provided pumped breast milk samples at 1, 2, and 3 hours after eating the curry.

Within an hour of the women eating the curry, the scientists were able to detect piperine, the compound that gives black pepper its bite, in the mothers’ breast milk. They did not find the compounds from ginger, chili, or curcumin – the main active ingredient in turmeric – in the breast milk. The piperine remained there for several hours, but there wasn’t enough for an adult to be able to taste it. It wasn’t possible to reliably tell whether the infants could consciously detect the flavor, but the researchers don’t think it’s likely they did.

But the scientists do suggest it’s possible that the piperine in breast milk could regularly activate a protein that detects pungent or potentially harmful substances. This is the same protein that produces the sensation of heat when eating a spicy food. If the piperine frequently activates that protein in a nursing baby at levels too low for the baby to notice, it may increase the baby’s tolerance for similar spicy substances later in life.

Ultimately, the findings suggest that some compounds in a mother’s diet have the potential to influence a child’s taste preferences later.

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

They say you are what you eat, but scientists have long wondered whether breastfeeding babies are what their mothers eat, too. Their question: How much of a nursing mother’s diet eventually plays a role in a child’s food preferences later in life?

The aroma, taste, and makeup of breast milk change from day to day, based mostly on the mother’s diet. But previous research has already shown that the foods a mother eats do not directly translate into the same smells and tastes of that food in breast milk. Some substances from the mother’s diet enter her breast milk, some don’t, and even ones that do may have a different scent or flavor than what the mother experiences.

But a new study suggests that the active ingredient in black pepper makes its way into breast milk and may help the infant develop a tolerance to pepper later. The researchers published their findings in the journal Molecular Nutrition & Food Research.
 

Pinch of pepper

The study authors thought that maybe some food preferences could result from sensory programming that occurs through breast milk in the first few months of life. Though past studies have looked at which odor-producing substances transfer into breast milk, not many have explored specific substances that give food its distinctive flavor, or even what makes up the taste of breast milk. So they decided to investigate what happens when a mother consumes a meal containing three specific compounds: those that give pepper, chili, and ginger their particularly pungent flavors.

The researchers recruited 18 healthy, nonsmoking, nursing mothers who were producing more than enough milk for their baby’s needs. Their breastfeeding children ranged in age from 8 weeks to 1 year old. The women all ate a curry dish after having spent 2 days avoiding onion, garlic, and the spices in the curry. Then they provided pumped breast milk samples at 1, 2, and 3 hours after eating the curry.

Within an hour of the women eating the curry, the scientists were able to detect piperine, the compound that gives black pepper its bite, in the mothers’ breast milk. They did not find the compounds from ginger, chili, or curcumin – the main active ingredient in turmeric – in the breast milk. The piperine remained there for several hours, but there wasn’t enough for an adult to be able to taste it. It wasn’t possible to reliably tell whether the infants could consciously detect the flavor, but the researchers don’t think it’s likely they did.

But the scientists do suggest it’s possible that the piperine in breast milk could regularly activate a protein that detects pungent or potentially harmful substances. This is the same protein that produces the sensation of heat when eating a spicy food. If the piperine frequently activates that protein in a nursing baby at levels too low for the baby to notice, it may increase the baby’s tolerance for similar spicy substances later in life.

Ultimately, the findings suggest that some compounds in a mother’s diet have the potential to influence a child’s taste preferences later.

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

After a brief lull in activity, weekly COVID-19 cases in children returned to the upward trend that began in early November, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Vaccinations in children, however, continued to do the opposite by falling for the fourth consecutive week, with the largest decline for the week of Dec. 7-13 coming from those most recently eligible, according to the Centers for Disease Control and Prevention.

New COVID-19 cases were up by 23.5% for the week of Dec. 3-9, after a 2-week period that saw a drop and then just a slight increase, the AAP and CHA said in their latest weekly COVID report. There were 164,000 new cases from Dec. 3 to Dec. 9 in 46 states (Alabama, Nebraska, and Texas stopped reporting over the summer of 2021 and New York has never reported by age), the District of Columbia, New York City, Puerto Rico, and Guam.

The increase occurred across all four regions of the country, but the largest share came in the Midwest, with over 65,000 new cases, followed by the West (just over 35,000), the Northeast (just under 35,000), and the South (close to 28,000), the AAP/CHA data show.

The 7.2 million cumulative cases in children as of Dec. 9 represent 17.2% of all cases reported in the United States since the start of the pandemic, with available state reports showing that proportion ranges from 12.3% in Florida to 26.1% in Vermont. Alaska has the highest incidence of COVID at 19,000 cases per 100,000 children, and Hawaii has the lowest (5,300 per 100,000) among the states currently reporting, the AAP and CHA said.

State reporting on vaccinations shows that 37% of children aged 5-11 years in Massachusetts have received at least one dose, the highest of any state, while West Virginia is lowest at just 4%. The highest vaccination rate for children aged 12-17 goes to Massachusetts at 84%, with Wyoming lowest at 37%, the AAP said in a separate report.

Nationally, new vaccinations fell by a third during the week of Dec. 7-13, compared with the previous week, with the largest decline (34.7%) coming from the 5- to 11-year-olds, who still represented the majority (almost 84%) of the 430,000 new child vaccinations received, according to the CDC’s COVID Data Tracker. Corresponding declines for the last week were 27.5% for 12- to 15-year-olds and 22.7% for those aged 16-17.

Altogether, 21.2 million children aged 5-17 had received at least one dose and 16.0 million were fully vaccinated as of Dec. 13. By age group, 19.2% of children aged 5-11 years have gotten at least one dose and 9.6% are fully vaccinated, compared with 62.1% and 52.3%, respectively, among children aged 12-17, the CDC said.

[email protected]

After a brief lull in activity, weekly COVID-19 cases in children returned to the upward trend that began in early November, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Vaccinations in children, however, continued to do the opposite by falling for the fourth consecutive week, with the largest decline for the week of Dec. 7-13 coming from those most recently eligible, according to the Centers for Disease Control and Prevention.

New COVID-19 cases were up by 23.5% for the week of Dec. 3-9, after a 2-week period that saw a drop and then just a slight increase, the AAP and CHA said in their latest weekly COVID report. There were 164,000 new cases from Dec. 3 to Dec. 9 in 46 states (Alabama, Nebraska, and Texas stopped reporting over the summer of 2021 and New York has never reported by age), the District of Columbia, New York City, Puerto Rico, and Guam.

The increase occurred across all four regions of the country, but the largest share came in the Midwest, with over 65,000 new cases, followed by the West (just over 35,000), the Northeast (just under 35,000), and the South (close to 28,000), the AAP/CHA data show.

The 7.2 million cumulative cases in children as of Dec. 9 represent 17.2% of all cases reported in the United States since the start of the pandemic, with available state reports showing that proportion ranges from 12.3% in Florida to 26.1% in Vermont. Alaska has the highest incidence of COVID at 19,000 cases per 100,000 children, and Hawaii has the lowest (5,300 per 100,000) among the states currently reporting, the AAP and CHA said.

State reporting on vaccinations shows that 37% of children aged 5-11 years in Massachusetts have received at least one dose, the highest of any state, while West Virginia is lowest at just 4%. The highest vaccination rate for children aged 12-17 goes to Massachusetts at 84%, with Wyoming lowest at 37%, the AAP said in a separate report.

Nationally, new vaccinations fell by a third during the week of Dec. 7-13, compared with the previous week, with the largest decline (34.7%) coming from the 5- to 11-year-olds, who still represented the majority (almost 84%) of the 430,000 new child vaccinations received, according to the CDC’s COVID Data Tracker. Corresponding declines for the last week were 27.5% for 12- to 15-year-olds and 22.7% for those aged 16-17.

Altogether, 21.2 million children aged 5-17 had received at least one dose and 16.0 million were fully vaccinated as of Dec. 13. By age group, 19.2% of children aged 5-11 years have gotten at least one dose and 9.6% are fully vaccinated, compared with 62.1% and 52.3%, respectively, among children aged 12-17, the CDC said.

[email protected]

After a brief lull in activity, weekly COVID-19 cases in children returned to the upward trend that began in early November, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

Vaccinations in children, however, continued to do the opposite by falling for the fourth consecutive week, with the largest decline for the week of Dec. 7-13 coming from those most recently eligible, according to the Centers for Disease Control and Prevention.

New COVID-19 cases were up by 23.5% for the week of Dec. 3-9, after a 2-week period that saw a drop and then just a slight increase, the AAP and CHA said in their latest weekly COVID report. There were 164,000 new cases from Dec. 3 to Dec. 9 in 46 states (Alabama, Nebraska, and Texas stopped reporting over the summer of 2021 and New York has never reported by age), the District of Columbia, New York City, Puerto Rico, and Guam.

The increase occurred across all four regions of the country, but the largest share came in the Midwest, with over 65,000 new cases, followed by the West (just over 35,000), the Northeast (just under 35,000), and the South (close to 28,000), the AAP/CHA data show.

The 7.2 million cumulative cases in children as of Dec. 9 represent 17.2% of all cases reported in the United States since the start of the pandemic, with available state reports showing that proportion ranges from 12.3% in Florida to 26.1% in Vermont. Alaska has the highest incidence of COVID at 19,000 cases per 100,000 children, and Hawaii has the lowest (5,300 per 100,000) among the states currently reporting, the AAP and CHA said.

State reporting on vaccinations shows that 37% of children aged 5-11 years in Massachusetts have received at least one dose, the highest of any state, while West Virginia is lowest at just 4%. The highest vaccination rate for children aged 12-17 goes to Massachusetts at 84%, with Wyoming lowest at 37%, the AAP said in a separate report.

Nationally, new vaccinations fell by a third during the week of Dec. 7-13, compared with the previous week, with the largest decline (34.7%) coming from the 5- to 11-year-olds, who still represented the majority (almost 84%) of the 430,000 new child vaccinations received, according to the CDC’s COVID Data Tracker. Corresponding declines for the last week were 27.5% for 12- to 15-year-olds and 22.7% for those aged 16-17.

Altogether, 21.2 million children aged 5-17 had received at least one dose and 16.0 million were fully vaccinated as of Dec. 13. By age group, 19.2% of children aged 5-11 years have gotten at least one dose and 9.6% are fully vaccinated, compared with 62.1% and 52.3%, respectively, among children aged 12-17, the CDC said.

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Abortion rates remained stable and adverse events were rare after removal of mifepristone prescribing restrictions in Canada, a new study shows.

“Our study is a signal to other countries that restrictions are not necessary to ensure patient safety,” senior author Wendy V. Norman, MD, professor in the department of family practice at the University of British Columbia, Vancouver, said in a press release.

“This is the strongest evidence yet that it is safe to provide the abortion pill like most other prescriptions – meaning any doctor or nurse practitioner can prescribe, any pharmacist can dispense, and patients can take the pills if, when, and where they choose,” said lead author Laura Schummers, ScD, a postdoctoral fellow in the same department.

The findings “add to the accumulating evidence that removing restrictions from medication abortion is safe, effective, and improves access,” agreed Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, who was not part of the research team. “This is additional confirmation that it is safe for patients to receive abortion care medications in the ‘normal’ fashion, through a prescription available at a pharmacy,” she said in an interview.

The study, published in the New England Journal of Medicine, compared medical abortion use, safety, and effectiveness in the province of Ontario before the Canadian availability of mifepristone and after it became available without restrictions that are similar to the Risk Evaluation and Mitigation Strategy (REMS) restrictions in place for mifepristone in the United States.

Using linked administrative health data, the researchers created a population-based cohort of all Ontario residents aged 12-49 years who had received abortion services during the study period. In total, 195,183 abortions were performed in the period before mifepristone was approved (January 2012–December 2016), and 84,032 were performed after it was made available without restrictions (Nov. 7, 2017, through March 15, 2020). The vast majority of these abortions (89.3%) were surgical, with about 10% being medically induced, the authors reported.

The study found that, while the overall abortion rate declined over the study period (from 11.9 to 11.3 per 1,000 female residents), the proportion of medical abortions jumped sharply from 2.2% to 31.4%, and the rate of second-trimester abortions declined from 5.5% of all abortions to 5.1%.

Abortion safety outcomes within 6 weeks of abortion remained stable over the two study periods. This included severe adverse events (0.03% vs. 0.04%) such as blood transfusions, abdominal surgery, admission to an ICU, or sepsis during an abortion-related hospitalization; and complications (0.74% vs. 0.69%,) such as genital tract or pelvic infection, hemorrhage, embolism, shock, renal failure, damage to pelvic organs or tissues, and venous complications among other things.

There were slight declines in overall abortion effectiveness, but ongoing pregnancy rates “remained infrequent,” the authors noted. While there was a modest rise in the rates of subsequent uterine evacuation (from 1.0% to 2.2%), and ongoing intrauterine pregnancy continuing until delivery (from 0.03% to 0.08%), the rate of ectopic pregnancy diagnosed within 6 weeks after the abortion date remained stable (from 0.15% to 0.22%).

Canada was the first country in the world to remove all supplemental restrictions on the dispensing and administration of mifepristone, according to the press release. And while professional organizations have called for the removal of such restrictions “because they impede access to abortion services without improving safety,” high-quality data on this are lacking, they added.

The study’s finding are consistent with existing U.S. and U.K. data showing Food and Drug Administration REMS restrictions requiring abortion care medications to be dispensed in a clinic by a certified provider “are unnecessary and create obstacles to early abortion access,” said Dr. Espey. “For clinicians and patients in the U.S., it’s important to note that the increasing number of legislative restrictions on abortion, including medication abortion, are non–evidence based. Politically motivated false claims of safety concerns are countered by this study and others conducted during the pandemic when both the U.S. and U.K. removed REMS-type restrictions. These studies show that receiving abortion care through usual pharmacy channels and through telemedicine is safe, effective, and reduces barriers to care.”

Dr. Norman reported receiving grants from the Canadian Institutes of Health Research, providing expert witness services to the government of Ontario and Office of the Attorney General, and serving on the board of directors of the Society of Family Planning. No other researchers reported conflicts of interest. Dr. Espey reported no conflicts of interest. The Canadian Institutes of Health Research and the Women’s Health Research Institute with the support of ICES (formerly known as the Institute for Clinical Evaluative Sciences).

Abortion rates remained stable and adverse events were rare after removal of mifepristone prescribing restrictions in Canada, a new study shows.

“Our study is a signal to other countries that restrictions are not necessary to ensure patient safety,” senior author Wendy V. Norman, MD, professor in the department of family practice at the University of British Columbia, Vancouver, said in a press release.

“This is the strongest evidence yet that it is safe to provide the abortion pill like most other prescriptions – meaning any doctor or nurse practitioner can prescribe, any pharmacist can dispense, and patients can take the pills if, when, and where they choose,” said lead author Laura Schummers, ScD, a postdoctoral fellow in the same department.

The findings “add to the accumulating evidence that removing restrictions from medication abortion is safe, effective, and improves access,” agreed Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, who was not part of the research team. “This is additional confirmation that it is safe for patients to receive abortion care medications in the ‘normal’ fashion, through a prescription available at a pharmacy,” she said in an interview.

The study, published in the New England Journal of Medicine, compared medical abortion use, safety, and effectiveness in the province of Ontario before the Canadian availability of mifepristone and after it became available without restrictions that are similar to the Risk Evaluation and Mitigation Strategy (REMS) restrictions in place for mifepristone in the United States.

Using linked administrative health data, the researchers created a population-based cohort of all Ontario residents aged 12-49 years who had received abortion services during the study period. In total, 195,183 abortions were performed in the period before mifepristone was approved (January 2012–December 2016), and 84,032 were performed after it was made available without restrictions (Nov. 7, 2017, through March 15, 2020). The vast majority of these abortions (89.3%) were surgical, with about 10% being medically induced, the authors reported.

The study found that, while the overall abortion rate declined over the study period (from 11.9 to 11.3 per 1,000 female residents), the proportion of medical abortions jumped sharply from 2.2% to 31.4%, and the rate of second-trimester abortions declined from 5.5% of all abortions to 5.1%.

Abortion safety outcomes within 6 weeks of abortion remained stable over the two study periods. This included severe adverse events (0.03% vs. 0.04%) such as blood transfusions, abdominal surgery, admission to an ICU, or sepsis during an abortion-related hospitalization; and complications (0.74% vs. 0.69%,) such as genital tract or pelvic infection, hemorrhage, embolism, shock, renal failure, damage to pelvic organs or tissues, and venous complications among other things.

There were slight declines in overall abortion effectiveness, but ongoing pregnancy rates “remained infrequent,” the authors noted. While there was a modest rise in the rates of subsequent uterine evacuation (from 1.0% to 2.2%), and ongoing intrauterine pregnancy continuing until delivery (from 0.03% to 0.08%), the rate of ectopic pregnancy diagnosed within 6 weeks after the abortion date remained stable (from 0.15% to 0.22%).

Canada was the first country in the world to remove all supplemental restrictions on the dispensing and administration of mifepristone, according to the press release. And while professional organizations have called for the removal of such restrictions “because they impede access to abortion services without improving safety,” high-quality data on this are lacking, they added.

The study’s finding are consistent with existing U.S. and U.K. data showing Food and Drug Administration REMS restrictions requiring abortion care medications to be dispensed in a clinic by a certified provider “are unnecessary and create obstacles to early abortion access,” said Dr. Espey. “For clinicians and patients in the U.S., it’s important to note that the increasing number of legislative restrictions on abortion, including medication abortion, are non–evidence based. Politically motivated false claims of safety concerns are countered by this study and others conducted during the pandemic when both the U.S. and U.K. removed REMS-type restrictions. These studies show that receiving abortion care through usual pharmacy channels and through telemedicine is safe, effective, and reduces barriers to care.”

Dr. Norman reported receiving grants from the Canadian Institutes of Health Research, providing expert witness services to the government of Ontario and Office of the Attorney General, and serving on the board of directors of the Society of Family Planning. No other researchers reported conflicts of interest. Dr. Espey reported no conflicts of interest. The Canadian Institutes of Health Research and the Women’s Health Research Institute with the support of ICES (formerly known as the Institute for Clinical Evaluative Sciences).

Abortion rates remained stable and adverse events were rare after removal of mifepristone prescribing restrictions in Canada, a new study shows.

“Our study is a signal to other countries that restrictions are not necessary to ensure patient safety,” senior author Wendy V. Norman, MD, professor in the department of family practice at the University of British Columbia, Vancouver, said in a press release.

“This is the strongest evidence yet that it is safe to provide the abortion pill like most other prescriptions – meaning any doctor or nurse practitioner can prescribe, any pharmacist can dispense, and patients can take the pills if, when, and where they choose,” said lead author Laura Schummers, ScD, a postdoctoral fellow in the same department.

The findings “add to the accumulating evidence that removing restrictions from medication abortion is safe, effective, and improves access,” agreed Eve Espey, MD, professor and chair of the department of obstetrics and gynecology at the University of New Mexico, Albuquerque, who was not part of the research team. “This is additional confirmation that it is safe for patients to receive abortion care medications in the ‘normal’ fashion, through a prescription available at a pharmacy,” she said in an interview.

The study, published in the New England Journal of Medicine, compared medical abortion use, safety, and effectiveness in the province of Ontario before the Canadian availability of mifepristone and after it became available without restrictions that are similar to the Risk Evaluation and Mitigation Strategy (REMS) restrictions in place for mifepristone in the United States.

Using linked administrative health data, the researchers created a population-based cohort of all Ontario residents aged 12-49 years who had received abortion services during the study period. In total, 195,183 abortions were performed in the period before mifepristone was approved (January 2012–December 2016), and 84,032 were performed after it was made available without restrictions (Nov. 7, 2017, through March 15, 2020). The vast majority of these abortions (89.3%) were surgical, with about 10% being medically induced, the authors reported.

The study found that, while the overall abortion rate declined over the study period (from 11.9 to 11.3 per 1,000 female residents), the proportion of medical abortions jumped sharply from 2.2% to 31.4%, and the rate of second-trimester abortions declined from 5.5% of all abortions to 5.1%.

Abortion safety outcomes within 6 weeks of abortion remained stable over the two study periods. This included severe adverse events (0.03% vs. 0.04%) such as blood transfusions, abdominal surgery, admission to an ICU, or sepsis during an abortion-related hospitalization; and complications (0.74% vs. 0.69%,) such as genital tract or pelvic infection, hemorrhage, embolism, shock, renal failure, damage to pelvic organs or tissues, and venous complications among other things.

There were slight declines in overall abortion effectiveness, but ongoing pregnancy rates “remained infrequent,” the authors noted. While there was a modest rise in the rates of subsequent uterine evacuation (from 1.0% to 2.2%), and ongoing intrauterine pregnancy continuing until delivery (from 0.03% to 0.08%), the rate of ectopic pregnancy diagnosed within 6 weeks after the abortion date remained stable (from 0.15% to 0.22%).

Canada was the first country in the world to remove all supplemental restrictions on the dispensing and administration of mifepristone, according to the press release. And while professional organizations have called for the removal of such restrictions “because they impede access to abortion services without improving safety,” high-quality data on this are lacking, they added.

The study’s finding are consistent with existing U.S. and U.K. data showing Food and Drug Administration REMS restrictions requiring abortion care medications to be dispensed in a clinic by a certified provider “are unnecessary and create obstacles to early abortion access,” said Dr. Espey. “For clinicians and patients in the U.S., it’s important to note that the increasing number of legislative restrictions on abortion, including medication abortion, are non–evidence based. Politically motivated false claims of safety concerns are countered by this study and others conducted during the pandemic when both the U.S. and U.K. removed REMS-type restrictions. These studies show that receiving abortion care through usual pharmacy channels and through telemedicine is safe, effective, and reduces barriers to care.”

Dr. Norman reported receiving grants from the Canadian Institutes of Health Research, providing expert witness services to the government of Ontario and Office of the Attorney General, and serving on the board of directors of the Society of Family Planning. No other researchers reported conflicts of interest. Dr. Espey reported no conflicts of interest. The Canadian Institutes of Health Research and the Women’s Health Research Institute with the support of ICES (formerly known as the Institute for Clinical Evaluative Sciences).

Although their ages were similar, patients with epilepsy were nearly 1.5 times more likely to die of COVID-19 than other infected patients at a hospital system during the first 14 months of the pandemic, according to a new study presented at the annual meeting of the American Epilepsy Society. While the findings are preliminary and not yet adjusted for various confounders, the authors say they are a warning sign that patients with epilepsy may face higher risks.

“These findings suggest that epilepsy may be a pre-existing condition that places patients at increased risk for death if hospitalized with a COVID-19 infection. It may offer neurologists guidance when counseling patients on critical preventative measures such as masking, social distancing, and most importantly, vaccination,” lead author Claire Ufongene, a student at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

According to Ms. Ufongene, there’s sparse data about COVID-19 outcomes in patients with epilepsy, although she highlighted a 2021 meta-analysis of 13 studies that found a higher risk of severity (odds ratio, 1.69; 95% confidence interval, 1.11-2.59, P = .010) and mortality (OR, 1.71; 95% CI, 1.14-2.56, P = .010).

For the new study, researchers retrospectively tracked identified 334 patients with epilepsy and COVID-19 and 9,499 other patients with COVID-19 from March 15, 2020, to May 17, 2021. All were treated at hospitals within the New York–based Icahn School of Medicine at Mount Sinai.

The groups of patients with and without epilepsy were similar in some ways: 45% and 46%, respectively, were female (P = .674), and their ages were similar (average, 62 years and 65 years, respectively; P = .02). Racial makeup was also similar (non-Hispanic groups made up 27.8% of those with epilepsy and 24.5% of those without; the difference was not statistically significant).

“In addition, more of those with epilepsy were English speaking [83.2% vs. 77.9%] and had Medicaid insurance [50.9% vs. 38.9%], while fewer of those with epilepsy had private insurance [16.2% vs. 25.5%] or were Spanish speaking [14.0% vs. 9.3%],” study coauthor Nathalie Jette, MD, MSc, a neurologist at Icahn School of Medicine at Mount Sinai, said in an interview.

In terms of outcomes, patients with epilepsy were much more likely to need ventilator support (37.7% vs. 14.3%; P < .001), to be admitted to the ICU (39.2% vs. 17.7%; P < .001), and to die in the hospital (29.6% vs. 19.9%; P < .001).

“Most patients we follow in our practices with epilepsy who experienced COVID-19 in general have had symptoms similar to the general population,” Dr. Jette said. “There are rare instances where COVID-19 can result in an exacerbation of seizures in some with pre-existing epilepsy. This is not surprising as infections in particular can decrease the seizure threshold and result in breakthrough seizures in people living with epilepsy.”
 

Loss of seizure control

How might epilepsy be related to worse outcomes in COVID-19? Andrew Wilner, MD, a neurologist and internist at University of Tennessee Health Science Center, Memphis, who’s familiar with the study findings, said COVID-19 itself may not worsen epilepsy. “Evidence to suggest that COVID-19 directly affects the central nervous system is extremely limited. As such, one would not expect that a COVID-19 infection would cause epilepsy or exacerbate epilepsy,” he said. “However, patients with epilepsy who suffer from infections may be predisposed to decreased seizure control. Consequently, it would not be surprising if patients with epilepsy who also had COVID-19 had loss of seizure control and even status epilepticus, which could adversely affect their hospital course. However, there are no data on this potential phenomenon.”

Dr. Wilner suspected that comorbidities explain the higher mortality in patients with epilepsy. “The findings are probably most useful in that they call attention to the fact that epilepsy patients are more vulnerable to a host of comorbidities and resultant poorer outcomes due to any acute illness.”

As for treatment, Dr. Wilner urged colleagues to make sure that hospitalized patients with epilepsy “continue to receive their antiepileptic medications, which they may no longer be able to take orally. They may need to be switched temporarily to an intravenous formulation.”

In an interview, Selim Benbadis, MD, a neurologist from the University of South Florida, Tampa, suggested that antiseizure medications may play a role in the COVID-19 disease course because they can reduce the efficacy of other medications, although he noted that drug treatments for COVID-19 were limited early on. He recommended that neurologists “avoid old enzyme-inducing seizure medications, as is generally recommended.”

No study funding is reported. The study authors and Dr. Benbadis reported no relevant disclosures. Dr. Wilner is a medical adviser for the epilepsy disease management program for CVS/Health.

Although their ages were similar, patients with epilepsy were nearly 1.5 times more likely to die of COVID-19 than other infected patients at a hospital system during the first 14 months of the pandemic, according to a new study presented at the annual meeting of the American Epilepsy Society. While the findings are preliminary and not yet adjusted for various confounders, the authors say they are a warning sign that patients with epilepsy may face higher risks.

“These findings suggest that epilepsy may be a pre-existing condition that places patients at increased risk for death if hospitalized with a COVID-19 infection. It may offer neurologists guidance when counseling patients on critical preventative measures such as masking, social distancing, and most importantly, vaccination,” lead author Claire Ufongene, a student at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

According to Ms. Ufongene, there’s sparse data about COVID-19 outcomes in patients with epilepsy, although she highlighted a 2021 meta-analysis of 13 studies that found a higher risk of severity (odds ratio, 1.69; 95% confidence interval, 1.11-2.59, P = .010) and mortality (OR, 1.71; 95% CI, 1.14-2.56, P = .010).

For the new study, researchers retrospectively tracked identified 334 patients with epilepsy and COVID-19 and 9,499 other patients with COVID-19 from March 15, 2020, to May 17, 2021. All were treated at hospitals within the New York–based Icahn School of Medicine at Mount Sinai.

The groups of patients with and without epilepsy were similar in some ways: 45% and 46%, respectively, were female (P = .674), and their ages were similar (average, 62 years and 65 years, respectively; P = .02). Racial makeup was also similar (non-Hispanic groups made up 27.8% of those with epilepsy and 24.5% of those without; the difference was not statistically significant).

“In addition, more of those with epilepsy were English speaking [83.2% vs. 77.9%] and had Medicaid insurance [50.9% vs. 38.9%], while fewer of those with epilepsy had private insurance [16.2% vs. 25.5%] or were Spanish speaking [14.0% vs. 9.3%],” study coauthor Nathalie Jette, MD, MSc, a neurologist at Icahn School of Medicine at Mount Sinai, said in an interview.

In terms of outcomes, patients with epilepsy were much more likely to need ventilator support (37.7% vs. 14.3%; P < .001), to be admitted to the ICU (39.2% vs. 17.7%; P < .001), and to die in the hospital (29.6% vs. 19.9%; P < .001).

“Most patients we follow in our practices with epilepsy who experienced COVID-19 in general have had symptoms similar to the general population,” Dr. Jette said. “There are rare instances where COVID-19 can result in an exacerbation of seizures in some with pre-existing epilepsy. This is not surprising as infections in particular can decrease the seizure threshold and result in breakthrough seizures in people living with epilepsy.”
 

Loss of seizure control

How might epilepsy be related to worse outcomes in COVID-19? Andrew Wilner, MD, a neurologist and internist at University of Tennessee Health Science Center, Memphis, who’s familiar with the study findings, said COVID-19 itself may not worsen epilepsy. “Evidence to suggest that COVID-19 directly affects the central nervous system is extremely limited. As such, one would not expect that a COVID-19 infection would cause epilepsy or exacerbate epilepsy,” he said. “However, patients with epilepsy who suffer from infections may be predisposed to decreased seizure control. Consequently, it would not be surprising if patients with epilepsy who also had COVID-19 had loss of seizure control and even status epilepticus, which could adversely affect their hospital course. However, there are no data on this potential phenomenon.”

Dr. Wilner suspected that comorbidities explain the higher mortality in patients with epilepsy. “The findings are probably most useful in that they call attention to the fact that epilepsy patients are more vulnerable to a host of comorbidities and resultant poorer outcomes due to any acute illness.”

As for treatment, Dr. Wilner urged colleagues to make sure that hospitalized patients with epilepsy “continue to receive their antiepileptic medications, which they may no longer be able to take orally. They may need to be switched temporarily to an intravenous formulation.”

In an interview, Selim Benbadis, MD, a neurologist from the University of South Florida, Tampa, suggested that antiseizure medications may play a role in the COVID-19 disease course because they can reduce the efficacy of other medications, although he noted that drug treatments for COVID-19 were limited early on. He recommended that neurologists “avoid old enzyme-inducing seizure medications, as is generally recommended.”

No study funding is reported. The study authors and Dr. Benbadis reported no relevant disclosures. Dr. Wilner is a medical adviser for the epilepsy disease management program for CVS/Health.

Although their ages were similar, patients with epilepsy were nearly 1.5 times more likely to die of COVID-19 than other infected patients at a hospital system during the first 14 months of the pandemic, according to a new study presented at the annual meeting of the American Epilepsy Society. While the findings are preliminary and not yet adjusted for various confounders, the authors say they are a warning sign that patients with epilepsy may face higher risks.

“These findings suggest that epilepsy may be a pre-existing condition that places patients at increased risk for death if hospitalized with a COVID-19 infection. It may offer neurologists guidance when counseling patients on critical preventative measures such as masking, social distancing, and most importantly, vaccination,” lead author Claire Ufongene, a student at Icahn School of Medicine at Mount Sinai, New York, said in an interview.

According to Ms. Ufongene, there’s sparse data about COVID-19 outcomes in patients with epilepsy, although she highlighted a 2021 meta-analysis of 13 studies that found a higher risk of severity (odds ratio, 1.69; 95% confidence interval, 1.11-2.59, P = .010) and mortality (OR, 1.71; 95% CI, 1.14-2.56, P = .010).

For the new study, researchers retrospectively tracked identified 334 patients with epilepsy and COVID-19 and 9,499 other patients with COVID-19 from March 15, 2020, to May 17, 2021. All were treated at hospitals within the New York–based Icahn School of Medicine at Mount Sinai.

The groups of patients with and without epilepsy were similar in some ways: 45% and 46%, respectively, were female (P = .674), and their ages were similar (average, 62 years and 65 years, respectively; P = .02). Racial makeup was also similar (non-Hispanic groups made up 27.8% of those with epilepsy and 24.5% of those without; the difference was not statistically significant).

“In addition, more of those with epilepsy were English speaking [83.2% vs. 77.9%] and had Medicaid insurance [50.9% vs. 38.9%], while fewer of those with epilepsy had private insurance [16.2% vs. 25.5%] or were Spanish speaking [14.0% vs. 9.3%],” study coauthor Nathalie Jette, MD, MSc, a neurologist at Icahn School of Medicine at Mount Sinai, said in an interview.

In terms of outcomes, patients with epilepsy were much more likely to need ventilator support (37.7% vs. 14.3%; P < .001), to be admitted to the ICU (39.2% vs. 17.7%; P < .001), and to die in the hospital (29.6% vs. 19.9%; P < .001).

“Most patients we follow in our practices with epilepsy who experienced COVID-19 in general have had symptoms similar to the general population,” Dr. Jette said. “There are rare instances where COVID-19 can result in an exacerbation of seizures in some with pre-existing epilepsy. This is not surprising as infections in particular can decrease the seizure threshold and result in breakthrough seizures in people living with epilepsy.”
 

Loss of seizure control

How might epilepsy be related to worse outcomes in COVID-19? Andrew Wilner, MD, a neurologist and internist at University of Tennessee Health Science Center, Memphis, who’s familiar with the study findings, said COVID-19 itself may not worsen epilepsy. “Evidence to suggest that COVID-19 directly affects the central nervous system is extremely limited. As such, one would not expect that a COVID-19 infection would cause epilepsy or exacerbate epilepsy,” he said. “However, patients with epilepsy who suffer from infections may be predisposed to decreased seizure control. Consequently, it would not be surprising if patients with epilepsy who also had COVID-19 had loss of seizure control and even status epilepticus, which could adversely affect their hospital course. However, there are no data on this potential phenomenon.”

Dr. Wilner suspected that comorbidities explain the higher mortality in patients with epilepsy. “The findings are probably most useful in that they call attention to the fact that epilepsy patients are more vulnerable to a host of comorbidities and resultant poorer outcomes due to any acute illness.”

As for treatment, Dr. Wilner urged colleagues to make sure that hospitalized patients with epilepsy “continue to receive their antiepileptic medications, which they may no longer be able to take orally. They may need to be switched temporarily to an intravenous formulation.”

In an interview, Selim Benbadis, MD, a neurologist from the University of South Florida, Tampa, suggested that antiseizure medications may play a role in the COVID-19 disease course because they can reduce the efficacy of other medications, although he noted that drug treatments for COVID-19 were limited early on. He recommended that neurologists “avoid old enzyme-inducing seizure medications, as is generally recommended.”

No study funding is reported. The study authors and Dr. Benbadis reported no relevant disclosures. Dr. Wilner is a medical adviser for the epilepsy disease management program for CVS/Health.

I still, on occasion, use Felbatol (felbamate).

Thirty years since its explosive entrance to the market, then even more explosive collapse, it remains, in my opinion, the most effective of the second generation of anti-seizure medications. Arguably, even more effective than any of the third generation, too.

That’s not to say I use a lot of it. I don’t. It’s like handling unstable dynamite. Tremendous power, but also an above-average degree of risk. Even after things hit the fan with it in the mid-90s, I remember one of my epilepsy clinic attendings telling me, “This is a home-run drug. In refractory patients you might see some benefit by adding another agent, but with this one, you could stop their seizures and hit it out of the park.”

Like most neurologists, I use other epilepsy options first and second line. But sometimes you get the patient who’s failed the usual ones. Then I start to think about Felbatol. I explain the situation to the patients and their families and let them make the final decision. I worry and watch labs very closely for a while. I probably have no more than three to five patients on it in the practice. But when it works, it’s amazing stuff.

Now, let’s jump ahead to 2021. The year of Aduhelm (and several similar agents racing up behind it).

None of these drugs are even close to hitting home runs. For that matter, I’m not convinced they’re even able to get a man on base. To stretch my baseball analogy a bit, imagine watching a game by looking only at the RBI and ERA stats changing. The numbers change slightly, but you have no evidence that either team is winning. Which is, after all, the whole point.

And, to some extent, that’s the basis of Aduhelm’s approval, and likely the same standards its competitors will be held to.

Although they treat different conditions, and are chemically unrelated, the similarities between Felbatol and the currently advancing bunch of monoclonal antibody (MAB) agents for Alzheimer’s disease make an interesting contrast.

Unlike Felbatol’s proven efficacy for epilepsy, the current MABs offer minimal statistically significant clinical benefit for Alzheimer’s disease. At the same time the risk of amyloid-related imaging abnormalities (ARIA) and its complications with them is significantly higher than that of either of Felbatol’s known, potentially lethal, idiosyncratic effects.

With those odds, I’m far more willing (as are my patients) to take chances with Felbatol for epilepsy than the current MAB bunch for Alzheimer’s disease. In medicine, every day is an exercise in working through the risks and benefits of each patient’s individual situation.

As I’ve stated before, I’m not in the grandstand rooting for these Alzheimer’s drugs to fail. I’ve lost a few family members, and certainly my share of patients, to dementia. I’d be thrilled, and more than willing to prescribe it, if something truly effective came along for it.

Nor do I take any kind of pleasure in the recent news that, because of Aduhelm’s failings, around 1,000 Biogen employees will lose their jobs. I feel terrible for them, as most had nothing to do with the decision to forge ahead with the product. More may soon follow at other companies working with similar agents.

Here we are, though, going into 2022. I’m still, albeit rarely, writing for Felbatol 30 years after it came to market for one reason: It works. But it seems pretty unlikely that future neurologists in 2052 will say the same about the current crops of MABs for Alzheimer’s disease.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I still, on occasion, use Felbatol (felbamate).

Thirty years since its explosive entrance to the market, then even more explosive collapse, it remains, in my opinion, the most effective of the second generation of anti-seizure medications. Arguably, even more effective than any of the third generation, too.

That’s not to say I use a lot of it. I don’t. It’s like handling unstable dynamite. Tremendous power, but also an above-average degree of risk. Even after things hit the fan with it in the mid-90s, I remember one of my epilepsy clinic attendings telling me, “This is a home-run drug. In refractory patients you might see some benefit by adding another agent, but with this one, you could stop their seizures and hit it out of the park.”

Like most neurologists, I use other epilepsy options first and second line. But sometimes you get the patient who’s failed the usual ones. Then I start to think about Felbatol. I explain the situation to the patients and their families and let them make the final decision. I worry and watch labs very closely for a while. I probably have no more than three to five patients on it in the practice. But when it works, it’s amazing stuff.

Now, let’s jump ahead to 2021. The year of Aduhelm (and several similar agents racing up behind it).

None of these drugs are even close to hitting home runs. For that matter, I’m not convinced they’re even able to get a man on base. To stretch my baseball analogy a bit, imagine watching a game by looking only at the RBI and ERA stats changing. The numbers change slightly, but you have no evidence that either team is winning. Which is, after all, the whole point.

And, to some extent, that’s the basis of Aduhelm’s approval, and likely the same standards its competitors will be held to.

Although they treat different conditions, and are chemically unrelated, the similarities between Felbatol and the currently advancing bunch of monoclonal antibody (MAB) agents for Alzheimer’s disease make an interesting contrast.

Unlike Felbatol’s proven efficacy for epilepsy, the current MABs offer minimal statistically significant clinical benefit for Alzheimer’s disease. At the same time the risk of amyloid-related imaging abnormalities (ARIA) and its complications with them is significantly higher than that of either of Felbatol’s known, potentially lethal, idiosyncratic effects.

With those odds, I’m far more willing (as are my patients) to take chances with Felbatol for epilepsy than the current MAB bunch for Alzheimer’s disease. In medicine, every day is an exercise in working through the risks and benefits of each patient’s individual situation.

As I’ve stated before, I’m not in the grandstand rooting for these Alzheimer’s drugs to fail. I’ve lost a few family members, and certainly my share of patients, to dementia. I’d be thrilled, and more than willing to prescribe it, if something truly effective came along for it.

Nor do I take any kind of pleasure in the recent news that, because of Aduhelm’s failings, around 1,000 Biogen employees will lose their jobs. I feel terrible for them, as most had nothing to do with the decision to forge ahead with the product. More may soon follow at other companies working with similar agents.

Here we are, though, going into 2022. I’m still, albeit rarely, writing for Felbatol 30 years after it came to market for one reason: It works. But it seems pretty unlikely that future neurologists in 2052 will say the same about the current crops of MABs for Alzheimer’s disease.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

I still, on occasion, use Felbatol (felbamate).

Thirty years since its explosive entrance to the market, then even more explosive collapse, it remains, in my opinion, the most effective of the second generation of anti-seizure medications. Arguably, even more effective than any of the third generation, too.

That’s not to say I use a lot of it. I don’t. It’s like handling unstable dynamite. Tremendous power, but also an above-average degree of risk. Even after things hit the fan with it in the mid-90s, I remember one of my epilepsy clinic attendings telling me, “This is a home-run drug. In refractory patients you might see some benefit by adding another agent, but with this one, you could stop their seizures and hit it out of the park.”

Like most neurologists, I use other epilepsy options first and second line. But sometimes you get the patient who’s failed the usual ones. Then I start to think about Felbatol. I explain the situation to the patients and their families and let them make the final decision. I worry and watch labs very closely for a while. I probably have no more than three to five patients on it in the practice. But when it works, it’s amazing stuff.

Now, let’s jump ahead to 2021. The year of Aduhelm (and several similar agents racing up behind it).

None of these drugs are even close to hitting home runs. For that matter, I’m not convinced they’re even able to get a man on base. To stretch my baseball analogy a bit, imagine watching a game by looking only at the RBI and ERA stats changing. The numbers change slightly, but you have no evidence that either team is winning. Which is, after all, the whole point.

And, to some extent, that’s the basis of Aduhelm’s approval, and likely the same standards its competitors will be held to.

Although they treat different conditions, and are chemically unrelated, the similarities between Felbatol and the currently advancing bunch of monoclonal antibody (MAB) agents for Alzheimer’s disease make an interesting contrast.

Unlike Felbatol’s proven efficacy for epilepsy, the current MABs offer minimal statistically significant clinical benefit for Alzheimer’s disease. At the same time the risk of amyloid-related imaging abnormalities (ARIA) and its complications with them is significantly higher than that of either of Felbatol’s known, potentially lethal, idiosyncratic effects.

With those odds, I’m far more willing (as are my patients) to take chances with Felbatol for epilepsy than the current MAB bunch for Alzheimer’s disease. In medicine, every day is an exercise in working through the risks and benefits of each patient’s individual situation.

As I’ve stated before, I’m not in the grandstand rooting for these Alzheimer’s drugs to fail. I’ve lost a few family members, and certainly my share of patients, to dementia. I’d be thrilled, and more than willing to prescribe it, if something truly effective came along for it.

Nor do I take any kind of pleasure in the recent news that, because of Aduhelm’s failings, around 1,000 Biogen employees will lose their jobs. I feel terrible for them, as most had nothing to do with the decision to forge ahead with the product. More may soon follow at other companies working with similar agents.

Here we are, though, going into 2022. I’m still, albeit rarely, writing for Felbatol 30 years after it came to market for one reason: It works. But it seems pretty unlikely that future neurologists in 2052 will say the same about the current crops of MABs for Alzheimer’s disease.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Case

A 35-year-old woman with opioid use disorder (OUD) presents with fever, left arm redness, and swelling. She is admitted to the hospital for cellulitis treatment. On the day after admission she becomes agitated and develops nausea, diarrhea, and generalized pain. Opioid withdrawal is suspected. How should her opioid use be addressed while in the hospital?

Brief overview of the issue

Since 1999, there have been more than 800,000 deaths related to drug overdose in the United States, and in 2019 more than 70% of drug overdose deaths involved an opioid.^1,2 Although effective treatments for OUD exist, less than 20% of those with OUD are engaged in treatment.³

In America, 4%-11% of hospitalized patients have OUD. Hospitalized patients with OUD often experience stigma surrounding their disease, and many inpatient clinicians lack knowledge regarding the care of patients with OUD. As a result, withdrawal symptoms may go untreated, which can erode trust in the medical system and contribute to patients’ leaving the hospital before their primary medical issue is fully addressed. Therefore, it is essential that inpatient clinicians be familiar with the management of this complex and vulnerable patient population. Initiating treatment for OUD in the hospital setting is feasible and effective, and can lead to increased engagement in OUD treatment even after the hospital stay.
 

Overview of the data

Assessing patients with suspected OUD

Assessment for OUD starts with an in-depth opioid use history including frequency, amount, and method of administration. Clinicians should gather information regarding use of other substances or nonprescribed medications, and take thorough psychiatric and social histories. A formal diagnosis of OUD can be made using the Fifth Edition Diagnostic and Statistical Manual for Mental Disorders (DSM-5) diagnostic criteria.

Recognizing and managing opioid withdrawal

OUD in hospitalized patients often becomes apparent when patients develop signs and symptoms of withdrawal. Decreasing physical discomfort related to withdrawal can allow inpatient clinicians to address the condition for which the patient was hospitalized, help to strengthen the patient-clinician relationship, and provide an opportunity to discuss long-term OUD treatment.

Signs and symptoms of opioid withdrawal include anxiety, restlessness, irritability, generalized pain, rhinorrhea, yawning, lacrimation, piloerection, anorexia, and nausea. Withdrawal can last days to weeks, depending on the half-life of the opioid that was used. Opioids with shorter half-lives, such as heroin or oxycodone, cause withdrawal with earlier onset and shorter duration than do opioids with longer half-lives, such as methadone. The degree of withdrawal can be quantified with validated tools, such as the Clinical Opiate Withdrawal Scale (COWS).

Treatment of opioid withdrawal should generally include the use of an opioid agonist such as methadone or buprenorphine. A 2017 Cochrane meta-analysis found methadone or buprenorphine to be more effective than clonidine in alleviating symptoms of withdrawal and in retaining patients in treatment.⁴ Clonidine, an alpha2-adrenergic agonist that binds to receptors in the locus coeruleus, does not alleviate opioid cravings, but may be used as an adjunctive treatment for associated autonomic withdrawal symptoms. Other adjunctive medications include analgesics, antiemetics, antidiarrheals, and antihistamines.

Dr. Anne Linker

Opioid agonist treatment for opioid use disorder

Opioid agonist treatment (OAT) with methadone or buprenorphine is associated with decreased mortality, opioid use, and infectious complications, but remains underutilized.⁵ Hospitalized patients with OUD are frequently managed with a rapid opioid detoxification and then discharged without continued OUD treatment. Detoxification alone can lead to a relapse rate as high as 90%.⁶ Patients are at increased risk for overdose after withdrawal due to loss of tolerance. Inpatient clinicians can close this OUD treatment gap by familiarizing themselves with OAT and offering to initiate OAT for maintenance treatment in interested patients. In one study, patients started on buprenorphine while hospitalized were more likely to be engaged in treatment and less likely to report drug use at follow-up, compared to patients who were referred without starting the medication.⁷

Buprenorphine

Buprenorphine is a partial agonist at the mu opioid receptor that can be ordered in the inpatient setting by any clinician. In the outpatient setting only DATA 2000 waivered clinicians can prescribe buprenorphine.⁸ Buprenorphine is most commonly coformulated with naloxone, an opioid antagonist, and is available in sublingual films or tablets. The naloxone component is not bioavailable when taken sublingually but becomes bioavailable if the drug is injected intravenously, leading to acute withdrawal.

Buprenorphine has a higher affinity for the mu opioid receptor than most opioids. If administered while other opioids are still present, it will displace the other opioid from the receptor but only partially stimulate the receptor, which can cause precipitated withdrawal. Buprenorphine initiation can start when the COWS score reflects moderate withdrawal. Many institutions use a threshold of 8-12 on the COWS scale. Typical dosing is 2-4 mg of buprenorphine at intervals of 1-2 hours as needed until the COWS score is less than 8, up to a maximum of 16 mg on day 1. The total dose from day 1 may be given as a daily dose beginning on day 2, up to a maximum total daily dose of 24 mg.

In recent years, a method of initiating buprenorphine called “micro-dosing” has gained traction. Very small doses of buprenorphine are given while a patient is receiving other opioids, thereby reducing the risk of precipitated withdrawal. This method can be helpful for patients who cannot tolerate withdrawal or who have recently taken long-acting opioids such as methadone. Such protocols should be utilized only at centers where consultation with an addiction specialist or experienced clinician is possible.

Despite evidence of buprenorphine’s efficacy, there are barriers to prescribing it. Physicians and advanced practitioners must be granted a waiver from the Drug Enforcement Administration to prescribe buprenorphine to outpatients. As of 2017, less than 10% of primary care physicians had obtained waivers.⁹ However, inpatient clinicians without a waiver can order buprenorphine and initiate treatment. Best practice is to do so with a specific plan for continuation at discharge. We encourage inpatient clinicians to obtain a waiver, so that a prescription can be given at discharge to bridge the patient to a first appointment with a community clinician who can continue treatment. As of April 27, 2021, providers treating fewer than 30 patients with OUD at one time may obtain a waiver without additional training.¹⁰

Methadone

Methadone is a full agonist at the mu opioid receptor. In the hospital setting, methadone can be ordered by any clinician to prevent and treat withdrawal. Commonly, doses of 10 mg can be given using the COWS score to guide the need for additional dosing. The patient can be reassessed every 1-2 hours to ensure that symptoms are improving, and that there is no sign of oversedation before giving additional methadone. For most patients, withdrawal can be managed with 20-40 mg of methadone daily.

In contrast to buprenorphine, methadone will not precipitate withdrawal and can be initiated even when patients are not yet showing withdrawal symptoms. Outpatient methadone treatment for OUD is federally regulated and can be delivered only in opioid treatment programs (OTPs).

 

Choosing methadone or buprenorphine in the inpatient setting

The choice between buprenorphine and methadone should take into consideration several factors, including patient preference, treatment history, and available outpatient treatment programs, which may vary widely by geographic region. Some patients benefit from the higher level of support and counseling available at OTPs. Methadone is available at all OTPs, and the availability of buprenorphine in this setting is increasing. Other patients may prefer the convenience and flexibility of buprenorphine treatment in an outpatient office setting.

Some patients have prior negative experiences with OAT. These can include prior precipitated withdrawal with buprenorphine induction, or negative experiences with the structure of OTPs. Clinicians are encouraged to provide counseling if patients have a history of precipitated withdrawal to assure them that this can be avoided with proper dosing. Clinicians should be familiar with available treatment options in their community and can refer to the Substance Abuse and Mental Health Services Administration (SAMHSA) website to locate OTPs and buprenorphine prescribers.

Herscher, M et al. Diagnosis and Management of Opioid Use Disorder in Hospitalized Patients. doi: 10.1016/j.mcna.2020.03.003.

Polypharmacy and safety

If combined with benzodiazepines, alcohol, or other sedating agents, methadone or buprenorphine can increase risk of overdose. However, OUD treatment should not be withheld because of other substance use. Clinicians initiating treatment should counsel patients on the risk of concomitant substance use and provide overdose prevention education.

A brief note on naltrexone

Naltrexone, an opioid antagonist, is used more commonly in outpatient addiction treatment than in the inpatient setting, but inpatient clinicians should be aware of its use. It is available in oral and long-acting injectable formulations. Its utility in the inpatient setting may be limited as safe administration requires 7-10 days of opioid abstinence.

Discharge planning

Patients with OUD or who are started on OAT during a hospitalization should be linked to continued outpatient treatment. Before discharge it is best to ensure vaccinations for HAV, HBV, pneumococcus, and tetanus are up to date, and perform screening for HIV, hepatitis C, tuberculosis, and sexually transmitted infections if appropriate. All patients with OUD should be prescribed or provided with take-home naloxone for overdose reversal. Patients can also be referred to syringe service programs for additional harm reduction counseling and services.

Application of the data to our patient

For our patient, either methadone or buprenorphine could be used to treat her withdrawal. The COWS score should be used to assess withdrawal severity, and to guide appropriate timing of medication initiation. If she wishes to continue OAT after discharge, she should be linked to a clinician who can engage her in ongoing medical care. Prior to discharge she should also receive relevant vaccines and screening for infectious diseases as outlined above, as well as take-home naloxone (or a prescription).

Bottom line

Inpatient clinicians can play a pivotal role in patients’ lives by ensuring that patients with OUD receive OAT and are connected to outpatient care at discharge.

Dr. Linker is assistant professor in the division of hospital medicine, Icahn School of Medicine at Mount Sinai, New York. Ms. Hirt, Mr. Fine, and Mr. Villasanivis are medical students at the Icahn School of Medicine at Mount Sinai. Dr. Wang is assistant professor in the division of general internal medicine, Icahn School of Medicine at Mount Sinai. Dr. Herscher is assistant professor in the division of hospital medicine, Icahn School of Medicine at Mount Sinai.

References

1. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics; 2020. Available at http://wonder.cdc.gov.

2. Mattson CL et al. Trends and geographic patterns in drug and synthetic opioid overdose deaths – United States, 2013-2019. MMWR Morb Mortal Wkly Rep. 2021;70:202-7. doi: 10.15585/mmwr.mm7006a4.

3. Wakeman SE et al. Comparative effectiveness of different treatment pathways for opioid use disorder. JAMA Netw Open. 2020 Feb 5;3(2):e1920622. doi: 10.1001/jamanetworkopen.2019.20622.

4. Gowing L et al. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD002025. doi: 10.1002/14651858.CD002025.pub5.

5. Sordo L et al. Mortality risk during and after opioid substitution treatment: Systematic review and meta-analysis of cohort studies. BMJ. 2017 Apr 26;357:j1550. doi: 10.1136/bmj.j1550.

6. Smyth BP et al. Lapse and relapse following inpatient treatment of opiate dependence. Ir Med J. 2010 Jun;103(6):176-9. Available at www.drugsandalcohol.ie/13405.

7. Liebschutz JM. Buprenorphine treatment for hospitalized, opioid-dependent patients: A randomized clinical trial. JAMA Intern Med. 2014 Aug;174(8):1369-76. doi: 10.1001/jamainternmed.2014.2556.

8. Substance Abuse and Mental Health Services Administration. (Aug 20, 2020) Statutes, Regulations, and Guidelines.

9. McBain RK et al. Growth and distribution of buprenorphine-waivered providers in the United States, 2007-2017. Ann Intern Med. 2020;172(7):504-6. doi: 10.7326/M19-2403.

10. HHS releases new buprenorphine practice guidelines, expanding access to treatment for opioid use disorder. Apr 27, 2021.

11. Herscher M et al. Diagnosis and management of opioid use disorder in hospitalized patients. Med Clin North Am. 2020 Jul;104(4):695-708. doi: 10.1016/j.mcna.2020.03.003.

Additional reading

Winetsky D. Expanding treatment opportunities for hospitalized patients with opioid use disorders. J Hosp Med. 2018 Jan;13(1):62-4. doi: 10.12788/jhm.2861.

Donroe JH. Caring for patients with opioid use disorder in the hospital. Can Med Assoc J. 2016 Dec 6;188(17-18):1232-9. doi: 10.1503/cmaj.160290.

Herscher M et al. Diagnosis and management of opioid use disorder in hospitalized patients. Med Clin North Am. 2020 Jul;104(4):695-708. doi: 10.1016/j.mcna.2020.03.003.
 

Key points

• Most patients with OUD are not engaged in evidence-based treatment. Clinicians have an opportunity to utilize the inpatient stay as a ‘reachable moment’ to engage patients with OUD in evidence-based treatment.
• Buprenorphine and methadone are effective opioid agonist medications used to treat OUD, and clinicians with the appropriate knowledge base can initiate either during the inpatient encounter, and link the patient to OUD treatment after the hospital stay.

Quiz

Caring for hospitalized patients with OUD

Most patients with OUD are not engaged in effective treatment. Hospitalization can be a ‘reachable moment’ to engage patients with OUD in evidence-based treatment.

1. Which is an effective and evidence-based medication for treating opioid withdrawal and OUD?

a) Naltrexone.

b) Buprenorphine.

c) Opioid detoxification.

d) Clonidine.

Explanation: Buprenorphine is effective for alleviating symptoms of withdrawal as well as for the long-term treatment of OUD. While naltrexone is also used to treat OUD, it is not useful for treating withdrawal. Clonidine can be a useful adjunctive medication for treating withdrawal but is not a long-term treatment for OUD. Nonpharmacologic detoxification is not an effective treatment for OUD and is associated with high relapse rates.



2. What scale can be used during a hospital stay to monitor patients with OUD at risk of opioid withdrawal, and to aid in buprenorphine initiation?

a) CIWA score.

b) PADUA score.

c) COWS score.

d) 4T score.

Explanation: COWS is the “clinical opiate withdrawal scale.” The COWS score should be calculated by a trained provider, and includes objective parameters (such as pulse) and subjective symptoms (such as GI upset, bone/joint aches.) It is recommended that agonist therapy be started when the COWS score is consistent with moderate withdrawal.



3. How can clinicians reliably find out if there are outpatient resources/clinics for patients with OUD in their area?

a) No way to find this out without personal knowledge.

b) Hospital providers and patients can visit www.samhsa.gov/find-help/national-helpline or call 1-800-662-HELP (4357) to find options for treatment for substance use disorders in their areas.

c) Dial “0” on any phone and ask.

d) Ask around at your hospital.

Explanation: The Substance Abuse and Mental Health Services Administration (SAMHSA) is an agency in the U.S. Department of Health and Human Services that is engaged in public health efforts to reduce the impact of substance abuse and mental illness on local communities. The agency’s website has helpful information about resources for substance use treatment.



4. Patients with OUD should be prescribed and given training about what medication that can be lifesaving when given during an opioid overdose?

a) Aspirin.

b) Naloxone.

c) Naltrexone.

d) Clonidine.

Explanation: Naloxone can be life-saving in the setting of an overdose. Best practice is to provide naloxone and training to patients with OUD.



5. When patients take buprenorphine soon after taking other opioids, there is concern for the development of which reaction:

a) Precipitated withdrawal.

b) Opioid overdose.

c) Allergic reaction.

d) Intoxication.

Explanation: Administering buprenorphine soon after taking other opioids can cause precipitated withdrawal, as buprenorphine binds with higher affinity to the mu receptor than many opioids. Precipitated withdrawal causes severe discomfort and can be dangerous for patients.

Case

A 35-year-old woman with opioid use disorder (OUD) presents with fever, left arm redness, and swelling. She is admitted to the hospital for cellulitis treatment. On the day after admission she becomes agitated and develops nausea, diarrhea, and generalized pain. Opioid withdrawal is suspected. How should her opioid use be addressed while in the hospital?

Brief overview of the issue

Since 1999, there have been more than 800,000 deaths related to drug overdose in the United States, and in 2019 more than 70% of drug overdose deaths involved an opioid.^1,2 Although effective treatments for OUD exist, less than 20% of those with OUD are engaged in treatment.³

In America, 4%-11% of hospitalized patients have OUD. Hospitalized patients with OUD often experience stigma surrounding their disease, and many inpatient clinicians lack knowledge regarding the care of patients with OUD. As a result, withdrawal symptoms may go untreated, which can erode trust in the medical system and contribute to patients’ leaving the hospital before their primary medical issue is fully addressed. Therefore, it is essential that inpatient clinicians be familiar with the management of this complex and vulnerable patient population. Initiating treatment for OUD in the hospital setting is feasible and effective, and can lead to increased engagement in OUD treatment even after the hospital stay.
 

Overview of the data

Assessing patients with suspected OUD

Assessment for OUD starts with an in-depth opioid use history including frequency, amount, and method of administration. Clinicians should gather information regarding use of other substances or nonprescribed medications, and take thorough psychiatric and social histories. A formal diagnosis of OUD can be made using the Fifth Edition Diagnostic and Statistical Manual for Mental Disorders (DSM-5) diagnostic criteria.

Recognizing and managing opioid withdrawal

OUD in hospitalized patients often becomes apparent when patients develop signs and symptoms of withdrawal. Decreasing physical discomfort related to withdrawal can allow inpatient clinicians to address the condition for which the patient was hospitalized, help to strengthen the patient-clinician relationship, and provide an opportunity to discuss long-term OUD treatment.

Signs and symptoms of opioid withdrawal include anxiety, restlessness, irritability, generalized pain, rhinorrhea, yawning, lacrimation, piloerection, anorexia, and nausea. Withdrawal can last days to weeks, depending on the half-life of the opioid that was used. Opioids with shorter half-lives, such as heroin or oxycodone, cause withdrawal with earlier onset and shorter duration than do opioids with longer half-lives, such as methadone. The degree of withdrawal can be quantified with validated tools, such as the Clinical Opiate Withdrawal Scale (COWS).

Treatment of opioid withdrawal should generally include the use of an opioid agonist such as methadone or buprenorphine. A 2017 Cochrane meta-analysis found methadone or buprenorphine to be more effective than clonidine in alleviating symptoms of withdrawal and in retaining patients in treatment.⁴ Clonidine, an alpha2-adrenergic agonist that binds to receptors in the locus coeruleus, does not alleviate opioid cravings, but may be used as an adjunctive treatment for associated autonomic withdrawal symptoms. Other adjunctive medications include analgesics, antiemetics, antidiarrheals, and antihistamines.

Dr. Anne Linker

Opioid agonist treatment for opioid use disorder

Opioid agonist treatment (OAT) with methadone or buprenorphine is associated with decreased mortality, opioid use, and infectious complications, but remains underutilized.⁵ Hospitalized patients with OUD are frequently managed with a rapid opioid detoxification and then discharged without continued OUD treatment. Detoxification alone can lead to a relapse rate as high as 90%.⁶ Patients are at increased risk for overdose after withdrawal due to loss of tolerance. Inpatient clinicians can close this OUD treatment gap by familiarizing themselves with OAT and offering to initiate OAT for maintenance treatment in interested patients. In one study, patients started on buprenorphine while hospitalized were more likely to be engaged in treatment and less likely to report drug use at follow-up, compared to patients who were referred without starting the medication.⁷

Buprenorphine

Buprenorphine is a partial agonist at the mu opioid receptor that can be ordered in the inpatient setting by any clinician. In the outpatient setting only DATA 2000 waivered clinicians can prescribe buprenorphine.⁸ Buprenorphine is most commonly coformulated with naloxone, an opioid antagonist, and is available in sublingual films or tablets. The naloxone component is not bioavailable when taken sublingually but becomes bioavailable if the drug is injected intravenously, leading to acute withdrawal.

Buprenorphine has a higher affinity for the mu opioid receptor than most opioids. If administered while other opioids are still present, it will displace the other opioid from the receptor but only partially stimulate the receptor, which can cause precipitated withdrawal. Buprenorphine initiation can start when the COWS score reflects moderate withdrawal. Many institutions use a threshold of 8-12 on the COWS scale. Typical dosing is 2-4 mg of buprenorphine at intervals of 1-2 hours as needed until the COWS score is less than 8, up to a maximum of 16 mg on day 1. The total dose from day 1 may be given as a daily dose beginning on day 2, up to a maximum total daily dose of 24 mg.

In recent years, a method of initiating buprenorphine called “micro-dosing” has gained traction. Very small doses of buprenorphine are given while a patient is receiving other opioids, thereby reducing the risk of precipitated withdrawal. This method can be helpful for patients who cannot tolerate withdrawal or who have recently taken long-acting opioids such as methadone. Such protocols should be utilized only at centers where consultation with an addiction specialist or experienced clinician is possible.

Despite evidence of buprenorphine’s efficacy, there are barriers to prescribing it. Physicians and advanced practitioners must be granted a waiver from the Drug Enforcement Administration to prescribe buprenorphine to outpatients. As of 2017, less than 10% of primary care physicians had obtained waivers.⁹ However, inpatient clinicians without a waiver can order buprenorphine and initiate treatment. Best practice is to do so with a specific plan for continuation at discharge. We encourage inpatient clinicians to obtain a waiver, so that a prescription can be given at discharge to bridge the patient to a first appointment with a community clinician who can continue treatment. As of April 27, 2021, providers treating fewer than 30 patients with OUD at one time may obtain a waiver without additional training.¹⁰

Methadone

Methadone is a full agonist at the mu opioid receptor. In the hospital setting, methadone can be ordered by any clinician to prevent and treat withdrawal. Commonly, doses of 10 mg can be given using the COWS score to guide the need for additional dosing. The patient can be reassessed every 1-2 hours to ensure that symptoms are improving, and that there is no sign of oversedation before giving additional methadone. For most patients, withdrawal can be managed with 20-40 mg of methadone daily.

In contrast to buprenorphine, methadone will not precipitate withdrawal and can be initiated even when patients are not yet showing withdrawal symptoms. Outpatient methadone treatment for OUD is federally regulated and can be delivered only in opioid treatment programs (OTPs).

 

Choosing methadone or buprenorphine in the inpatient setting

The choice between buprenorphine and methadone should take into consideration several factors, including patient preference, treatment history, and available outpatient treatment programs, which may vary widely by geographic region. Some patients benefit from the higher level of support and counseling available at OTPs. Methadone is available at all OTPs, and the availability of buprenorphine in this setting is increasing. Other patients may prefer the convenience and flexibility of buprenorphine treatment in an outpatient office setting.

Some patients have prior negative experiences with OAT. These can include prior precipitated withdrawal with buprenorphine induction, or negative experiences with the structure of OTPs. Clinicians are encouraged to provide counseling if patients have a history of precipitated withdrawal to assure them that this can be avoided with proper dosing. Clinicians should be familiar with available treatment options in their community and can refer to the Substance Abuse and Mental Health Services Administration (SAMHSA) website to locate OTPs and buprenorphine prescribers.

Herscher, M et al. Diagnosis and Management of Opioid Use Disorder in Hospitalized Patients. doi: 10.1016/j.mcna.2020.03.003.

Polypharmacy and safety

If combined with benzodiazepines, alcohol, or other sedating agents, methadone or buprenorphine can increase risk of overdose. However, OUD treatment should not be withheld because of other substance use. Clinicians initiating treatment should counsel patients on the risk of concomitant substance use and provide overdose prevention education.

A brief note on naltrexone

Naltrexone, an opioid antagonist, is used more commonly in outpatient addiction treatment than in the inpatient setting, but inpatient clinicians should be aware of its use. It is available in oral and long-acting injectable formulations. Its utility in the inpatient setting may be limited as safe administration requires 7-10 days of opioid abstinence.

Discharge planning

Patients with OUD or who are started on OAT during a hospitalization should be linked to continued outpatient treatment. Before discharge it is best to ensure vaccinations for HAV, HBV, pneumococcus, and tetanus are up to date, and perform screening for HIV, hepatitis C, tuberculosis, and sexually transmitted infections if appropriate. All patients with OUD should be prescribed or provided with take-home naloxone for overdose reversal. Patients can also be referred to syringe service programs for additional harm reduction counseling and services.

Application of the data to our patient

For our patient, either methadone or buprenorphine could be used to treat her withdrawal. The COWS score should be used to assess withdrawal severity, and to guide appropriate timing of medication initiation. If she wishes to continue OAT after discharge, she should be linked to a clinician who can engage her in ongoing medical care. Prior to discharge she should also receive relevant vaccines and screening for infectious diseases as outlined above, as well as take-home naloxone (or a prescription).

Bottom line

Inpatient clinicians can play a pivotal role in patients’ lives by ensuring that patients with OUD receive OAT and are connected to outpatient care at discharge.

Dr. Linker is assistant professor in the division of hospital medicine, Icahn School of Medicine at Mount Sinai, New York. Ms. Hirt, Mr. Fine, and Mr. Villasanivis are medical students at the Icahn School of Medicine at Mount Sinai. Dr. Wang is assistant professor in the division of general internal medicine, Icahn School of Medicine at Mount Sinai. Dr. Herscher is assistant professor in the division of hospital medicine, Icahn School of Medicine at Mount Sinai.

References

1. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics; 2020. Available at http://wonder.cdc.gov.

2. Mattson CL et al. Trends and geographic patterns in drug and synthetic opioid overdose deaths – United States, 2013-2019. MMWR Morb Mortal Wkly Rep. 2021;70:202-7. doi: 10.15585/mmwr.mm7006a4.

3. Wakeman SE et al. Comparative effectiveness of different treatment pathways for opioid use disorder. JAMA Netw Open. 2020 Feb 5;3(2):e1920622. doi: 10.1001/jamanetworkopen.2019.20622.

4. Gowing L et al. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD002025. doi: 10.1002/14651858.CD002025.pub5.

5. Sordo L et al. Mortality risk during and after opioid substitution treatment: Systematic review and meta-analysis of cohort studies. BMJ. 2017 Apr 26;357:j1550. doi: 10.1136/bmj.j1550.

6. Smyth BP et al. Lapse and relapse following inpatient treatment of opiate dependence. Ir Med J. 2010 Jun;103(6):176-9. Available at www.drugsandalcohol.ie/13405.

7. Liebschutz JM. Buprenorphine treatment for hospitalized, opioid-dependent patients: A randomized clinical trial. JAMA Intern Med. 2014 Aug;174(8):1369-76. doi: 10.1001/jamainternmed.2014.2556.

8. Substance Abuse and Mental Health Services Administration. (Aug 20, 2020) Statutes, Regulations, and Guidelines.

9. McBain RK et al. Growth and distribution of buprenorphine-waivered providers in the United States, 2007-2017. Ann Intern Med. 2020;172(7):504-6. doi: 10.7326/M19-2403.

10. HHS releases new buprenorphine practice guidelines, expanding access to treatment for opioid use disorder. Apr 27, 2021.

11. Herscher M et al. Diagnosis and management of opioid use disorder in hospitalized patients. Med Clin North Am. 2020 Jul;104(4):695-708. doi: 10.1016/j.mcna.2020.03.003.

Additional reading

Winetsky D. Expanding treatment opportunities for hospitalized patients with opioid use disorders. J Hosp Med. 2018 Jan;13(1):62-4. doi: 10.12788/jhm.2861.

Donroe JH. Caring for patients with opioid use disorder in the hospital. Can Med Assoc J. 2016 Dec 6;188(17-18):1232-9. doi: 10.1503/cmaj.160290.

Herscher M et al. Diagnosis and management of opioid use disorder in hospitalized patients. Med Clin North Am. 2020 Jul;104(4):695-708. doi: 10.1016/j.mcna.2020.03.003.
 

Key points

• Most patients with OUD are not engaged in evidence-based treatment. Clinicians have an opportunity to utilize the inpatient stay as a ‘reachable moment’ to engage patients with OUD in evidence-based treatment.
• Buprenorphine and methadone are effective opioid agonist medications used to treat OUD, and clinicians with the appropriate knowledge base can initiate either during the inpatient encounter, and link the patient to OUD treatment after the hospital stay.

Quiz

Caring for hospitalized patients with OUD

Most patients with OUD are not engaged in effective treatment. Hospitalization can be a ‘reachable moment’ to engage patients with OUD in evidence-based treatment.

1. Which is an effective and evidence-based medication for treating opioid withdrawal and OUD?

a) Naltrexone.

b) Buprenorphine.

c) Opioid detoxification.

d) Clonidine.

Explanation: Buprenorphine is effective for alleviating symptoms of withdrawal as well as for the long-term treatment of OUD. While naltrexone is also used to treat OUD, it is not useful for treating withdrawal. Clonidine can be a useful adjunctive medication for treating withdrawal but is not a long-term treatment for OUD. Nonpharmacologic detoxification is not an effective treatment for OUD and is associated with high relapse rates.



2. What scale can be used during a hospital stay to monitor patients with OUD at risk of opioid withdrawal, and to aid in buprenorphine initiation?

a) CIWA score.

b) PADUA score.

c) COWS score.

d) 4T score.

Explanation: COWS is the “clinical opiate withdrawal scale.” The COWS score should be calculated by a trained provider, and includes objective parameters (such as pulse) and subjective symptoms (such as GI upset, bone/joint aches.) It is recommended that agonist therapy be started when the COWS score is consistent with moderate withdrawal.



3. How can clinicians reliably find out if there are outpatient resources/clinics for patients with OUD in their area?

a) No way to find this out without personal knowledge.

b) Hospital providers and patients can visit www.samhsa.gov/find-help/national-helpline or call 1-800-662-HELP (4357) to find options for treatment for substance use disorders in their areas.

c) Dial “0” on any phone and ask.

d) Ask around at your hospital.

Explanation: The Substance Abuse and Mental Health Services Administration (SAMHSA) is an agency in the U.S. Department of Health and Human Services that is engaged in public health efforts to reduce the impact of substance abuse and mental illness on local communities. The agency’s website has helpful information about resources for substance use treatment.



4. Patients with OUD should be prescribed and given training about what medication that can be lifesaving when given during an opioid overdose?

a) Aspirin.

b) Naloxone.

c) Naltrexone.

d) Clonidine.

Explanation: Naloxone can be life-saving in the setting of an overdose. Best practice is to provide naloxone and training to patients with OUD.



5. When patients take buprenorphine soon after taking other opioids, there is concern for the development of which reaction:

a) Precipitated withdrawal.

b) Opioid overdose.

c) Allergic reaction.

d) Intoxication.

Explanation: Administering buprenorphine soon after taking other opioids can cause precipitated withdrawal, as buprenorphine binds with higher affinity to the mu receptor than many opioids. Precipitated withdrawal causes severe discomfort and can be dangerous for patients.

Case

A 35-year-old woman with opioid use disorder (OUD) presents with fever, left arm redness, and swelling. She is admitted to the hospital for cellulitis treatment. On the day after admission she becomes agitated and develops nausea, diarrhea, and generalized pain. Opioid withdrawal is suspected. How should her opioid use be addressed while in the hospital?

Brief overview of the issue

Since 1999, there have been more than 800,000 deaths related to drug overdose in the United States, and in 2019 more than 70% of drug overdose deaths involved an opioid.^1,2 Although effective treatments for OUD exist, less than 20% of those with OUD are engaged in treatment.³

In America, 4%-11% of hospitalized patients have OUD. Hospitalized patients with OUD often experience stigma surrounding their disease, and many inpatient clinicians lack knowledge regarding the care of patients with OUD. As a result, withdrawal symptoms may go untreated, which can erode trust in the medical system and contribute to patients’ leaving the hospital before their primary medical issue is fully addressed. Therefore, it is essential that inpatient clinicians be familiar with the management of this complex and vulnerable patient population. Initiating treatment for OUD in the hospital setting is feasible and effective, and can lead to increased engagement in OUD treatment even after the hospital stay.
 

Overview of the data

Assessing patients with suspected OUD

Assessment for OUD starts with an in-depth opioid use history including frequency, amount, and method of administration. Clinicians should gather information regarding use of other substances or nonprescribed medications, and take thorough psychiatric and social histories. A formal diagnosis of OUD can be made using the Fifth Edition Diagnostic and Statistical Manual for Mental Disorders (DSM-5) diagnostic criteria.

Recognizing and managing opioid withdrawal

OUD in hospitalized patients often becomes apparent when patients develop signs and symptoms of withdrawal. Decreasing physical discomfort related to withdrawal can allow inpatient clinicians to address the condition for which the patient was hospitalized, help to strengthen the patient-clinician relationship, and provide an opportunity to discuss long-term OUD treatment.

Signs and symptoms of opioid withdrawal include anxiety, restlessness, irritability, generalized pain, rhinorrhea, yawning, lacrimation, piloerection, anorexia, and nausea. Withdrawal can last days to weeks, depending on the half-life of the opioid that was used. Opioids with shorter half-lives, such as heroin or oxycodone, cause withdrawal with earlier onset and shorter duration than do opioids with longer half-lives, such as methadone. The degree of withdrawal can be quantified with validated tools, such as the Clinical Opiate Withdrawal Scale (COWS).

Treatment of opioid withdrawal should generally include the use of an opioid agonist such as methadone or buprenorphine. A 2017 Cochrane meta-analysis found methadone or buprenorphine to be more effective than clonidine in alleviating symptoms of withdrawal and in retaining patients in treatment.⁴ Clonidine, an alpha2-adrenergic agonist that binds to receptors in the locus coeruleus, does not alleviate opioid cravings, but may be used as an adjunctive treatment for associated autonomic withdrawal symptoms. Other adjunctive medications include analgesics, antiemetics, antidiarrheals, and antihistamines.

Dr. Anne Linker

Opioid agonist treatment for opioid use disorder

Opioid agonist treatment (OAT) with methadone or buprenorphine is associated with decreased mortality, opioid use, and infectious complications, but remains underutilized.⁵ Hospitalized patients with OUD are frequently managed with a rapid opioid detoxification and then discharged without continued OUD treatment. Detoxification alone can lead to a relapse rate as high as 90%.⁶ Patients are at increased risk for overdose after withdrawal due to loss of tolerance. Inpatient clinicians can close this OUD treatment gap by familiarizing themselves with OAT and offering to initiate OAT for maintenance treatment in interested patients. In one study, patients started on buprenorphine while hospitalized were more likely to be engaged in treatment and less likely to report drug use at follow-up, compared to patients who were referred without starting the medication.⁷

Buprenorphine

Buprenorphine is a partial agonist at the mu opioid receptor that can be ordered in the inpatient setting by any clinician. In the outpatient setting only DATA 2000 waivered clinicians can prescribe buprenorphine.⁸ Buprenorphine is most commonly coformulated with naloxone, an opioid antagonist, and is available in sublingual films or tablets. The naloxone component is not bioavailable when taken sublingually but becomes bioavailable if the drug is injected intravenously, leading to acute withdrawal.

Buprenorphine has a higher affinity for the mu opioid receptor than most opioids. If administered while other opioids are still present, it will displace the other opioid from the receptor but only partially stimulate the receptor, which can cause precipitated withdrawal. Buprenorphine initiation can start when the COWS score reflects moderate withdrawal. Many institutions use a threshold of 8-12 on the COWS scale. Typical dosing is 2-4 mg of buprenorphine at intervals of 1-2 hours as needed until the COWS score is less than 8, up to a maximum of 16 mg on day 1. The total dose from day 1 may be given as a daily dose beginning on day 2, up to a maximum total daily dose of 24 mg.

In recent years, a method of initiating buprenorphine called “micro-dosing” has gained traction. Very small doses of buprenorphine are given while a patient is receiving other opioids, thereby reducing the risk of precipitated withdrawal. This method can be helpful for patients who cannot tolerate withdrawal or who have recently taken long-acting opioids such as methadone. Such protocols should be utilized only at centers where consultation with an addiction specialist or experienced clinician is possible.

Despite evidence of buprenorphine’s efficacy, there are barriers to prescribing it. Physicians and advanced practitioners must be granted a waiver from the Drug Enforcement Administration to prescribe buprenorphine to outpatients. As of 2017, less than 10% of primary care physicians had obtained waivers.⁹ However, inpatient clinicians without a waiver can order buprenorphine and initiate treatment. Best practice is to do so with a specific plan for continuation at discharge. We encourage inpatient clinicians to obtain a waiver, so that a prescription can be given at discharge to bridge the patient to a first appointment with a community clinician who can continue treatment. As of April 27, 2021, providers treating fewer than 30 patients with OUD at one time may obtain a waiver without additional training.¹⁰

Methadone

Methadone is a full agonist at the mu opioid receptor. In the hospital setting, methadone can be ordered by any clinician to prevent and treat withdrawal. Commonly, doses of 10 mg can be given using the COWS score to guide the need for additional dosing. The patient can be reassessed every 1-2 hours to ensure that symptoms are improving, and that there is no sign of oversedation before giving additional methadone. For most patients, withdrawal can be managed with 20-40 mg of methadone daily.

In contrast to buprenorphine, methadone will not precipitate withdrawal and can be initiated even when patients are not yet showing withdrawal symptoms. Outpatient methadone treatment for OUD is federally regulated and can be delivered only in opioid treatment programs (OTPs).

 

Choosing methadone or buprenorphine in the inpatient setting

The choice between buprenorphine and methadone should take into consideration several factors, including patient preference, treatment history, and available outpatient treatment programs, which may vary widely by geographic region. Some patients benefit from the higher level of support and counseling available at OTPs. Methadone is available at all OTPs, and the availability of buprenorphine in this setting is increasing. Other patients may prefer the convenience and flexibility of buprenorphine treatment in an outpatient office setting.

Some patients have prior negative experiences with OAT. These can include prior precipitated withdrawal with buprenorphine induction, or negative experiences with the structure of OTPs. Clinicians are encouraged to provide counseling if patients have a history of precipitated withdrawal to assure them that this can be avoided with proper dosing. Clinicians should be familiar with available treatment options in their community and can refer to the Substance Abuse and Mental Health Services Administration (SAMHSA) website to locate OTPs and buprenorphine prescribers.

Herscher, M et al. Diagnosis and Management of Opioid Use Disorder in Hospitalized Patients. doi: 10.1016/j.mcna.2020.03.003.

Polypharmacy and safety

If combined with benzodiazepines, alcohol, or other sedating agents, methadone or buprenorphine can increase risk of overdose. However, OUD treatment should not be withheld because of other substance use. Clinicians initiating treatment should counsel patients on the risk of concomitant substance use and provide overdose prevention education.

A brief note on naltrexone

Naltrexone, an opioid antagonist, is used more commonly in outpatient addiction treatment than in the inpatient setting, but inpatient clinicians should be aware of its use. It is available in oral and long-acting injectable formulations. Its utility in the inpatient setting may be limited as safe administration requires 7-10 days of opioid abstinence.

Discharge planning

Patients with OUD or who are started on OAT during a hospitalization should be linked to continued outpatient treatment. Before discharge it is best to ensure vaccinations for HAV, HBV, pneumococcus, and tetanus are up to date, and perform screening for HIV, hepatitis C, tuberculosis, and sexually transmitted infections if appropriate. All patients with OUD should be prescribed or provided with take-home naloxone for overdose reversal. Patients can also be referred to syringe service programs for additional harm reduction counseling and services.

Application of the data to our patient

For our patient, either methadone or buprenorphine could be used to treat her withdrawal. The COWS score should be used to assess withdrawal severity, and to guide appropriate timing of medication initiation. If she wishes to continue OAT after discharge, she should be linked to a clinician who can engage her in ongoing medical care. Prior to discharge she should also receive relevant vaccines and screening for infectious diseases as outlined above, as well as take-home naloxone (or a prescription).

Bottom line

Inpatient clinicians can play a pivotal role in patients’ lives by ensuring that patients with OUD receive OAT and are connected to outpatient care at discharge.

Dr. Linker is assistant professor in the division of hospital medicine, Icahn School of Medicine at Mount Sinai, New York. Ms. Hirt, Mr. Fine, and Mr. Villasanivis are medical students at the Icahn School of Medicine at Mount Sinai. Dr. Wang is assistant professor in the division of general internal medicine, Icahn School of Medicine at Mount Sinai. Dr. Herscher is assistant professor in the division of hospital medicine, Icahn School of Medicine at Mount Sinai.

References

1. Wide-ranging online data for epidemiologic research (WONDER). Atlanta, GA: CDC, National Center for Health Statistics; 2020. Available at http://wonder.cdc.gov.

2. Mattson CL et al. Trends and geographic patterns in drug and synthetic opioid overdose deaths – United States, 2013-2019. MMWR Morb Mortal Wkly Rep. 2021;70:202-7. doi: 10.15585/mmwr.mm7006a4.

3. Wakeman SE et al. Comparative effectiveness of different treatment pathways for opioid use disorder. JAMA Netw Open. 2020 Feb 5;3(2):e1920622. doi: 10.1001/jamanetworkopen.2019.20622.

4. Gowing L et al. Buprenorphine for managing opioid withdrawal. Cochrane Database Syst Rev. 2017 Feb;2017(2):CD002025. doi: 10.1002/14651858.CD002025.pub5.

5. Sordo L et al. Mortality risk during and after opioid substitution treatment: Systematic review and meta-analysis of cohort studies. BMJ. 2017 Apr 26;357:j1550. doi: 10.1136/bmj.j1550.

6. Smyth BP et al. Lapse and relapse following inpatient treatment of opiate dependence. Ir Med J. 2010 Jun;103(6):176-9. Available at www.drugsandalcohol.ie/13405.

7. Liebschutz JM. Buprenorphine treatment for hospitalized, opioid-dependent patients: A randomized clinical trial. JAMA Intern Med. 2014 Aug;174(8):1369-76. doi: 10.1001/jamainternmed.2014.2556.

8. Substance Abuse and Mental Health Services Administration. (Aug 20, 2020) Statutes, Regulations, and Guidelines.

9. McBain RK et al. Growth and distribution of buprenorphine-waivered providers in the United States, 2007-2017. Ann Intern Med. 2020;172(7):504-6. doi: 10.7326/M19-2403.

10. HHS releases new buprenorphine practice guidelines, expanding access to treatment for opioid use disorder. Apr 27, 2021.

11. Herscher M et al. Diagnosis and management of opioid use disorder in hospitalized patients. Med Clin North Am. 2020 Jul;104(4):695-708. doi: 10.1016/j.mcna.2020.03.003.

Additional reading

Winetsky D. Expanding treatment opportunities for hospitalized patients with opioid use disorders. J Hosp Med. 2018 Jan;13(1):62-4. doi: 10.12788/jhm.2861.

Donroe JH. Caring for patients with opioid use disorder in the hospital. Can Med Assoc J. 2016 Dec 6;188(17-18):1232-9. doi: 10.1503/cmaj.160290.

Herscher M et al. Diagnosis and management of opioid use disorder in hospitalized patients. Med Clin North Am. 2020 Jul;104(4):695-708. doi: 10.1016/j.mcna.2020.03.003.
 

Key points

• Most patients with OUD are not engaged in evidence-based treatment. Clinicians have an opportunity to utilize the inpatient stay as a ‘reachable moment’ to engage patients with OUD in evidence-based treatment.
• Buprenorphine and methadone are effective opioid agonist medications used to treat OUD, and clinicians with the appropriate knowledge base can initiate either during the inpatient encounter, and link the patient to OUD treatment after the hospital stay.

Quiz

Caring for hospitalized patients with OUD

Most patients with OUD are not engaged in effective treatment. Hospitalization can be a ‘reachable moment’ to engage patients with OUD in evidence-based treatment.

1. Which is an effective and evidence-based medication for treating opioid withdrawal and OUD?

a) Naltrexone.

b) Buprenorphine.

c) Opioid detoxification.

d) Clonidine.

Explanation: Buprenorphine is effective for alleviating symptoms of withdrawal as well as for the long-term treatment of OUD. While naltrexone is also used to treat OUD, it is not useful for treating withdrawal. Clonidine can be a useful adjunctive medication for treating withdrawal but is not a long-term treatment for OUD. Nonpharmacologic detoxification is not an effective treatment for OUD and is associated with high relapse rates.



2. What scale can be used during a hospital stay to monitor patients with OUD at risk of opioid withdrawal, and to aid in buprenorphine initiation?

a) CIWA score.

b) PADUA score.

c) COWS score.

d) 4T score.

Explanation: COWS is the “clinical opiate withdrawal scale.” The COWS score should be calculated by a trained provider, and includes objective parameters (such as pulse) and subjective symptoms (such as GI upset, bone/joint aches.) It is recommended that agonist therapy be started when the COWS score is consistent with moderate withdrawal.



3. How can clinicians reliably find out if there are outpatient resources/clinics for patients with OUD in their area?

a) No way to find this out without personal knowledge.

b) Hospital providers and patients can visit www.samhsa.gov/find-help/national-helpline or call 1-800-662-HELP (4357) to find options for treatment for substance use disorders in their areas.

c) Dial “0” on any phone and ask.

d) Ask around at your hospital.

Explanation: The Substance Abuse and Mental Health Services Administration (SAMHSA) is an agency in the U.S. Department of Health and Human Services that is engaged in public health efforts to reduce the impact of substance abuse and mental illness on local communities. The agency’s website has helpful information about resources for substance use treatment.



4. Patients with OUD should be prescribed and given training about what medication that can be lifesaving when given during an opioid overdose?

a) Aspirin.

b) Naloxone.

c) Naltrexone.

d) Clonidine.

Explanation: Naloxone can be life-saving in the setting of an overdose. Best practice is to provide naloxone and training to patients with OUD.



5. When patients take buprenorphine soon after taking other opioids, there is concern for the development of which reaction:

a) Precipitated withdrawal.

b) Opioid overdose.

c) Allergic reaction.

d) Intoxication.

Explanation: Administering buprenorphine soon after taking other opioids can cause precipitated withdrawal, as buprenorphine binds with higher affinity to the mu receptor than many opioids. Precipitated withdrawal causes severe discomfort and can be dangerous for patients.

It is possible to talk to a patient for a brief moment and just know if he or she is a satisficer or a maximizer. A “satisficer” when presented with treatment options will invariably say: “I’ll do whatever you say, Doctor.” A “maximizer,” in contrast, would like a printed copy of treatment choices, then would seek a second opinion before ultimately buying an UpToDate subscription to research treatments for him or herself.

Which is more like you? Which should you be if you want to be happy? I’m mostly a satisficer and would like to present an argument for why this way is best.

This notion that we have tendencies toward maximizing or satisficing is thanks to Nobel Memorial Prize winner and all-around smart guy, Herbert A. Simon, PhD. Dr. Simon recognized that, although each person might be expected to make optimal decisions to benefit himself or herself, this is practically impossible. To do so would require an infinite amount of time and energy. He found therefore that we actually exhibit “bounded rationality;” that is, we make the best decision given the limits of time, the price of acquiring information, and even our cognitive abilities. The amount of effort we give to make a decision also depends on the situation: You might be very invested in choosing the right spouse, but not at all invested in choosing soup or salad. (Although, we all have friends who are: “Um, is there any thyme in the soup?”)

You’ll certainly recognize that people have different set points on the spectrum between being a satisficer, one who will take the first option that meets a standard, and a maximizer, one who will seek and accept only the best, even if choosing is at great cost. There are risks and benefits of each. In getting the best job, maximizers might be more successful, but satisficers seem to be happier.

How much this extends into other spheres of life is unclear. It is clear, though, that the work of choosing can come at a cost.

The psychologist Barry Schwartz, PhD, believes that, in general, having more choices leads to more anxiety, not more contentment. For example, which Christmas tree lot would you rather visit: One with hundreds of trees of half a dozen varieties? Or one with just a few trees each of Balsam and Douglas Firs? Dr. Schwartz would argue that you might waste an entire afternoon in the first lot only to bring it home and have remorse when you realize it’s a little lopsided. Or let’s say your child applied to all the Ivy League and Public Ivy schools and also threw in all the top liberal arts colleges. The anxiety of selecting the best and the terror that the “best one” might not choose him or her could be overwhelming. A key lesson is that more in life is by chance than we realize, including how straight your tree is and who gets into Princeton this year. Yet, our expectation that things will work out perfectly if only we maximize is ubiquitous. That confidence in our ability to choose correctly is, however, unwarranted. Better to do your best and know that your tree will be festive and there are many colleges which would lead to a happy life than to fret in choosing and then suffer from dashed expectations. Sometimes good enough is good enough.

Being a satisficer or maximizer is probably somewhat fixed, a personality trait, like being extroverted or conscientious. Yet, having insight can be helpful. If choosing a restaurant in Manhattan becomes an actual project for you with spreadsheets and your own statistical analysis, then go for it! Just know that if that process causes you angst and apprehension, then there is another way. Go to Eleven Madison Park, just because I say so. You might have the best dinner of your life or maybe not. At least by not choosing you’ll have the gift of time to spend picking out a tree instead.

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

It is possible to talk to a patient for a brief moment and just know if he or she is a satisficer or a maximizer. A “satisficer” when presented with treatment options will invariably say: “I’ll do whatever you say, Doctor.” A “maximizer,” in contrast, would like a printed copy of treatment choices, then would seek a second opinion before ultimately buying an UpToDate subscription to research treatments for him or herself.

Which is more like you? Which should you be if you want to be happy? I’m mostly a satisficer and would like to present an argument for why this way is best.

This notion that we have tendencies toward maximizing or satisficing is thanks to Nobel Memorial Prize winner and all-around smart guy, Herbert A. Simon, PhD. Dr. Simon recognized that, although each person might be expected to make optimal decisions to benefit himself or herself, this is practically impossible. To do so would require an infinite amount of time and energy. He found therefore that we actually exhibit “bounded rationality;” that is, we make the best decision given the limits of time, the price of acquiring information, and even our cognitive abilities. The amount of effort we give to make a decision also depends on the situation: You might be very invested in choosing the right spouse, but not at all invested in choosing soup or salad. (Although, we all have friends who are: “Um, is there any thyme in the soup?”)

You’ll certainly recognize that people have different set points on the spectrum between being a satisficer, one who will take the first option that meets a standard, and a maximizer, one who will seek and accept only the best, even if choosing is at great cost. There are risks and benefits of each. In getting the best job, maximizers might be more successful, but satisficers seem to be happier.

How much this extends into other spheres of life is unclear. It is clear, though, that the work of choosing can come at a cost.

The psychologist Barry Schwartz, PhD, believes that, in general, having more choices leads to more anxiety, not more contentment. For example, which Christmas tree lot would you rather visit: One with hundreds of trees of half a dozen varieties? Or one with just a few trees each of Balsam and Douglas Firs? Dr. Schwartz would argue that you might waste an entire afternoon in the first lot only to bring it home and have remorse when you realize it’s a little lopsided. Or let’s say your child applied to all the Ivy League and Public Ivy schools and also threw in all the top liberal arts colleges. The anxiety of selecting the best and the terror that the “best one” might not choose him or her could be overwhelming. A key lesson is that more in life is by chance than we realize, including how straight your tree is and who gets into Princeton this year. Yet, our expectation that things will work out perfectly if only we maximize is ubiquitous. That confidence in our ability to choose correctly is, however, unwarranted. Better to do your best and know that your tree will be festive and there are many colleges which would lead to a happy life than to fret in choosing and then suffer from dashed expectations. Sometimes good enough is good enough.

Being a satisficer or maximizer is probably somewhat fixed, a personality trait, like being extroverted or conscientious. Yet, having insight can be helpful. If choosing a restaurant in Manhattan becomes an actual project for you with spreadsheets and your own statistical analysis, then go for it! Just know that if that process causes you angst and apprehension, then there is another way. Go to Eleven Madison Park, just because I say so. You might have the best dinner of your life or maybe not. At least by not choosing you’ll have the gift of time to spend picking out a tree instead.

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

It is possible to talk to a patient for a brief moment and just know if he or she is a satisficer or a maximizer. A “satisficer” when presented with treatment options will invariably say: “I’ll do whatever you say, Doctor.” A “maximizer,” in contrast, would like a printed copy of treatment choices, then would seek a second opinion before ultimately buying an UpToDate subscription to research treatments for him or herself.

Which is more like you? Which should you be if you want to be happy? I’m mostly a satisficer and would like to present an argument for why this way is best.

This notion that we have tendencies toward maximizing or satisficing is thanks to Nobel Memorial Prize winner and all-around smart guy, Herbert A. Simon, PhD. Dr. Simon recognized that, although each person might be expected to make optimal decisions to benefit himself or herself, this is practically impossible. To do so would require an infinite amount of time and energy. He found therefore that we actually exhibit “bounded rationality;” that is, we make the best decision given the limits of time, the price of acquiring information, and even our cognitive abilities. The amount of effort we give to make a decision also depends on the situation: You might be very invested in choosing the right spouse, but not at all invested in choosing soup or salad. (Although, we all have friends who are: “Um, is there any thyme in the soup?”)

You’ll certainly recognize that people have different set points on the spectrum between being a satisficer, one who will take the first option that meets a standard, and a maximizer, one who will seek and accept only the best, even if choosing is at great cost. There are risks and benefits of each. In getting the best job, maximizers might be more successful, but satisficers seem to be happier.

How much this extends into other spheres of life is unclear. It is clear, though, that the work of choosing can come at a cost.

The psychologist Barry Schwartz, PhD, believes that, in general, having more choices leads to more anxiety, not more contentment. For example, which Christmas tree lot would you rather visit: One with hundreds of trees of half a dozen varieties? Or one with just a few trees each of Balsam and Douglas Firs? Dr. Schwartz would argue that you might waste an entire afternoon in the first lot only to bring it home and have remorse when you realize it’s a little lopsided. Or let’s say your child applied to all the Ivy League and Public Ivy schools and also threw in all the top liberal arts colleges. The anxiety of selecting the best and the terror that the “best one” might not choose him or her could be overwhelming. A key lesson is that more in life is by chance than we realize, including how straight your tree is and who gets into Princeton this year. Yet, our expectation that things will work out perfectly if only we maximize is ubiquitous. That confidence in our ability to choose correctly is, however, unwarranted. Better to do your best and know that your tree will be festive and there are many colleges which would lead to a happy life than to fret in choosing and then suffer from dashed expectations. Sometimes good enough is good enough.

Being a satisficer or maximizer is probably somewhat fixed, a personality trait, like being extroverted or conscientious. Yet, having insight can be helpful. If choosing a restaurant in Manhattan becomes an actual project for you with spreadsheets and your own statistical analysis, then go for it! Just know that if that process causes you angst and apprehension, then there is another way. Go to Eleven Madison Park, just because I say so. You might have the best dinner of your life or maybe not. At least by not choosing you’ll have the gift of time to spend picking out a tree instead.

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

Cara R. King, DO, MS, is a member of the Cleveland Clinic Section of Minimally Invasive Gynecologic Surgery (MIGS). She is the Director of Benign Gynecologic Surgery,  and Associate Program Director of the MIGS Fellowship, and Director of Innovation for the Women’s Health Institute. She is a member of the American Association of Gynecologic Laparoscopists (AAGL), the Society of Gynecologic Surgeons (SGS), American College of Surgeons (ACS), and the American Congress of Obstetricians and Gynecologists (ACOG).

Q: How much of your surgical practice is dedicated to patients with endometriosis?

Dr. King: The majority of my practice is dedicated to treating women with endometriosis. I practice at the Cleveland Clinic in Cleveland, Ohio, which is a high-volume referral center, so many of my patients are coming to me for endometriosis or pelvic pain-type symptoms. For most of my patients, I serve as a consultant, which means it's not their initial visit for this issue. I'm often seeing patients who have not found relief through alternate medical or surgical treatments and typically, have more deeply infiltrating or complex endometriosis disease.

Q: How do you make the treatment decision with patients that surgery is the next or proper needed step?

Dr. King: This decision depends on the goals and priorities of each of my patients. I don't have a one-size-fits-all type approach as every patient's journey and unique experiences vary. Ultimately, deciding on the available options and order of treatment depends on the patient's symptoms and priorities. I always start with a thorough history, including a detailed physical exam. The pelvic exam includes evaluation of the bladder, bowel, pelvic floor muscles, nerves, as well as the gynecologic organs including vagina, uterus, cervix and adnexa. If I palpate a nodule on the uterosacral ligaments or behind the cervix, I will sometimes perform a rectovaginal exam to assess for deeply infiltrating bowel disease. Various imaging modalities, including a transvaginal ultrasound or an MRI, can be helpful to further characterize the disease. This allows us to create a treatment plan that best aligns with the patients’ priorities and goals. As a general rule, surgery is usually indicated if empiric options have failed or if they desire definitive diagnosis; meaning the patient is still having pain symptoms despite conservative options or if they have failed or are intolerant to medical options. Some patients are not candidates for medical therapy, such as those who desire pregnancy or who are trying to conceive, so medical options wouldn't be an option for these patients. For patients who prefer an immediate diagnosis, surgical intervention may also be the best option. When I see initial consults for patients who haven't previously seen an endometriosis specialist, if they're not trying to conceive and if they are candidates for medical therapy, I think that's a reasonable first step. We must understand that medications are not curative, they are merely suppressive for endometriosis, so when patients come to me that have been on medical therapy for more than 3 months without pain improvement, and they haven't been offered a surgical approach, diagnostic laparoscopy is often the next best step.

Q: Please detail the presurgical discussion, or the consent process, that would allow you to go beyond the agreed-to procedure, if necessary?

Dr. King: Endometriosis is extremely unique in that you sometimes cannot tell how deeply infiltrative the disease is until you start excising it. So, my consent process and discussions are substantial parts of all patient presurgical conversations. This is crucial for understanding how comfortable the patient is with more aggressive surgery and to fully understand each individual’s symptoms and priorities. I spend a significant amount of time talking to patients about their exact goals for surgery and I conduct a thorough workup before we get into the operating room so that when coupled with a proper physical exam and detailed imaging, the element for surprise, such as finding disease that is much more advanced than you had thought, is decreased. Understanding your patient's symptoms as well as how aggressive they want you to be with regards to surgery is of utmost importance. The more accurate the description that I have of the type of disease that we're working with allows me to talk about all possibilities that could occur before the patients get into the operating room so that we can ensure expectations are met, for the patient and for the surgeon.

Q: Do you have any protocols to share with the audience that relate to limiting reoperation for residual disease?

Dr. King: Conducting a thorough history and physical exam in addition to having detailed imaging is crucial to optimize success. That said, there are times when imaging may appear “normal” when endometriosis is actually present, which is why it is of utmost importance to listen to your patient’s history. With deeply infiltrating endometriosis, superficially, if you look at the peritoneum, it can sometimes appear as if the disease is not that invasive. Again, endometriosis is unique in that until you start excising it, sometimes you don’t know the extent of the infiltration. So, having detailed imaging is going to allow for better mapping of the endometriosis beforehand which will allow you to properly focus in on those areas and enhance preoperative counseling.

My second level of advice is to know your limits with regards to surgical complexity and your laparoscopic skills. For instance, if an endometrioma is present on imaging, you will most likely encounter peritoneal disease and fibrosis below that ovary on the pelvic side wall adjacent to the ureter. If you are not comfortable excising this disease, you should consider referring the patient to an advanced pelvic surgeon. When you see certain characteristics on imaging, understanding what the disease process will look like when you get in there and understanding your own skill level at which you can safely and efficiently perform that dissection is very important. And if you do not have that skill level or if you are still working on detailed knowledge of retroperitoneal anatomy, then the opportunity exists to build up your team; consider including another subspecialist within GYN or urology, colorectal surgery, or cardiothoracic surgery, if you are working with diaphragmatic endometriosis. Loading your boat will allow you to safely and efficiently remove as much of the disease as you can and decrease the risk of leaving any behind. You could also consider video based surgical coaching to further enhance your own laparoscopic skills and surgical performance when treating this complex disease.

Q: How do you approach postsurgical management to maximize the pain-free period for patients?

Dr. King: We know that the best intervention for pain relief is complete excision of endometriosis. By performing a complete excision, we know that this procedure will prolong the length of time for pain-free interval. So, getting as close as possible to a complete excision is going to be the first step. It is also important to treat alternate sources of pain that can be impacted by endometriosis such as spasm of the pelvic floor muscles or central sensitization. While it is difficult to say whether recurrent endometriosis pain is secondary to reactivation of residual disease as opposed to new disease, we do know that complete excision provides longer relief. Assuming surgery has relieved a majority of or, all of the endometriosis associated pain, then the main strategy that we can use to postoperatively maximize that pain-free period is to minimize ovulation. This is typically accomplished with hormonal suppression. It is worth nothing that this isn't indicated for all patients and it is not mandatory as we, again, must be mindful of the patient's goals and priorities. But a recent systematic review did find that when we start hormonal suppression within 6 weeks of our endometriosis surgery, there is a significant reduction in recurrent endometriosis pain scores for up to one year postoperative. Currently, there are no non-hormonal medications that we can offer, nor do we have any interventions to alter genetics or immune aspects of the disease, though it is hoped such could possibly become available in the near future. At the current point in time, hormonal suppressive options are typically the best route but again, I want to reiterate that medications are suppressive and are not curative. And with regards to details of medical options, pulling in patient preference, financial aspects, underlying comorbidities, and long-term reproductive plans, are factors that are important to consider when making weighing decision.

Cara R. King, DO, MS, is a member of the Cleveland Clinic Section of Minimally Invasive Gynecologic Surgery (MIGS). She is the Director of Benign Gynecologic Surgery,  and Associate Program Director of the MIGS Fellowship, and Director of Innovation for the Women’s Health Institute. She is a member of the American Association of Gynecologic Laparoscopists (AAGL), the Society of Gynecologic Surgeons (SGS), American College of Surgeons (ACS), and the American Congress of Obstetricians and Gynecologists (ACOG).

Q: How much of your surgical practice is dedicated to patients with endometriosis?

Dr. King: The majority of my practice is dedicated to treating women with endometriosis. I practice at the Cleveland Clinic in Cleveland, Ohio, which is a high-volume referral center, so many of my patients are coming to me for endometriosis or pelvic pain-type symptoms. For most of my patients, I serve as a consultant, which means it's not their initial visit for this issue. I'm often seeing patients who have not found relief through alternate medical or surgical treatments and typically, have more deeply infiltrating or complex endometriosis disease.

Q: How do you make the treatment decision with patients that surgery is the next or proper needed step?

Dr. King: This decision depends on the goals and priorities of each of my patients. I don't have a one-size-fits-all type approach as every patient's journey and unique experiences vary. Ultimately, deciding on the available options and order of treatment depends on the patient's symptoms and priorities. I always start with a thorough history, including a detailed physical exam. The pelvic exam includes evaluation of the bladder, bowel, pelvic floor muscles, nerves, as well as the gynecologic organs including vagina, uterus, cervix and adnexa. If I palpate a nodule on the uterosacral ligaments or behind the cervix, I will sometimes perform a rectovaginal exam to assess for deeply infiltrating bowel disease. Various imaging modalities, including a transvaginal ultrasound or an MRI, can be helpful to further characterize the disease. This allows us to create a treatment plan that best aligns with the patients’ priorities and goals. As a general rule, surgery is usually indicated if empiric options have failed or if they desire definitive diagnosis; meaning the patient is still having pain symptoms despite conservative options or if they have failed or are intolerant to medical options. Some patients are not candidates for medical therapy, such as those who desire pregnancy or who are trying to conceive, so medical options wouldn't be an option for these patients. For patients who prefer an immediate diagnosis, surgical intervention may also be the best option. When I see initial consults for patients who haven't previously seen an endometriosis specialist, if they're not trying to conceive and if they are candidates for medical therapy, I think that's a reasonable first step. We must understand that medications are not curative, they are merely suppressive for endometriosis, so when patients come to me that have been on medical therapy for more than 3 months without pain improvement, and they haven't been offered a surgical approach, diagnostic laparoscopy is often the next best step.

Q: Please detail the presurgical discussion, or the consent process, that would allow you to go beyond the agreed-to procedure, if necessary?

Dr. King: Endometriosis is extremely unique in that you sometimes cannot tell how deeply infiltrative the disease is until you start excising it. So, my consent process and discussions are substantial parts of all patient presurgical conversations. This is crucial for understanding how comfortable the patient is with more aggressive surgery and to fully understand each individual’s symptoms and priorities. I spend a significant amount of time talking to patients about their exact goals for surgery and I conduct a thorough workup before we get into the operating room so that when coupled with a proper physical exam and detailed imaging, the element for surprise, such as finding disease that is much more advanced than you had thought, is decreased. Understanding your patient's symptoms as well as how aggressive they want you to be with regards to surgery is of utmost importance. The more accurate the description that I have of the type of disease that we're working with allows me to talk about all possibilities that could occur before the patients get into the operating room so that we can ensure expectations are met, for the patient and for the surgeon.

Q: Do you have any protocols to share with the audience that relate to limiting reoperation for residual disease?

Dr. King: Conducting a thorough history and physical exam in addition to having detailed imaging is crucial to optimize success. That said, there are times when imaging may appear “normal” when endometriosis is actually present, which is why it is of utmost importance to listen to your patient’s history. With deeply infiltrating endometriosis, superficially, if you look at the peritoneum, it can sometimes appear as if the disease is not that invasive. Again, endometriosis is unique in that until you start excising it, sometimes you don’t know the extent of the infiltration. So, having detailed imaging is going to allow for better mapping of the endometriosis beforehand which will allow you to properly focus in on those areas and enhance preoperative counseling.

My second level of advice is to know your limits with regards to surgical complexity and your laparoscopic skills. For instance, if an endometrioma is present on imaging, you will most likely encounter peritoneal disease and fibrosis below that ovary on the pelvic side wall adjacent to the ureter. If you are not comfortable excising this disease, you should consider referring the patient to an advanced pelvic surgeon. When you see certain characteristics on imaging, understanding what the disease process will look like when you get in there and understanding your own skill level at which you can safely and efficiently perform that dissection is very important. And if you do not have that skill level or if you are still working on detailed knowledge of retroperitoneal anatomy, then the opportunity exists to build up your team; consider including another subspecialist within GYN or urology, colorectal surgery, or cardiothoracic surgery, if you are working with diaphragmatic endometriosis. Loading your boat will allow you to safely and efficiently remove as much of the disease as you can and decrease the risk of leaving any behind. You could also consider video based surgical coaching to further enhance your own laparoscopic skills and surgical performance when treating this complex disease.

Q: How do you approach postsurgical management to maximize the pain-free period for patients?

Dr. King: We know that the best intervention for pain relief is complete excision of endometriosis. By performing a complete excision, we know that this procedure will prolong the length of time for pain-free interval. So, getting as close as possible to a complete excision is going to be the first step. It is also important to treat alternate sources of pain that can be impacted by endometriosis such as spasm of the pelvic floor muscles or central sensitization. While it is difficult to say whether recurrent endometriosis pain is secondary to reactivation of residual disease as opposed to new disease, we do know that complete excision provides longer relief. Assuming surgery has relieved a majority of or, all of the endometriosis associated pain, then the main strategy that we can use to postoperatively maximize that pain-free period is to minimize ovulation. This is typically accomplished with hormonal suppression. It is worth nothing that this isn't indicated for all patients and it is not mandatory as we, again, must be mindful of the patient's goals and priorities. But a recent systematic review did find that when we start hormonal suppression within 6 weeks of our endometriosis surgery, there is a significant reduction in recurrent endometriosis pain scores for up to one year postoperative. Currently, there are no non-hormonal medications that we can offer, nor do we have any interventions to alter genetics or immune aspects of the disease, though it is hoped such could possibly become available in the near future. At the current point in time, hormonal suppressive options are typically the best route but again, I want to reiterate that medications are suppressive and are not curative. And with regards to details of medical options, pulling in patient preference, financial aspects, underlying comorbidities, and long-term reproductive plans, are factors that are important to consider when making weighing decision.

Cara R. King, DO, MS, is a member of the Cleveland Clinic Section of Minimally Invasive Gynecologic Surgery (MIGS). She is the Director of Benign Gynecologic Surgery,  and Associate Program Director of the MIGS Fellowship, and Director of Innovation for the Women’s Health Institute. She is a member of the American Association of Gynecologic Laparoscopists (AAGL), the Society of Gynecologic Surgeons (SGS), American College of Surgeons (ACS), and the American Congress of Obstetricians and Gynecologists (ACOG).

Q: How much of your surgical practice is dedicated to patients with endometriosis?

Dr. King: The majority of my practice is dedicated to treating women with endometriosis. I practice at the Cleveland Clinic in Cleveland, Ohio, which is a high-volume referral center, so many of my patients are coming to me for endometriosis or pelvic pain-type symptoms. For most of my patients, I serve as a consultant, which means it's not their initial visit for this issue. I'm often seeing patients who have not found relief through alternate medical or surgical treatments and typically, have more deeply infiltrating or complex endometriosis disease.

Q: How do you make the treatment decision with patients that surgery is the next or proper needed step?

Dr. King: This decision depends on the goals and priorities of each of my patients. I don't have a one-size-fits-all type approach as every patient's journey and unique experiences vary. Ultimately, deciding on the available options and order of treatment depends on the patient's symptoms and priorities. I always start with a thorough history, including a detailed physical exam. The pelvic exam includes evaluation of the bladder, bowel, pelvic floor muscles, nerves, as well as the gynecologic organs including vagina, uterus, cervix and adnexa. If I palpate a nodule on the uterosacral ligaments or behind the cervix, I will sometimes perform a rectovaginal exam to assess for deeply infiltrating bowel disease. Various imaging modalities, including a transvaginal ultrasound or an MRI, can be helpful to further characterize the disease. This allows us to create a treatment plan that best aligns with the patients’ priorities and goals. As a general rule, surgery is usually indicated if empiric options have failed or if they desire definitive diagnosis; meaning the patient is still having pain symptoms despite conservative options or if they have failed or are intolerant to medical options. Some patients are not candidates for medical therapy, such as those who desire pregnancy or who are trying to conceive, so medical options wouldn't be an option for these patients. For patients who prefer an immediate diagnosis, surgical intervention may also be the best option. When I see initial consults for patients who haven't previously seen an endometriosis specialist, if they're not trying to conceive and if they are candidates for medical therapy, I think that's a reasonable first step. We must understand that medications are not curative, they are merely suppressive for endometriosis, so when patients come to me that have been on medical therapy for more than 3 months without pain improvement, and they haven't been offered a surgical approach, diagnostic laparoscopy is often the next best step.

Q: Please detail the presurgical discussion, or the consent process, that would allow you to go beyond the agreed-to procedure, if necessary?

Dr. King: Endometriosis is extremely unique in that you sometimes cannot tell how deeply infiltrative the disease is until you start excising it. So, my consent process and discussions are substantial parts of all patient presurgical conversations. This is crucial for understanding how comfortable the patient is with more aggressive surgery and to fully understand each individual’s symptoms and priorities. I spend a significant amount of time talking to patients about their exact goals for surgery and I conduct a thorough workup before we get into the operating room so that when coupled with a proper physical exam and detailed imaging, the element for surprise, such as finding disease that is much more advanced than you had thought, is decreased. Understanding your patient's symptoms as well as how aggressive they want you to be with regards to surgery is of utmost importance. The more accurate the description that I have of the type of disease that we're working with allows me to talk about all possibilities that could occur before the patients get into the operating room so that we can ensure expectations are met, for the patient and for the surgeon.

Q: Do you have any protocols to share with the audience that relate to limiting reoperation for residual disease?

Dr. King: Conducting a thorough history and physical exam in addition to having detailed imaging is crucial to optimize success. That said, there are times when imaging may appear “normal” when endometriosis is actually present, which is why it is of utmost importance to listen to your patient’s history. With deeply infiltrating endometriosis, superficially, if you look at the peritoneum, it can sometimes appear as if the disease is not that invasive. Again, endometriosis is unique in that until you start excising it, sometimes you don’t know the extent of the infiltration. So, having detailed imaging is going to allow for better mapping of the endometriosis beforehand which will allow you to properly focus in on those areas and enhance preoperative counseling.

My second level of advice is to know your limits with regards to surgical complexity and your laparoscopic skills. For instance, if an endometrioma is present on imaging, you will most likely encounter peritoneal disease and fibrosis below that ovary on the pelvic side wall adjacent to the ureter. If you are not comfortable excising this disease, you should consider referring the patient to an advanced pelvic surgeon. When you see certain characteristics on imaging, understanding what the disease process will look like when you get in there and understanding your own skill level at which you can safely and efficiently perform that dissection is very important. And if you do not have that skill level or if you are still working on detailed knowledge of retroperitoneal anatomy, then the opportunity exists to build up your team; consider including another subspecialist within GYN or urology, colorectal surgery, or cardiothoracic surgery, if you are working with diaphragmatic endometriosis. Loading your boat will allow you to safely and efficiently remove as much of the disease as you can and decrease the risk of leaving any behind. You could also consider video based surgical coaching to further enhance your own laparoscopic skills and surgical performance when treating this complex disease.

Q: How do you approach postsurgical management to maximize the pain-free period for patients?

Dr. King: We know that the best intervention for pain relief is complete excision of endometriosis. By performing a complete excision, we know that this procedure will prolong the length of time for pain-free interval. So, getting as close as possible to a complete excision is going to be the first step. It is also important to treat alternate sources of pain that can be impacted by endometriosis such as spasm of the pelvic floor muscles or central sensitization. While it is difficult to say whether recurrent endometriosis pain is secondary to reactivation of residual disease as opposed to new disease, we do know that complete excision provides longer relief. Assuming surgery has relieved a majority of or, all of the endometriosis associated pain, then the main strategy that we can use to postoperatively maximize that pain-free period is to minimize ovulation. This is typically accomplished with hormonal suppression. It is worth nothing that this isn't indicated for all patients and it is not mandatory as we, again, must be mindful of the patient's goals and priorities. But a recent systematic review did find that when we start hormonal suppression within 6 weeks of our endometriosis surgery, there is a significant reduction in recurrent endometriosis pain scores for up to one year postoperative. Currently, there are no non-hormonal medications that we can offer, nor do we have any interventions to alter genetics or immune aspects of the disease, though it is hoped such could possibly become available in the near future. At the current point in time, hormonal suppressive options are typically the best route but again, I want to reiterate that medications are suppressive and are not curative. And with regards to details of medical options, pulling in patient preference, financial aspects, underlying comorbidities, and long-term reproductive plans, are factors that are important to consider when making weighing decision.