Mr. S, age 64, presents for an outpatient follow-up after a recent hospital discharge for alcohol detoxification. He reports a long history of alcohol use, which has resulted in numerous hospital admissions. He has recently been receiving care from a gastroenterologist because the results of laboratory testing suggested hepatic impairment (Table 1). Mr. S says that a friend of his was able to stop drinking by taking a medication, and he wonders if he can be prescribed a medication to help him as well.

A chart review shows that Mr. S recently underwent paracentesis, during which 6 liters of fluid were removed. Additionally, an abdominal ultrasound confirmed hepatic cirrhosis.

According to the World Health Organization, alcohol consumption contributes to 3 million deaths annually.² The highest proportion of these deaths (21.3%) is due to alcohol-associated gastrointestinal complications, including alcoholic and infectious hepatitis, pancreatitis, and cirrhosis. Because the liver is the primary site of ethanol metabolism, it sustains the greatest degree of tissue injury with heavy alcohol consumption. Additionally, the association of harmful use of alcohol with risky sexual behavior may partially explain the higher prevalence of viral hepatitis among persons with alcohol use disorder (AUD) compared with the general population. Alcoholic liver disease (ALD) progresses through several stages, beginning with hepatic steatosis and progressing through alcohol-related hepatitis, fibrosis, cirrhosis, and potentially hepatocellular carcinoma.³

Liver markers of alcohol use

Although biological markers can be used in clinical practice to screen and monitor for alcohol abuse, making a diagnosis of ALD can be challenging. Typically, a history of heavy alcohol consumption in addition to certain physical signs and laboratory tests for liver disease are the best indicators of ALD. However, the clinical assessment can be confounded by patients who deny or minimize how much alcohol they have consumed. Furthermore, physical and laboratory findings may not be specific to ALD.

Liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), have historically been used as the basis of diagnosing ALD. In addition to elevated bilirubin and evidence of macrocytic anemia, elevations in these enzymes may suggest heavy alcohol use, but these values alone are inadequate to establish ALD. Gamma-glutamyltransferase is found in cell membranes of several body tissues, including the liver and spleen, and therefore is not specific to liver damage. However, elevated GGT is the best indicator of excessive alcohol consumption because it has greater sensitivity than AST and ALT.^1,3,4

Although these biomarkers are helpful in diagnosing ALD, they lose some of their utility in patients with advanced liver disease. Patients with severe liver dysfunction may not have elevated serum aminotransferase levels because the degree of liver enzyme elevation does not correlate well with the severity of ALD. For example, patients with advanced cirrhosis may have liver enzyme levels that appear normal. However, the pattern of elevation in transaminases can be helpful in making a diagnosis of liver dysfunction; using the ratio of AST to ALT may aid in diagnosing ALD, because AST is elevated more than twice that of ALT in >80% of patients with ALD.^1,3,4

Table 2^1,3,4 shows the progression of ALD from steatohepatitis to alcoholic hepatitis to cirrhosis. In steatohepatitis, transaminitis is present but all other biomarkers normal. In alcoholic hepatitis, transaminitis is present along with elevated alkaline phosphatase, elevated bilirubin, and elevated international normalized ratio (INR). In alcoholic cirrhosis, the AST-to-ALT ratio is >2, and hypoalbuminemia, hyperbilirubinemia, and coagulopathy (evidenced by elevated INR) are present, consistent with long-term liver damage.^1,3,4

Continue to: FDA-approved medications

FDA-approved medications

Three medications—acamprosate, naltrexone, and disulfiram—currently are FDA-approved for treating AUD.^5,6 Additionally, several other medications have shown varying levels of efficacy in treating patients with AUD but are not FDA-approved for this indication (Table 3).^5-8

Acamprosate is thought to create a balance of inhibitor and excitatory neurotransmitters by functioning as a glutamate antagonist and gamma-aminobutyric acid (GABA) agonist. This is speculated to aid in abstinence from alcohol. Data suggests that acamprosate may be more effective for maintaining abstinence than for inducing remission in individuals who have not yet detoxified from alcohol. Because of its renal excretion, acamprosate is the only FDA-approved medication for AUD that is not associated with liver toxicity. The most commonly reported adverse effect with acamprosate use is diarrhea.

Naltrexone, a mu-opioid receptor antagonist, is available in both tablet and long-acting IM injection formulations. Naltrexone blocks the binding of endorphins created by alcohol consumption to opioid receptors. This results in diminished dopamine release and is speculated to decrease reward and positive reinforcement with alcohol consumption, leading to fewer heavy drinking days. Due to hepatic metabolism, naltrexone use carries a risk of liver injury. Cases of hepatitis and clinically significant liver dysfunction as well as transient, asymptomatic, hepatic transaminase elevations have been observed in patients who receive naltrexone. Because of the absence of first-pass metabolism, long-acting IM naltrexone may produce less hepatotoxicity than the oral formulation. When the FDA approved both formulations of naltrexone, a “black-box” warning was issued concerning the risk of liver damage; however, these warnings have since been removed from their respective prescribing information.

Disulfiram inhibits acetaldehyde dehydrogenase, resulting in elevated acetaldehyde concentrations after consuming alcohol. In theory, this medication reduces a person’s desire to drink due to the negative physiological and physical effects associated with increased acetaldehyde, including hypotension, flushing, nausea, and vomiting. Although most of these reactions are short-lived, disulfiram can induce hepatotoxicity and liver failure that may prove fatal. Disulfiram should be avoided in patients with advanced ALD.

Off-label medications for AUD

Additional pharmacotherapeutic agents have been evaluated in patients with AUD. Baclofen, topiramate, gabapentin, and ondansetron have shown varying levels of efficacy and pose minimal concern in patients with ALD.

Continue to: Baclofen

Baclofen. Although findings are conflicting, baclofen is the only agent that has been specifically studied for treating AUD in patients with ALD. A GABA B receptor antagonist, baclofen is currently FDA-approved for treating spasticity. In a series of open-label and double-blind studies, baclofen has been shown to effectively reduce alcohol intake, promote abstinence, and prevent relapse.^5,6 Further studies identified a possible dose-related response, noting that 20 mg taken 3 times daily may confer additional response over 10 mg taken 3 times daily.^5,6 Conversely, the ALPADIR study failed to demonstrate superiority of baclofen vs placebo in the maintenance of abstinence from alcohol despite dosing at 180 mg/d.⁹ This study did, however, find a significant reduction in alcohol craving in favor of baclofen.⁹ Further, in a randomized controlled trial (RCT) conducted in veterans with chronic hepatitis C, baclofen 30 mg/d failed to show superiority over placebo with regard to increasing abstinence or reducing alcohol use.¹⁰

Topiramate. A recent meta-analysis found that topiramate use may result in fewer drinking days, heavy drinking days, and number of drinks per drinking day.⁷ Additionally, topiramate has demonstrated a statistically significant reduction in alcohol craving as well as the ability to decrease all liver function test values.⁵ This agent should be used with caution in patients with hepatic encephalopathy because the adverse cognitive effects associated with topiramate may confound the clinical course and treatment of such.

Gabapentin. The use of gabapentin to treat patients with AUD is supported by multiple RCTs. In studies that evaluated dose-related response, higher doses of gabapentin (up to 1,800 mg/d) showed greater efficacy than lower doses (ie, 900 mg/d).⁸ Because gabapentin does not undergo hepatic metabolism, its use in patients with ALD is considered safe. Although the abuse potential of gabapentin is less defined in patients with AUD, there have been reports of abuse in other high-risk populations (ie, those with opioid use disorder, incarcerated persons, and those who misuse prescriptions recreationally).⁸

Ondansetron is speculated to decrease the reward from alcohol via the down-regulation of dopaminergic neurons. Studies examining ondansetron for patients with AUD have found that it decreases alcohol cravings in those with early-onset alcoholism (initial onset at age ≤25), but not in late-onset alcoholism (initial onset at age >25).⁵ However, the ondansetron doses used in these trials were very low (4 mcg/kg), and those doses are not available commercially.⁵

CASE CONTINUED

Following a discussion of available pharma­cotherapeutic options for AUD, Mr. S is started on baclofen, 10 mg 3 times daily, with plans for dose titration. At a 2-week follow-up appointment, Mr. S reports that he had not been taking baclofen as often as instructed; however, he denies further alcohol consumption and re-commits to baclofen treatment. Unfortunately, Mr. S is soon admitted to hospice care due to continued decompensation and is unable to attend any additional outpatient follow-up appointments. Three months after his initial outpatient contact, Mr. S dies due to alcoholic cirrhosis.

Related Resources

• Crabb DW, Im GY, Szabo G, et al. Diagnosis and treatment of alcohol-related liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2020;71(1):306-333.
• Murail AR, Carey WD. Disease management. Liver test interpretation - approach to the patient with liver disease: a guide to commonly used liver tests. Cleveland Clinic Center for Continuing Education. Updated August 2017. www.clevelandclinicmeded. com/medicalpubs/diseasemanagement/hepatology/ guide-to-common-liver-tests/

Drug Brand Names

Acamprosate • Campral
Baclofen • Lioresal
Disulfiram • Antabuse
Gabapentin • Neurontin
Naltrexone • Revia, Vivitrol
Ondansetron • Zofran
Topiramate • Topamax

Mr. S, age 64, presents for an outpatient follow-up after a recent hospital discharge for alcohol detoxification. He reports a long history of alcohol use, which has resulted in numerous hospital admissions. He has recently been receiving care from a gastroenterologist because the results of laboratory testing suggested hepatic impairment (Table 1). Mr. S says that a friend of his was able to stop drinking by taking a medication, and he wonders if he can be prescribed a medication to help him as well.

A chart review shows that Mr. S recently underwent paracentesis, during which 6 liters of fluid were removed. Additionally, an abdominal ultrasound confirmed hepatic cirrhosis.

According to the World Health Organization, alcohol consumption contributes to 3 million deaths annually.² The highest proportion of these deaths (21.3%) is due to alcohol-associated gastrointestinal complications, including alcoholic and infectious hepatitis, pancreatitis, and cirrhosis. Because the liver is the primary site of ethanol metabolism, it sustains the greatest degree of tissue injury with heavy alcohol consumption. Additionally, the association of harmful use of alcohol with risky sexual behavior may partially explain the higher prevalence of viral hepatitis among persons with alcohol use disorder (AUD) compared with the general population. Alcoholic liver disease (ALD) progresses through several stages, beginning with hepatic steatosis and progressing through alcohol-related hepatitis, fibrosis, cirrhosis, and potentially hepatocellular carcinoma.³

Liver markers of alcohol use

Although biological markers can be used in clinical practice to screen and monitor for alcohol abuse, making a diagnosis of ALD can be challenging. Typically, a history of heavy alcohol consumption in addition to certain physical signs and laboratory tests for liver disease are the best indicators of ALD. However, the clinical assessment can be confounded by patients who deny or minimize how much alcohol they have consumed. Furthermore, physical and laboratory findings may not be specific to ALD.

Liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), have historically been used as the basis of diagnosing ALD. In addition to elevated bilirubin and evidence of macrocytic anemia, elevations in these enzymes may suggest heavy alcohol use, but these values alone are inadequate to establish ALD. Gamma-glutamyltransferase is found in cell membranes of several body tissues, including the liver and spleen, and therefore is not specific to liver damage. However, elevated GGT is the best indicator of excessive alcohol consumption because it has greater sensitivity than AST and ALT.^1,3,4

Although these biomarkers are helpful in diagnosing ALD, they lose some of their utility in patients with advanced liver disease. Patients with severe liver dysfunction may not have elevated serum aminotransferase levels because the degree of liver enzyme elevation does not correlate well with the severity of ALD. For example, patients with advanced cirrhosis may have liver enzyme levels that appear normal. However, the pattern of elevation in transaminases can be helpful in making a diagnosis of liver dysfunction; using the ratio of AST to ALT may aid in diagnosing ALD, because AST is elevated more than twice that of ALT in >80% of patients with ALD.^1,3,4

Table 2^1,3,4 shows the progression of ALD from steatohepatitis to alcoholic hepatitis to cirrhosis. In steatohepatitis, transaminitis is present but all other biomarkers normal. In alcoholic hepatitis, transaminitis is present along with elevated alkaline phosphatase, elevated bilirubin, and elevated international normalized ratio (INR). In alcoholic cirrhosis, the AST-to-ALT ratio is >2, and hypoalbuminemia, hyperbilirubinemia, and coagulopathy (evidenced by elevated INR) are present, consistent with long-term liver damage.^1,3,4

Continue to: FDA-approved medications

FDA-approved medications

Three medications—acamprosate, naltrexone, and disulfiram—currently are FDA-approved for treating AUD.^5,6 Additionally, several other medications have shown varying levels of efficacy in treating patients with AUD but are not FDA-approved for this indication (Table 3).^5-8

Acamprosate is thought to create a balance of inhibitor and excitatory neurotransmitters by functioning as a glutamate antagonist and gamma-aminobutyric acid (GABA) agonist. This is speculated to aid in abstinence from alcohol. Data suggests that acamprosate may be more effective for maintaining abstinence than for inducing remission in individuals who have not yet detoxified from alcohol. Because of its renal excretion, acamprosate is the only FDA-approved medication for AUD that is not associated with liver toxicity. The most commonly reported adverse effect with acamprosate use is diarrhea.

Naltrexone, a mu-opioid receptor antagonist, is available in both tablet and long-acting IM injection formulations. Naltrexone blocks the binding of endorphins created by alcohol consumption to opioid receptors. This results in diminished dopamine release and is speculated to decrease reward and positive reinforcement with alcohol consumption, leading to fewer heavy drinking days. Due to hepatic metabolism, naltrexone use carries a risk of liver injury. Cases of hepatitis and clinically significant liver dysfunction as well as transient, asymptomatic, hepatic transaminase elevations have been observed in patients who receive naltrexone. Because of the absence of first-pass metabolism, long-acting IM naltrexone may produce less hepatotoxicity than the oral formulation. When the FDA approved both formulations of naltrexone, a “black-box” warning was issued concerning the risk of liver damage; however, these warnings have since been removed from their respective prescribing information.

Disulfiram inhibits acetaldehyde dehydrogenase, resulting in elevated acetaldehyde concentrations after consuming alcohol. In theory, this medication reduces a person’s desire to drink due to the negative physiological and physical effects associated with increased acetaldehyde, including hypotension, flushing, nausea, and vomiting. Although most of these reactions are short-lived, disulfiram can induce hepatotoxicity and liver failure that may prove fatal. Disulfiram should be avoided in patients with advanced ALD.

Off-label medications for AUD

Additional pharmacotherapeutic agents have been evaluated in patients with AUD. Baclofen, topiramate, gabapentin, and ondansetron have shown varying levels of efficacy and pose minimal concern in patients with ALD.

Continue to: Baclofen

Baclofen. Although findings are conflicting, baclofen is the only agent that has been specifically studied for treating AUD in patients with ALD. A GABA B receptor antagonist, baclofen is currently FDA-approved for treating spasticity. In a series of open-label and double-blind studies, baclofen has been shown to effectively reduce alcohol intake, promote abstinence, and prevent relapse.^5,6 Further studies identified a possible dose-related response, noting that 20 mg taken 3 times daily may confer additional response over 10 mg taken 3 times daily.^5,6 Conversely, the ALPADIR study failed to demonstrate superiority of baclofen vs placebo in the maintenance of abstinence from alcohol despite dosing at 180 mg/d.⁹ This study did, however, find a significant reduction in alcohol craving in favor of baclofen.⁹ Further, in a randomized controlled trial (RCT) conducted in veterans with chronic hepatitis C, baclofen 30 mg/d failed to show superiority over placebo with regard to increasing abstinence or reducing alcohol use.¹⁰

Topiramate. A recent meta-analysis found that topiramate use may result in fewer drinking days, heavy drinking days, and number of drinks per drinking day.⁷ Additionally, topiramate has demonstrated a statistically significant reduction in alcohol craving as well as the ability to decrease all liver function test values.⁵ This agent should be used with caution in patients with hepatic encephalopathy because the adverse cognitive effects associated with topiramate may confound the clinical course and treatment of such.

Gabapentin. The use of gabapentin to treat patients with AUD is supported by multiple RCTs. In studies that evaluated dose-related response, higher doses of gabapentin (up to 1,800 mg/d) showed greater efficacy than lower doses (ie, 900 mg/d).⁸ Because gabapentin does not undergo hepatic metabolism, its use in patients with ALD is considered safe. Although the abuse potential of gabapentin is less defined in patients with AUD, there have been reports of abuse in other high-risk populations (ie, those with opioid use disorder, incarcerated persons, and those who misuse prescriptions recreationally).⁸

Ondansetron is speculated to decrease the reward from alcohol via the down-regulation of dopaminergic neurons. Studies examining ondansetron for patients with AUD have found that it decreases alcohol cravings in those with early-onset alcoholism (initial onset at age ≤25), but not in late-onset alcoholism (initial onset at age >25).⁵ However, the ondansetron doses used in these trials were very low (4 mcg/kg), and those doses are not available commercially.⁵

CASE CONTINUED

Following a discussion of available pharma­cotherapeutic options for AUD, Mr. S is started on baclofen, 10 mg 3 times daily, with plans for dose titration. At a 2-week follow-up appointment, Mr. S reports that he had not been taking baclofen as often as instructed; however, he denies further alcohol consumption and re-commits to baclofen treatment. Unfortunately, Mr. S is soon admitted to hospice care due to continued decompensation and is unable to attend any additional outpatient follow-up appointments. Three months after his initial outpatient contact, Mr. S dies due to alcoholic cirrhosis.

Related Resources

• Crabb DW, Im GY, Szabo G, et al. Diagnosis and treatment of alcohol-related liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2020;71(1):306-333.
• Murail AR, Carey WD. Disease management. Liver test interpretation - approach to the patient with liver disease: a guide to commonly used liver tests. Cleveland Clinic Center for Continuing Education. Updated August 2017. www.clevelandclinicmeded. com/medicalpubs/diseasemanagement/hepatology/ guide-to-common-liver-tests/

Drug Brand Names

Acamprosate • Campral
Baclofen • Lioresal
Disulfiram • Antabuse
Gabapentin • Neurontin
Naltrexone • Revia, Vivitrol
Ondansetron • Zofran
Topiramate • Topamax

Mr. S, age 64, presents for an outpatient follow-up after a recent hospital discharge for alcohol detoxification. He reports a long history of alcohol use, which has resulted in numerous hospital admissions. He has recently been receiving care from a gastroenterologist because the results of laboratory testing suggested hepatic impairment (Table 1). Mr. S says that a friend of his was able to stop drinking by taking a medication, and he wonders if he can be prescribed a medication to help him as well.

A chart review shows that Mr. S recently underwent paracentesis, during which 6 liters of fluid were removed. Additionally, an abdominal ultrasound confirmed hepatic cirrhosis.

According to the World Health Organization, alcohol consumption contributes to 3 million deaths annually.² The highest proportion of these deaths (21.3%) is due to alcohol-associated gastrointestinal complications, including alcoholic and infectious hepatitis, pancreatitis, and cirrhosis. Because the liver is the primary site of ethanol metabolism, it sustains the greatest degree of tissue injury with heavy alcohol consumption. Additionally, the association of harmful use of alcohol with risky sexual behavior may partially explain the higher prevalence of viral hepatitis among persons with alcohol use disorder (AUD) compared with the general population. Alcoholic liver disease (ALD) progresses through several stages, beginning with hepatic steatosis and progressing through alcohol-related hepatitis, fibrosis, cirrhosis, and potentially hepatocellular carcinoma.³

Liver markers of alcohol use

Although biological markers can be used in clinical practice to screen and monitor for alcohol abuse, making a diagnosis of ALD can be challenging. Typically, a history of heavy alcohol consumption in addition to certain physical signs and laboratory tests for liver disease are the best indicators of ALD. However, the clinical assessment can be confounded by patients who deny or minimize how much alcohol they have consumed. Furthermore, physical and laboratory findings may not be specific to ALD.

Liver enzymes, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT), have historically been used as the basis of diagnosing ALD. In addition to elevated bilirubin and evidence of macrocytic anemia, elevations in these enzymes may suggest heavy alcohol use, but these values alone are inadequate to establish ALD. Gamma-glutamyltransferase is found in cell membranes of several body tissues, including the liver and spleen, and therefore is not specific to liver damage. However, elevated GGT is the best indicator of excessive alcohol consumption because it has greater sensitivity than AST and ALT.^1,3,4

Although these biomarkers are helpful in diagnosing ALD, they lose some of their utility in patients with advanced liver disease. Patients with severe liver dysfunction may not have elevated serum aminotransferase levels because the degree of liver enzyme elevation does not correlate well with the severity of ALD. For example, patients with advanced cirrhosis may have liver enzyme levels that appear normal. However, the pattern of elevation in transaminases can be helpful in making a diagnosis of liver dysfunction; using the ratio of AST to ALT may aid in diagnosing ALD, because AST is elevated more than twice that of ALT in >80% of patients with ALD.^1,3,4

Table 2^1,3,4 shows the progression of ALD from steatohepatitis to alcoholic hepatitis to cirrhosis. In steatohepatitis, transaminitis is present but all other biomarkers normal. In alcoholic hepatitis, transaminitis is present along with elevated alkaline phosphatase, elevated bilirubin, and elevated international normalized ratio (INR). In alcoholic cirrhosis, the AST-to-ALT ratio is >2, and hypoalbuminemia, hyperbilirubinemia, and coagulopathy (evidenced by elevated INR) are present, consistent with long-term liver damage.^1,3,4

Continue to: FDA-approved medications

FDA-approved medications

Three medications—acamprosate, naltrexone, and disulfiram—currently are FDA-approved for treating AUD.^5,6 Additionally, several other medications have shown varying levels of efficacy in treating patients with AUD but are not FDA-approved for this indication (Table 3).^5-8

Acamprosate is thought to create a balance of inhibitor and excitatory neurotransmitters by functioning as a glutamate antagonist and gamma-aminobutyric acid (GABA) agonist. This is speculated to aid in abstinence from alcohol. Data suggests that acamprosate may be more effective for maintaining abstinence than for inducing remission in individuals who have not yet detoxified from alcohol. Because of its renal excretion, acamprosate is the only FDA-approved medication for AUD that is not associated with liver toxicity. The most commonly reported adverse effect with acamprosate use is diarrhea.

Naltrexone, a mu-opioid receptor antagonist, is available in both tablet and long-acting IM injection formulations. Naltrexone blocks the binding of endorphins created by alcohol consumption to opioid receptors. This results in diminished dopamine release and is speculated to decrease reward and positive reinforcement with alcohol consumption, leading to fewer heavy drinking days. Due to hepatic metabolism, naltrexone use carries a risk of liver injury. Cases of hepatitis and clinically significant liver dysfunction as well as transient, asymptomatic, hepatic transaminase elevations have been observed in patients who receive naltrexone. Because of the absence of first-pass metabolism, long-acting IM naltrexone may produce less hepatotoxicity than the oral formulation. When the FDA approved both formulations of naltrexone, a “black-box” warning was issued concerning the risk of liver damage; however, these warnings have since been removed from their respective prescribing information.

Disulfiram inhibits acetaldehyde dehydrogenase, resulting in elevated acetaldehyde concentrations after consuming alcohol. In theory, this medication reduces a person’s desire to drink due to the negative physiological and physical effects associated with increased acetaldehyde, including hypotension, flushing, nausea, and vomiting. Although most of these reactions are short-lived, disulfiram can induce hepatotoxicity and liver failure that may prove fatal. Disulfiram should be avoided in patients with advanced ALD.

Off-label medications for AUD

Additional pharmacotherapeutic agents have been evaluated in patients with AUD. Baclofen, topiramate, gabapentin, and ondansetron have shown varying levels of efficacy and pose minimal concern in patients with ALD.

Continue to: Baclofen

Baclofen. Although findings are conflicting, baclofen is the only agent that has been specifically studied for treating AUD in patients with ALD. A GABA B receptor antagonist, baclofen is currently FDA-approved for treating spasticity. In a series of open-label and double-blind studies, baclofen has been shown to effectively reduce alcohol intake, promote abstinence, and prevent relapse.^5,6 Further studies identified a possible dose-related response, noting that 20 mg taken 3 times daily may confer additional response over 10 mg taken 3 times daily.^5,6 Conversely, the ALPADIR study failed to demonstrate superiority of baclofen vs placebo in the maintenance of abstinence from alcohol despite dosing at 180 mg/d.⁹ This study did, however, find a significant reduction in alcohol craving in favor of baclofen.⁹ Further, in a randomized controlled trial (RCT) conducted in veterans with chronic hepatitis C, baclofen 30 mg/d failed to show superiority over placebo with regard to increasing abstinence or reducing alcohol use.¹⁰

Topiramate. A recent meta-analysis found that topiramate use may result in fewer drinking days, heavy drinking days, and number of drinks per drinking day.⁷ Additionally, topiramate has demonstrated a statistically significant reduction in alcohol craving as well as the ability to decrease all liver function test values.⁵ This agent should be used with caution in patients with hepatic encephalopathy because the adverse cognitive effects associated with topiramate may confound the clinical course and treatment of such.

Gabapentin. The use of gabapentin to treat patients with AUD is supported by multiple RCTs. In studies that evaluated dose-related response, higher doses of gabapentin (up to 1,800 mg/d) showed greater efficacy than lower doses (ie, 900 mg/d).⁸ Because gabapentin does not undergo hepatic metabolism, its use in patients with ALD is considered safe. Although the abuse potential of gabapentin is less defined in patients with AUD, there have been reports of abuse in other high-risk populations (ie, those with opioid use disorder, incarcerated persons, and those who misuse prescriptions recreationally).⁸

Ondansetron is speculated to decrease the reward from alcohol via the down-regulation of dopaminergic neurons. Studies examining ondansetron for patients with AUD have found that it decreases alcohol cravings in those with early-onset alcoholism (initial onset at age ≤25), but not in late-onset alcoholism (initial onset at age >25).⁵ However, the ondansetron doses used in these trials were very low (4 mcg/kg), and those doses are not available commercially.⁵

CASE CONTINUED

Following a discussion of available pharma­cotherapeutic options for AUD, Mr. S is started on baclofen, 10 mg 3 times daily, with plans for dose titration. At a 2-week follow-up appointment, Mr. S reports that he had not been taking baclofen as often as instructed; however, he denies further alcohol consumption and re-commits to baclofen treatment. Unfortunately, Mr. S is soon admitted to hospice care due to continued decompensation and is unable to attend any additional outpatient follow-up appointments. Three months after his initial outpatient contact, Mr. S dies due to alcoholic cirrhosis.

Related Resources

• Crabb DW, Im GY, Szabo G, et al. Diagnosis and treatment of alcohol-related liver diseases: 2019 practice guidance from the American Association for the Study of Liver Diseases. Hepatology. 2020;71(1):306-333.
• Murail AR, Carey WD. Disease management. Liver test interpretation - approach to the patient with liver disease: a guide to commonly used liver tests. Cleveland Clinic Center for Continuing Education. Updated August 2017. www.clevelandclinicmeded. com/medicalpubs/diseasemanagement/hepatology/ guide-to-common-liver-tests/

Drug Brand Names

Acamprosate • Campral
Baclofen • Lioresal
Disulfiram • Antabuse
Gabapentin • Neurontin
Naltrexone • Revia, Vivitrol
Ondansetron • Zofran
Topiramate • Topamax

Newer therapies for actinic keratoses (AKs) are expected to provide high rates of skin clearance with high rates of local skin reactions, according to an expert speaking at the annual Coastal Dermatology Symposium, held virtually.

This relationship is not new. In a review of treatments for AKs, Neal Bhatia, MD, a dermatologist and researcher at Therapeutics Dermatology, San Diego, advised that most effective agents trade a higher risk of inflammatory reactions – including erythema, flaking, and scaling – for greater therapeutic gain. In many cases, local skin reactions are an inevitable consequence of their mechanism of action.

Data from the completed phase 3 trials of tirbanibulin 1% ointment (KX01-AK-003 and KX01-AK-004), are illustrative. (Tirbanibulin 1% ointment was approved by the Food and Drug Administration in mid-December, after the Coastal Derm meeting was held.)

In the phase 3 trials, which have not yet been published, tirbanibulin, an inhibitor of Src kinase, which has an antiproliferative action, was four to five times more effective than vehicle by day 57 for overall complete clearance (P < .0001) of AKs and complete clearance of the face (P < .0001), but rates of local skin reactions were generally two to three times higher, according to Dr. Bhatia.

In the KX01-AK-004 trial, for example, 61% of patients had complete clearance of the face, versus 14% of those randomized to vehicle. The difference for overall partial clearance (76% vs. 20%; P < .0001), partial clearance of the face (80% vs. 22%; P < .0001), and partial clearance of the scalp (69% vs. 15%; P < .0001) was even greater. When compared with placebo, tirbanibulin was also associated with greater rates of erythema (90% vs. 31%), crusting (45% vs. 8%), flaking (84% vs. 35%), swelling (38% vs. 2%) and erosions or ulcers (12% vs. 1%).

Although these events might be a challenge with regard to tolerability for some patients, they might best be described as evidence that the drug is working.

“Local skin reactions are anticipated. They are not adverse events. They are not side effects,” Dr. Bhatia said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. “Patients are going to get red, and you need to counsel patients about the 5 days when they can expected to be red. It is a sign of the civil war, if you will, that your skin is taking on with the actinic keratoses.”

Both 3- and 5-day courses of the drug were tested in the clinical trials. (The approved prescribing information recommends treatment on the face or scalp once a day for 5 consecutive days).

Other studies evaluating treatments for AKs have also associated an increased risk of local skin reactions with greater efficacy, Dr. Bhatia noted. As an example, he cited a phase 4 study comparing 0.015% ingenol mebutate gel to diclofenac sodium 3% gel in people with facial and scalp AK lesions.

At the end of the 3-month study, complete clearance was higher among those on ingenol mebutate, which was applied for 3 days, when compared with diclofenac sodium gel, which was applied daily for 3 months (34% vs. 23%; P = .006). However, patients randomized to ingenol mebutate gel had to first weather a higher rate of application-site erythema (19% vs. 12%) before achieving a greater level of clearance.

The correlation between efficacy and local reactions at the site of treatment application emphasizes the importance of educating patients about this relationship and in engaging in shared decision-making, Dr. Bhatia said.

“It is basically a tradeoff between local skin reactions, between frequency [of applications], compliance, and, of course, duration of therapy, even though both drugs served their purposes well,” said Dr. Bhatia, referring to the comparison of the ingenol mebutate and diclofenac gels.

Although not absolute, efficacy and tolerability were also generally inversely related in a recent four-treatment comparison of four commonly used field-directed therapies. In that trial, the primary endpoint was at least a 75% reduction from baseline in the number of AKs to 12 months after treatment ended.

For that outcome, 5% fluorouracil (5-FU) cream (74.7%) was significantly more effective than 5% imiquimod cream (53.9%), methyl aminolevulinate photodynamic therapy (37.7%), and 0.015% ingenol mebutate gel (28.9%). Also, 5-FU treatment was associated with the moderate or severe erythema (81.5%), severe pain (16.%), and a severe burning sensation (21.5%).

Other therapies on the horizon, some of which are already available in Europe or Canada, show a relationship between efficacy and local skin reactions. Of two that Dr. Bhatia cited, 5-FU and salicylic acid combined in a solution and 5-FU and calcipotriene combined in an ointment have demonstrated high rates of efficacy but at the cost of substantial rates of erythema and flaking.

Transient skin reactions can be made acceptable to patients who are informed of the goals of clearing AKs, which includes lowering the risk of cancer, as well as cosmetic improvement. In the phase 4 study comparing ingenol mebutate gel to diclofenac sodium gel, the end-of-study global satisfaction rates were higher (P < .001) for those randomized to the most effective therapy despite the local skin reactions.

Preparing patients for the consequences of therapy for AKs is essential, because optimal therapy involves treating uninvolved skin, according to Hassan Galadari, MD, assistant professor of dermatology, United Arab Emirates University, Dubai. A coauthor of a recent review article on actinic keratoses, Dr. Galadari said in an interview that field treatment means patients might have local skin reactions where they did not previously have lesions.

“Actinic damage may not be visible with the naked eye. That is why field treatment, which is applying medicine in adjacent areas that may appear normal, is indicated,” he said. As a result, “areas that otherwise may have appeared as normal start to react by becoming red, itchy, and even inflamed.”

He agreed with Dr. Bhatia that local skin reactions are typically the price paid for effective control of these precancerous lesions.

This publication and Global Academy for Medical Education are owned by the same parent company.

Dr. Bhatia reports financial relationships with more than 30 pharmaceutical companies with dermatologic products, including Almirall and other companies with products relevant to AK therapies.

Newer therapies for actinic keratoses (AKs) are expected to provide high rates of skin clearance with high rates of local skin reactions, according to an expert speaking at the annual Coastal Dermatology Symposium, held virtually.

This relationship is not new. In a review of treatments for AKs, Neal Bhatia, MD, a dermatologist and researcher at Therapeutics Dermatology, San Diego, advised that most effective agents trade a higher risk of inflammatory reactions – including erythema, flaking, and scaling – for greater therapeutic gain. In many cases, local skin reactions are an inevitable consequence of their mechanism of action.

Data from the completed phase 3 trials of tirbanibulin 1% ointment (KX01-AK-003 and KX01-AK-004), are illustrative. (Tirbanibulin 1% ointment was approved by the Food and Drug Administration in mid-December, after the Coastal Derm meeting was held.)

In the phase 3 trials, which have not yet been published, tirbanibulin, an inhibitor of Src kinase, which has an antiproliferative action, was four to five times more effective than vehicle by day 57 for overall complete clearance (P < .0001) of AKs and complete clearance of the face (P < .0001), but rates of local skin reactions were generally two to three times higher, according to Dr. Bhatia.

In the KX01-AK-004 trial, for example, 61% of patients had complete clearance of the face, versus 14% of those randomized to vehicle. The difference for overall partial clearance (76% vs. 20%; P < .0001), partial clearance of the face (80% vs. 22%; P < .0001), and partial clearance of the scalp (69% vs. 15%; P < .0001) was even greater. When compared with placebo, tirbanibulin was also associated with greater rates of erythema (90% vs. 31%), crusting (45% vs. 8%), flaking (84% vs. 35%), swelling (38% vs. 2%) and erosions or ulcers (12% vs. 1%).

Although these events might be a challenge with regard to tolerability for some patients, they might best be described as evidence that the drug is working.

“Local skin reactions are anticipated. They are not adverse events. They are not side effects,” Dr. Bhatia said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. “Patients are going to get red, and you need to counsel patients about the 5 days when they can expected to be red. It is a sign of the civil war, if you will, that your skin is taking on with the actinic keratoses.”

Both 3- and 5-day courses of the drug were tested in the clinical trials. (The approved prescribing information recommends treatment on the face or scalp once a day for 5 consecutive days).

Other studies evaluating treatments for AKs have also associated an increased risk of local skin reactions with greater efficacy, Dr. Bhatia noted. As an example, he cited a phase 4 study comparing 0.015% ingenol mebutate gel to diclofenac sodium 3% gel in people with facial and scalp AK lesions.

At the end of the 3-month study, complete clearance was higher among those on ingenol mebutate, which was applied for 3 days, when compared with diclofenac sodium gel, which was applied daily for 3 months (34% vs. 23%; P = .006). However, patients randomized to ingenol mebutate gel had to first weather a higher rate of application-site erythema (19% vs. 12%) before achieving a greater level of clearance.

The correlation between efficacy and local reactions at the site of treatment application emphasizes the importance of educating patients about this relationship and in engaging in shared decision-making, Dr. Bhatia said.

“It is basically a tradeoff between local skin reactions, between frequency [of applications], compliance, and, of course, duration of therapy, even though both drugs served their purposes well,” said Dr. Bhatia, referring to the comparison of the ingenol mebutate and diclofenac gels.

Although not absolute, efficacy and tolerability were also generally inversely related in a recent four-treatment comparison of four commonly used field-directed therapies. In that trial, the primary endpoint was at least a 75% reduction from baseline in the number of AKs to 12 months after treatment ended.

For that outcome, 5% fluorouracil (5-FU) cream (74.7%) was significantly more effective than 5% imiquimod cream (53.9%), methyl aminolevulinate photodynamic therapy (37.7%), and 0.015% ingenol mebutate gel (28.9%). Also, 5-FU treatment was associated with the moderate or severe erythema (81.5%), severe pain (16.%), and a severe burning sensation (21.5%).

Other therapies on the horizon, some of which are already available in Europe or Canada, show a relationship between efficacy and local skin reactions. Of two that Dr. Bhatia cited, 5-FU and salicylic acid combined in a solution and 5-FU and calcipotriene combined in an ointment have demonstrated high rates of efficacy but at the cost of substantial rates of erythema and flaking.

Transient skin reactions can be made acceptable to patients who are informed of the goals of clearing AKs, which includes lowering the risk of cancer, as well as cosmetic improvement. In the phase 4 study comparing ingenol mebutate gel to diclofenac sodium gel, the end-of-study global satisfaction rates were higher (P < .001) for those randomized to the most effective therapy despite the local skin reactions.

Preparing patients for the consequences of therapy for AKs is essential, because optimal therapy involves treating uninvolved skin, according to Hassan Galadari, MD, assistant professor of dermatology, United Arab Emirates University, Dubai. A coauthor of a recent review article on actinic keratoses, Dr. Galadari said in an interview that field treatment means patients might have local skin reactions where they did not previously have lesions.

“Actinic damage may not be visible with the naked eye. That is why field treatment, which is applying medicine in adjacent areas that may appear normal, is indicated,” he said. As a result, “areas that otherwise may have appeared as normal start to react by becoming red, itchy, and even inflamed.”

He agreed with Dr. Bhatia that local skin reactions are typically the price paid for effective control of these precancerous lesions.

This publication and Global Academy for Medical Education are owned by the same parent company.

Dr. Bhatia reports financial relationships with more than 30 pharmaceutical companies with dermatologic products, including Almirall and other companies with products relevant to AK therapies.

Newer therapies for actinic keratoses (AKs) are expected to provide high rates of skin clearance with high rates of local skin reactions, according to an expert speaking at the annual Coastal Dermatology Symposium, held virtually.

This relationship is not new. In a review of treatments for AKs, Neal Bhatia, MD, a dermatologist and researcher at Therapeutics Dermatology, San Diego, advised that most effective agents trade a higher risk of inflammatory reactions – including erythema, flaking, and scaling – for greater therapeutic gain. In many cases, local skin reactions are an inevitable consequence of their mechanism of action.

Data from the completed phase 3 trials of tirbanibulin 1% ointment (KX01-AK-003 and KX01-AK-004), are illustrative. (Tirbanibulin 1% ointment was approved by the Food and Drug Administration in mid-December, after the Coastal Derm meeting was held.)

In the phase 3 trials, which have not yet been published, tirbanibulin, an inhibitor of Src kinase, which has an antiproliferative action, was four to five times more effective than vehicle by day 57 for overall complete clearance (P < .0001) of AKs and complete clearance of the face (P < .0001), but rates of local skin reactions were generally two to three times higher, according to Dr. Bhatia.

In the KX01-AK-004 trial, for example, 61% of patients had complete clearance of the face, versus 14% of those randomized to vehicle. The difference for overall partial clearance (76% vs. 20%; P < .0001), partial clearance of the face (80% vs. 22%; P < .0001), and partial clearance of the scalp (69% vs. 15%; P < .0001) was even greater. When compared with placebo, tirbanibulin was also associated with greater rates of erythema (90% vs. 31%), crusting (45% vs. 8%), flaking (84% vs. 35%), swelling (38% vs. 2%) and erosions or ulcers (12% vs. 1%).

Although these events might be a challenge with regard to tolerability for some patients, they might best be described as evidence that the drug is working.

“Local skin reactions are anticipated. They are not adverse events. They are not side effects,” Dr. Bhatia said at the meeting, jointly presented by the University of Louisville and Global Academy for Medical Education. “Patients are going to get red, and you need to counsel patients about the 5 days when they can expected to be red. It is a sign of the civil war, if you will, that your skin is taking on with the actinic keratoses.”

Both 3- and 5-day courses of the drug were tested in the clinical trials. (The approved prescribing information recommends treatment on the face or scalp once a day for 5 consecutive days).

Other studies evaluating treatments for AKs have also associated an increased risk of local skin reactions with greater efficacy, Dr. Bhatia noted. As an example, he cited a phase 4 study comparing 0.015% ingenol mebutate gel to diclofenac sodium 3% gel in people with facial and scalp AK lesions.

At the end of the 3-month study, complete clearance was higher among those on ingenol mebutate, which was applied for 3 days, when compared with diclofenac sodium gel, which was applied daily for 3 months (34% vs. 23%; P = .006). However, patients randomized to ingenol mebutate gel had to first weather a higher rate of application-site erythema (19% vs. 12%) before achieving a greater level of clearance.

The correlation between efficacy and local reactions at the site of treatment application emphasizes the importance of educating patients about this relationship and in engaging in shared decision-making, Dr. Bhatia said.

“It is basically a tradeoff between local skin reactions, between frequency [of applications], compliance, and, of course, duration of therapy, even though both drugs served their purposes well,” said Dr. Bhatia, referring to the comparison of the ingenol mebutate and diclofenac gels.

Although not absolute, efficacy and tolerability were also generally inversely related in a recent four-treatment comparison of four commonly used field-directed therapies. In that trial, the primary endpoint was at least a 75% reduction from baseline in the number of AKs to 12 months after treatment ended.

For that outcome, 5% fluorouracil (5-FU) cream (74.7%) was significantly more effective than 5% imiquimod cream (53.9%), methyl aminolevulinate photodynamic therapy (37.7%), and 0.015% ingenol mebutate gel (28.9%). Also, 5-FU treatment was associated with the moderate or severe erythema (81.5%), severe pain (16.%), and a severe burning sensation (21.5%).

Other therapies on the horizon, some of which are already available in Europe or Canada, show a relationship between efficacy and local skin reactions. Of two that Dr. Bhatia cited, 5-FU and salicylic acid combined in a solution and 5-FU and calcipotriene combined in an ointment have demonstrated high rates of efficacy but at the cost of substantial rates of erythema and flaking.

Transient skin reactions can be made acceptable to patients who are informed of the goals of clearing AKs, which includes lowering the risk of cancer, as well as cosmetic improvement. In the phase 4 study comparing ingenol mebutate gel to diclofenac sodium gel, the end-of-study global satisfaction rates were higher (P < .001) for those randomized to the most effective therapy despite the local skin reactions.

Preparing patients for the consequences of therapy for AKs is essential, because optimal therapy involves treating uninvolved skin, according to Hassan Galadari, MD, assistant professor of dermatology, United Arab Emirates University, Dubai. A coauthor of a recent review article on actinic keratoses, Dr. Galadari said in an interview that field treatment means patients might have local skin reactions where they did not previously have lesions.

“Actinic damage may not be visible with the naked eye. That is why field treatment, which is applying medicine in adjacent areas that may appear normal, is indicated,” he said. As a result, “areas that otherwise may have appeared as normal start to react by becoming red, itchy, and even inflamed.”

He agreed with Dr. Bhatia that local skin reactions are typically the price paid for effective control of these precancerous lesions.

This publication and Global Academy for Medical Education are owned by the same parent company.

Dr. Bhatia reports financial relationships with more than 30 pharmaceutical companies with dermatologic products, including Almirall and other companies with products relevant to AK therapies.

Everywhere they look within hospitals, researchers find RNA from SARS-CoV-2 in the air. But viable viruses typically are found only close to patients, according to a review of published studies.

The finding supports recommendations to use surgical masks in most parts of the hospital, reserving respirators (such as N95 or FFP2) for aerosol-generating procedures on patients’ respiratory tracts, said Gabriel Birgand, PhD, an infectious disease researcher at Imperial College London.

“When the virus is spreading a lot in the community, it’s probably more likely for you to be contaminated in your friends’ areas or in your building than in your work area, where you are well equipped and compliant with all the measures,” he said in an interview. “So it’s pretty good news.”

The systematic review by Dr. Birgand and colleagues was published in JAMA Network Open.

Recommended precautions to protect health care workers from SARS-CoV-2 infections remain controversial. Most authorities believe droplets are the primary route of transmission, which would mean surgical masks may be sufficient protection. But some research has suggested transmission by aerosols as well, making N95 respirators seem necessary. There is even disagreement about the definitions of the words “aerosol” and “droplet.”

To better understand where traces of the virus can be found in the air in hospitals, Dr. Birgand and colleagues analyzed all the studies they could find on the subject in English.

They identified 24 articles with original data. All of the studies used reverse transcription–polymerase chain reaction (PCR) tests to identify SARS-CoV-2 RNA. In five studies, attempts were also made to culture viable viruses. Three studies assessed the particle size relative to RNA concentration or viral titer.

Of 893 air samples across the 24 studies, 52.7% were taken from areas close to patients, 26.5% were taken in clinical areas, 13.7% in staff areas, 4.7% in public areas, and 2.4% in toilets or bathrooms.

Among those studies that quantified RNA, the median interquartile range of concentrations varied from 1.0 x 103 copies/m3 in clinical areas to 9.7 x 10³ copies/m³ in toilets or bathrooms.

One study found an RNA concentration of 2.0 x 10³ copies for particle sizes >4 mcm and 1.3 x 103 copies/m³ for particle sizes ≤4 mcm, both in patients’ rooms.

Three studies included viral cultures; of those, two resulted in positive cultures, both in a non-ICU setting. In one study, 3 of 39 samples were positive, and in the other, 4 of 4 were positive. Viral cultures in toilets, clinical areas, staff areas, and public areas were negative.

One of these studies assessed viral concentration and found that the median interquartile range was 4.8 tissue culture infectious dose (TCID50)/m³ for particles <1 mcm, 4.27 TCID50/m³ for particles 1-4 mcm, and 1.82 TCID50/m³ for particles >4 mcm.

Although viable viruses weren’t found in staff areas, the presence of viral RNA in places such as dining rooms and meeting rooms raises a concern, Dr. Birgand said.

“All of these staff areas are probably playing an important role in contamination,” he said. “It’s pretty easy to see when you are dining, you are not wearing a face mask, and it’s associated with a strong risk when there is a strong dissemination of the virus in the community.”

Studies on contact tracing among health care workers have also identified meeting rooms and dining rooms as the second most common source of infection after community contact, he said.

In general, the findings of the review correspond to epidemiologic studies, said Angela Rasmussen, PhD, a virologist with the Georgetown University Center for Global Health Science and Security, Washington, who was not involved in the review. “Absent aerosol-generating procedures, health care workers are largely not getting infected when they take droplet precautions.”

One reason may be that patients shed the most infectious viruses a couple of days before and after symptoms begin. By the time they’re hospitalized, they’re less likely to be contagious but may continue to shed viral RNA.

“We don’t really know the basis for the persistence of RNA being produced long after people have been infected and have recovered from the acute infection,” she said, “but it has been observed quite frequently.”

Although the virus cannot remain viable for very long in the air, remnants may still be detected in the form of RNA, Dr. Rasmussen said. In addition, hospitals often do a good job of ventilation.

She pointed out that it can be difficult to cultivate viruses in air samples because of contaminants such as bacteria and fungi. “That’s one of the limitations of a study like this. You’re not really sure if it’s because there’s no viable virus there or because you just aren’t able to collect samples that would allow you to determine that.”

Dr. Birgand and colleagues acknowledged other limitations. The studies they reviewed used different approaches to sampling. Different procedures may have been underway in the rooms being sampled, and factors such as temperature and humidity could have affected the results. In addition, the studies used different cycle thresholds for PCR positivity.

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

Everywhere they look within hospitals, researchers find RNA from SARS-CoV-2 in the air. But viable viruses typically are found only close to patients, according to a review of published studies.

The finding supports recommendations to use surgical masks in most parts of the hospital, reserving respirators (such as N95 or FFP2) for aerosol-generating procedures on patients’ respiratory tracts, said Gabriel Birgand, PhD, an infectious disease researcher at Imperial College London.

“When the virus is spreading a lot in the community, it’s probably more likely for you to be contaminated in your friends’ areas or in your building than in your work area, where you are well equipped and compliant with all the measures,” he said in an interview. “So it’s pretty good news.”

The systematic review by Dr. Birgand and colleagues was published in JAMA Network Open.

Recommended precautions to protect health care workers from SARS-CoV-2 infections remain controversial. Most authorities believe droplets are the primary route of transmission, which would mean surgical masks may be sufficient protection. But some research has suggested transmission by aerosols as well, making N95 respirators seem necessary. There is even disagreement about the definitions of the words “aerosol” and “droplet.”

To better understand where traces of the virus can be found in the air in hospitals, Dr. Birgand and colleagues analyzed all the studies they could find on the subject in English.

They identified 24 articles with original data. All of the studies used reverse transcription–polymerase chain reaction (PCR) tests to identify SARS-CoV-2 RNA. In five studies, attempts were also made to culture viable viruses. Three studies assessed the particle size relative to RNA concentration or viral titer.

Of 893 air samples across the 24 studies, 52.7% were taken from areas close to patients, 26.5% were taken in clinical areas, 13.7% in staff areas, 4.7% in public areas, and 2.4% in toilets or bathrooms.

Among those studies that quantified RNA, the median interquartile range of concentrations varied from 1.0 x 103 copies/m3 in clinical areas to 9.7 x 10³ copies/m³ in toilets or bathrooms.

One study found an RNA concentration of 2.0 x 10³ copies for particle sizes >4 mcm and 1.3 x 103 copies/m³ for particle sizes ≤4 mcm, both in patients’ rooms.

Three studies included viral cultures; of those, two resulted in positive cultures, both in a non-ICU setting. In one study, 3 of 39 samples were positive, and in the other, 4 of 4 were positive. Viral cultures in toilets, clinical areas, staff areas, and public areas were negative.

One of these studies assessed viral concentration and found that the median interquartile range was 4.8 tissue culture infectious dose (TCID50)/m³ for particles <1 mcm, 4.27 TCID50/m³ for particles 1-4 mcm, and 1.82 TCID50/m³ for particles >4 mcm.

Although viable viruses weren’t found in staff areas, the presence of viral RNA in places such as dining rooms and meeting rooms raises a concern, Dr. Birgand said.

“All of these staff areas are probably playing an important role in contamination,” he said. “It’s pretty easy to see when you are dining, you are not wearing a face mask, and it’s associated with a strong risk when there is a strong dissemination of the virus in the community.”

Studies on contact tracing among health care workers have also identified meeting rooms and dining rooms as the second most common source of infection after community contact, he said.

In general, the findings of the review correspond to epidemiologic studies, said Angela Rasmussen, PhD, a virologist with the Georgetown University Center for Global Health Science and Security, Washington, who was not involved in the review. “Absent aerosol-generating procedures, health care workers are largely not getting infected when they take droplet precautions.”

One reason may be that patients shed the most infectious viruses a couple of days before and after symptoms begin. By the time they’re hospitalized, they’re less likely to be contagious but may continue to shed viral RNA.

“We don’t really know the basis for the persistence of RNA being produced long after people have been infected and have recovered from the acute infection,” she said, “but it has been observed quite frequently.”

Although the virus cannot remain viable for very long in the air, remnants may still be detected in the form of RNA, Dr. Rasmussen said. In addition, hospitals often do a good job of ventilation.

She pointed out that it can be difficult to cultivate viruses in air samples because of contaminants such as bacteria and fungi. “That’s one of the limitations of a study like this. You’re not really sure if it’s because there’s no viable virus there or because you just aren’t able to collect samples that would allow you to determine that.”

Dr. Birgand and colleagues acknowledged other limitations. The studies they reviewed used different approaches to sampling. Different procedures may have been underway in the rooms being sampled, and factors such as temperature and humidity could have affected the results. In addition, the studies used different cycle thresholds for PCR positivity.

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

Everywhere they look within hospitals, researchers find RNA from SARS-CoV-2 in the air. But viable viruses typically are found only close to patients, according to a review of published studies.

The finding supports recommendations to use surgical masks in most parts of the hospital, reserving respirators (such as N95 or FFP2) for aerosol-generating procedures on patients’ respiratory tracts, said Gabriel Birgand, PhD, an infectious disease researcher at Imperial College London.

“When the virus is spreading a lot in the community, it’s probably more likely for you to be contaminated in your friends’ areas or in your building than in your work area, where you are well equipped and compliant with all the measures,” he said in an interview. “So it’s pretty good news.”

The systematic review by Dr. Birgand and colleagues was published in JAMA Network Open.

Recommended precautions to protect health care workers from SARS-CoV-2 infections remain controversial. Most authorities believe droplets are the primary route of transmission, which would mean surgical masks may be sufficient protection. But some research has suggested transmission by aerosols as well, making N95 respirators seem necessary. There is even disagreement about the definitions of the words “aerosol” and “droplet.”

To better understand where traces of the virus can be found in the air in hospitals, Dr. Birgand and colleagues analyzed all the studies they could find on the subject in English.

They identified 24 articles with original data. All of the studies used reverse transcription–polymerase chain reaction (PCR) tests to identify SARS-CoV-2 RNA. In five studies, attempts were also made to culture viable viruses. Three studies assessed the particle size relative to RNA concentration or viral titer.

Of 893 air samples across the 24 studies, 52.7% were taken from areas close to patients, 26.5% were taken in clinical areas, 13.7% in staff areas, 4.7% in public areas, and 2.4% in toilets or bathrooms.

Among those studies that quantified RNA, the median interquartile range of concentrations varied from 1.0 x 103 copies/m3 in clinical areas to 9.7 x 10³ copies/m³ in toilets or bathrooms.

One study found an RNA concentration of 2.0 x 10³ copies for particle sizes >4 mcm and 1.3 x 103 copies/m³ for particle sizes ≤4 mcm, both in patients’ rooms.

Three studies included viral cultures; of those, two resulted in positive cultures, both in a non-ICU setting. In one study, 3 of 39 samples were positive, and in the other, 4 of 4 were positive. Viral cultures in toilets, clinical areas, staff areas, and public areas were negative.

One of these studies assessed viral concentration and found that the median interquartile range was 4.8 tissue culture infectious dose (TCID50)/m³ for particles <1 mcm, 4.27 TCID50/m³ for particles 1-4 mcm, and 1.82 TCID50/m³ for particles >4 mcm.

Although viable viruses weren’t found in staff areas, the presence of viral RNA in places such as dining rooms and meeting rooms raises a concern, Dr. Birgand said.

“All of these staff areas are probably playing an important role in contamination,” he said. “It’s pretty easy to see when you are dining, you are not wearing a face mask, and it’s associated with a strong risk when there is a strong dissemination of the virus in the community.”

Studies on contact tracing among health care workers have also identified meeting rooms and dining rooms as the second most common source of infection after community contact, he said.

In general, the findings of the review correspond to epidemiologic studies, said Angela Rasmussen, PhD, a virologist with the Georgetown University Center for Global Health Science and Security, Washington, who was not involved in the review. “Absent aerosol-generating procedures, health care workers are largely not getting infected when they take droplet precautions.”

One reason may be that patients shed the most infectious viruses a couple of days before and after symptoms begin. By the time they’re hospitalized, they’re less likely to be contagious but may continue to shed viral RNA.

“We don’t really know the basis for the persistence of RNA being produced long after people have been infected and have recovered from the acute infection,” she said, “but it has been observed quite frequently.”

Although the virus cannot remain viable for very long in the air, remnants may still be detected in the form of RNA, Dr. Rasmussen said. In addition, hospitals often do a good job of ventilation.

She pointed out that it can be difficult to cultivate viruses in air samples because of contaminants such as bacteria and fungi. “That’s one of the limitations of a study like this. You’re not really sure if it’s because there’s no viable virus there or because you just aren’t able to collect samples that would allow you to determine that.”

Dr. Birgand and colleagues acknowledged other limitations. The studies they reviewed used different approaches to sampling. Different procedures may have been underway in the rooms being sampled, and factors such as temperature and humidity could have affected the results. In addition, the studies used different cycle thresholds for PCR positivity.

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

A physician assistant participating in a virtual workshop began to cry, confessing that she felt overwhelmed with guilt because New Yorkers were hailing her as a frontline hero in the pandemic. That was when Joe Ciavarro knew he was in the right place.

rclassenlayouts/Getty Images

“She was saying all the things I could not verbalize because I, too, didn’t feel like I deserved all this praise and thousands of people cheering for us every evening when people were losing jobs, didn’t have money for food, and their loved ones were dying without family at their side,” says Mr. Ciavarro, a PA at Mount Sinai Medical Center in New York.

Mr. Ciavarro, who also manages 170 other PAs on two of Mount Sinai’s campuses in Manhattan, has been on the front lines since COVID-19 first hit; he lost a colleague and friend to suicide in September.

The mental anguish from his job prompted him to sign up for the resilience workshop offered by Mount Sinai’s Center for Stress, Resilience, and Personal Growth. The center – the first of its kind in North America – was launched in June to help health care workers like him cope with the intense psychological pressures they were facing. The weekly workshops became a safe place where Mr. Ciavarro and other staff members could share their darkest fears and learn ways to help them deal with their situation.

“It’s been grueling but we learned how to take care of ourselves so we can take care of our patients,” said Mr. Ciavarro. “This has become like a guided group therapy session on ways to manage and develop resilience. And I feel like my emotions are validated, knowing that others feel the same way.”
 

Caring for their own

Medical professionals treating patients with COVID-19 are in similar predicaments, and the psychological fallout is enormous: They’re exhausted by the seemingly never-ending patient load and staffing shortages, and haunted by fears for their own safety and that of their families. Studies in China, Canada, and Italy have revealed that a significant number of doctors and nurses in the early days of the pandemic experienced high levels of distress, depression, anxiety, nightmares, and insomnia.

Trauma experts at Mount Sinai believe that, globally, up to 40% of first responders and health care workers – tens of thousands of people – will suffer from PTSD after witnessing the deaths of so many patients who were alone, without family.

How to protect in midst of trauma

In formulating the program’s platform, Mount Sinai experts drew upon their extensive experience aiding 9/11 responders at the World Trade Center (WTC), as well as their system-wide wellness program that aids demoralized and burned-out physicians. While the reach of the pandemic is much broader than 9/11, experts see some commonalities in conditions that emerge after traumatic events, and they also discovered what can help.

“We learned from our WTC experience about what are protective factors – what are the social supports that buffer against depression, anxiety, and PTSD,” said Jonathan DePierro, PhD, clinical director of CSRPG and a psychologist at the Mount Sinai WTC Mental Health Program. “We also learned that people who have more prolonged exposures are at greater risk of developing mental health difficulties.”

The program itself reflects these lessons – and that’s why it’s open to all employees, not just medical professionals. Housekeepers, security staffers, even construction workers are also dealing with their lives being in danger. “That wasn’t in their job description,” said Dr. DePierro. “These people tend to have fewer social and economic resources, make less money and have fewer structural supports, which makes them even more vulnerable.”

Dr. Charney’s strategies on building resilience became a bible of sorts for the workshops, according to Dr. Katz, who authored the training curriculum. Sessions deal with how to build up reservoirs of realistic optimism, keep gratitude journals, find spiritual meaning in their lives, maintain physical wellness and create networks of social support. The workshops are meant to help participants create action plans, to reach out for support in their social networks, and keep the focus on the positives.

The goal is to give demoralized health care workers a renewed sense of competence. “The resilience workshop is a launching point to get people to show up and talk,” said Dr. Katz. “And if we do that, we’ve accomplished a lot just getting people in the door.”

The center will also have a research component to identify what works and what doesn’t so their platform can provide a template for other institutions; Dr. Marin said they’ve gotten inquiries about the program from major hospital systems in Michigan and California. They’ll also conduct longitudinal research to determine what lingering problems persist among healthcare workers over time.

Since the center opened its virtual doors, the curriculum has also been altered in response to feedback from the support staff, many of whom live in the community that surrounds Mount Sinai in northern Manhattan, which is largely lower-income Latinx and Black individuals. Workshop materials have been translated into Spanish and now feature people who reflect a more diverse set of experiences.

“Many of our employees and the population we serve identify as non-White so we’ve been doing outreach with a lot of the local unions,” said Dr. Marin. “Our next step is to take what we’re doing and work with local community organizations.”

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

A physician assistant participating in a virtual workshop began to cry, confessing that she felt overwhelmed with guilt because New Yorkers were hailing her as a frontline hero in the pandemic. That was when Joe Ciavarro knew he was in the right place.

rclassenlayouts/Getty Images

“She was saying all the things I could not verbalize because I, too, didn’t feel like I deserved all this praise and thousands of people cheering for us every evening when people were losing jobs, didn’t have money for food, and their loved ones were dying without family at their side,” says Mr. Ciavarro, a PA at Mount Sinai Medical Center in New York.

Mr. Ciavarro, who also manages 170 other PAs on two of Mount Sinai’s campuses in Manhattan, has been on the front lines since COVID-19 first hit; he lost a colleague and friend to suicide in September.

The mental anguish from his job prompted him to sign up for the resilience workshop offered by Mount Sinai’s Center for Stress, Resilience, and Personal Growth. The center – the first of its kind in North America – was launched in June to help health care workers like him cope with the intense psychological pressures they were facing. The weekly workshops became a safe place where Mr. Ciavarro and other staff members could share their darkest fears and learn ways to help them deal with their situation.

“It’s been grueling but we learned how to take care of ourselves so we can take care of our patients,” said Mr. Ciavarro. “This has become like a guided group therapy session on ways to manage and develop resilience. And I feel like my emotions are validated, knowing that others feel the same way.”
 

Caring for their own

Medical professionals treating patients with COVID-19 are in similar predicaments, and the psychological fallout is enormous: They’re exhausted by the seemingly never-ending patient load and staffing shortages, and haunted by fears for their own safety and that of their families. Studies in China, Canada, and Italy have revealed that a significant number of doctors and nurses in the early days of the pandemic experienced high levels of distress, depression, anxiety, nightmares, and insomnia.

Trauma experts at Mount Sinai believe that, globally, up to 40% of first responders and health care workers – tens of thousands of people – will suffer from PTSD after witnessing the deaths of so many patients who were alone, without family.

How to protect in midst of trauma

In formulating the program’s platform, Mount Sinai experts drew upon their extensive experience aiding 9/11 responders at the World Trade Center (WTC), as well as their system-wide wellness program that aids demoralized and burned-out physicians. While the reach of the pandemic is much broader than 9/11, experts see some commonalities in conditions that emerge after traumatic events, and they also discovered what can help.

“We learned from our WTC experience about what are protective factors – what are the social supports that buffer against depression, anxiety, and PTSD,” said Jonathan DePierro, PhD, clinical director of CSRPG and a psychologist at the Mount Sinai WTC Mental Health Program. “We also learned that people who have more prolonged exposures are at greater risk of developing mental health difficulties.”

The program itself reflects these lessons – and that’s why it’s open to all employees, not just medical professionals. Housekeepers, security staffers, even construction workers are also dealing with their lives being in danger. “That wasn’t in their job description,” said Dr. DePierro. “These people tend to have fewer social and economic resources, make less money and have fewer structural supports, which makes them even more vulnerable.”

Dr. Charney’s strategies on building resilience became a bible of sorts for the workshops, according to Dr. Katz, who authored the training curriculum. Sessions deal with how to build up reservoirs of realistic optimism, keep gratitude journals, find spiritual meaning in their lives, maintain physical wellness and create networks of social support. The workshops are meant to help participants create action plans, to reach out for support in their social networks, and keep the focus on the positives.

The goal is to give demoralized health care workers a renewed sense of competence. “The resilience workshop is a launching point to get people to show up and talk,” said Dr. Katz. “And if we do that, we’ve accomplished a lot just getting people in the door.”

The center will also have a research component to identify what works and what doesn’t so their platform can provide a template for other institutions; Dr. Marin said they’ve gotten inquiries about the program from major hospital systems in Michigan and California. They’ll also conduct longitudinal research to determine what lingering problems persist among healthcare workers over time.

Since the center opened its virtual doors, the curriculum has also been altered in response to feedback from the support staff, many of whom live in the community that surrounds Mount Sinai in northern Manhattan, which is largely lower-income Latinx and Black individuals. Workshop materials have been translated into Spanish and now feature people who reflect a more diverse set of experiences.

“Many of our employees and the population we serve identify as non-White so we’ve been doing outreach with a lot of the local unions,” said Dr. Marin. “Our next step is to take what we’re doing and work with local community organizations.”

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

A physician assistant participating in a virtual workshop began to cry, confessing that she felt overwhelmed with guilt because New Yorkers were hailing her as a frontline hero in the pandemic. That was when Joe Ciavarro knew he was in the right place.

rclassenlayouts/Getty Images

“She was saying all the things I could not verbalize because I, too, didn’t feel like I deserved all this praise and thousands of people cheering for us every evening when people were losing jobs, didn’t have money for food, and their loved ones were dying without family at their side,” says Mr. Ciavarro, a PA at Mount Sinai Medical Center in New York.

Mr. Ciavarro, who also manages 170 other PAs on two of Mount Sinai’s campuses in Manhattan, has been on the front lines since COVID-19 first hit; he lost a colleague and friend to suicide in September.

The mental anguish from his job prompted him to sign up for the resilience workshop offered by Mount Sinai’s Center for Stress, Resilience, and Personal Growth. The center – the first of its kind in North America – was launched in June to help health care workers like him cope with the intense psychological pressures they were facing. The weekly workshops became a safe place where Mr. Ciavarro and other staff members could share their darkest fears and learn ways to help them deal with their situation.

“It’s been grueling but we learned how to take care of ourselves so we can take care of our patients,” said Mr. Ciavarro. “This has become like a guided group therapy session on ways to manage and develop resilience. And I feel like my emotions are validated, knowing that others feel the same way.”
 

Caring for their own

Medical professionals treating patients with COVID-19 are in similar predicaments, and the psychological fallout is enormous: They’re exhausted by the seemingly never-ending patient load and staffing shortages, and haunted by fears for their own safety and that of their families. Studies in China, Canada, and Italy have revealed that a significant number of doctors and nurses in the early days of the pandemic experienced high levels of distress, depression, anxiety, nightmares, and insomnia.

Trauma experts at Mount Sinai believe that, globally, up to 40% of first responders and health care workers – tens of thousands of people – will suffer from PTSD after witnessing the deaths of so many patients who were alone, without family.

How to protect in midst of trauma

In formulating the program’s platform, Mount Sinai experts drew upon their extensive experience aiding 9/11 responders at the World Trade Center (WTC), as well as their system-wide wellness program that aids demoralized and burned-out physicians. While the reach of the pandemic is much broader than 9/11, experts see some commonalities in conditions that emerge after traumatic events, and they also discovered what can help.

“We learned from our WTC experience about what are protective factors – what are the social supports that buffer against depression, anxiety, and PTSD,” said Jonathan DePierro, PhD, clinical director of CSRPG and a psychologist at the Mount Sinai WTC Mental Health Program. “We also learned that people who have more prolonged exposures are at greater risk of developing mental health difficulties.”

The program itself reflects these lessons – and that’s why it’s open to all employees, not just medical professionals. Housekeepers, security staffers, even construction workers are also dealing with their lives being in danger. “That wasn’t in their job description,” said Dr. DePierro. “These people tend to have fewer social and economic resources, make less money and have fewer structural supports, which makes them even more vulnerable.”

Dr. Charney’s strategies on building resilience became a bible of sorts for the workshops, according to Dr. Katz, who authored the training curriculum. Sessions deal with how to build up reservoirs of realistic optimism, keep gratitude journals, find spiritual meaning in their lives, maintain physical wellness and create networks of social support. The workshops are meant to help participants create action plans, to reach out for support in their social networks, and keep the focus on the positives.

The goal is to give demoralized health care workers a renewed sense of competence. “The resilience workshop is a launching point to get people to show up and talk,” said Dr. Katz. “And if we do that, we’ve accomplished a lot just getting people in the door.”

The center will also have a research component to identify what works and what doesn’t so their platform can provide a template for other institutions; Dr. Marin said they’ve gotten inquiries about the program from major hospital systems in Michigan and California. They’ll also conduct longitudinal research to determine what lingering problems persist among healthcare workers over time.

Since the center opened its virtual doors, the curriculum has also been altered in response to feedback from the support staff, many of whom live in the community that surrounds Mount Sinai in northern Manhattan, which is largely lower-income Latinx and Black individuals. Workshop materials have been translated into Spanish and now feature people who reflect a more diverse set of experiences.

“Many of our employees and the population we serve identify as non-White so we’ve been doing outreach with a lot of the local unions,” said Dr. Marin. “Our next step is to take what we’re doing and work with local community organizations.”

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

An intense and assertive “won’t take no for an answer” approach is effective for engaging in treatment young adults with substance abuse who have been in and out of various recovery programs for years, new research suggests.

The Youth Opioid Recovery Support (YORS) program is a team effort that includes home delivery of the prescribed medication, family engagement, assertive outreach, and contingency management.

In a new study of 42 patients in recovery for substance use disorder (SUD), those who were treated with extended-release naltrexone or extended-release buprenorphine plus YORS received more outpatient doses of their medication, and rates of opioid relapse at 12 and 24 weeks were lower compared with their peers who received only treatment as usual.

“These developmentally vulnerable youths need something extra that is specifically targeted to who they are and their vulnerabilities,” coinvestigator Marc Fishman, MD, director of the Maryland Treatment Centers, Johns Hopkins University, Baltimore, said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

Treatment barriers

Young adults with SUD are difficult to reach, which leads to decreased addiction program retention, decreased medication adherence, early drop out, waxing and waning motivation, and worse outcomes, compared with older adults with SUD, Dr. Fishman said.

In July, positive results from a pilot trial conducted by the investigators of YORS were published online in Addiction.

In that study, 41 young adults aged 18-26 years who intended to undergo treatment for SUD with extended-release naltrexone were randomly assigned to also undergo YORS or treatment as usual, which consisted of a standard referral to outpatient care following an inpatient stay.

The primary outcomes were number of medication doses received over 24 weeks and relapse to opioid use, which was defined as 10 or more days of use within 28 days at 24 weeks.

Participants in the YORS group received more doses of extended-release naltrexone (mean, 4.28; standard deviation, 2.3) than participants in the treatment-as-usual group (mean, 0.70; SD, 1.2; P < .01).

In the YORS group, rates of relapse at both 12 and 24 weeks were lower, and there were fewer overall days of opioid use.

For the current study, the investigators wanted to test whether there was a possible effect when patients were given a choice of medication. In the earlier trial, patients did not have a choice – they had to take extended-release naltrexone. In this study, they could opt for it or extended-release buprenorphine.

The researchers recruited 22 young adults (aged 18-26 years) from their inpatient clinic to participate. Half the patients chose to take extended-release naltrexone, and the other half chose extended-release buprenorphine.

The groups were then compared to a historical group of 20 patients who received treatment as usual and served as the control group.
 

Positive outcomes

As in the first study, outcomes in the new study were better with YORS.

All participants who underwent YORS received more outpatient medication doses at 12 weeks and 24 weeks than those who received treatment as usual (1.91 vs. 0.40 and 3.76 vs. 0.70, respectively; P < .001).

For the YORS group, rates of opioid relapse were lower at 12 weeks (27.3% vs. 75.0%) and at 24 weeks (52.9% vs. 95.0%; P < .01.)

All components of YORS work together to improve retention, Dr. Fishman noted. Patients do much better if a relative such as a mother, father, or grandmother is closely involved, he added.

Also important is drug delivery.

“In some ways, this is similar to the assertive community treatment, or ACT, for schizophrenia. Like substance use disorder, schizophrenia requires long-acting injectable antipsychotics. When that is delivered to the patient through an organized delivery service like YORS, it improves outcomes,” said Dr. Fishman.

SUD is a chronic, relapsing illness in which an individual’s judgment is impaired, he added.

“ACT has become a relatively standard feature of treatment in most communities in this country and internationally and is sustainable under public sector funding, so it’s not an impossible leap to say it could be done. But it will not be cheap,” Dr. Fishman said.
 

Removing barriers

In a comment, Serra Akyar, MD, a psychiatry resident at Northwell Health’s Staten Island University Hospital, New York, said that the YORS program may appear to be labor intensive.

“However, the combination of medication-assisted treatment and support are essential to the treatment of opioid use disorder, especially for young adults. Developing effective interventions for young adults is particularly important, given the plasticity of their brains,” said Dr. Akyar, who was not involved with the research.

Inability to access medication and a lack of a supportive environment, both in everyday life and in regards to therapy, are barriers to successful treatment, she noted.

“The YORS intervention aims to remove these barriers to further enhance engagement to care through a combination of medication delivery and family engagement and assertive outreach via text messaging, a modality presumed to be well received by youth,” Dr. Akyar said.

Despite having a limited sample size, the study shows how a comprehensive intervention can have a large impact on the maintenance of medication adherence and reduction of relapse in young adults, she added.

“Its early success is encouraging and warrants further study on a larger scale to determine long-term effectiveness, overall costs and feasibility, generalizability, and whether certain independent factors exist that may predict medication adherence and reduction of relapse,” she said.
 

Wraparound support

The study is also a significant reminder that the opioid crisis has affected the young adult population, who are very vulnerable to OUD, said Jose Vito, MD, child, adolescent, and addiction psychiatrist at New York University.

“The study made me realize the importance of the four components of YORS, which were the outreach, family involvement, home delivery, and monetary incentives,” Dr. Vito said in an interview.

All of these components, in addition to extended-release naltrexone or extended-release buprenorphine, “have contributed to lower rates of opioid relapse, and the relapses are much later in the course of treatment if they do occur,” he said.

Overall, the findings demonstrate the importance of not giving up on these youths, he noted.

“Programs like YORS that provide wraparound support can help alleviate the opioid health care crisis by keeping these young adults in treatment,” Dr. Vito concluded.

The study was funded by the University of Maryland Center for Addiction Research, Education, and Service. Dr. Fishman has a financial relationship with Alkermes.

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

An intense and assertive “won’t take no for an answer” approach is effective for engaging in treatment young adults with substance abuse who have been in and out of various recovery programs for years, new research suggests.

The Youth Opioid Recovery Support (YORS) program is a team effort that includes home delivery of the prescribed medication, family engagement, assertive outreach, and contingency management.

In a new study of 42 patients in recovery for substance use disorder (SUD), those who were treated with extended-release naltrexone or extended-release buprenorphine plus YORS received more outpatient doses of their medication, and rates of opioid relapse at 12 and 24 weeks were lower compared with their peers who received only treatment as usual.

“These developmentally vulnerable youths need something extra that is specifically targeted to who they are and their vulnerabilities,” coinvestigator Marc Fishman, MD, director of the Maryland Treatment Centers, Johns Hopkins University, Baltimore, said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

Treatment barriers

Young adults with SUD are difficult to reach, which leads to decreased addiction program retention, decreased medication adherence, early drop out, waxing and waning motivation, and worse outcomes, compared with older adults with SUD, Dr. Fishman said.

In July, positive results from a pilot trial conducted by the investigators of YORS were published online in Addiction.

In that study, 41 young adults aged 18-26 years who intended to undergo treatment for SUD with extended-release naltrexone were randomly assigned to also undergo YORS or treatment as usual, which consisted of a standard referral to outpatient care following an inpatient stay.

The primary outcomes were number of medication doses received over 24 weeks and relapse to opioid use, which was defined as 10 or more days of use within 28 days at 24 weeks.

Participants in the YORS group received more doses of extended-release naltrexone (mean, 4.28; standard deviation, 2.3) than participants in the treatment-as-usual group (mean, 0.70; SD, 1.2; P < .01).

In the YORS group, rates of relapse at both 12 and 24 weeks were lower, and there were fewer overall days of opioid use.

For the current study, the investigators wanted to test whether there was a possible effect when patients were given a choice of medication. In the earlier trial, patients did not have a choice – they had to take extended-release naltrexone. In this study, they could opt for it or extended-release buprenorphine.

The researchers recruited 22 young adults (aged 18-26 years) from their inpatient clinic to participate. Half the patients chose to take extended-release naltrexone, and the other half chose extended-release buprenorphine.

The groups were then compared to a historical group of 20 patients who received treatment as usual and served as the control group.
 

Positive outcomes

As in the first study, outcomes in the new study were better with YORS.

All participants who underwent YORS received more outpatient medication doses at 12 weeks and 24 weeks than those who received treatment as usual (1.91 vs. 0.40 and 3.76 vs. 0.70, respectively; P < .001).

For the YORS group, rates of opioid relapse were lower at 12 weeks (27.3% vs. 75.0%) and at 24 weeks (52.9% vs. 95.0%; P < .01.)

All components of YORS work together to improve retention, Dr. Fishman noted. Patients do much better if a relative such as a mother, father, or grandmother is closely involved, he added.

Also important is drug delivery.

“In some ways, this is similar to the assertive community treatment, or ACT, for schizophrenia. Like substance use disorder, schizophrenia requires long-acting injectable antipsychotics. When that is delivered to the patient through an organized delivery service like YORS, it improves outcomes,” said Dr. Fishman.

SUD is a chronic, relapsing illness in which an individual’s judgment is impaired, he added.

“ACT has become a relatively standard feature of treatment in most communities in this country and internationally and is sustainable under public sector funding, so it’s not an impossible leap to say it could be done. But it will not be cheap,” Dr. Fishman said.
 

Removing barriers

In a comment, Serra Akyar, MD, a psychiatry resident at Northwell Health’s Staten Island University Hospital, New York, said that the YORS program may appear to be labor intensive.

“However, the combination of medication-assisted treatment and support are essential to the treatment of opioid use disorder, especially for young adults. Developing effective interventions for young adults is particularly important, given the plasticity of their brains,” said Dr. Akyar, who was not involved with the research.

Inability to access medication and a lack of a supportive environment, both in everyday life and in regards to therapy, are barriers to successful treatment, she noted.

“The YORS intervention aims to remove these barriers to further enhance engagement to care through a combination of medication delivery and family engagement and assertive outreach via text messaging, a modality presumed to be well received by youth,” Dr. Akyar said.

Despite having a limited sample size, the study shows how a comprehensive intervention can have a large impact on the maintenance of medication adherence and reduction of relapse in young adults, she added.

“Its early success is encouraging and warrants further study on a larger scale to determine long-term effectiveness, overall costs and feasibility, generalizability, and whether certain independent factors exist that may predict medication adherence and reduction of relapse,” she said.
 

Wraparound support

The study is also a significant reminder that the opioid crisis has affected the young adult population, who are very vulnerable to OUD, said Jose Vito, MD, child, adolescent, and addiction psychiatrist at New York University.

“The study made me realize the importance of the four components of YORS, which were the outreach, family involvement, home delivery, and monetary incentives,” Dr. Vito said in an interview.

All of these components, in addition to extended-release naltrexone or extended-release buprenorphine, “have contributed to lower rates of opioid relapse, and the relapses are much later in the course of treatment if they do occur,” he said.

Overall, the findings demonstrate the importance of not giving up on these youths, he noted.

“Programs like YORS that provide wraparound support can help alleviate the opioid health care crisis by keeping these young adults in treatment,” Dr. Vito concluded.

The study was funded by the University of Maryland Center for Addiction Research, Education, and Service. Dr. Fishman has a financial relationship with Alkermes.

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

An intense and assertive “won’t take no for an answer” approach is effective for engaging in treatment young adults with substance abuse who have been in and out of various recovery programs for years, new research suggests.

The Youth Opioid Recovery Support (YORS) program is a team effort that includes home delivery of the prescribed medication, family engagement, assertive outreach, and contingency management.

In a new study of 42 patients in recovery for substance use disorder (SUD), those who were treated with extended-release naltrexone or extended-release buprenorphine plus YORS received more outpatient doses of their medication, and rates of opioid relapse at 12 and 24 weeks were lower compared with their peers who received only treatment as usual.

“These developmentally vulnerable youths need something extra that is specifically targeted to who they are and their vulnerabilities,” coinvestigator Marc Fishman, MD, director of the Maryland Treatment Centers, Johns Hopkins University, Baltimore, said in an interview.

The findings were presented at the virtual American Academy of Addiction Psychiatry 31st Annual Meeting.
 

Treatment barriers

Young adults with SUD are difficult to reach, which leads to decreased addiction program retention, decreased medication adherence, early drop out, waxing and waning motivation, and worse outcomes, compared with older adults with SUD, Dr. Fishman said.

In July, positive results from a pilot trial conducted by the investigators of YORS were published online in Addiction.

In that study, 41 young adults aged 18-26 years who intended to undergo treatment for SUD with extended-release naltrexone were randomly assigned to also undergo YORS or treatment as usual, which consisted of a standard referral to outpatient care following an inpatient stay.

The primary outcomes were number of medication doses received over 24 weeks and relapse to opioid use, which was defined as 10 or more days of use within 28 days at 24 weeks.

Participants in the YORS group received more doses of extended-release naltrexone (mean, 4.28; standard deviation, 2.3) than participants in the treatment-as-usual group (mean, 0.70; SD, 1.2; P < .01).

In the YORS group, rates of relapse at both 12 and 24 weeks were lower, and there were fewer overall days of opioid use.

For the current study, the investigators wanted to test whether there was a possible effect when patients were given a choice of medication. In the earlier trial, patients did not have a choice – they had to take extended-release naltrexone. In this study, they could opt for it or extended-release buprenorphine.

The researchers recruited 22 young adults (aged 18-26 years) from their inpatient clinic to participate. Half the patients chose to take extended-release naltrexone, and the other half chose extended-release buprenorphine.

The groups were then compared to a historical group of 20 patients who received treatment as usual and served as the control group.
 

Positive outcomes

As in the first study, outcomes in the new study were better with YORS.

All participants who underwent YORS received more outpatient medication doses at 12 weeks and 24 weeks than those who received treatment as usual (1.91 vs. 0.40 and 3.76 vs. 0.70, respectively; P < .001).

For the YORS group, rates of opioid relapse were lower at 12 weeks (27.3% vs. 75.0%) and at 24 weeks (52.9% vs. 95.0%; P < .01.)

All components of YORS work together to improve retention, Dr. Fishman noted. Patients do much better if a relative such as a mother, father, or grandmother is closely involved, he added.

Also important is drug delivery.

“In some ways, this is similar to the assertive community treatment, or ACT, for schizophrenia. Like substance use disorder, schizophrenia requires long-acting injectable antipsychotics. When that is delivered to the patient through an organized delivery service like YORS, it improves outcomes,” said Dr. Fishman.

SUD is a chronic, relapsing illness in which an individual’s judgment is impaired, he added.

“ACT has become a relatively standard feature of treatment in most communities in this country and internationally and is sustainable under public sector funding, so it’s not an impossible leap to say it could be done. But it will not be cheap,” Dr. Fishman said.
 

Removing barriers

In a comment, Serra Akyar, MD, a psychiatry resident at Northwell Health’s Staten Island University Hospital, New York, said that the YORS program may appear to be labor intensive.

“However, the combination of medication-assisted treatment and support are essential to the treatment of opioid use disorder, especially for young adults. Developing effective interventions for young adults is particularly important, given the plasticity of their brains,” said Dr. Akyar, who was not involved with the research.

Inability to access medication and a lack of a supportive environment, both in everyday life and in regards to therapy, are barriers to successful treatment, she noted.

“The YORS intervention aims to remove these barriers to further enhance engagement to care through a combination of medication delivery and family engagement and assertive outreach via text messaging, a modality presumed to be well received by youth,” Dr. Akyar said.

Despite having a limited sample size, the study shows how a comprehensive intervention can have a large impact on the maintenance of medication adherence and reduction of relapse in young adults, she added.

“Its early success is encouraging and warrants further study on a larger scale to determine long-term effectiveness, overall costs and feasibility, generalizability, and whether certain independent factors exist that may predict medication adherence and reduction of relapse,” she said.
 

Wraparound support

The study is also a significant reminder that the opioid crisis has affected the young adult population, who are very vulnerable to OUD, said Jose Vito, MD, child, adolescent, and addiction psychiatrist at New York University.

“The study made me realize the importance of the four components of YORS, which were the outreach, family involvement, home delivery, and monetary incentives,” Dr. Vito said in an interview.

All of these components, in addition to extended-release naltrexone or extended-release buprenorphine, “have contributed to lower rates of opioid relapse, and the relapses are much later in the course of treatment if they do occur,” he said.

Overall, the findings demonstrate the importance of not giving up on these youths, he noted.

“Programs like YORS that provide wraparound support can help alleviate the opioid health care crisis by keeping these young adults in treatment,” Dr. Vito concluded.

The study was funded by the University of Maryland Center for Addiction Research, Education, and Service. Dr. Fishman has a financial relationship with Alkermes.

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

There is a substantial mismatch between patient and physician reports of toxicity during radiotherapy for breast cancer, according to an analysis of nearly 10,000 U.S. patients.

Researchers assessed physician underrecognition of four key symptoms – pain, pruritus, edema, and fatigue – during radiotherapy. Physicians underrecognized one of these four symptoms at least once in 53.2% of patients who reported having at least one substantial symptom.

“Understanding whether physicians detect when their patients are experiencing substantial toxicity is important, not only because recognition of symptoms is necessary for appropriate supportive care, but also because it influences what techniques and treatments we adopt,” said Reshma Jagsi, MD, DPhil, of the University of Michigan, Ann Arbor.

Dr. Jagsi presented the study results at the 2020 San Antonio Breast Cancer Symposium.

The underrecognition of symptoms during radiotherapy may reflect differences in physician or patient behaviors, according to Dr. Jagsi. “It’s absolutely something we need to understand better.”

Ian E. Krop, MD, PhD, of the Dana-Farber Cancer Institute in Boston, moderated the session where this research was presented and called the work “striking,” noting that it “clearly identifies an important area that needs improvement.”

“We need to do a better job. We as physicians need to listen more to our patients,” said Virginia Kaklamani, MD, of the University of Texas Health Science Center, San Antonio, and codirector of the SABCS 2020 meeting.
 

Comparing patient and physician reports

Dr. Jagsi and colleagues analyzed data on patients who had received radiotherapy after lumpectomy for breast cancer and had completed patient-reported outcome measures (PROs) as part of the Michigan Radiation Oncology Quality Consortium (MROQC). The MROQC registry collects data on patients receiving radiation for breast, lung, and prostate cancers, as well as for bone metastases.

Results of the PROs were compared with physician reports of toxicity as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) system.

The researchers evaluated underrecognition of toxicity in 9,868 patients by comparing 37,593 independent paired observations from patients and their doctors. Patient and physician reports were made on the same day (n = 35,797) or within 3 days of each other (n = 1,796).

The comparison showed underrecognition of all four symptoms assessed – pain, pruritus, edema, and fatigue.

Underrecognition of pain was defined as patients reporting moderate pain while physicians graded pain as absent or as patients reporting severe pain while physicians rated pain as grade 1 or lower. Underrecognition of fatigue, bother from pruritus, or bother from edema were defined as physicians grading these symptoms as absent when patients reported fatigue or bother from pruritus/edema often or all of the time.

The percentage of observations with underrecognized symptoms was 30.9% for moderate to severe pain, 36.7% for frequent bother from pruritus, 51.4% for frequent bother from edema, and 18.8% for severe fatigue.

Factors independently associated with symptom underrecognition were younger age (odds ratio, 1.4 for <50 years and 1.2 for 50-59 years), Black or other non-White race (OR, 1.9 and 1.8, respectively), conventional fractionation (OR, 1.2), not having a supraclavicular field (OR, 1.3), and being treated at an academic center (OR, 1.1).
 

Underreporting worse in the time of COVID?

Data collection for this study ended before the start of the COVID-19 pandemic, but Dr. Jagsi expressed concern that the pandemic could lead to underrecognition of toxicity as well.

“We are doing more virtual visits, and I think the relationships between physicians and patients are a bit more strained,” Dr. Jagsi said. While virtual visits mean that patients can be seen safely, they are “not the same as being in the same room as one another.”

On the other hand, in-person visits during the pandemic may pose challenges as well. The need to wear masks during in-person consultations could lead to a lot of nonverbal communication being missed.

“I wouldn’t be surprised at all if underrecognition were worse in this context,” Dr. Jagsi said.
 

Encourage patients to speak up, use PROs

“I think we need to encourage patients that when we’ve told them that certain side effects are expected, it doesn’t mean that they shouldn’t tell us if they’re bothered by those side effects,” Dr. Jagsi said. “They’re not bothering us. They’re not troubling us to bring those symptoms to our attention, because there actually are things that we can do to help support them through the experience.”

Dr. Jagsi also said PROs should be included in clinical trials. Trials tend to rely on physician assessment of possible toxicity using the CTCAE system, but this can miss important symptoms that patients experience during radiotherapy.

The current study and MROQC were sponsored by Blue Cross Blue Shield of Michigan and the Blue Care Network as part of the BCBSM Value Partnership program. Dr. Jagsi disclosed financial relationships with Amgen, Equity Quotient, Genentech, Vizient, law firms, various foundations, the National Institutes of Health, and BCBSM for the MROQC. Dr. Kaklamani and Dr. Krop disclosed relationships with many pharmaceutical companies.

SOURCE: Jagsi R J et al. SABCS 2020, Abstract GS3-07.

There is a substantial mismatch between patient and physician reports of toxicity during radiotherapy for breast cancer, according to an analysis of nearly 10,000 U.S. patients.

Researchers assessed physician underrecognition of four key symptoms – pain, pruritus, edema, and fatigue – during radiotherapy. Physicians underrecognized one of these four symptoms at least once in 53.2% of patients who reported having at least one substantial symptom.

“Understanding whether physicians detect when their patients are experiencing substantial toxicity is important, not only because recognition of symptoms is necessary for appropriate supportive care, but also because it influences what techniques and treatments we adopt,” said Reshma Jagsi, MD, DPhil, of the University of Michigan, Ann Arbor.

Dr. Jagsi presented the study results at the 2020 San Antonio Breast Cancer Symposium.

The underrecognition of symptoms during radiotherapy may reflect differences in physician or patient behaviors, according to Dr. Jagsi. “It’s absolutely something we need to understand better.”

Ian E. Krop, MD, PhD, of the Dana-Farber Cancer Institute in Boston, moderated the session where this research was presented and called the work “striking,” noting that it “clearly identifies an important area that needs improvement.”

“We need to do a better job. We as physicians need to listen more to our patients,” said Virginia Kaklamani, MD, of the University of Texas Health Science Center, San Antonio, and codirector of the SABCS 2020 meeting.
 

Comparing patient and physician reports

Dr. Jagsi and colleagues analyzed data on patients who had received radiotherapy after lumpectomy for breast cancer and had completed patient-reported outcome measures (PROs) as part of the Michigan Radiation Oncology Quality Consortium (MROQC). The MROQC registry collects data on patients receiving radiation for breast, lung, and prostate cancers, as well as for bone metastases.

Results of the PROs were compared with physician reports of toxicity as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) system.

The researchers evaluated underrecognition of toxicity in 9,868 patients by comparing 37,593 independent paired observations from patients and their doctors. Patient and physician reports were made on the same day (n = 35,797) or within 3 days of each other (n = 1,796).

The comparison showed underrecognition of all four symptoms assessed – pain, pruritus, edema, and fatigue.

Underrecognition of pain was defined as patients reporting moderate pain while physicians graded pain as absent or as patients reporting severe pain while physicians rated pain as grade 1 or lower. Underrecognition of fatigue, bother from pruritus, or bother from edema were defined as physicians grading these symptoms as absent when patients reported fatigue or bother from pruritus/edema often or all of the time.

The percentage of observations with underrecognized symptoms was 30.9% for moderate to severe pain, 36.7% for frequent bother from pruritus, 51.4% for frequent bother from edema, and 18.8% for severe fatigue.

Factors independently associated with symptom underrecognition were younger age (odds ratio, 1.4 for <50 years and 1.2 for 50-59 years), Black or other non-White race (OR, 1.9 and 1.8, respectively), conventional fractionation (OR, 1.2), not having a supraclavicular field (OR, 1.3), and being treated at an academic center (OR, 1.1).
 

Underreporting worse in the time of COVID?

Data collection for this study ended before the start of the COVID-19 pandemic, but Dr. Jagsi expressed concern that the pandemic could lead to underrecognition of toxicity as well.

“We are doing more virtual visits, and I think the relationships between physicians and patients are a bit more strained,” Dr. Jagsi said. While virtual visits mean that patients can be seen safely, they are “not the same as being in the same room as one another.”

On the other hand, in-person visits during the pandemic may pose challenges as well. The need to wear masks during in-person consultations could lead to a lot of nonverbal communication being missed.

“I wouldn’t be surprised at all if underrecognition were worse in this context,” Dr. Jagsi said.
 

Encourage patients to speak up, use PROs

“I think we need to encourage patients that when we’ve told them that certain side effects are expected, it doesn’t mean that they shouldn’t tell us if they’re bothered by those side effects,” Dr. Jagsi said. “They’re not bothering us. They’re not troubling us to bring those symptoms to our attention, because there actually are things that we can do to help support them through the experience.”

Dr. Jagsi also said PROs should be included in clinical trials. Trials tend to rely on physician assessment of possible toxicity using the CTCAE system, but this can miss important symptoms that patients experience during radiotherapy.

The current study and MROQC were sponsored by Blue Cross Blue Shield of Michigan and the Blue Care Network as part of the BCBSM Value Partnership program. Dr. Jagsi disclosed financial relationships with Amgen, Equity Quotient, Genentech, Vizient, law firms, various foundations, the National Institutes of Health, and BCBSM for the MROQC. Dr. Kaklamani and Dr. Krop disclosed relationships with many pharmaceutical companies.

SOURCE: Jagsi R J et al. SABCS 2020, Abstract GS3-07.

There is a substantial mismatch between patient and physician reports of toxicity during radiotherapy for breast cancer, according to an analysis of nearly 10,000 U.S. patients.

Researchers assessed physician underrecognition of four key symptoms – pain, pruritus, edema, and fatigue – during radiotherapy. Physicians underrecognized one of these four symptoms at least once in 53.2% of patients who reported having at least one substantial symptom.

“Understanding whether physicians detect when their patients are experiencing substantial toxicity is important, not only because recognition of symptoms is necessary for appropriate supportive care, but also because it influences what techniques and treatments we adopt,” said Reshma Jagsi, MD, DPhil, of the University of Michigan, Ann Arbor.

Dr. Jagsi presented the study results at the 2020 San Antonio Breast Cancer Symposium.

The underrecognition of symptoms during radiotherapy may reflect differences in physician or patient behaviors, according to Dr. Jagsi. “It’s absolutely something we need to understand better.”

Ian E. Krop, MD, PhD, of the Dana-Farber Cancer Institute in Boston, moderated the session where this research was presented and called the work “striking,” noting that it “clearly identifies an important area that needs improvement.”

“We need to do a better job. We as physicians need to listen more to our patients,” said Virginia Kaklamani, MD, of the University of Texas Health Science Center, San Antonio, and codirector of the SABCS 2020 meeting.
 

Comparing patient and physician reports

Dr. Jagsi and colleagues analyzed data on patients who had received radiotherapy after lumpectomy for breast cancer and had completed patient-reported outcome measures (PROs) as part of the Michigan Radiation Oncology Quality Consortium (MROQC). The MROQC registry collects data on patients receiving radiation for breast, lung, and prostate cancers, as well as for bone metastases.

Results of the PROs were compared with physician reports of toxicity as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) system.

The researchers evaluated underrecognition of toxicity in 9,868 patients by comparing 37,593 independent paired observations from patients and their doctors. Patient and physician reports were made on the same day (n = 35,797) or within 3 days of each other (n = 1,796).

The comparison showed underrecognition of all four symptoms assessed – pain, pruritus, edema, and fatigue.

Underrecognition of pain was defined as patients reporting moderate pain while physicians graded pain as absent or as patients reporting severe pain while physicians rated pain as grade 1 or lower. Underrecognition of fatigue, bother from pruritus, or bother from edema were defined as physicians grading these symptoms as absent when patients reported fatigue or bother from pruritus/edema often or all of the time.

The percentage of observations with underrecognized symptoms was 30.9% for moderate to severe pain, 36.7% for frequent bother from pruritus, 51.4% for frequent bother from edema, and 18.8% for severe fatigue.

Factors independently associated with symptom underrecognition were younger age (odds ratio, 1.4 for <50 years and 1.2 for 50-59 years), Black or other non-White race (OR, 1.9 and 1.8, respectively), conventional fractionation (OR, 1.2), not having a supraclavicular field (OR, 1.3), and being treated at an academic center (OR, 1.1).
 

Underreporting worse in the time of COVID?

Data collection for this study ended before the start of the COVID-19 pandemic, but Dr. Jagsi expressed concern that the pandemic could lead to underrecognition of toxicity as well.

“We are doing more virtual visits, and I think the relationships between physicians and patients are a bit more strained,” Dr. Jagsi said. While virtual visits mean that patients can be seen safely, they are “not the same as being in the same room as one another.”

On the other hand, in-person visits during the pandemic may pose challenges as well. The need to wear masks during in-person consultations could lead to a lot of nonverbal communication being missed.

“I wouldn’t be surprised at all if underrecognition were worse in this context,” Dr. Jagsi said.
 

Encourage patients to speak up, use PROs

“I think we need to encourage patients that when we’ve told them that certain side effects are expected, it doesn’t mean that they shouldn’t tell us if they’re bothered by those side effects,” Dr. Jagsi said. “They’re not bothering us. They’re not troubling us to bring those symptoms to our attention, because there actually are things that we can do to help support them through the experience.”

Dr. Jagsi also said PROs should be included in clinical trials. Trials tend to rely on physician assessment of possible toxicity using the CTCAE system, but this can miss important symptoms that patients experience during radiotherapy.

The current study and MROQC were sponsored by Blue Cross Blue Shield of Michigan and the Blue Care Network as part of the BCBSM Value Partnership program. Dr. Jagsi disclosed financial relationships with Amgen, Equity Quotient, Genentech, Vizient, law firms, various foundations, the National Institutes of Health, and BCBSM for the MROQC. Dr. Kaklamani and Dr. Krop disclosed relationships with many pharmaceutical companies.

SOURCE: Jagsi R J et al. SABCS 2020, Abstract GS3-07.

Joshua Brody, MD, Director of the Lymphoma Immunotherapy Program at Icahn School of Medicine at Mount Sinai, highlights some of the exciting findings on classical Hodgkin lymphoma from the 62nd ASH Annual Meeting and Exposition, held virtually from December 5 to 8, 2020.

The efficacy of brentuximab vedotin (BV) as monotherapy or in combination was evaluated in patients aged 60 and older. Although all regimens appear to be effective, BV plus dacarbazine and BV plus nivolumab were shown to be the most promising combinations.

A 5-year update from the ECHELON-1 trial demonstrated that treatment with BV, doxorubicin, vinblastine, and dacarbazine (A+AVD) maintained reported initial efficacy findings. Many patients with peripheral neuropathy showed improvement or complete resolution at follow up, and most with persisting symptoms had low-grade (grade 1 or 2) neuropathy.

Advanced immune monitoring techniques have revealed details about the T cells in Hodgkin tumors at single-cell resolution. Cytotoxic CD8+ T cells might be antitumor T cells that mediate response to anti-PD1 antibody therapies.

--

Joshua Brody, MD, is the director of the Lymphoma Immunotherapy Program, Icahn School of Medicine at Mount Sinai, Hess Center for Science and Medicine

Dr. Brody has no relevant disclosures.

Joshua Brody, MD, Director of the Lymphoma Immunotherapy Program at Icahn School of Medicine at Mount Sinai, highlights some of the exciting findings on classical Hodgkin lymphoma from the 62nd ASH Annual Meeting and Exposition, held virtually from December 5 to 8, 2020.

The efficacy of brentuximab vedotin (BV) as monotherapy or in combination was evaluated in patients aged 60 and older. Although all regimens appear to be effective, BV plus dacarbazine and BV plus nivolumab were shown to be the most promising combinations.

A 5-year update from the ECHELON-1 trial demonstrated that treatment with BV, doxorubicin, vinblastine, and dacarbazine (A+AVD) maintained reported initial efficacy findings. Many patients with peripheral neuropathy showed improvement or complete resolution at follow up, and most with persisting symptoms had low-grade (grade 1 or 2) neuropathy.

Advanced immune monitoring techniques have revealed details about the T cells in Hodgkin tumors at single-cell resolution. Cytotoxic CD8+ T cells might be antitumor T cells that mediate response to anti-PD1 antibody therapies.

--

Joshua Brody, MD, is the director of the Lymphoma Immunotherapy Program, Icahn School of Medicine at Mount Sinai, Hess Center for Science and Medicine

Dr. Brody has no relevant disclosures.

Joshua Brody, MD, Director of the Lymphoma Immunotherapy Program at Icahn School of Medicine at Mount Sinai, highlights some of the exciting findings on classical Hodgkin lymphoma from the 62nd ASH Annual Meeting and Exposition, held virtually from December 5 to 8, 2020.

The efficacy of brentuximab vedotin (BV) as monotherapy or in combination was evaluated in patients aged 60 and older. Although all regimens appear to be effective, BV plus dacarbazine and BV plus nivolumab were shown to be the most promising combinations.

A 5-year update from the ECHELON-1 trial demonstrated that treatment with BV, doxorubicin, vinblastine, and dacarbazine (A+AVD) maintained reported initial efficacy findings. Many patients with peripheral neuropathy showed improvement or complete resolution at follow up, and most with persisting symptoms had low-grade (grade 1 or 2) neuropathy.

Advanced immune monitoring techniques have revealed details about the T cells in Hodgkin tumors at single-cell resolution. Cytotoxic CD8+ T cells might be antitumor T cells that mediate response to anti-PD1 antibody therapies.

--

Joshua Brody, MD, is the director of the Lymphoma Immunotherapy Program, Icahn School of Medicine at Mount Sinai, Hess Center for Science and Medicine

Dr. Brody has no relevant disclosures.

Elite American soccer players have, on average, larger, thicker, and heavier hearts than the general population, according to a new study that provides clinicians with normative echocardiogram and electrocardiogram (ECG) cutoffs to use when assessing the heart health of competitive athletes.

Nikada/Getty Images

To provide these age- and sex-specific reference values, a team from Massachusetts General Hospital, Boston, led by Timothy W. Churchill, MD, and Aaron L. Baggish, MD, analyzed data from 122 female and 116 male soccer players from the American national teams preparing for World Cup play and undergoing FIFA-mandated preparticipation screening.

The athletes frequently exceeded normal echocardiographic ranges for left ventricular (LV) mass, volume, and wall thickness – structural cardiac parameters responsive to exercise-induced remodeling – but with none showing pathologic findings that might indicate the need to restrict their participation in the sport.

Almost one-third (30%) of female athletes and 41% of male athletes exceeded the American Society of Echocardiography’s upper limit of normal for LV wall thickness, with a measure greater than 12 mm seen in 12% of men and 1% of women.

The majority (51% of females and 59% of males) exceeded normal ranges for body surface area–indexed LV mass, with 77% and 68%, respectively, having LV volumes above the normal range.

Dr. Baggish stressed in an interview, however, that these data tell a story about healthy hearts, not at-risk hearts.

“These are the healthiest, highest-performing elite soccer players that we have in the United States, and this is really a look at how adaptive the heart can be, how much it can grow and change in size, shape, structure, and function in response to sport,” said Dr. Baggish.

The mean age of screened athletes was 20 years (range, 15-40 years). The majority of the female players were White (71%), whereas the male players were more evenly divided between Black (34%), Hispanic (33%), and White (32%).

Screening was performed at U.S. Soccer training sites by experienced clinicians affiliated with the Massachusetts General Hospital cardiovascular performance program.

Interestingly, the study debunks the idea that women, on average, have smaller chamber sizes. “When we did body-size correction, the men and women actually looked pretty similar with respect to their ability to adapt to strenuous exercise,” noted Dr. Baggish.

They did see, however, that women were more likely than men to have abnormal ECG findings. Male athletes showed a higher prevalence of “normal” training-related ECG findings, whereas female athletes were more likely to have abnormal ECG patterns (11.5% vs. 0.0% in the male cohort), most often pathologic T-wave inversions (TWI) confined to the anterior precordial lead distribution.

“This is important because ECGs are the most common screening tool used and we wanted to alert people to the fact that these women who showed some abnormalities on ECG went on to have a total healthy-looking echo, so a false-positive ECG is something to consider,” said Dr. Baggish.

This excess in anterior TWIs has been seen in previous studies and is thought to be benign, although the mechanism remains unclear. Four of the nine female athletes with abnormal ECG findings on initial evaluation had normalized on repeat testing 2-4 years later. Serial data were available in only a subset of athletes.
 

Clarity needed after COVID

The data, published recently in JAMA Cardiology, are particularly valuable these days given concern over the effects of COVID-19 on the heart and return-to-play recommendations.

“Athletes who have had COVID are being sent for echocardiograms before they can return to play to check for COVID-induced heart disease – which is real – but what we’re seeing is that there’s confusion out there in terms of what is a COVID-related abnormality and what is a normal, adapted athletic heart,” said Dr. Baggish.

“In this paper, we provide a dataset of normal values – generated before COVID was on anyone’s radar – to let cardiologists know what’s ‘big good’ and not ‘big bad.’ ”
 

More sport-specific data needed

“Although these numbers are still small, this dataset is an important step forward in our understanding of athletic adaptations,” said Matthew Martinez, MD, in an interview. “Many factors impact physiologic athletic changes, and the study aids in our understanding of gender- and sport-specific changes in athletes.”

Dr. Martinez, who is the director of sports cardiology at Atlantic Health–Morristown (N.J.) Medical Center and the Gagnon Cardiovascular Institute, also in Morristown, and the chair of Sports and Exercise Cardiology Section Leadership Council for the American College of Cardiology, noted the relatively young mean age of screened athletes.

“The data represent collegiate-age athletes with some older groups mixed in, but it does not represent older established elite athlete changes,” he said.

Mean age was 21 years in the female players but only 18 years in the males because the men’s senior national team failed to qualify for the World Cup during the study period and was therefore not screened. The authors acknowledged the “dearth of older men in the cohort.”

There is, overall, little age-, sport-, and sex-specific normative data for differentiating training-related cardiovascular adaptations from potentially pathologic phenotypes, wrote the authors.

It exists for men playing in the National Football League and for both sexes participating in the National Basketball Association, but most other studies have mixed the sports and focused mainly on men. That said, Dr. Baggish does not consider these data to be applicable to all elite athletes.

“Soccer is kind of in a league of its own with respect to the mixed amount of explosive or resistant and aerobic work that these athletes have to do, and also it’s the most popular sport in the world, so we really wanted to focus on them,” said Dr. Baggish.

Although the findings are perhaps applicable to athletes from other team sports characterized by explosive spurts of high-intensity activity – like hockey, lacrosse, and field hockey – he would not suggest they be applied to, say, long-distance runners, cyclists, or other sports that require a similar type of aerobic output.

Dr. Baggish reported no relevant conflict of interest. Dr. Martinez is league cardiologist for Major League Soccer.

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

Elite American soccer players have, on average, larger, thicker, and heavier hearts than the general population, according to a new study that provides clinicians with normative echocardiogram and electrocardiogram (ECG) cutoffs to use when assessing the heart health of competitive athletes.

Nikada/Getty Images

To provide these age- and sex-specific reference values, a team from Massachusetts General Hospital, Boston, led by Timothy W. Churchill, MD, and Aaron L. Baggish, MD, analyzed data from 122 female and 116 male soccer players from the American national teams preparing for World Cup play and undergoing FIFA-mandated preparticipation screening.

The athletes frequently exceeded normal echocardiographic ranges for left ventricular (LV) mass, volume, and wall thickness – structural cardiac parameters responsive to exercise-induced remodeling – but with none showing pathologic findings that might indicate the need to restrict their participation in the sport.

Almost one-third (30%) of female athletes and 41% of male athletes exceeded the American Society of Echocardiography’s upper limit of normal for LV wall thickness, with a measure greater than 12 mm seen in 12% of men and 1% of women.

The majority (51% of females and 59% of males) exceeded normal ranges for body surface area–indexed LV mass, with 77% and 68%, respectively, having LV volumes above the normal range.

Dr. Baggish stressed in an interview, however, that these data tell a story about healthy hearts, not at-risk hearts.

“These are the healthiest, highest-performing elite soccer players that we have in the United States, and this is really a look at how adaptive the heart can be, how much it can grow and change in size, shape, structure, and function in response to sport,” said Dr. Baggish.

The mean age of screened athletes was 20 years (range, 15-40 years). The majority of the female players were White (71%), whereas the male players were more evenly divided between Black (34%), Hispanic (33%), and White (32%).

Screening was performed at U.S. Soccer training sites by experienced clinicians affiliated with the Massachusetts General Hospital cardiovascular performance program.

Interestingly, the study debunks the idea that women, on average, have smaller chamber sizes. “When we did body-size correction, the men and women actually looked pretty similar with respect to their ability to adapt to strenuous exercise,” noted Dr. Baggish.

They did see, however, that women were more likely than men to have abnormal ECG findings. Male athletes showed a higher prevalence of “normal” training-related ECG findings, whereas female athletes were more likely to have abnormal ECG patterns (11.5% vs. 0.0% in the male cohort), most often pathologic T-wave inversions (TWI) confined to the anterior precordial lead distribution.

“This is important because ECGs are the most common screening tool used and we wanted to alert people to the fact that these women who showed some abnormalities on ECG went on to have a total healthy-looking echo, so a false-positive ECG is something to consider,” said Dr. Baggish.

This excess in anterior TWIs has been seen in previous studies and is thought to be benign, although the mechanism remains unclear. Four of the nine female athletes with abnormal ECG findings on initial evaluation had normalized on repeat testing 2-4 years later. Serial data were available in only a subset of athletes.
 

Clarity needed after COVID

The data, published recently in JAMA Cardiology, are particularly valuable these days given concern over the effects of COVID-19 on the heart and return-to-play recommendations.

“Athletes who have had COVID are being sent for echocardiograms before they can return to play to check for COVID-induced heart disease – which is real – but what we’re seeing is that there’s confusion out there in terms of what is a COVID-related abnormality and what is a normal, adapted athletic heart,” said Dr. Baggish.

“In this paper, we provide a dataset of normal values – generated before COVID was on anyone’s radar – to let cardiologists know what’s ‘big good’ and not ‘big bad.’ ”
 

More sport-specific data needed

“Although these numbers are still small, this dataset is an important step forward in our understanding of athletic adaptations,” said Matthew Martinez, MD, in an interview. “Many factors impact physiologic athletic changes, and the study aids in our understanding of gender- and sport-specific changes in athletes.”

Dr. Martinez, who is the director of sports cardiology at Atlantic Health–Morristown (N.J.) Medical Center and the Gagnon Cardiovascular Institute, also in Morristown, and the chair of Sports and Exercise Cardiology Section Leadership Council for the American College of Cardiology, noted the relatively young mean age of screened athletes.

“The data represent collegiate-age athletes with some older groups mixed in, but it does not represent older established elite athlete changes,” he said.

Mean age was 21 years in the female players but only 18 years in the males because the men’s senior national team failed to qualify for the World Cup during the study period and was therefore not screened. The authors acknowledged the “dearth of older men in the cohort.”

There is, overall, little age-, sport-, and sex-specific normative data for differentiating training-related cardiovascular adaptations from potentially pathologic phenotypes, wrote the authors.

It exists for men playing in the National Football League and for both sexes participating in the National Basketball Association, but most other studies have mixed the sports and focused mainly on men. That said, Dr. Baggish does not consider these data to be applicable to all elite athletes.

“Soccer is kind of in a league of its own with respect to the mixed amount of explosive or resistant and aerobic work that these athletes have to do, and also it’s the most popular sport in the world, so we really wanted to focus on them,” said Dr. Baggish.

Although the findings are perhaps applicable to athletes from other team sports characterized by explosive spurts of high-intensity activity – like hockey, lacrosse, and field hockey – he would not suggest they be applied to, say, long-distance runners, cyclists, or other sports that require a similar type of aerobic output.

Dr. Baggish reported no relevant conflict of interest. Dr. Martinez is league cardiologist for Major League Soccer.

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

Elite American soccer players have, on average, larger, thicker, and heavier hearts than the general population, according to a new study that provides clinicians with normative echocardiogram and electrocardiogram (ECG) cutoffs to use when assessing the heart health of competitive athletes.

Nikada/Getty Images

To provide these age- and sex-specific reference values, a team from Massachusetts General Hospital, Boston, led by Timothy W. Churchill, MD, and Aaron L. Baggish, MD, analyzed data from 122 female and 116 male soccer players from the American national teams preparing for World Cup play and undergoing FIFA-mandated preparticipation screening.

The athletes frequently exceeded normal echocardiographic ranges for left ventricular (LV) mass, volume, and wall thickness – structural cardiac parameters responsive to exercise-induced remodeling – but with none showing pathologic findings that might indicate the need to restrict their participation in the sport.

Almost one-third (30%) of female athletes and 41% of male athletes exceeded the American Society of Echocardiography’s upper limit of normal for LV wall thickness, with a measure greater than 12 mm seen in 12% of men and 1% of women.

The majority (51% of females and 59% of males) exceeded normal ranges for body surface area–indexed LV mass, with 77% and 68%, respectively, having LV volumes above the normal range.

Dr. Baggish stressed in an interview, however, that these data tell a story about healthy hearts, not at-risk hearts.

“These are the healthiest, highest-performing elite soccer players that we have in the United States, and this is really a look at how adaptive the heart can be, how much it can grow and change in size, shape, structure, and function in response to sport,” said Dr. Baggish.

The mean age of screened athletes was 20 years (range, 15-40 years). The majority of the female players were White (71%), whereas the male players were more evenly divided between Black (34%), Hispanic (33%), and White (32%).

Screening was performed at U.S. Soccer training sites by experienced clinicians affiliated with the Massachusetts General Hospital cardiovascular performance program.

Interestingly, the study debunks the idea that women, on average, have smaller chamber sizes. “When we did body-size correction, the men and women actually looked pretty similar with respect to their ability to adapt to strenuous exercise,” noted Dr. Baggish.

They did see, however, that women were more likely than men to have abnormal ECG findings. Male athletes showed a higher prevalence of “normal” training-related ECG findings, whereas female athletes were more likely to have abnormal ECG patterns (11.5% vs. 0.0% in the male cohort), most often pathologic T-wave inversions (TWI) confined to the anterior precordial lead distribution.

“This is important because ECGs are the most common screening tool used and we wanted to alert people to the fact that these women who showed some abnormalities on ECG went on to have a total healthy-looking echo, so a false-positive ECG is something to consider,” said Dr. Baggish.

This excess in anterior TWIs has been seen in previous studies and is thought to be benign, although the mechanism remains unclear. Four of the nine female athletes with abnormal ECG findings on initial evaluation had normalized on repeat testing 2-4 years later. Serial data were available in only a subset of athletes.
 

Clarity needed after COVID

The data, published recently in JAMA Cardiology, are particularly valuable these days given concern over the effects of COVID-19 on the heart and return-to-play recommendations.

“Athletes who have had COVID are being sent for echocardiograms before they can return to play to check for COVID-induced heart disease – which is real – but what we’re seeing is that there’s confusion out there in terms of what is a COVID-related abnormality and what is a normal, adapted athletic heart,” said Dr. Baggish.

“In this paper, we provide a dataset of normal values – generated before COVID was on anyone’s radar – to let cardiologists know what’s ‘big good’ and not ‘big bad.’ ”
 

More sport-specific data needed

“Although these numbers are still small, this dataset is an important step forward in our understanding of athletic adaptations,” said Matthew Martinez, MD, in an interview. “Many factors impact physiologic athletic changes, and the study aids in our understanding of gender- and sport-specific changes in athletes.”

Dr. Martinez, who is the director of sports cardiology at Atlantic Health–Morristown (N.J.) Medical Center and the Gagnon Cardiovascular Institute, also in Morristown, and the chair of Sports and Exercise Cardiology Section Leadership Council for the American College of Cardiology, noted the relatively young mean age of screened athletes.

“The data represent collegiate-age athletes with some older groups mixed in, but it does not represent older established elite athlete changes,” he said.

Mean age was 21 years in the female players but only 18 years in the males because the men’s senior national team failed to qualify for the World Cup during the study period and was therefore not screened. The authors acknowledged the “dearth of older men in the cohort.”

There is, overall, little age-, sport-, and sex-specific normative data for differentiating training-related cardiovascular adaptations from potentially pathologic phenotypes, wrote the authors.

It exists for men playing in the National Football League and for both sexes participating in the National Basketball Association, but most other studies have mixed the sports and focused mainly on men. That said, Dr. Baggish does not consider these data to be applicable to all elite athletes.

“Soccer is kind of in a league of its own with respect to the mixed amount of explosive or resistant and aerobic work that these athletes have to do, and also it’s the most popular sport in the world, so we really wanted to focus on them,” said Dr. Baggish.

Although the findings are perhaps applicable to athletes from other team sports characterized by explosive spurts of high-intensity activity – like hockey, lacrosse, and field hockey – he would not suggest they be applied to, say, long-distance runners, cyclists, or other sports that require a similar type of aerobic output.

Dr. Baggish reported no relevant conflict of interest. Dr. Martinez is league cardiologist for Major League Soccer.

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

Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.

Raycat/Getty Images

“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.

The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.

“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.

It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.

The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
 

Study adds important new evidence

However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.

“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.

“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.

“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.

But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.

“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.

“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
 

Possible that 7 years is better than 5 but remains to be proven

The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.

Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.

Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.

During these 5 years of treatment, 507 hip fractures occurred.

The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.

After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.

The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.

“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.

“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
 

Limitations: Subgroups not identified, adherence hard to assess

The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.

Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.

Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.

Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.

“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”

The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.

The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.

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

Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.

Raycat/Getty Images

“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.

The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.

“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.

It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.

The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
 

Study adds important new evidence

However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.

“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.

“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.

“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.

But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.

“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.

“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
 

Possible that 7 years is better than 5 but remains to be proven

The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.

Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.

Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.

During these 5 years of treatment, 507 hip fractures occurred.

The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.

After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.

The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.

“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.

“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
 

Limitations: Subgroups not identified, adherence hard to assess

The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.

Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.

Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.

Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.

“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”

The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.

The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.

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

Women treated with oral bisphosphonate drugs for osteoporosis for 5 years get no additional benefit – in terms of hip fracture risk – if the treatment is extended for another 5 years, new research shows.

Raycat/Getty Images

“We found that hip fracture risk in women did not differ if women stopped bisphosphonate use after 5 years or stayed on the medication for 10 years,” coauthor Joan C. Lo, MD, Kaiser Permanente Northern California, Oakland, said in an interview.

The new study, published Dec. 7 in JAMA Network Open, did show a small benefit in continuing the treatment through 7 years vs. 5 years, but it wasn’t clear if this was significant.

“Whether there is a benefit to staying on the drug for 7 years needs to be further studied in randomized trials,” Dr. Lo stressed.

It is well established that oral bisphosphonates are effective in reducing the risk for fracture within the first 3-5 years of treatment; however, evidence on the effects of treatment beyond 5 years is lacking.

The most recent guidance from the American Society of Bone and Mineral Research (ASBMR) on the issue, which were released in 2015, recommends continuation of bisphosphonates beyond 5 years for high-risk patients, but it recommends a “drug holiday” for low-risk patients.
 

Study adds important new evidence

However, that guidance acknowledges that data are limited regarding long-term use. This large new study adds important new evidence to the discussion, Robert A. Adler, MD, who was a member of the ASBMR Task Force for the recent guidance, said in an interview.

“[With the lack of recent research,] this new study from Kaiser Permanente is of great interest,” said Dr. Adler, chief of endocrinology and metabolism at Central Virginia Veterans Affairs Health Care System and professor of internal medicine and of epidemiology at Virginia Commonwealth University, Richmond.

“It is new data and suggests we might temper our enthusiasm for long-term treatment with bisphosphonates,” he said.

“Importantly, it is the first large observational trial and is closer to a real-world setting than a randomized controlled trial,” he said.

But, Dr. Adler emphasized: “The take-home message is that while this suggests that patients can probably be given a drug holiday for a couple of years ... they should be retested, and if they appear to be at an increased risk of fracture, they probably should restart again.

“Osteoporosis is a chronic disorder,” he emphasized. “It isn’t cured by any of our treatments, and as people get older, they are at a higher fracture risk.

“So we really need to follow our patients for a lifetime and reassess their fracture risk every couple of years – whether they are still on therapy or on a drug holiday.”
 

Possible that 7 years is better than 5 but remains to be proven

The new study involved data from Kaiser Permanente Northern and Southern California on 29,685 women who had completed 5 years of treatment with oral bisphosphonates, including alendronate, risedronate, or ibandronate, between 2002 and 2014.

Among the women, 11,105 (37%) continued taking the drugs beyond 5 years to 7 years, and 2,725 (9.2%) completed a total of 10 years of treatment.

Their median age was 71. Among those for whom bone mineral density data were available, 37% had osteoporosis after the first 5 years of treatment.

During these 5 years of treatment, 507 hip fractures occurred.

The cumulative incidence of hip fracture among for those who discontinued study therapy at entry, i.e., those who underwent treatment for 5 years, was 23.0 per 1,000 individuals.

After 7 years of treatment, the rate was 20.8 per 1000. For those who continued therapy for 10 years, the rate was 26.8 per 1000 individuals.

The rate in the 7-year treatment group was based on patients taking a 6-month drug holiday after the initial 5 years, but the results are hard to interpret, Dr. Lo said.

“It’s possible that 7 years is better than 5, but this is not a randomized trial, and some of the data analyses done in the study suggest more research should be done to look at a benefit after 7 years.

“At the end of the day, doctors and women need to decide at 5 years what an individual woman’s risk fracture risk is and determine if she should stay on the drug longer,” Dr. Lo emphasized.
 

Limitations: Subgroups not identified, adherence hard to assess

The uncertainty of any benefit of treatment with bisphosphonates beyond 5 years is further reflected in U.S. recommendations – the Food and Drug Administration has concluded on the basis of pooled data from the extension phase of major clinical trials that any advantages of treatment beyond 3-5 years are unclear.

Key limitations of the current study include the fact that the incidence of hip fracture was not evaluated in low-risk vs. high-risk subgroups; therefore, “these findings may not be applicable to older women at higher risk of osteoporotic fracture,” the authors wrote.

Furthermore, the study did not assess outcomes of fractures other than hip fractures, such as vertebral fractures, they noted.

Dr. Adler pointed out that another limitation is that adherence in the trial was defined as taking 60% of prescribed pills.

“I think this is the biggest weakness with the study,” he said. “Particularly with medications like oral bisphosphonates that don’t really make patients feel any different, it’s a real challenge to make sure patients continue to take these drugs properly.”

The findings should give some reassurance for patients who take a break from the drugs after 5 years. However, reassessment of their risk is critical, Dr. Adler reiterated.

The study was supported by a grant from the National Institute on Aging and the National Institute of Arthritis, Musculoskeletal, and Skin Diseases of the National Institutes of Health. The authors and Adler have disclosed no relevant financial relationships.

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

Heart transplant recipients infected with SARS-CoV-2 are about twice as likely to die from COVID-19 and should be immediately referred to a transplant center for care, according to transplant experts from Northern Italy.

In a COVID Rapid Report published Dec. 9 in JACC Heart Failure, a group led by Tomaso Bottio, MD, PhD, from the University of Padua, Italy, presented findings on 47 heart transplant recipients who tested positive for SARS-Cov-2 between Feb. 21 and June 30.

The investigators found a case fatality rate of 29.7%, compared with 15.4% in the general population. Prevalence of infection was also much higher at 18 cases (vs. 7) per 1,000 population.

“In our opinion, prompt referral to a heart transplant center is crucial for immunosuppressive therapy optimization and cardiologic follow-up,” Dr. Bottio said in an interview.

Beyond the need for careful adjustment of immunosuppression, graft function should be assessed to “avoid acute rejection or decompensation,” he added.

Dr. Bottio and colleagues tracked COVID-19 cases from among the 2,676 heart transplant recipients alive before the onset of the pandemic at seven heart transplant centers in Northern Italy.

Of the 47 recipients who contracted SARS-CoV-2, 38 required hospitalization while 9 remained at home and 14 died. Mean length of stay in hospital was 17.8 days, much longer in survivors than nonsurvivors (23.2 days vs. 8.5 days; P < .001).  

Nonsurvivors were significantly older than survivors (72 vs. 58 years; P = .002). Nonsurvivors were also more likely to present with diabetes (P = .04), extra-cardiac arteriopathy (P = .04), previous percutaneous coronary intervention (P = .04), more allograft vasculopathy (P = .04), and more symptoms of heart failure (P = .02).

Although the authors said the high case fatality rate was, unfortunately, expected, they did not expect so many patients to do well at home.

“What most surprised us was the proportion of a- or pauci-symptomatic heart transplanted patients who did well being treated at home without any therapy modifications,” Dr. Bottio shared. They were also surprised to see there were no cases of graft failure caused by infection-related myocarditis.

These findings from Northern Italy are not dissimilar from the 25% case fatality rate seen in a cohort of heart transplant recipients who caught COVID-19 in New York City early in the pandemic.

In another study, this time looking at a wider group of solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City, 16 of 90 patients (18%) died.
 

Treatment recommendations?

Recognizing that there is no randomized trial data informing the treatment of this vulnerable patient population, Dr. Bottio and colleagues suggested that, based on their experience, no change in immunosuppression is needed in those who are “pauci-symptomatic” (mildly symptomatic).

“On the other hand, in hospitalized patients a partial reduction in immunosuppressive therapy avoiding full discontinuation and risk of graft rejection seems to be a common strategy in facing the viral infection,” he said. “In addition, the introduction of corticosteroids could help to suspend the onset of the inflammatory cascade responsible for severe forms of the disease.”

Antibiotic prophylaxis appears to be “fundamental,” he added, particularly in hospitalized patients, but “the role of specific antiviral therapies is still not fully understood in our population.”

Since July 1, they’ve seen an additional six patients with a positive test for SARS-CoV-2. Five were asymptomatic and quarantined at home without changing their immunosuppressive therapy. One patient was hospitalized for pneumonia and had immunosuppressive therapy reduced.

Dr. Bottio and the study coauthors have disclosed no relevant financial relationships.

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

Heart transplant recipients infected with SARS-CoV-2 are about twice as likely to die from COVID-19 and should be immediately referred to a transplant center for care, according to transplant experts from Northern Italy.

In a COVID Rapid Report published Dec. 9 in JACC Heart Failure, a group led by Tomaso Bottio, MD, PhD, from the University of Padua, Italy, presented findings on 47 heart transplant recipients who tested positive for SARS-Cov-2 between Feb. 21 and June 30.

The investigators found a case fatality rate of 29.7%, compared with 15.4% in the general population. Prevalence of infection was also much higher at 18 cases (vs. 7) per 1,000 population.

“In our opinion, prompt referral to a heart transplant center is crucial for immunosuppressive therapy optimization and cardiologic follow-up,” Dr. Bottio said in an interview.

Beyond the need for careful adjustment of immunosuppression, graft function should be assessed to “avoid acute rejection or decompensation,” he added.

Dr. Bottio and colleagues tracked COVID-19 cases from among the 2,676 heart transplant recipients alive before the onset of the pandemic at seven heart transplant centers in Northern Italy.

Of the 47 recipients who contracted SARS-CoV-2, 38 required hospitalization while 9 remained at home and 14 died. Mean length of stay in hospital was 17.8 days, much longer in survivors than nonsurvivors (23.2 days vs. 8.5 days; P < .001).  

Nonsurvivors were significantly older than survivors (72 vs. 58 years; P = .002). Nonsurvivors were also more likely to present with diabetes (P = .04), extra-cardiac arteriopathy (P = .04), previous percutaneous coronary intervention (P = .04), more allograft vasculopathy (P = .04), and more symptoms of heart failure (P = .02).

Although the authors said the high case fatality rate was, unfortunately, expected, they did not expect so many patients to do well at home.

“What most surprised us was the proportion of a- or pauci-symptomatic heart transplanted patients who did well being treated at home without any therapy modifications,” Dr. Bottio shared. They were also surprised to see there were no cases of graft failure caused by infection-related myocarditis.

These findings from Northern Italy are not dissimilar from the 25% case fatality rate seen in a cohort of heart transplant recipients who caught COVID-19 in New York City early in the pandemic.

In another study, this time looking at a wider group of solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City, 16 of 90 patients (18%) died.
 

Treatment recommendations?

Recognizing that there is no randomized trial data informing the treatment of this vulnerable patient population, Dr. Bottio and colleagues suggested that, based on their experience, no change in immunosuppression is needed in those who are “pauci-symptomatic” (mildly symptomatic).

“On the other hand, in hospitalized patients a partial reduction in immunosuppressive therapy avoiding full discontinuation and risk of graft rejection seems to be a common strategy in facing the viral infection,” he said. “In addition, the introduction of corticosteroids could help to suspend the onset of the inflammatory cascade responsible for severe forms of the disease.”

Antibiotic prophylaxis appears to be “fundamental,” he added, particularly in hospitalized patients, but “the role of specific antiviral therapies is still not fully understood in our population.”

Since July 1, they’ve seen an additional six patients with a positive test for SARS-CoV-2. Five were asymptomatic and quarantined at home without changing their immunosuppressive therapy. One patient was hospitalized for pneumonia and had immunosuppressive therapy reduced.

Dr. Bottio and the study coauthors have disclosed no relevant financial relationships.

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

Heart transplant recipients infected with SARS-CoV-2 are about twice as likely to die from COVID-19 and should be immediately referred to a transplant center for care, according to transplant experts from Northern Italy.

In a COVID Rapid Report published Dec. 9 in JACC Heart Failure, a group led by Tomaso Bottio, MD, PhD, from the University of Padua, Italy, presented findings on 47 heart transplant recipients who tested positive for SARS-Cov-2 between Feb. 21 and June 30.

The investigators found a case fatality rate of 29.7%, compared with 15.4% in the general population. Prevalence of infection was also much higher at 18 cases (vs. 7) per 1,000 population.

“In our opinion, prompt referral to a heart transplant center is crucial for immunosuppressive therapy optimization and cardiologic follow-up,” Dr. Bottio said in an interview.

Beyond the need for careful adjustment of immunosuppression, graft function should be assessed to “avoid acute rejection or decompensation,” he added.

Dr. Bottio and colleagues tracked COVID-19 cases from among the 2,676 heart transplant recipients alive before the onset of the pandemic at seven heart transplant centers in Northern Italy.

Of the 47 recipients who contracted SARS-CoV-2, 38 required hospitalization while 9 remained at home and 14 died. Mean length of stay in hospital was 17.8 days, much longer in survivors than nonsurvivors (23.2 days vs. 8.5 days; P < .001).  

Nonsurvivors were significantly older than survivors (72 vs. 58 years; P = .002). Nonsurvivors were also more likely to present with diabetes (P = .04), extra-cardiac arteriopathy (P = .04), previous percutaneous coronary intervention (P = .04), more allograft vasculopathy (P = .04), and more symptoms of heart failure (P = .02).

Although the authors said the high case fatality rate was, unfortunately, expected, they did not expect so many patients to do well at home.

“What most surprised us was the proportion of a- or pauci-symptomatic heart transplanted patients who did well being treated at home without any therapy modifications,” Dr. Bottio shared. They were also surprised to see there were no cases of graft failure caused by infection-related myocarditis.

These findings from Northern Italy are not dissimilar from the 25% case fatality rate seen in a cohort of heart transplant recipients who caught COVID-19 in New York City early in the pandemic.

In another study, this time looking at a wider group of solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City, 16 of 90 patients (18%) died.
 

Treatment recommendations?

Recognizing that there is no randomized trial data informing the treatment of this vulnerable patient population, Dr. Bottio and colleagues suggested that, based on their experience, no change in immunosuppression is needed in those who are “pauci-symptomatic” (mildly symptomatic).

“On the other hand, in hospitalized patients a partial reduction in immunosuppressive therapy avoiding full discontinuation and risk of graft rejection seems to be a common strategy in facing the viral infection,” he said. “In addition, the introduction of corticosteroids could help to suspend the onset of the inflammatory cascade responsible for severe forms of the disease.”

Antibiotic prophylaxis appears to be “fundamental,” he added, particularly in hospitalized patients, but “the role of specific antiviral therapies is still not fully understood in our population.”

Since July 1, they’ve seen an additional six patients with a positive test for SARS-CoV-2. Five were asymptomatic and quarantined at home without changing their immunosuppressive therapy. One patient was hospitalized for pneumonia and had immunosuppressive therapy reduced.

Dr. Bottio and the study coauthors have disclosed no relevant financial relationships.

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