The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.

Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m²) or are overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity.

Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.

Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.

This weight-loss drug is currently under review by the European Medicines Agency.

Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.


 

‘Game changer’ drug tested in STEP clinical trial program

The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.

The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.

As previously reported by this news organization, all trials were in adults with overweight or obesity:

•  was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
•  was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
•  was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
•  was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).

In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.

The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.

The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.

A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”

“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
 

Welcome Addition, But Will Insurance Coverage, Price Thwart Access?

Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”

The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.

And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.

Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.

However, insurance coverage and price could block uptake.

“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”

“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.

“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”

However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”

“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.

Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.

The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.

And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
 

CVOT and oral format trials for obesity on the horizon

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.

And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.

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

This article was updated 6/7/21.

The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.

Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m²) or are overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity.

Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.

Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.

This weight-loss drug is currently under review by the European Medicines Agency.

Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.


 

‘Game changer’ drug tested in STEP clinical trial program

The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.

The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.

As previously reported by this news organization, all trials were in adults with overweight or obesity:

•  was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
•  was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
•  was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
•  was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).

In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.

The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.

The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.

A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”

“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
 

Welcome Addition, But Will Insurance Coverage, Price Thwart Access?

Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”

The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.

And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.

Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.

However, insurance coverage and price could block uptake.

“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”

“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.

“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”

However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”

“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.

Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.

The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.

And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
 

CVOT and oral format trials for obesity on the horizon

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.

And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.

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

This article was updated 6/7/21.

The U.S. Food and Drug Administration has approved a 2.4 mg/week subcutaneous dose of the glucagonlike peptide–1 (GLP-1) receptor agonist semaglutide (Wegovy, Novo Nordisk) for weight loss.

Specifically, this drug format and dosage are approved as an adjunct to a reduced-calorie diet and increased physical activity to treat adults who have obesity (body mass index [BMI] ≥ 30 kg/m²) or are overweight (BMI ≥ 27 kg/m²) with at least one weight-related comorbidity.

Semaglutide “induces weight loss by reducing hunger, increasing feelings of fullness, and thereby helping people eat less and reduce their calorie intake,” according to a company statement.

Novo Nordisk plans to launch Wegovy later this month in the United States. The prescribing information can be found here.

This weight-loss drug is currently under review by the European Medicines Agency.

Several experts told Medscape that they believe the approval of this drug – as long as it is reimbursed – has the potential to change the paradigm of care when it comes to weight loss.


 

‘Game changer’ drug tested in STEP clinical trial program

The favorable FDA ruling is based on results from the Semaglutide Treatment Effect in People With Obesity (STEP) program of four phase 3 clinical trials that tested the drug’s safety and efficacy in more than 4,500 adults with overweight or obesity obesity who were randomized to receive a reduced a calorie meal plan and increased physical activity (placebo) or this lifestyle intervention plus semaglutide.

The four 68-week trials of subcutaneous semaglutide 2.4 mg/week versus placebo were published in February and March 2021.

As previously reported by this news organization, all trials were in adults with overweight or obesity:

•  was in 1,961 adults (N Engl J Med. 2021 March 18;384:989-1002).
•  was in 1,210 adults who also had diabetes (Lancet. 2021 Mar 13;397;971-84).
•  was in 611 adults, where those in the treatment group also underwent an intensive lifestyle intervention (JAMA. 2021 Feb 24;325:1403-13.
•  was in 803 adults who had reached a target dose of 2.4 mg semaglutide after a 20-week run-in (and the trial examined further weight loss in the subsequent 48 weeks) (JAMA 2021 Mar 23;325:1414-25).

In the STEP 1, 2, and 4 trials of individuals with overweight and obesity, those in the semaglutide groups attained a 15%-18% weight loss over 68 weeks.

The dosage was well-tolerated. The most common side effects were gastrointestinal, and they were transient and mild or moderate in severity.

The side effects, contraindications, and a black box warning about thyroid C-cell tumors are spelled out in the prescribing information.

A coauthor of the STEP 1 trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College London, said at the time of publication: “The findings of this study represent a major breakthrough for improving the health of people with obesity.”

“No other drug has come close to producing this level of weight loss – this really is a gamechanger. For the first time, people can achieve through drugs what was only possible through weight-loss surgery,” she added.
 

Welcome Addition, But Will Insurance Coverage, Price Thwart Access?

Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and lead author of STEP 3, commented in an email to this news organization that “semaglutide 2.4 mg appears to be the breakthrough in weight management that healthcare providers and their patients with obesity have been waiting for.”

The mean 15% weight loss at 68 weeks is nearly twice what is seen with other FDA-approved anti-obesity medications, he noted, and moreover, 70% of patients taking semaglutide lost at least 10% of their initial weight, which is associated with clinically meaningful improvements in obesity-related type 2 diabetes, hypertension, obstructive sleep apnea, and impaired quality of life.

And “nearly one-third of users are likely to lose 20% or more of their starting weight, an outcome which eludes traditional diet and exercise interventions and which approaches weight losses produced by the most widely performed bariatric surgery, sleeve gastrectomy (with mean losses of 25% of initial weight at 1 year).” Dr. Wadden stressed.

Thus “the efficacy of semaglutide 2.4 mg, combined with its favorable safety profile, makes this medication a potential game changer,” he summarized, echoing Dr. Batterham.

However, insurance coverage and price could block uptake.

“I hope that the millions of people – in the U.S. and worldwide – who could benefit from this medication eventually will have access to it,” said Dr. Wadden. “In the U.S., the coverage of anti-obesity medications by insurers and employers will need to improve to ensure this happens, and the medication must be reasonably priced. These changes are critical to making this medication the game changer it could be.”

“This approval is an important development,” Scott Kahan, MD, director of the National Center for Weight and Wellness, Washington, who was not involved in the clinical trials of this drug, similarly wrote in an email.

“In a field with relatively few medication options, the availability of additional obesity pharmacotherapy agents is welcome,” he said. “In particular, semaglutide has shown impressive efficacy and safety data; as such it should be a valuable clinical option for many patients.”

However, it is concerning that “access to obesity treatments has traditionally been a challenge,” Dr. Kahan warned. “Novo Nordisk’s other obesity medication, Saxenda, has been a valuable tool, but one that exceedingly few patients are able to utilize due to minimal insurance reimbursement and very high cost.”

“It remains to be seen how accessible semaglutide will be for patients,” according to Dr. Kahan, “Still, if the challenge of limited coverage and high cost can be mitigated, this medication has a chance to significantly change the current paradigm of care, which until till now has included minimal use of pharmacotherapy outside specialty clinics,” he maintains.

Subcutaneous semaglutide at doses up to 1 mg/week (Ozempic, Novo Nordisk), which comes as prefilled pens at doses of 0.5 mg or 1.0 mg, is already approved for the treatment of type 2 diabetes.

The company is also applying for approval for a higher dose of semaglutide, 2 mg/week, for use in type 2 diabetes, and has just resubmitted its label expansion application to the FDA, after the agency issued a refusal to file letter in March.

And in September 2019, the FDA approved oral semaglutide (Rybelsus, Novo Nordisk), in doses of 7 and 14 mg/day, to improve glycemic control in type 2 diabetes, making it the first GLP-1 receptor agonist available in tablet form.
 

CVOT and oral format trials for obesity on the horizon

The ongoing Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity (SELECT) trial will shed light on cardiovascular outcomes after 2.5-5 years in patients with cardiovascular disease and overweight or obesity but without type 2 diabetes. Participants will receive semaglutide in doses up to a maximum of 2.4 mg/week, or placebo, as an adjunct to lifestyle recommendations focused on cardiovascular risk reduction. The study is expected to complete in 2023.

And Novo Nordisk plans to initiate a global 68-week phase 3 trial in the second half of 2021 on the efficacy and safety of oral semaglutide 50 mg compared with placebo in 1000 people with obesity or overweight and comorbidities.

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

This article was updated 6/7/21.

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

New guidelines from the American College of Gastroenterology on idiosyncratic drug-induced liver injury (DILI) emphasize that idiosyncratic DILI is increasingly driven by the burgeoning popularity of herbal and dietary supplements, as well as tyrosine kinase inhibitors and immune checkpoint inhibitors used to treat cancer.

Sebastian Kaulitzki/Science Photo Library

The guidelines, which represent an update from 2014, are published in The American Journal of Gastroenterology.

DILI is commonly seen by gastroenterologists and hepatologists, but it is challenging to diagnose because there are many potential causes, and no objective diagnostic tests. Its incidence in the general population is low, but it must be considered when facing unexplained liver injury. Its potential presence should also be considered when prescribing gastrointestinal medications like azathioprine, anti–tumor necrosis factor agents, and sulfonamides.

DILI can be characterized as intrinsic or idiosyncratic. Intrinsic DILI is somewhat predictable, based on human or animal studies that have revealed the potential for liver toxicity at higher doses. The best-known example is acetaminophen. Idiosyncratic DILI is rarer and shows up in individuals with a preexisting susceptibility. Clinical signs of idiosyncratic DILI are more diverse than intrinsic DILI. The ACG guideline focuses on idiosyncratic DILI, since guidelines are already available for intrinsic DILI.

Idiosyncratic DILI diagnosis can have a wide range of presentations, including asymptomatic liver biochemistry, jaundice, liver failure, and chronic hepatitis. Diagnosis is made by eliminating other potential causes.

In the presence of hepatocellular jaundice, mortality can reach 10%. DILI patients who develop progressive jaundice, regardless of concomitant coagulopathy, should be sent to a tertiary center and may be a candidate for liver transplantation.

Corticosteroids may be considered when there is uncertainty if a liver injury is from DILI or autoimmune hepatitis, but this remains controversial because some studies have shown benefit, while others have not, according to Bubu Banini, MD, PhD, assistant professor of medicine and research director of the metabolic health and weight management program at Yale University, New Haven, Conn. “Large-scale randomized controlled trials are needed for further elucidation of the role of steroids in DILI. For now, the guideline recommends consideration of steroid therapy, particularly in patients with features of autoimmune hepatitis,” she added.

An important factor driving DILI is the increasing popularity of herbal supplements, as well as increased use of some cancer therapies. “With the advent of immune checkpoint inhibitors as effective therapies for a variety of malignancies, physicians need to be aware of the potential side effects of these agents and the possibility of immune checkpoint inhibitor–related drug induced liver injury,” Dr. Banini said. The updated ACG guideline summarizes current FDA-approved immune checkpoint inhibitors and their potential to cause DILI. The drugs can also lead to reactivation of hepatitis B infection. Studies have shown liver enzyme elevation occurs in about 30% of patients treated with immune checkpoint inhibitors.

The guidelines recommend assessing DILI patients for hepatitis B and C, and treating patients prior to, or in combination with, immune checkpoint inhibitors or other chemotherapy drugs. The recommendations are in line with preliminary data from the ICI field, according to Dr. Banini.

Dr. Banini also noted there has been an increase in the use of herbal and dietary supplements in the United States over the past decade, and these now account for about one-fifth of DILI cases. The guidelines recommend that severe cholestatic disease from these agents should be managed similarly to cases caused by prescription drugs, and patients should be considered for liver transplant if necessary.

A web-based 6-month mortality calculator for suspected DILI is available. It uses Model for End-Stage Liver Disease, Charlson comorbidity Index, and serum albumin data. Those variables predict mortality in liver disease, and an independent analysis showed they predict 6-month mortality in DILI.

DILI is difficult to diagnose, but physicians should keep it in mind when faced with a case of liver enzyme abnormality, where other possibilities have been excluded. “With over a thousand medications potentially causing DILI, physicians should be familiar with LiverTox as a very useful and practical resource. The DILI mortality calculator can serve as a clinical tool to predict 6-month mortality in patients with suspected DILI,” Dr. Banini said.

Some authors disclosed relationships with several pharmaceutical companies. Dr. Banini reports having nothing to disclose.

On the medication front, there are now “four pillars of survival” in the setting of heart failure with reduced ejection fraction (EF), a cardiologist told hospitalists recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

The quartet of drugs are beta blockers, angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, and the newest addition – sodium-glucose cotransporter 2 inhibitors.

“If we use all four of these medications, the absolute risk reduction [in mortality] is 25% over a 2-year period,” said cardiologist Celeste T. Williams, MD, of Henry Ford Hospital, Detroit. “So it is very important that we use these medications,” she said.

But managing the medications, she said, can be challenging. Dr. Williams offered these tips about the use of medication in heart failure.
 

Beta blockers are crucial players

“Beta blockers save lives,” Dr. Williams said, “but there’s always a debate about how much we should titrate beta blockers.”

How can you determine the proper titration? Focus on heart rates, she recommended. “We know that higher heart rates in heart failure patients are associated with worse outcomes. There was subgroup analysis in the BEAUTIFUL study that looked at 5,300 patients with EF less than 40% who had CAD [coronary artery disease]. They found that patients with heart rates greater than 70 had a 34% increased risk of cardiovascular death and a 53% increased risk of heart failure hospitalization compared to heart rates less than 70.”

Focus on getting your patient’s heart rate lower than 70 while maintaining their blood pressure, she said.

“Another question we have is, ‘When these patients come into hospitals, what should we do with the beta blocker? Should we continue it? Should we stop it?’ If you can, you always want to continue the beta blocker or the ACE [angiotensin-converting enzyme] inhibitor, because studies have shown us that the likelihood for patients to be on these medications 90 days later is dismal,” she said. “But you also need to look at the patient. If the patient is in cardiogenic shock, their beta blocker should be stopped.”
 

Consider multiple factors when titrating various medications

“In the hospital, we always will look at hemodynamic compromise in the patient. Is the patient in cardiogenic shock?” Dr. Williams said. “We also must think about compliance concerns. Are the patients even taking their medication? And if they are taking their medications, are they tolerating standard medical therapy? Are they hypotensive? Are they only able to tolerate minimal meds? Have you seen that their creatine continues to rise? Or are they having poor diuresis with the rise in diuretics?”

All these questions are useful, she said, as you determine whether you should titrate medication yourself or refer the patient to an advanced heart failure specialist.
 

Understand when to stick with guideline-directed medical therapy

Dr. Williams said another question often arises: “If your patient’s EF recovers, should you stop guideline-directed medical therapy [GDMT]?” She highlighted a TRED-HF study that evaluated patients who had recovered from dilated, nonischemic cardiomyopathy and were receiving GDMT. “They withdrew GDMT for half of the patients and looked at their echoes 6 months later. They found that 40% of the patients relapsed. Their EFs went below 40% again. Stopping medications is not the best idea for most of these patients.”

However, she said, there are scenarios in which GDMT may be withdrawn, such as for patients with tachycardia-induced cardiomyopathies whose EF recovers after ablation, those whose EF recovers after alcoholic cardiomyopathy, and those who receive valve replacements. “We need to remember that a lot of the patients who develop stage C heart failure have risk factors. Even though their heart failure has recovered, they have risks that need to be treated, and you can use the same medications that you use for heart failure to control their risk. Therefore, you would not get into trouble by withdrawing their medications.”

She added: “If you’re unable to titrate GDMT because the blood pressure is too soft, the creatine continues to rise, or the patient just has a lot of heart failure symptoms, this is indicative that the patient is sicker than they may appear.” At this point, defer to a heart failure specialist, she said.
 

Consider ivabradine as an add-on when appropriate

In some cases, a heart rate of less than 70 bpm will not be achieved even with GDMT and maximum tolerated doses, Dr. Williams said. “If they’re in sinus, you can add on a medication called ivabradine, which was studied in the SHIFT study. This looked at patients with EF of less than 35% who had class 2-3 heart failure in sinus rhythm. They had to have a hospitalization within the last 12 months. The patients were randomized to either ivabradine or placebo. The primary outcome was [cardiovascular] death or heart failure hospitalization. They found that patients who had ivabradine had a decrease in heart failure hospitalization.”

The lesson, she said, is that “ivabradine is a great medication to add on to patients who are still tachycardic in sinus when you cannot titrate up the beta blocker.”

Dr. Williams reports no relevant financial relationships.

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

On the medication front, there are now “four pillars of survival” in the setting of heart failure with reduced ejection fraction (EF), a cardiologist told hospitalists recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

The quartet of drugs are beta blockers, angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, and the newest addition – sodium-glucose cotransporter 2 inhibitors.

“If we use all four of these medications, the absolute risk reduction [in mortality] is 25% over a 2-year period,” said cardiologist Celeste T. Williams, MD, of Henry Ford Hospital, Detroit. “So it is very important that we use these medications,” she said.

But managing the medications, she said, can be challenging. Dr. Williams offered these tips about the use of medication in heart failure.
 

Beta blockers are crucial players

“Beta blockers save lives,” Dr. Williams said, “but there’s always a debate about how much we should titrate beta blockers.”

How can you determine the proper titration? Focus on heart rates, she recommended. “We know that higher heart rates in heart failure patients are associated with worse outcomes. There was subgroup analysis in the BEAUTIFUL study that looked at 5,300 patients with EF less than 40% who had CAD [coronary artery disease]. They found that patients with heart rates greater than 70 had a 34% increased risk of cardiovascular death and a 53% increased risk of heart failure hospitalization compared to heart rates less than 70.”

Focus on getting your patient’s heart rate lower than 70 while maintaining their blood pressure, she said.

“Another question we have is, ‘When these patients come into hospitals, what should we do with the beta blocker? Should we continue it? Should we stop it?’ If you can, you always want to continue the beta blocker or the ACE [angiotensin-converting enzyme] inhibitor, because studies have shown us that the likelihood for patients to be on these medications 90 days later is dismal,” she said. “But you also need to look at the patient. If the patient is in cardiogenic shock, their beta blocker should be stopped.”
 

Consider multiple factors when titrating various medications

“In the hospital, we always will look at hemodynamic compromise in the patient. Is the patient in cardiogenic shock?” Dr. Williams said. “We also must think about compliance concerns. Are the patients even taking their medication? And if they are taking their medications, are they tolerating standard medical therapy? Are they hypotensive? Are they only able to tolerate minimal meds? Have you seen that their creatine continues to rise? Or are they having poor diuresis with the rise in diuretics?”

All these questions are useful, she said, as you determine whether you should titrate medication yourself or refer the patient to an advanced heart failure specialist.
 

Understand when to stick with guideline-directed medical therapy

Dr. Williams said another question often arises: “If your patient’s EF recovers, should you stop guideline-directed medical therapy [GDMT]?” She highlighted a TRED-HF study that evaluated patients who had recovered from dilated, nonischemic cardiomyopathy and were receiving GDMT. “They withdrew GDMT for half of the patients and looked at their echoes 6 months later. They found that 40% of the patients relapsed. Their EFs went below 40% again. Stopping medications is not the best idea for most of these patients.”

However, she said, there are scenarios in which GDMT may be withdrawn, such as for patients with tachycardia-induced cardiomyopathies whose EF recovers after ablation, those whose EF recovers after alcoholic cardiomyopathy, and those who receive valve replacements. “We need to remember that a lot of the patients who develop stage C heart failure have risk factors. Even though their heart failure has recovered, they have risks that need to be treated, and you can use the same medications that you use for heart failure to control their risk. Therefore, you would not get into trouble by withdrawing their medications.”

She added: “If you’re unable to titrate GDMT because the blood pressure is too soft, the creatine continues to rise, or the patient just has a lot of heart failure symptoms, this is indicative that the patient is sicker than they may appear.” At this point, defer to a heart failure specialist, she said.
 

Consider ivabradine as an add-on when appropriate

In some cases, a heart rate of less than 70 bpm will not be achieved even with GDMT and maximum tolerated doses, Dr. Williams said. “If they’re in sinus, you can add on a medication called ivabradine, which was studied in the SHIFT study. This looked at patients with EF of less than 35% who had class 2-3 heart failure in sinus rhythm. They had to have a hospitalization within the last 12 months. The patients were randomized to either ivabradine or placebo. The primary outcome was [cardiovascular] death or heart failure hospitalization. They found that patients who had ivabradine had a decrease in heart failure hospitalization.”

The lesson, she said, is that “ivabradine is a great medication to add on to patients who are still tachycardic in sinus when you cannot titrate up the beta blocker.”

Dr. Williams reports no relevant financial relationships.

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

On the medication front, there are now “four pillars of survival” in the setting of heart failure with reduced ejection fraction (EF), a cardiologist told hospitalists recently at SHM Converge, the annual conference of the Society of Hospital Medicine.

The quartet of drugs are beta blockers, angiotensin receptor–neprilysin inhibitors, mineralocorticoid receptor antagonists, and the newest addition – sodium-glucose cotransporter 2 inhibitors.

“If we use all four of these medications, the absolute risk reduction [in mortality] is 25% over a 2-year period,” said cardiologist Celeste T. Williams, MD, of Henry Ford Hospital, Detroit. “So it is very important that we use these medications,” she said.

But managing the medications, she said, can be challenging. Dr. Williams offered these tips about the use of medication in heart failure.
 

Beta blockers are crucial players

“Beta blockers save lives,” Dr. Williams said, “but there’s always a debate about how much we should titrate beta blockers.”

How can you determine the proper titration? Focus on heart rates, she recommended. “We know that higher heart rates in heart failure patients are associated with worse outcomes. There was subgroup analysis in the BEAUTIFUL study that looked at 5,300 patients with EF less than 40% who had CAD [coronary artery disease]. They found that patients with heart rates greater than 70 had a 34% increased risk of cardiovascular death and a 53% increased risk of heart failure hospitalization compared to heart rates less than 70.”

Focus on getting your patient’s heart rate lower than 70 while maintaining their blood pressure, she said.

“Another question we have is, ‘When these patients come into hospitals, what should we do with the beta blocker? Should we continue it? Should we stop it?’ If you can, you always want to continue the beta blocker or the ACE [angiotensin-converting enzyme] inhibitor, because studies have shown us that the likelihood for patients to be on these medications 90 days later is dismal,” she said. “But you also need to look at the patient. If the patient is in cardiogenic shock, their beta blocker should be stopped.”
 

Consider multiple factors when titrating various medications

“In the hospital, we always will look at hemodynamic compromise in the patient. Is the patient in cardiogenic shock?” Dr. Williams said. “We also must think about compliance concerns. Are the patients even taking their medication? And if they are taking their medications, are they tolerating standard medical therapy? Are they hypotensive? Are they only able to tolerate minimal meds? Have you seen that their creatine continues to rise? Or are they having poor diuresis with the rise in diuretics?”

All these questions are useful, she said, as you determine whether you should titrate medication yourself or refer the patient to an advanced heart failure specialist.
 

Understand when to stick with guideline-directed medical therapy

Dr. Williams said another question often arises: “If your patient’s EF recovers, should you stop guideline-directed medical therapy [GDMT]?” She highlighted a TRED-HF study that evaluated patients who had recovered from dilated, nonischemic cardiomyopathy and were receiving GDMT. “They withdrew GDMT for half of the patients and looked at their echoes 6 months later. They found that 40% of the patients relapsed. Their EFs went below 40% again. Stopping medications is not the best idea for most of these patients.”

However, she said, there are scenarios in which GDMT may be withdrawn, such as for patients with tachycardia-induced cardiomyopathies whose EF recovers after ablation, those whose EF recovers after alcoholic cardiomyopathy, and those who receive valve replacements. “We need to remember that a lot of the patients who develop stage C heart failure have risk factors. Even though their heart failure has recovered, they have risks that need to be treated, and you can use the same medications that you use for heart failure to control their risk. Therefore, you would not get into trouble by withdrawing their medications.”

She added: “If you’re unable to titrate GDMT because the blood pressure is too soft, the creatine continues to rise, or the patient just has a lot of heart failure symptoms, this is indicative that the patient is sicker than they may appear.” At this point, defer to a heart failure specialist, she said.
 

Consider ivabradine as an add-on when appropriate

In some cases, a heart rate of less than 70 bpm will not be achieved even with GDMT and maximum tolerated doses, Dr. Williams said. “If they’re in sinus, you can add on a medication called ivabradine, which was studied in the SHIFT study. This looked at patients with EF of less than 35% who had class 2-3 heart failure in sinus rhythm. They had to have a hospitalization within the last 12 months. The patients were randomized to either ivabradine or placebo. The primary outcome was [cardiovascular] death or heart failure hospitalization. They found that patients who had ivabradine had a decrease in heart failure hospitalization.”

The lesson, she said, is that “ivabradine is a great medication to add on to patients who are still tachycardic in sinus when you cannot titrate up the beta blocker.”

Dr. Williams reports no relevant financial relationships.

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

On May 25, Jena Hausmann, CEO of Children’s Hospital Colorado, Aurora, declared a state of emergency in youth mental health in response to an astronomical increase in pediatric mental health cases, including suicide, which has overwhelmed the institution.

From April 2019 to April 2021, the demand for pediatric behavioral health treatment at the hospital system increased by 90%. In Colorado, suicide is now the number one cause of death among youth and occurs in children as young as 10 years of age.

“Now we are seeing our pediatric emergency departments and our inpatient units overrun with kids attempting suicide and suffering from other forms of major mental health illness,” Dr. Hausmann said in a press release.

“We had to draw attention to what we’re seeing in our hospital and our community on an everyday basis – an unprecedented number of suicidal children who need acute treatment for behavioral health problems – and when I say ‘unprecedented,’ I’m serious – I’ve been in pediatrics for two decades and have never seen anything like this before,” David Brumbaugh, MD, a pediatric gastroenterologist and chief medical officer for Children’s Colorado, told this news organization.

Christine Crawford, MD, associate medical director of the National Alliance on Mental Illness, stated in an interview that she “commends the CEO of the hospital for making this announcement, because it is outrageous to see what is happening with more and more children with significant psychiatric symptoms who are not getting adequate care.”

Jenna Glover, PhD, child psychologist and director of psychology training at Children’s Hospital, said that during the past decade, there has been a steady increase in depression, anxiety, and suicide among youth in Colorado. Suicide, she added, is now the number one cause of death in youth, “so we were already in a state of crisis.” She added that COVID-19 was “the straw that broke the camel’s back.”

“In January to April of this year, behavioral health ED visits to Children’s Hospital were 72% higher than they were 2 years ago at this time,” she said. “Colorado Springs had a 145% increase for ED behavioral health visits during the first 4 months of 2021, compared to the first 4 months of 2020.”
 

COVID’s impact

Other problems that have been “skyrocketing” in youth are self-harm, substance use, and eating disorders. Younger children are experiencing an increase in behavioral problems, including developmental regression, such as tantrums, and problems with sleeping, toileting, and eating, Dr. Glover noted.

The youth mental health crisis has mushroomed, although social distancing requirements are now beginning to ease and we are in the “home stretch of the pandemic,” Dr. Brumbaugh said.

One possible reason “is that we took kids out of their normal routines, social circles, friendships, etc., for 12 months, and that was the limit of their physiological or mental resistance, and they got to the end of their rope,” he speculated.

Dr. Glover said, “Kids are burned out, and although they’re asking to return to their life, they don’t feel they have the resources. They feel so behind; they don’t know how to catch up.”

Dr. Brumbaugh said that there are not enough child psychiatrists to provide outpatient services or enough inpatient beds for children in crisis.

“This is an unacceptable situation. We would never allow a child with leukemia or appendicitis to go several weeks without treatment,” he said.

Community donors have come forward, enabling an anticipated 50% increase in Children’s Hospital’s mental health outpatient, inpatient, and day services by March 2022.

“On a hospital level, we are continuing to do things to expand access to care, like opening units that provide different levels of care for patients with psychiatric problems, as well as expanding into areas that are more rural,” Dr. Glover said.

However, the “blueprint is not in action yet, and a lot of money still needs to be allocated. A workforce has to be created, because there are not enough clinicians to fill these roles,” she added.
 

Chronic underfunding

Dr. Brumbaugh said Colorado has always had a “relatively underfunded behavioral health system for kids.” A 2021 report by Mental Health America ranks Colorado among the lowest states in the country in terms of overall pediatric behavioral health funding.

However, Dr. Glover noted that Colorado is “not exceptional.” The increased vulnerability to youth mental illness and suicide is characteristic of other mountain states, which have larger rural areas, less access to care, and increased access to guns, she said.

Mass shootings may have amped up stress levels. “For some kids, this is happening in their schools or towns, and they feel traumatized and unsafe,” Dr. Glover added.

Dr. Crawford, who is an assistant professor of psychiatry at Boston University, also pointed out that the mental health crisis in youth is not unique to Colorado.

“Throughout the country, we’ve seen these colliding pandemics – inadequate mental health resources for children and COVID-19, which exacerbated the existing mental health crisis,” she said.

“The pandemic led to an increase in telehealth services, making individual and group psychotherapy available to kids in areas that never had access to these before, which is a ‘silver lining’ of the pandemic,” Dr. Glover said.

Dr. Crawford is “encouraged that we are having more conversations about pediatric mental health, because the pandemic amplified what was already going on and made it impossible to ignore.”
 

Screening is essential

Screening for mental health problems should be at the top of the mind of pediatricians and other clinicians who work with children, Dr. Glover said.

“Pediatricians are in the best place to catch potentially suicidal kids, because they are more likely to see these kids than therapists,” she noted.

She suggested using a rapid screen for depression, such as the Patient Health Questionnaire-9 (PHQ-9) modified for adolescents. Parents can also fill out a PHQ-9 for younger children and even for themselves.

“Depression, anxiety, and suicidality affect the whole family, so screening for these conditions in adults will benefit the children too,” she said. Teachers should also “be aware of what depression and anxiety symptoms look like in kids, because sometimes they can manifest more as irritability,” Dr. Glover added.

Policymakers and insurers need to prioritize pediatric mental health when determining allocation of health care, said Dr. Crawford.

“Financial incentives should be provided for hospitals to want to reserve beds for psychiatric patients, and in the outpatient setting, we also need to look at the payment structure of psychiatric visits,” she added.

Many psychiatrists do not want to accept insurance because of the increased bureaucracy and low reimbursement rates of insurance companies, and families cannot afford to pay out of pocket, “so we really need to look at the insurance issue at a policy level,” Dr. Crawford said.

Dr. Brumbaugh, Dr. Glover, and Dr. Crawford have disclosed no relevant financial relationships.

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

On May 25, Jena Hausmann, CEO of Children’s Hospital Colorado, Aurora, declared a state of emergency in youth mental health in response to an astronomical increase in pediatric mental health cases, including suicide, which has overwhelmed the institution.

From April 2019 to April 2021, the demand for pediatric behavioral health treatment at the hospital system increased by 90%. In Colorado, suicide is now the number one cause of death among youth and occurs in children as young as 10 years of age.

“Now we are seeing our pediatric emergency departments and our inpatient units overrun with kids attempting suicide and suffering from other forms of major mental health illness,” Dr. Hausmann said in a press release.

“We had to draw attention to what we’re seeing in our hospital and our community on an everyday basis – an unprecedented number of suicidal children who need acute treatment for behavioral health problems – and when I say ‘unprecedented,’ I’m serious – I’ve been in pediatrics for two decades and have never seen anything like this before,” David Brumbaugh, MD, a pediatric gastroenterologist and chief medical officer for Children’s Colorado, told this news organization.

Christine Crawford, MD, associate medical director of the National Alliance on Mental Illness, stated in an interview that she “commends the CEO of the hospital for making this announcement, because it is outrageous to see what is happening with more and more children with significant psychiatric symptoms who are not getting adequate care.”

Jenna Glover, PhD, child psychologist and director of psychology training at Children’s Hospital, said that during the past decade, there has been a steady increase in depression, anxiety, and suicide among youth in Colorado. Suicide, she added, is now the number one cause of death in youth, “so we were already in a state of crisis.” She added that COVID-19 was “the straw that broke the camel’s back.”

“In January to April of this year, behavioral health ED visits to Children’s Hospital were 72% higher than they were 2 years ago at this time,” she said. “Colorado Springs had a 145% increase for ED behavioral health visits during the first 4 months of 2021, compared to the first 4 months of 2020.”
 

COVID’s impact

Other problems that have been “skyrocketing” in youth are self-harm, substance use, and eating disorders. Younger children are experiencing an increase in behavioral problems, including developmental regression, such as tantrums, and problems with sleeping, toileting, and eating, Dr. Glover noted.

The youth mental health crisis has mushroomed, although social distancing requirements are now beginning to ease and we are in the “home stretch of the pandemic,” Dr. Brumbaugh said.

One possible reason “is that we took kids out of their normal routines, social circles, friendships, etc., for 12 months, and that was the limit of their physiological or mental resistance, and they got to the end of their rope,” he speculated.

Dr. Glover said, “Kids are burned out, and although they’re asking to return to their life, they don’t feel they have the resources. They feel so behind; they don’t know how to catch up.”

Dr. Brumbaugh said that there are not enough child psychiatrists to provide outpatient services or enough inpatient beds for children in crisis.

“This is an unacceptable situation. We would never allow a child with leukemia or appendicitis to go several weeks without treatment,” he said.

Community donors have come forward, enabling an anticipated 50% increase in Children’s Hospital’s mental health outpatient, inpatient, and day services by March 2022.

“On a hospital level, we are continuing to do things to expand access to care, like opening units that provide different levels of care for patients with psychiatric problems, as well as expanding into areas that are more rural,” Dr. Glover said.

However, the “blueprint is not in action yet, and a lot of money still needs to be allocated. A workforce has to be created, because there are not enough clinicians to fill these roles,” she added.
 

Chronic underfunding

Dr. Brumbaugh said Colorado has always had a “relatively underfunded behavioral health system for kids.” A 2021 report by Mental Health America ranks Colorado among the lowest states in the country in terms of overall pediatric behavioral health funding.

However, Dr. Glover noted that Colorado is “not exceptional.” The increased vulnerability to youth mental illness and suicide is characteristic of other mountain states, which have larger rural areas, less access to care, and increased access to guns, she said.

Mass shootings may have amped up stress levels. “For some kids, this is happening in their schools or towns, and they feel traumatized and unsafe,” Dr. Glover added.

Dr. Crawford, who is an assistant professor of psychiatry at Boston University, also pointed out that the mental health crisis in youth is not unique to Colorado.

“Throughout the country, we’ve seen these colliding pandemics – inadequate mental health resources for children and COVID-19, which exacerbated the existing mental health crisis,” she said.

“The pandemic led to an increase in telehealth services, making individual and group psychotherapy available to kids in areas that never had access to these before, which is a ‘silver lining’ of the pandemic,” Dr. Glover said.

Dr. Crawford is “encouraged that we are having more conversations about pediatric mental health, because the pandemic amplified what was already going on and made it impossible to ignore.”
 

Screening is essential

Screening for mental health problems should be at the top of the mind of pediatricians and other clinicians who work with children, Dr. Glover said.

“Pediatricians are in the best place to catch potentially suicidal kids, because they are more likely to see these kids than therapists,” she noted.

She suggested using a rapid screen for depression, such as the Patient Health Questionnaire-9 (PHQ-9) modified for adolescents. Parents can also fill out a PHQ-9 for younger children and even for themselves.

“Depression, anxiety, and suicidality affect the whole family, so screening for these conditions in adults will benefit the children too,” she said. Teachers should also “be aware of what depression and anxiety symptoms look like in kids, because sometimes they can manifest more as irritability,” Dr. Glover added.

Policymakers and insurers need to prioritize pediatric mental health when determining allocation of health care, said Dr. Crawford.

“Financial incentives should be provided for hospitals to want to reserve beds for psychiatric patients, and in the outpatient setting, we also need to look at the payment structure of psychiatric visits,” she added.

Many psychiatrists do not want to accept insurance because of the increased bureaucracy and low reimbursement rates of insurance companies, and families cannot afford to pay out of pocket, “so we really need to look at the insurance issue at a policy level,” Dr. Crawford said.

Dr. Brumbaugh, Dr. Glover, and Dr. Crawford have disclosed no relevant financial relationships.

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

On May 25, Jena Hausmann, CEO of Children’s Hospital Colorado, Aurora, declared a state of emergency in youth mental health in response to an astronomical increase in pediatric mental health cases, including suicide, which has overwhelmed the institution.

From April 2019 to April 2021, the demand for pediatric behavioral health treatment at the hospital system increased by 90%. In Colorado, suicide is now the number one cause of death among youth and occurs in children as young as 10 years of age.

“Now we are seeing our pediatric emergency departments and our inpatient units overrun with kids attempting suicide and suffering from other forms of major mental health illness,” Dr. Hausmann said in a press release.

“We had to draw attention to what we’re seeing in our hospital and our community on an everyday basis – an unprecedented number of suicidal children who need acute treatment for behavioral health problems – and when I say ‘unprecedented,’ I’m serious – I’ve been in pediatrics for two decades and have never seen anything like this before,” David Brumbaugh, MD, a pediatric gastroenterologist and chief medical officer for Children’s Colorado, told this news organization.

Christine Crawford, MD, associate medical director of the National Alliance on Mental Illness, stated in an interview that she “commends the CEO of the hospital for making this announcement, because it is outrageous to see what is happening with more and more children with significant psychiatric symptoms who are not getting adequate care.”

Jenna Glover, PhD, child psychologist and director of psychology training at Children’s Hospital, said that during the past decade, there has been a steady increase in depression, anxiety, and suicide among youth in Colorado. Suicide, she added, is now the number one cause of death in youth, “so we were already in a state of crisis.” She added that COVID-19 was “the straw that broke the camel’s back.”

“In January to April of this year, behavioral health ED visits to Children’s Hospital were 72% higher than they were 2 years ago at this time,” she said. “Colorado Springs had a 145% increase for ED behavioral health visits during the first 4 months of 2021, compared to the first 4 months of 2020.”
 

COVID’s impact

Other problems that have been “skyrocketing” in youth are self-harm, substance use, and eating disorders. Younger children are experiencing an increase in behavioral problems, including developmental regression, such as tantrums, and problems with sleeping, toileting, and eating, Dr. Glover noted.

The youth mental health crisis has mushroomed, although social distancing requirements are now beginning to ease and we are in the “home stretch of the pandemic,” Dr. Brumbaugh said.

One possible reason “is that we took kids out of their normal routines, social circles, friendships, etc., for 12 months, and that was the limit of their physiological or mental resistance, and they got to the end of their rope,” he speculated.

Dr. Glover said, “Kids are burned out, and although they’re asking to return to their life, they don’t feel they have the resources. They feel so behind; they don’t know how to catch up.”

Dr. Brumbaugh said that there are not enough child psychiatrists to provide outpatient services or enough inpatient beds for children in crisis.

“This is an unacceptable situation. We would never allow a child with leukemia or appendicitis to go several weeks without treatment,” he said.

Community donors have come forward, enabling an anticipated 50% increase in Children’s Hospital’s mental health outpatient, inpatient, and day services by March 2022.

“On a hospital level, we are continuing to do things to expand access to care, like opening units that provide different levels of care for patients with psychiatric problems, as well as expanding into areas that are more rural,” Dr. Glover said.

However, the “blueprint is not in action yet, and a lot of money still needs to be allocated. A workforce has to be created, because there are not enough clinicians to fill these roles,” she added.
 

Chronic underfunding

Dr. Brumbaugh said Colorado has always had a “relatively underfunded behavioral health system for kids.” A 2021 report by Mental Health America ranks Colorado among the lowest states in the country in terms of overall pediatric behavioral health funding.

However, Dr. Glover noted that Colorado is “not exceptional.” The increased vulnerability to youth mental illness and suicide is characteristic of other mountain states, which have larger rural areas, less access to care, and increased access to guns, she said.

Mass shootings may have amped up stress levels. “For some kids, this is happening in their schools or towns, and they feel traumatized and unsafe,” Dr. Glover added.

Dr. Crawford, who is an assistant professor of psychiatry at Boston University, also pointed out that the mental health crisis in youth is not unique to Colorado.

“Throughout the country, we’ve seen these colliding pandemics – inadequate mental health resources for children and COVID-19, which exacerbated the existing mental health crisis,” she said.

“The pandemic led to an increase in telehealth services, making individual and group psychotherapy available to kids in areas that never had access to these before, which is a ‘silver lining’ of the pandemic,” Dr. Glover said.

Dr. Crawford is “encouraged that we are having more conversations about pediatric mental health, because the pandemic amplified what was already going on and made it impossible to ignore.”
 

Screening is essential

Screening for mental health problems should be at the top of the mind of pediatricians and other clinicians who work with children, Dr. Glover said.

“Pediatricians are in the best place to catch potentially suicidal kids, because they are more likely to see these kids than therapists,” she noted.

She suggested using a rapid screen for depression, such as the Patient Health Questionnaire-9 (PHQ-9) modified for adolescents. Parents can also fill out a PHQ-9 for younger children and even for themselves.

“Depression, anxiety, and suicidality affect the whole family, so screening for these conditions in adults will benefit the children too,” she said. Teachers should also “be aware of what depression and anxiety symptoms look like in kids, because sometimes they can manifest more as irritability,” Dr. Glover added.

Policymakers and insurers need to prioritize pediatric mental health when determining allocation of health care, said Dr. Crawford.

“Financial incentives should be provided for hospitals to want to reserve beds for psychiatric patients, and in the outpatient setting, we also need to look at the payment structure of psychiatric visits,” she added.

Many psychiatrists do not want to accept insurance because of the increased bureaucracy and low reimbursement rates of insurance companies, and families cannot afford to pay out of pocket, “so we really need to look at the insurance issue at a policy level,” Dr. Crawford said.

Dr. Brumbaugh, Dr. Glover, and Dr. Crawford have disclosed no relevant financial relationships.

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

Communication and relationships cannot be taken for granted, particularly in the physician-patient relationship, where life-altering diagnoses may be given. With one diagnosis, someone’s life may be changed, and both physicians and patients need to be cognizant of the importance of a strong relationship and clear communication.

In the current US health care system, both physicians and patients often are not getting their needs met, and studies that include factors of race, ethnicity, and socioeconomic status suggest that physician-patient relationship barriers contribute to racial disparities in health care.^1,2 Although patient-centered care is a widely recognized and upheld model, relationship-centered care between physician and patient involves focusing on the patient and the physician-patient relationship through recognizing personhood, affect (being empathic), and reciprocal influence.^3,4 Although it is not necessarily intuitive because it can appear to be yet another task for busy physicians, relationship-centered care improves health care delivery for both physicians and patients through decreased physician burnout, reduced medical errors, and better patient outcomes and satisfaction.^5,6

Every physician, patient, and physician-patient relationship is different; unlike the standard questions directed at a routine patient history focused on gathering data, there is no one-size-fits-all relationship-centered conversation.^7-10 As with any successful interaction between 2 people, there is a certain amount of necessary self-awareness (Table 1)¹¹ that allows for improvisation and appropriate responsiveness to what is seen, heard, and felt. Rather than attending solely to disease states, the focus of relationship-centered care is on patients, interpersonal interaction, and promoting health and well-being.¹⁵

This review summarizes the existing literature on relationship-centered care, introduces the use of metacognition (Table 1), and suggests creating simple habits to promote such care. The following databases were searched from inception through November 23, 2020, using the term relationship-centered care: MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), Scopus, Web of Science Core Collection, CINAHL Complete (EBSCO), Academic Search Premier (EBSCOhost), and ERIC (ProQuest). A total of 1772 records were retrieved through searches, and after deduplication of 1116 studies, 350 records were screened through a 2-part process. Articles were first screened by title and abstract for relevance to the relationship between physician and patient, with 185 studies deemed irrelevant (eg, pertaining to the relationship of veterinarian to animal). The remaining 165 studies were assessed for eligibility, with 69 further studies excluded for various reasons. The screening process resulted in 96 articles considered in this review.

Definitions/key terms, as used in this article, are listed in Table 1.

Background of Relationship-Centered Care

Given time constraints, the diagnosis and treatment of medical problems often are the focus of physicians. Although proper medical diagnosis and treatment are important, and their delivery is made possible by the physician having the appropriate knowledge, a physician-patient relationship that focuses solely on disease without acknowledging the patient creates a system that ultimately neglects both patients and physicians.¹⁵ This prevailing physician-patient relationship paradigm is suboptimal, and a proposed remedy is relationship-centered care, which focuses on relationships among the human beings in health care interactions.³ Relationship-centered care has 4 principles: (1) the personhood of each party must be recognized, (2) emotion is part of relationships, (3) relationships are reciprocal and not just one way, and (4) creating these types of relationships is morally valuable³ and beneficial to patient care.¹⁶

Assessment of the Need for Relationship-Centered Care

Relationship-centered care has been studied in physician-patient interactions in various health care settings.^17-23 For at least 2 decades, relationship-centered care has been set forth as a model,^4,24,25 but there are challenges. Physicians tend to overrate or underrate their communication skills in patient interactions.^26,27 A given physician’s preferences often still seem to supersede those of the patient.^3,28,29 The impetus to develop relationship-centered care skills generally needs to be internally driven,^4,30 as, ultimately, physicians and patients have varying needs.^4,31 However, providing physicians with a potential structure is helpful.³²

A Solution: Metacognition in the Physician-Patient Interaction

Metacognition is important to integrating basic science knowledge into medical learning and practice,^33,34 and it is no less important in translating interpersonal knowledge to the physician-patient interaction. Decreased metacognitive effort³⁵ may underpin the decline in empathy seen with increasing medical training.^36,37 Understanding how metacognitive practices foster relationship-centered care is important for teaching, developing, and maintaining that care.

Metacognition is already embedded in the fabric of the physician-patient interaction.^33,34 The complex interplay of the physician-patient interview, patient examination, and integration of physical as well as ancillary data requires higher-order thinking and the ability to parse out that thinking successfully. As a concrete example, coming to a diagnosis requires thinking about what has been presented during the physician-patient interaction and considering what supports and suggests the disease while a list of potential differential diagnosis alternatives is being generated. Physicians are trained to apply this clinical reasoning approach to their patient care.

Conversely, although communication skills are a key component of doctoring,³⁸ both between physician and patient as well as among other colleagues and staff, many physicians have never received formal training in communication skills,^26,32,39 though it is now an integral part of medical school curricula.⁴⁰ When such training is mandatory, less than 1% of physicians continue to believe that there was no benefit, even from a single 8-hour communications skills training session.⁴¹ Communication cannot be taught comprehensively in 8 hours; thus, the benefit of such training may be the end result of metacognition and increased self-awareness (Table 1).^42,43

Building Relationship-Centered Care Through Metacognitive Attention

Metacognition as manifested by such self-awareness can build relationship-centered care.⁴ Self-awareness can be taught through mentorship or role models.⁴⁴ Journaling,⁴⁰ meditation, and appreciation of beauty and the arts⁴⁵ can contribute, as well as more formal training programs,^32,38,42 as offered by the Academy of Communication in Healthcare. Creating opportunities for patient empowerment also supports relationship-centered care, as does applying knowledge of implicit bias.⁴⁶

Even without formal training, relationship-centered care can be built through attention to cues⁹—visual (eg, sitting down, other body language),^47,48 auditory (eg, knocking, language, tone, conversational flow),^48,49 and emotional (eg, clinical empathy, emotional intelligence)(Table 2). Such attention is familiar to everyone, not just physicians or patients, through interactions outside of health care; inattention may be due to the hidden curriculum or culture of medicine⁴⁰ as well as real-time changes, such as the introduction of the electronic health record.⁵¹ Inattention to these cues also may be a result of context-specific knowledge, in which a physician’s real-life communication skills are not applied to the unique context of patient care.

Metacognitive Attention Can Generate Habit

Taking metacognition a step further, these small interventions can become habit^11,14,39 through self-awareness, deliberate practice, and feedback.⁴³ Habit is generated by linking a given intervention to another defined cue. For example, placing a hand on a doorknob to enter an examination room can be the cue to generate a habit of entering with presence.¹⁴ Alternatively, before entering an examination room, taking 3 deep breaths can be the cue to trigger presence.¹⁴ Habits can be created in just 3 weeks,⁵⁷ and other proposed cues to generate habits toward relationship-centered care are listed in Table 2. By creating habit through metacognitive attention, relationship-centered care will become something that happens subconsciously without further burdening physicians with another task. Asking patients for permission to record video of an interaction also can create opportunities for self-awareness and self-evaluation through rewatching the video.⁵⁸

Final Thoughts

Physicians already have the tools to create relationship-centered care in physician-patient interactions. A critical mental shift is to develop habits and apply thinking patterns toward understanding and responding appropriately to patients of all ethnicities and their emotions in the physician-patient interaction. This shift is aided by metacognitive awareness (Table 1) and the development of useful habits (Table 2).

Communication and relationships cannot be taken for granted, particularly in the physician-patient relationship, where life-altering diagnoses may be given. With one diagnosis, someone’s life may be changed, and both physicians and patients need to be cognizant of the importance of a strong relationship and clear communication.

In the current US health care system, both physicians and patients often are not getting their needs met, and studies that include factors of race, ethnicity, and socioeconomic status suggest that physician-patient relationship barriers contribute to racial disparities in health care.^1,2 Although patient-centered care is a widely recognized and upheld model, relationship-centered care between physician and patient involves focusing on the patient and the physician-patient relationship through recognizing personhood, affect (being empathic), and reciprocal influence.^3,4 Although it is not necessarily intuitive because it can appear to be yet another task for busy physicians, relationship-centered care improves health care delivery for both physicians and patients through decreased physician burnout, reduced medical errors, and better patient outcomes and satisfaction.^5,6

Every physician, patient, and physician-patient relationship is different; unlike the standard questions directed at a routine patient history focused on gathering data, there is no one-size-fits-all relationship-centered conversation.^7-10 As with any successful interaction between 2 people, there is a certain amount of necessary self-awareness (Table 1)¹¹ that allows for improvisation and appropriate responsiveness to what is seen, heard, and felt. Rather than attending solely to disease states, the focus of relationship-centered care is on patients, interpersonal interaction, and promoting health and well-being.¹⁵

This review summarizes the existing literature on relationship-centered care, introduces the use of metacognition (Table 1), and suggests creating simple habits to promote such care. The following databases were searched from inception through November 23, 2020, using the term relationship-centered care: MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), Scopus, Web of Science Core Collection, CINAHL Complete (EBSCO), Academic Search Premier (EBSCOhost), and ERIC (ProQuest). A total of 1772 records were retrieved through searches, and after deduplication of 1116 studies, 350 records were screened through a 2-part process. Articles were first screened by title and abstract for relevance to the relationship between physician and patient, with 185 studies deemed irrelevant (eg, pertaining to the relationship of veterinarian to animal). The remaining 165 studies were assessed for eligibility, with 69 further studies excluded for various reasons. The screening process resulted in 96 articles considered in this review.

Definitions/key terms, as used in this article, are listed in Table 1.

Background of Relationship-Centered Care

Given time constraints, the diagnosis and treatment of medical problems often are the focus of physicians. Although proper medical diagnosis and treatment are important, and their delivery is made possible by the physician having the appropriate knowledge, a physician-patient relationship that focuses solely on disease without acknowledging the patient creates a system that ultimately neglects both patients and physicians.¹⁵ This prevailing physician-patient relationship paradigm is suboptimal, and a proposed remedy is relationship-centered care, which focuses on relationships among the human beings in health care interactions.³ Relationship-centered care has 4 principles: (1) the personhood of each party must be recognized, (2) emotion is part of relationships, (3) relationships are reciprocal and not just one way, and (4) creating these types of relationships is morally valuable³ and beneficial to patient care.¹⁶

Assessment of the Need for Relationship-Centered Care

Relationship-centered care has been studied in physician-patient interactions in various health care settings.^17-23 For at least 2 decades, relationship-centered care has been set forth as a model,^4,24,25 but there are challenges. Physicians tend to overrate or underrate their communication skills in patient interactions.^26,27 A given physician’s preferences often still seem to supersede those of the patient.^3,28,29 The impetus to develop relationship-centered care skills generally needs to be internally driven,^4,30 as, ultimately, physicians and patients have varying needs.^4,31 However, providing physicians with a potential structure is helpful.³²

A Solution: Metacognition in the Physician-Patient Interaction

Metacognition is important to integrating basic science knowledge into medical learning and practice,^33,34 and it is no less important in translating interpersonal knowledge to the physician-patient interaction. Decreased metacognitive effort³⁵ may underpin the decline in empathy seen with increasing medical training.^36,37 Understanding how metacognitive practices foster relationship-centered care is important for teaching, developing, and maintaining that care.

Metacognition is already embedded in the fabric of the physician-patient interaction.^33,34 The complex interplay of the physician-patient interview, patient examination, and integration of physical as well as ancillary data requires higher-order thinking and the ability to parse out that thinking successfully. As a concrete example, coming to a diagnosis requires thinking about what has been presented during the physician-patient interaction and considering what supports and suggests the disease while a list of potential differential diagnosis alternatives is being generated. Physicians are trained to apply this clinical reasoning approach to their patient care.

Conversely, although communication skills are a key component of doctoring,³⁸ both between physician and patient as well as among other colleagues and staff, many physicians have never received formal training in communication skills,^26,32,39 though it is now an integral part of medical school curricula.⁴⁰ When such training is mandatory, less than 1% of physicians continue to believe that there was no benefit, even from a single 8-hour communications skills training session.⁴¹ Communication cannot be taught comprehensively in 8 hours; thus, the benefit of such training may be the end result of metacognition and increased self-awareness (Table 1).^42,43

Building Relationship-Centered Care Through Metacognitive Attention

Metacognition as manifested by such self-awareness can build relationship-centered care.⁴ Self-awareness can be taught through mentorship or role models.⁴⁴ Journaling,⁴⁰ meditation, and appreciation of beauty and the arts⁴⁵ can contribute, as well as more formal training programs,^32,38,42 as offered by the Academy of Communication in Healthcare. Creating opportunities for patient empowerment also supports relationship-centered care, as does applying knowledge of implicit bias.⁴⁶

Even without formal training, relationship-centered care can be built through attention to cues⁹—visual (eg, sitting down, other body language),^47,48 auditory (eg, knocking, language, tone, conversational flow),^48,49 and emotional (eg, clinical empathy, emotional intelligence)(Table 2). Such attention is familiar to everyone, not just physicians or patients, through interactions outside of health care; inattention may be due to the hidden curriculum or culture of medicine⁴⁰ as well as real-time changes, such as the introduction of the electronic health record.⁵¹ Inattention to these cues also may be a result of context-specific knowledge, in which a physician’s real-life communication skills are not applied to the unique context of patient care.

Metacognitive Attention Can Generate Habit

Taking metacognition a step further, these small interventions can become habit^11,14,39 through self-awareness, deliberate practice, and feedback.⁴³ Habit is generated by linking a given intervention to another defined cue. For example, placing a hand on a doorknob to enter an examination room can be the cue to generate a habit of entering with presence.¹⁴ Alternatively, before entering an examination room, taking 3 deep breaths can be the cue to trigger presence.¹⁴ Habits can be created in just 3 weeks,⁵⁷ and other proposed cues to generate habits toward relationship-centered care are listed in Table 2. By creating habit through metacognitive attention, relationship-centered care will become something that happens subconsciously without further burdening physicians with another task. Asking patients for permission to record video of an interaction also can create opportunities for self-awareness and self-evaluation through rewatching the video.⁵⁸

Final Thoughts

Physicians already have the tools to create relationship-centered care in physician-patient interactions. A critical mental shift is to develop habits and apply thinking patterns toward understanding and responding appropriately to patients of all ethnicities and their emotions in the physician-patient interaction. This shift is aided by metacognitive awareness (Table 1) and the development of useful habits (Table 2).

Communication and relationships cannot be taken for granted, particularly in the physician-patient relationship, where life-altering diagnoses may be given. With one diagnosis, someone’s life may be changed, and both physicians and patients need to be cognizant of the importance of a strong relationship and clear communication.

In the current US health care system, both physicians and patients often are not getting their needs met, and studies that include factors of race, ethnicity, and socioeconomic status suggest that physician-patient relationship barriers contribute to racial disparities in health care.^1,2 Although patient-centered care is a widely recognized and upheld model, relationship-centered care between physician and patient involves focusing on the patient and the physician-patient relationship through recognizing personhood, affect (being empathic), and reciprocal influence.^3,4 Although it is not necessarily intuitive because it can appear to be yet another task for busy physicians, relationship-centered care improves health care delivery for both physicians and patients through decreased physician burnout, reduced medical errors, and better patient outcomes and satisfaction.^5,6

Every physician, patient, and physician-patient relationship is different; unlike the standard questions directed at a routine patient history focused on gathering data, there is no one-size-fits-all relationship-centered conversation.^7-10 As with any successful interaction between 2 people, there is a certain amount of necessary self-awareness (Table 1)¹¹ that allows for improvisation and appropriate responsiveness to what is seen, heard, and felt. Rather than attending solely to disease states, the focus of relationship-centered care is on patients, interpersonal interaction, and promoting health and well-being.¹⁵

This review summarizes the existing literature on relationship-centered care, introduces the use of metacognition (Table 1), and suggests creating simple habits to promote such care. The following databases were searched from inception through November 23, 2020, using the term relationship-centered care: MEDLINE (Ovid), EMBASE (Ovid), APA PsycInfo (Ovid), Scopus, Web of Science Core Collection, CINAHL Complete (EBSCO), Academic Search Premier (EBSCOhost), and ERIC (ProQuest). A total of 1772 records were retrieved through searches, and after deduplication of 1116 studies, 350 records were screened through a 2-part process. Articles were first screened by title and abstract for relevance to the relationship between physician and patient, with 185 studies deemed irrelevant (eg, pertaining to the relationship of veterinarian to animal). The remaining 165 studies were assessed for eligibility, with 69 further studies excluded for various reasons. The screening process resulted in 96 articles considered in this review.

Definitions/key terms, as used in this article, are listed in Table 1.

Background of Relationship-Centered Care

Given time constraints, the diagnosis and treatment of medical problems often are the focus of physicians. Although proper medical diagnosis and treatment are important, and their delivery is made possible by the physician having the appropriate knowledge, a physician-patient relationship that focuses solely on disease without acknowledging the patient creates a system that ultimately neglects both patients and physicians.¹⁵ This prevailing physician-patient relationship paradigm is suboptimal, and a proposed remedy is relationship-centered care, which focuses on relationships among the human beings in health care interactions.³ Relationship-centered care has 4 principles: (1) the personhood of each party must be recognized, (2) emotion is part of relationships, (3) relationships are reciprocal and not just one way, and (4) creating these types of relationships is morally valuable³ and beneficial to patient care.¹⁶

Assessment of the Need for Relationship-Centered Care

Relationship-centered care has been studied in physician-patient interactions in various health care settings.^17-23 For at least 2 decades, relationship-centered care has been set forth as a model,^4,24,25 but there are challenges. Physicians tend to overrate or underrate their communication skills in patient interactions.^26,27 A given physician’s preferences often still seem to supersede those of the patient.^3,28,29 The impetus to develop relationship-centered care skills generally needs to be internally driven,^4,30 as, ultimately, physicians and patients have varying needs.^4,31 However, providing physicians with a potential structure is helpful.³²

A Solution: Metacognition in the Physician-Patient Interaction

Metacognition is important to integrating basic science knowledge into medical learning and practice,^33,34 and it is no less important in translating interpersonal knowledge to the physician-patient interaction. Decreased metacognitive effort³⁵ may underpin the decline in empathy seen with increasing medical training.^36,37 Understanding how metacognitive practices foster relationship-centered care is important for teaching, developing, and maintaining that care.

Metacognition is already embedded in the fabric of the physician-patient interaction.^33,34 The complex interplay of the physician-patient interview, patient examination, and integration of physical as well as ancillary data requires higher-order thinking and the ability to parse out that thinking successfully. As a concrete example, coming to a diagnosis requires thinking about what has been presented during the physician-patient interaction and considering what supports and suggests the disease while a list of potential differential diagnosis alternatives is being generated. Physicians are trained to apply this clinical reasoning approach to their patient care.

Conversely, although communication skills are a key component of doctoring,³⁸ both between physician and patient as well as among other colleagues and staff, many physicians have never received formal training in communication skills,^26,32,39 though it is now an integral part of medical school curricula.⁴⁰ When such training is mandatory, less than 1% of physicians continue to believe that there was no benefit, even from a single 8-hour communications skills training session.⁴¹ Communication cannot be taught comprehensively in 8 hours; thus, the benefit of such training may be the end result of metacognition and increased self-awareness (Table 1).^42,43

Building Relationship-Centered Care Through Metacognitive Attention

Metacognition as manifested by such self-awareness can build relationship-centered care.⁴ Self-awareness can be taught through mentorship or role models.⁴⁴ Journaling,⁴⁰ meditation, and appreciation of beauty and the arts⁴⁵ can contribute, as well as more formal training programs,^32,38,42 as offered by the Academy of Communication in Healthcare. Creating opportunities for patient empowerment also supports relationship-centered care, as does applying knowledge of implicit bias.⁴⁶

Even without formal training, relationship-centered care can be built through attention to cues⁹—visual (eg, sitting down, other body language),^47,48 auditory (eg, knocking, language, tone, conversational flow),^48,49 and emotional (eg, clinical empathy, emotional intelligence)(Table 2). Such attention is familiar to everyone, not just physicians or patients, through interactions outside of health care; inattention may be due to the hidden curriculum or culture of medicine⁴⁰ as well as real-time changes, such as the introduction of the electronic health record.⁵¹ Inattention to these cues also may be a result of context-specific knowledge, in which a physician’s real-life communication skills are not applied to the unique context of patient care.

Metacognitive Attention Can Generate Habit

Taking metacognition a step further, these small interventions can become habit^11,14,39 through self-awareness, deliberate practice, and feedback.⁴³ Habit is generated by linking a given intervention to another defined cue. For example, placing a hand on a doorknob to enter an examination room can be the cue to generate a habit of entering with presence.¹⁴ Alternatively, before entering an examination room, taking 3 deep breaths can be the cue to trigger presence.¹⁴ Habits can be created in just 3 weeks,⁵⁷ and other proposed cues to generate habits toward relationship-centered care are listed in Table 2. By creating habit through metacognitive attention, relationship-centered care will become something that happens subconsciously without further burdening physicians with another task. Asking patients for permission to record video of an interaction also can create opportunities for self-awareness and self-evaluation through rewatching the video.⁵⁸

Final Thoughts

Physicians already have the tools to create relationship-centered care in physician-patient interactions. A critical mental shift is to develop habits and apply thinking patterns toward understanding and responding appropriately to patients of all ethnicities and their emotions in the physician-patient interaction. This shift is aided by metacognitive awareness (Table 1) and the development of useful habits (Table 2).

Background: Current U.S. guidelines recommend colonoscopy within 24 hours for patients presenting with high-risk or severe acute lower gastrointestinal bleeding. However, prior meta-analyses of the timing of colonoscopy relied primarily on observational studies, and a recent multicenter randomized, controlled trial suggests no substantial benefit for early colonoscopy.

Synopsis: The authors identified four randomized, controlled trials that compared early colonoscopy (defined as within 24 hours) with elective colonoscopy (defined as beyond 24 hours) and/or other diagnostic tests for patients presenting with acute lower GI bleeding. They performed a meta-analysis, including 463 patients, which showed no significant difference in risk of persistent or recurrent bleeding for early versus elective colonoscopy. The authors also found no significant differences in secondary outcomes of mortality, endoscopic intervention, primary hemostatic intervention, or identification of bleeding source. Limitations of this research include the relatively small number of studies included, and potential for selection bias in the original studies. Notably two of the four studies included were prematurely terminated before their planned sample sizes were reached.

Bottom line: In patients hospitalized with acute lower GI bleeding, colonoscopy within 24 hours may not reduce further bleeding or mortality when compared with elective colonoscopy.

Citation: Tsay C et al. Early colonoscopy does not improve outcomes of patients with lower gastrointestinal bleeding: Systematic review of randomized trials. Clin Gastroenterol Hepatol. 2019 Dec 13. doi: 10.1016/j.cgh.2019.11.061.

Dr. Hu is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Current U.S. guidelines recommend colonoscopy within 24 hours for patients presenting with high-risk or severe acute lower gastrointestinal bleeding. However, prior meta-analyses of the timing of colonoscopy relied primarily on observational studies, and a recent multicenter randomized, controlled trial suggests no substantial benefit for early colonoscopy.

Synopsis: The authors identified four randomized, controlled trials that compared early colonoscopy (defined as within 24 hours) with elective colonoscopy (defined as beyond 24 hours) and/or other diagnostic tests for patients presenting with acute lower GI bleeding. They performed a meta-analysis, including 463 patients, which showed no significant difference in risk of persistent or recurrent bleeding for early versus elective colonoscopy. The authors also found no significant differences in secondary outcomes of mortality, endoscopic intervention, primary hemostatic intervention, or identification of bleeding source. Limitations of this research include the relatively small number of studies included, and potential for selection bias in the original studies. Notably two of the four studies included were prematurely terminated before their planned sample sizes were reached.

Bottom line: In patients hospitalized with acute lower GI bleeding, colonoscopy within 24 hours may not reduce further bleeding or mortality when compared with elective colonoscopy.

Citation: Tsay C et al. Early colonoscopy does not improve outcomes of patients with lower gastrointestinal bleeding: Systematic review of randomized trials. Clin Gastroenterol Hepatol. 2019 Dec 13. doi: 10.1016/j.cgh.2019.11.061.

Dr. Hu is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

Background: Current U.S. guidelines recommend colonoscopy within 24 hours for patients presenting with high-risk or severe acute lower gastrointestinal bleeding. However, prior meta-analyses of the timing of colonoscopy relied primarily on observational studies, and a recent multicenter randomized, controlled trial suggests no substantial benefit for early colonoscopy.

Synopsis: The authors identified four randomized, controlled trials that compared early colonoscopy (defined as within 24 hours) with elective colonoscopy (defined as beyond 24 hours) and/or other diagnostic tests for patients presenting with acute lower GI bleeding. They performed a meta-analysis, including 463 patients, which showed no significant difference in risk of persistent or recurrent bleeding for early versus elective colonoscopy. The authors also found no significant differences in secondary outcomes of mortality, endoscopic intervention, primary hemostatic intervention, or identification of bleeding source. Limitations of this research include the relatively small number of studies included, and potential for selection bias in the original studies. Notably two of the four studies included were prematurely terminated before their planned sample sizes were reached.

Bottom line: In patients hospitalized with acute lower GI bleeding, colonoscopy within 24 hours may not reduce further bleeding or mortality when compared with elective colonoscopy.

Citation: Tsay C et al. Early colonoscopy does not improve outcomes of patients with lower gastrointestinal bleeding: Systematic review of randomized trials. Clin Gastroenterol Hepatol. 2019 Dec 13. doi: 10.1016/j.cgh.2019.11.061.

Dr. Hu is a hospitalist at Beth Israel Deaconess Medical Center, and instructor in medicine, Harvard Medical School, both in Boston.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

A 56-year-old woman with type 2 diabetes presents for evaluation of painful neuropathy. She has had a diagnosis of type 2 diabetes for the past 4 years. She initially presented with polyuria/polydipsia and a hemoglobin A1c level of 9.5. She has previously not tolerated metformin, and did not want to take any subsequent medications. She was seen 4 months ago and at that time had an A1c level of 12.5. She decided she wanted to really treat her diabetes as well as she could. She started consuming a low carbohydrate diet, restarted metformin and began using a continuous glucose monitor. She also started taking nighttime glargine insulin, and mealtime insulin apart. She reports she lost 20 pounds over the past 4 months, her blood sugars now run between 100-120 fasting, and up to 180 before meals. She has had a severe, sharp pain in both of her feet over the past month that is interfering with sleep and makes walking painful for her. An exam reveals hyperesthesia of both feet, and her A1c level is 7.5. What is the most likely cause of her neuropathic symptoms?

A. Vitamin B₁₂ deficiency

B. Diabetic neuropathy

C. Insulin neuritis

D. Charcot-Marie-Tooth disease

The most likely cause

In this case, certainly considering vitamin B₁₂ deficiency is reasonable. It is highly unlikely though, given the rapidity of onset of symptoms, and that the patient has been on metformin for a very short period of time. Chronic metformin use is associated with low B₁₂ levels, and the American Diabetes Association has advised that regular monitoring of vitamin B₁₂ levels should be done on patients who are on long-term metformin.¹

Diabetic neuropathy is also unlikely, given the rapidity of symptoms in this patient. What is most likely in this patient is treatment-induced neuropathy (TIN), first described with the name “insulin neuritis”.
 

Research on TIN

Gibbons and colleagues evaluated 16 patients with diabetes with recent marked, rapid improvement in glycemic control who developed a sudden, painful neuropathy.² All developed symptoms within 8 weeks of intensive glucose control, with 69% having autonomic dysfunction as well, and all developing worsening retinopathy.

Gibbons and Freeman did a retrospective study of patients referred to a diabetic neuropathy clinic over a 5-year period to try to understand how prevalent TIN is.³

A total of 954 patients were evaluated for diabetic neuropathy. Treatment induced neuropathy was defined as a painful neuropathy and/or autonomic dysfunction occurring within 8 weeks of intensified treatment and a drop of the A1c level greater than 2 over a 3-month period.

A total of 104 patients (10.9%) met the criteria for treatment induced neuropathy. Patients who had a decrease in A1c had a much greater chance of developing a painful or autonomic neuropathy than patients who had no change in A1c (P < .0001). The same patients had a much higher risk of developing retinopathy (P < .001). The greater the reduction in A1c, the greater the risk. Patients whose A1c decreased by 2%-3% over 3 months had an absolute risk of 20%, whereas those with a A1c decease of greater than 4% had an 80% absolute risk.

Siddique and colleagues reported on three cases with very different clinical presentations of TIN.⁴ One patient had an acute third nerve palsy, another patient had a lumbosacral radiculoplexus neuropathy, and the third patient presented with a diffuse painful sensory neuropathy and postural hypotension.

Most patients improve over time from their neuropathic symptoms, with better recovery in patients with type 1 diabetes.²

Pearl

Strongly consider treatment induced neuropathy in your patients with diabetes who present with acute painful neuropathy and/or autonomic dysfunction in the setting of rapid improvement of glucose control.

Dr. Paauw is professor of medicine in the division of general internal medicine at the University of Washington, Seattle, and serves as third-year medical student clerkship director at the University of Washington. He is a member of the editorial advisory board of Internal Medicine News. Dr. Paauw has no conflicts to disclose. Contact him at [email protected].

References

1. American Diabetes Association. Diabetes Care. 2019 Jan;42(Suppl 1):S90-102.

2. Gibbons CH and Freeman R. Ann Neurol 2010; 67:534–41.

3. Gibbons CH and Freeman R. Brain. 2015;138:43-52.

4. Siddique N et al. Endocrinol Diabetes Metab Case Rep. 2020 Feb 26;2020:19-0140.

Updated guidelines from the American College of Gastroenterology address upper gastrointestinal and ulcer bleeding. Many recommendations are similar to the 2012 version, but some important changes place an emphasis on risk-stratification tools to reduce hospitalization in low-risk patients, and the timing of endoscopy for patients who are admitted to the hospital.

The guidelines were published in the American Journal of Gastroenterology.

One key change was the expansion of the Glasgow-Blatchford score (GBS) that could be used to identify patients at very low risk for a hospital intervention, from 0 in the 2012 guidelines to 0-1 in the current version. That expands the group of patients that could be discharged with outpatient follow-up.

A cutoff score of 0 identifies very few people, said Neil Sengupta, MD, who is an assistant professor of medicine at University of Chicago Medicine. Although expanding the qualification to 0-1 can increase the number of patients sent home, “which is certainly a good thing,” Dr. Sengupta said, it may be difficult to put into practice – especially in EDs. In most situations, GBS requires manual inputs. A few hospital systems have implemented automatic calculation of GBS from medical records, but the practice is not widespread.

“No. 1, the compliance of measuring the score is pretty low. No. 2, it’s difficult for an emergency room physician to discharge a patient with upper GI bleeding if patients don’t have good social support, or if they don’t have a good follow-up plan. So it’s hard to know whether this will really make a difference in terms of the number of people being discharged,” said Dr. Sengupta, who served as a monitor for the ACG committee that produced this guideline, and will become chair of the ACG guideline committee in October.

Another key message in the updated guidelines centers around timing of endoscopy. The 2012 guidelines recommended considering endoscopy within 12 hours for patients with high-risk clinical features. The new guidelines recommend that all patients should undergo endoscopy within 24 hours, and they do not specifically recommend endoscopy within 12 hours. Earlier endoscopy can lead to a more accurate prognosis, but can also cause mortality or complications if resuscitation and management of active comorbidities is insufficient, and outcomes can be worse during after-hours endoscopies. The change is based on a recent randomized, controlled trial that showed no 30-day mortality benefit to endoscopy performed within 6 hours of a consult, versus endoscopy performed between 6 and 24 hours.

That change still leaves uncertainty, because there may be some patients who would potentially benefit from earlier endoscopy. “I think that’s kind of the unknown: Whether there’s a subset of people who may benefit from going in very early and limiting the amount of resuscitation they get,” Dr. Sengupta said.

Another important message in the new guideline addresses proton pump inhibitor (PPI) therapy before endoscopy. Although the 2012 guidelines recommended considering pre-endoscopy PPI infusions, the new version states that there is no clear benefit for clinical outcomes. The authors of the guidelines did not recommend against it, either, because it is associated with a modest reduction in the need to perform endoscopic therapy. “And there’s a theoretical possibility that PPIs may benefit a minority of patients in whom endoscopy may not be possible in a timely fashion,” he said.

This advice may generate some controversy, since PPI use is very common prior to endoscopy, and in some places in the world, it might not be possible to complete an endoscopy within 24 hours. “As such, a lot of providers use PPIs routinely prior to endoscopy. It’s a little challenging just because this is such a common clinical scenario, and PPI use is so widespread that I don’t think it’s likely that practice is going to change based on this guideline,” Dr. Sengupta said. He did suggest that the benefit of PPIs after endoscopic therapy is well established, “so it’s going to be important to identify people who are at high risk (after an endoscopic treatment).

“The other the other thing is that you don’t really have too much guidance on whether there’s a benefit of using a continuous intravenous PPI versus intermittent PPI [either oral or intravenous] after endoscopy in high-risk patients, primarily [because of] the lack of high-quality data,” Dr. Sengupta said.

There is also good evidence that patients with ulcers and high-risk stigmata should receive endoscopic therapy, and these patients can benefit from posttherapy high-dose PPIs for 3 days.

Some guideline authors reported relationships with Phathom Pharmaceuticals, Olympus, and Cook. Dr. Sengupta is the upcoming chair of the ACG Practice Parameters Committees, which oversees the commissioning, updating, and review of all ACG clinical practice guidelines.

Updated guidelines from the American College of Gastroenterology address upper gastrointestinal and ulcer bleeding. Many recommendations are similar to the 2012 version, but some important changes place an emphasis on risk-stratification tools to reduce hospitalization in low-risk patients, and the timing of endoscopy for patients who are admitted to the hospital.

The guidelines were published in the American Journal of Gastroenterology.

One key change was the expansion of the Glasgow-Blatchford score (GBS) that could be used to identify patients at very low risk for a hospital intervention, from 0 in the 2012 guidelines to 0-1 in the current version. That expands the group of patients that could be discharged with outpatient follow-up.

A cutoff score of 0 identifies very few people, said Neil Sengupta, MD, who is an assistant professor of medicine at University of Chicago Medicine. Although expanding the qualification to 0-1 can increase the number of patients sent home, “which is certainly a good thing,” Dr. Sengupta said, it may be difficult to put into practice – especially in EDs. In most situations, GBS requires manual inputs. A few hospital systems have implemented automatic calculation of GBS from medical records, but the practice is not widespread.

“No. 1, the compliance of measuring the score is pretty low. No. 2, it’s difficult for an emergency room physician to discharge a patient with upper GI bleeding if patients don’t have good social support, or if they don’t have a good follow-up plan. So it’s hard to know whether this will really make a difference in terms of the number of people being discharged,” said Dr. Sengupta, who served as a monitor for the ACG committee that produced this guideline, and will become chair of the ACG guideline committee in October.

Another key message in the updated guidelines centers around timing of endoscopy. The 2012 guidelines recommended considering endoscopy within 12 hours for patients with high-risk clinical features. The new guidelines recommend that all patients should undergo endoscopy within 24 hours, and they do not specifically recommend endoscopy within 12 hours. Earlier endoscopy can lead to a more accurate prognosis, but can also cause mortality or complications if resuscitation and management of active comorbidities is insufficient, and outcomes can be worse during after-hours endoscopies. The change is based on a recent randomized, controlled trial that showed no 30-day mortality benefit to endoscopy performed within 6 hours of a consult, versus endoscopy performed between 6 and 24 hours.

That change still leaves uncertainty, because there may be some patients who would potentially benefit from earlier endoscopy. “I think that’s kind of the unknown: Whether there’s a subset of people who may benefit from going in very early and limiting the amount of resuscitation they get,” Dr. Sengupta said.

Another important message in the new guideline addresses proton pump inhibitor (PPI) therapy before endoscopy. Although the 2012 guidelines recommended considering pre-endoscopy PPI infusions, the new version states that there is no clear benefit for clinical outcomes. The authors of the guidelines did not recommend against it, either, because it is associated with a modest reduction in the need to perform endoscopic therapy. “And there’s a theoretical possibility that PPIs may benefit a minority of patients in whom endoscopy may not be possible in a timely fashion,” he said.

This advice may generate some controversy, since PPI use is very common prior to endoscopy, and in some places in the world, it might not be possible to complete an endoscopy within 24 hours. “As such, a lot of providers use PPIs routinely prior to endoscopy. It’s a little challenging just because this is such a common clinical scenario, and PPI use is so widespread that I don’t think it’s likely that practice is going to change based on this guideline,” Dr. Sengupta said. He did suggest that the benefit of PPIs after endoscopic therapy is well established, “so it’s going to be important to identify people who are at high risk (after an endoscopic treatment).

“The other the other thing is that you don’t really have too much guidance on whether there’s a benefit of using a continuous intravenous PPI versus intermittent PPI [either oral or intravenous] after endoscopy in high-risk patients, primarily [because of] the lack of high-quality data,” Dr. Sengupta said.

There is also good evidence that patients with ulcers and high-risk stigmata should receive endoscopic therapy, and these patients can benefit from posttherapy high-dose PPIs for 3 days.

Some guideline authors reported relationships with Phathom Pharmaceuticals, Olympus, and Cook. Dr. Sengupta is the upcoming chair of the ACG Practice Parameters Committees, which oversees the commissioning, updating, and review of all ACG clinical practice guidelines.

Updated guidelines from the American College of Gastroenterology address upper gastrointestinal and ulcer bleeding. Many recommendations are similar to the 2012 version, but some important changes place an emphasis on risk-stratification tools to reduce hospitalization in low-risk patients, and the timing of endoscopy for patients who are admitted to the hospital.

The guidelines were published in the American Journal of Gastroenterology.

One key change was the expansion of the Glasgow-Blatchford score (GBS) that could be used to identify patients at very low risk for a hospital intervention, from 0 in the 2012 guidelines to 0-1 in the current version. That expands the group of patients that could be discharged with outpatient follow-up.

A cutoff score of 0 identifies very few people, said Neil Sengupta, MD, who is an assistant professor of medicine at University of Chicago Medicine. Although expanding the qualification to 0-1 can increase the number of patients sent home, “which is certainly a good thing,” Dr. Sengupta said, it may be difficult to put into practice – especially in EDs. In most situations, GBS requires manual inputs. A few hospital systems have implemented automatic calculation of GBS from medical records, but the practice is not widespread.

“No. 1, the compliance of measuring the score is pretty low. No. 2, it’s difficult for an emergency room physician to discharge a patient with upper GI bleeding if patients don’t have good social support, or if they don’t have a good follow-up plan. So it’s hard to know whether this will really make a difference in terms of the number of people being discharged,” said Dr. Sengupta, who served as a monitor for the ACG committee that produced this guideline, and will become chair of the ACG guideline committee in October.

Another key message in the updated guidelines centers around timing of endoscopy. The 2012 guidelines recommended considering endoscopy within 12 hours for patients with high-risk clinical features. The new guidelines recommend that all patients should undergo endoscopy within 24 hours, and they do not specifically recommend endoscopy within 12 hours. Earlier endoscopy can lead to a more accurate prognosis, but can also cause mortality or complications if resuscitation and management of active comorbidities is insufficient, and outcomes can be worse during after-hours endoscopies. The change is based on a recent randomized, controlled trial that showed no 30-day mortality benefit to endoscopy performed within 6 hours of a consult, versus endoscopy performed between 6 and 24 hours.

That change still leaves uncertainty, because there may be some patients who would potentially benefit from earlier endoscopy. “I think that’s kind of the unknown: Whether there’s a subset of people who may benefit from going in very early and limiting the amount of resuscitation they get,” Dr. Sengupta said.

Another important message in the new guideline addresses proton pump inhibitor (PPI) therapy before endoscopy. Although the 2012 guidelines recommended considering pre-endoscopy PPI infusions, the new version states that there is no clear benefit for clinical outcomes. The authors of the guidelines did not recommend against it, either, because it is associated with a modest reduction in the need to perform endoscopic therapy. “And there’s a theoretical possibility that PPIs may benefit a minority of patients in whom endoscopy may not be possible in a timely fashion,” he said.

This advice may generate some controversy, since PPI use is very common prior to endoscopy, and in some places in the world, it might not be possible to complete an endoscopy within 24 hours. “As such, a lot of providers use PPIs routinely prior to endoscopy. It’s a little challenging just because this is such a common clinical scenario, and PPI use is so widespread that I don’t think it’s likely that practice is going to change based on this guideline,” Dr. Sengupta said. He did suggest that the benefit of PPIs after endoscopic therapy is well established, “so it’s going to be important to identify people who are at high risk (after an endoscopic treatment).

“The other the other thing is that you don’t really have too much guidance on whether there’s a benefit of using a continuous intravenous PPI versus intermittent PPI [either oral or intravenous] after endoscopy in high-risk patients, primarily [because of] the lack of high-quality data,” Dr. Sengupta said.

There is also good evidence that patients with ulcers and high-risk stigmata should receive endoscopic therapy, and these patients can benefit from posttherapy high-dose PPIs for 3 days.

Some guideline authors reported relationships with Phathom Pharmaceuticals, Olympus, and Cook. Dr. Sengupta is the upcoming chair of the ACG Practice Parameters Committees, which oversees the commissioning, updating, and review of all ACG clinical practice guidelines.

Imagine a hospitalist, part of a group with 35 hospitalists, is in her second year of practice and is caring for a 55-year-old woman with a history of congestive heart failure and cirrhosis from hepatitis C due to heroin use. The patient was hospitalized with acute back pain and found to have vertebral osteomyelitis confirmed on MRI.

The hospitalist calls a surgeon to get a biopsy so that antibiotic therapy can be chosen. The surgeon says it’s the second time the patient has been hospitalized for this condition, and asks, “Why do you need me to see this patient?” He says the hospitalist should just give IV antibiotics and consult infectious disease.

The hospitalist says, “The patient needs this biopsy. I’ll just call your chair.”

In the course of a busy day, conflicts arise all the time in the hospital – between clinicians, between patients and clinicians, and as internal battles when clinicians face uncertain situations. There are ways to make these conflicts less tense and more in tune with patient care, panelists said recently during a session at SHM Converge, the annual conference of the Society of Hospital Medicine.

In the case of vertebral osteomyelitis, for instance, the hospitalist was using a “position-based” strategy to deal with the conflict with the surgeon – she came in knowing she wanted a biopsy – rather than an “interest-based” strategy, or what is in the patient’s interest, said Patrick Rendon, MD, FHM, assistant professor in the hospital medicine division at the University of New Mexico, Albuquerque.

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

Imagine a hospitalist, part of a group with 35 hospitalists, is in her second year of practice and is caring for a 55-year-old woman with a history of congestive heart failure and cirrhosis from hepatitis C due to heroin use. The patient was hospitalized with acute back pain and found to have vertebral osteomyelitis confirmed on MRI.

The hospitalist calls a surgeon to get a biopsy so that antibiotic therapy can be chosen. The surgeon says it’s the second time the patient has been hospitalized for this condition, and asks, “Why do you need me to see this patient?” He says the hospitalist should just give IV antibiotics and consult infectious disease.

The hospitalist says, “The patient needs this biopsy. I’ll just call your chair.”

In the course of a busy day, conflicts arise all the time in the hospital – between clinicians, between patients and clinicians, and as internal battles when clinicians face uncertain situations. There are ways to make these conflicts less tense and more in tune with patient care, panelists said recently during a session at SHM Converge, the annual conference of the Society of Hospital Medicine.

In the case of vertebral osteomyelitis, for instance, the hospitalist was using a “position-based” strategy to deal with the conflict with the surgeon – she came in knowing she wanted a biopsy – rather than an “interest-based” strategy, or what is in the patient’s interest, said Patrick Rendon, MD, FHM, assistant professor in the hospital medicine division at the University of New Mexico, Albuquerque.

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

Imagine a hospitalist, part of a group with 35 hospitalists, is in her second year of practice and is caring for a 55-year-old woman with a history of congestive heart failure and cirrhosis from hepatitis C due to heroin use. The patient was hospitalized with acute back pain and found to have vertebral osteomyelitis confirmed on MRI.

The hospitalist calls a surgeon to get a biopsy so that antibiotic therapy can be chosen. The surgeon says it’s the second time the patient has been hospitalized for this condition, and asks, “Why do you need me to see this patient?” He says the hospitalist should just give IV antibiotics and consult infectious disease.

The hospitalist says, “The patient needs this biopsy. I’ll just call your chair.”

In the course of a busy day, conflicts arise all the time in the hospital – between clinicians, between patients and clinicians, and as internal battles when clinicians face uncertain situations. There are ways to make these conflicts less tense and more in tune with patient care, panelists said recently during a session at SHM Converge, the annual conference of the Society of Hospital Medicine.

In the case of vertebral osteomyelitis, for instance, the hospitalist was using a “position-based” strategy to deal with the conflict with the surgeon – she came in knowing she wanted a biopsy – rather than an “interest-based” strategy, or what is in the patient’s interest, said Patrick Rendon, MD, FHM, assistant professor in the hospital medicine division at the University of New Mexico, Albuquerque.

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

Subthalamic nucleus deep brain stimulation (STN-DBS) continues to be effective for patients with Parkinson’s disease more than 15 years after device implantation, with significant improvement in motor complications and a stable reduction in dopaminergic drug use, new research indicates.

“Subthalamic nucleus stimulation is a well recognized treatment used for improving motor conditions and quality of life in people with Parkinson’s disease. Our study, for the first time, supports its efficacy in the very long term – 15 years after surgery and 25 years since the Parkinson’s disease diagnosis,” said Elena Moro, MD, PhD, Grenoble Alpes University, Grenoble, France.

“This information is relevant for physicians, patients, and their families when they need to decide about the surgical option to deal with Parkinson’s disease,” said Dr. Moro.

The study was published online June 2 in Neurology.
 

‘Don’t delay’

The findings are based on 51 patients with Parkinson’s disease who underwent treatment with bilateral STN-DBS for an average of 17 years (range, 15-24 years). Their average age at diagnosis was 40 years, and the average age at device implantation was 51 years.

The results demonstrate that STN-DBS continues to be effective for motor complications for longer than 15 years, reducing time spent with dyskinesia by 75% and time spent in the off-state by 58.7%. This is similar to the amount of improvement seen 1 year after surgery.

Doses of dopaminergic medications continued to be low at long-term follow-up; dosing was reduced by 50.6% compared with baseline.

There was also continued improvement in quality of life. Scores on the Parkinson’s Disease Quality of Life Questionnaire in the very long term were 13.8% better compared with baseline.

“Few and mostly manageable device-related adverse events were observed during the follow-up,” the authors reported in their article.

“Deep brain stimulation is already recommended when a patient’s conditions are not optimized by medical treatment. Patients with Parkinson’s disease without dementia and in good general health conditions are the best candidates for this surgery,” said Dr. Moro.

“Taking into account our results and the data available in the literature, DBS surgery should not be delayed when motor conditions and quality of life decline despite medical treatment, if patients meet the inclusion criteria,” she added.
 

A revolutionary treatment

The authors of an accompanying editorial say these results, which indicate better motor outcomes with less medication, “reinforce why STN-DBS has revolutionized treatment for advanced Parkinson’s disease.”

Kelvin Chou, MD, of the University of Michigan, Ann Arbor, and David Charles, MD, of Vanderbilt University, Nashville, Tenn., pointed out that longer disease duration is associated with an increase in the likelihood of cognitive impairment and psychosis, both of which are risk factors for nursing home placement, and they limit the ability to use dopaminergic medications.

Although many of the patients in this cohort experienced hallucinations and psychosis over the long follow-up period, “one can imagine that the number and severity would be higher without DBS therapy,” they wrote.

Key caveats, said Dr. Chou and Dr. Charles, are that the results are based on a highly selected cohort and that the patients were managed by experts in the field of movement disorders and DBS.

Additionally, the patients’ conditions were highly responsive to levodopa; there was a 75.3% baseline improvement in Unified Parkinson’s Disease Rating Scale motor scores from the off-state to the on-state. In general, most DBS centers consider a levodopa response of approximately 30% as an acceptable cutoff for moving forward with STN-DBS, they noted.

Despite these caveats and limitations, the results of the study are important with respect to counseling potential candidates for DBS, Dr. Chou and Dr. Charles said.

“A common question that patients have is, ‘How long do the benefits of DBS last?’ We can now reassure them that, at least for STN-DBS, improvement in motor complications lasts beyond 15 years and is often accompanied by improvement in quality of life. In other words, with STN-DBS, we can uncomplicate their motor complications for the long haul,” the editorial writers concluded.

The research had no targeted funding. Moro has received honoraria from Medtronic and Abbott for consulting and lecturing and an educational grant from Boston and Newronika. A complete list of disclosures is available with the original articles.

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

Subthalamic nucleus deep brain stimulation (STN-DBS) continues to be effective for patients with Parkinson’s disease more than 15 years after device implantation, with significant improvement in motor complications and a stable reduction in dopaminergic drug use, new research indicates.

“Subthalamic nucleus stimulation is a well recognized treatment used for improving motor conditions and quality of life in people with Parkinson’s disease. Our study, for the first time, supports its efficacy in the very long term – 15 years after surgery and 25 years since the Parkinson’s disease diagnosis,” said Elena Moro, MD, PhD, Grenoble Alpes University, Grenoble, France.

“This information is relevant for physicians, patients, and their families when they need to decide about the surgical option to deal with Parkinson’s disease,” said Dr. Moro.

The study was published online June 2 in Neurology.
 

‘Don’t delay’

The findings are based on 51 patients with Parkinson’s disease who underwent treatment with bilateral STN-DBS for an average of 17 years (range, 15-24 years). Their average age at diagnosis was 40 years, and the average age at device implantation was 51 years.

The results demonstrate that STN-DBS continues to be effective for motor complications for longer than 15 years, reducing time spent with dyskinesia by 75% and time spent in the off-state by 58.7%. This is similar to the amount of improvement seen 1 year after surgery.

Doses of dopaminergic medications continued to be low at long-term follow-up; dosing was reduced by 50.6% compared with baseline.

There was also continued improvement in quality of life. Scores on the Parkinson’s Disease Quality of Life Questionnaire in the very long term were 13.8% better compared with baseline.

“Few and mostly manageable device-related adverse events were observed during the follow-up,” the authors reported in their article.

“Deep brain stimulation is already recommended when a patient’s conditions are not optimized by medical treatment. Patients with Parkinson’s disease without dementia and in good general health conditions are the best candidates for this surgery,” said Dr. Moro.

“Taking into account our results and the data available in the literature, DBS surgery should not be delayed when motor conditions and quality of life decline despite medical treatment, if patients meet the inclusion criteria,” she added.
 

A revolutionary treatment

The authors of an accompanying editorial say these results, which indicate better motor outcomes with less medication, “reinforce why STN-DBS has revolutionized treatment for advanced Parkinson’s disease.”

Kelvin Chou, MD, of the University of Michigan, Ann Arbor, and David Charles, MD, of Vanderbilt University, Nashville, Tenn., pointed out that longer disease duration is associated with an increase in the likelihood of cognitive impairment and psychosis, both of which are risk factors for nursing home placement, and they limit the ability to use dopaminergic medications.

Although many of the patients in this cohort experienced hallucinations and psychosis over the long follow-up period, “one can imagine that the number and severity would be higher without DBS therapy,” they wrote.

Key caveats, said Dr. Chou and Dr. Charles, are that the results are based on a highly selected cohort and that the patients were managed by experts in the field of movement disorders and DBS.

Additionally, the patients’ conditions were highly responsive to levodopa; there was a 75.3% baseline improvement in Unified Parkinson’s Disease Rating Scale motor scores from the off-state to the on-state. In general, most DBS centers consider a levodopa response of approximately 30% as an acceptable cutoff for moving forward with STN-DBS, they noted.

Despite these caveats and limitations, the results of the study are important with respect to counseling potential candidates for DBS, Dr. Chou and Dr. Charles said.

“A common question that patients have is, ‘How long do the benefits of DBS last?’ We can now reassure them that, at least for STN-DBS, improvement in motor complications lasts beyond 15 years and is often accompanied by improvement in quality of life. In other words, with STN-DBS, we can uncomplicate their motor complications for the long haul,” the editorial writers concluded.

The research had no targeted funding. Moro has received honoraria from Medtronic and Abbott for consulting and lecturing and an educational grant from Boston and Newronika. A complete list of disclosures is available with the original articles.

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

Subthalamic nucleus deep brain stimulation (STN-DBS) continues to be effective for patients with Parkinson’s disease more than 15 years after device implantation, with significant improvement in motor complications and a stable reduction in dopaminergic drug use, new research indicates.

“Subthalamic nucleus stimulation is a well recognized treatment used for improving motor conditions and quality of life in people with Parkinson’s disease. Our study, for the first time, supports its efficacy in the very long term – 15 years after surgery and 25 years since the Parkinson’s disease diagnosis,” said Elena Moro, MD, PhD, Grenoble Alpes University, Grenoble, France.

“This information is relevant for physicians, patients, and their families when they need to decide about the surgical option to deal with Parkinson’s disease,” said Dr. Moro.

The study was published online June 2 in Neurology.
 

‘Don’t delay’

The findings are based on 51 patients with Parkinson’s disease who underwent treatment with bilateral STN-DBS for an average of 17 years (range, 15-24 years). Their average age at diagnosis was 40 years, and the average age at device implantation was 51 years.

The results demonstrate that STN-DBS continues to be effective for motor complications for longer than 15 years, reducing time spent with dyskinesia by 75% and time spent in the off-state by 58.7%. This is similar to the amount of improvement seen 1 year after surgery.

Doses of dopaminergic medications continued to be low at long-term follow-up; dosing was reduced by 50.6% compared with baseline.

There was also continued improvement in quality of life. Scores on the Parkinson’s Disease Quality of Life Questionnaire in the very long term were 13.8% better compared with baseline.

“Few and mostly manageable device-related adverse events were observed during the follow-up,” the authors reported in their article.

“Deep brain stimulation is already recommended when a patient’s conditions are not optimized by medical treatment. Patients with Parkinson’s disease without dementia and in good general health conditions are the best candidates for this surgery,” said Dr. Moro.

“Taking into account our results and the data available in the literature, DBS surgery should not be delayed when motor conditions and quality of life decline despite medical treatment, if patients meet the inclusion criteria,” she added.
 

A revolutionary treatment

The authors of an accompanying editorial say these results, which indicate better motor outcomes with less medication, “reinforce why STN-DBS has revolutionized treatment for advanced Parkinson’s disease.”

Kelvin Chou, MD, of the University of Michigan, Ann Arbor, and David Charles, MD, of Vanderbilt University, Nashville, Tenn., pointed out that longer disease duration is associated with an increase in the likelihood of cognitive impairment and psychosis, both of which are risk factors for nursing home placement, and they limit the ability to use dopaminergic medications.

Although many of the patients in this cohort experienced hallucinations and psychosis over the long follow-up period, “one can imagine that the number and severity would be higher without DBS therapy,” they wrote.

Key caveats, said Dr. Chou and Dr. Charles, are that the results are based on a highly selected cohort and that the patients were managed by experts in the field of movement disorders and DBS.

Additionally, the patients’ conditions were highly responsive to levodopa; there was a 75.3% baseline improvement in Unified Parkinson’s Disease Rating Scale motor scores from the off-state to the on-state. In general, most DBS centers consider a levodopa response of approximately 30% as an acceptable cutoff for moving forward with STN-DBS, they noted.

Despite these caveats and limitations, the results of the study are important with respect to counseling potential candidates for DBS, Dr. Chou and Dr. Charles said.

“A common question that patients have is, ‘How long do the benefits of DBS last?’ We can now reassure them that, at least for STN-DBS, improvement in motor complications lasts beyond 15 years and is often accompanied by improvement in quality of life. In other words, with STN-DBS, we can uncomplicate their motor complications for the long haul,” the editorial writers concluded.

The research had no targeted funding. Moro has received honoraria from Medtronic and Abbott for consulting and lecturing and an educational grant from Boston and Newronika. A complete list of disclosures is available with the original articles.

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