CHICAGO – In a busy clinic it can be hard to find the time to stop, talk, and listen. But doing so will “pay dividends in time spent later – and in reduced complications” of nail surgery, according to Molly A. Hinshaw, MD.

Dr. Hinshaw, director of the nail clinic at the University of Wisconsin–Madison, shared her clinical pearls for patient care through the entire nail surgery process at the American Academy of Dermatology summer meeting.

“One pearl is the importance of patient education before we start,” Dr. Hinshaw said. Preoperatively, she takes time to talk through the entire surgery and expected postoperative course. Critically, she reassures patients that pain will be controlled; she also reviews in detail what the pharmacologic and nonpharmacologic pain control strategies will be.

In addition, it’s important to address patients’ natural anxiety about what the surgical site will look and feel like and how healing will progress, particularly in those first few days after surgery. “I offer a first dressing change in my practice, either at 24 or 48 hours. This can be very anxiolytic for the patient,” she said.

At the preoperative stage, Dr. Hinshaw also tells patients that, from a healing and pain management standpoint, to make sure they plan “to have a restful 48 hours after surgery.” Her patient instructions for the immediate postoperative period include keeping the limb elevated and avoiding unnecessary activity with the affected limb while the digit, whether a finger or toe, is still anesthetized. To stay on top of the pain, the appropriate oral pain medication should be started once sensation starts to return to the digit. She recommends patients also take a dose of their pain medication at bedtime, as this will help them get a restful night of sleep.

“One thing that I’ve learned over the years is that throbbing and a little bit of swelling after surgery is not uncommon,” said Dr. Hinshaw, who uses elastic self-adherent wrap for the top layer of wound dressings after nail surgery. She tells her patients, “if you’re feeling throbbing, you’re welcome to unwrap it and rewrap it more loosely.” Just giving the patient the ability to find a comfortable level of pressure on the affected digit is often enough to alleviate the throbbing, as opposed to treating that throbbing with pain medication.

Dr. Hinshaw said she’s learned to tailor her postoperative analgesia to the surgery and to the patient. With all patients, she is sure to make medication and dosing choices that take comorbidities and potential drug-drug interactions into account. She does not ask patients to stop anticoagulation before nail procedures.

For phenolization procedures and punch biopsies, she’ll advise patients to use acetaminophen or NSAIDs. Some procedures are going to have a more painful recovery course, said Dr. Hinshaw, so she’ll use an opioid such as hydrocodone with acetaminophen for shave excisions and fusiform longitudinal excisions.

The physician and patient can also plan ahead for a brief course of more potent opioids for some procedures. “Certainly for lateral longitudinal excisions, they will need narcotic pain management for at least 48 hours after surgery,” she noted. “It’s a painful surgery.”

Other procedures that will need more postoperative analgesia include flaps and nail unit grafts, she said. In general, NSAIDs are useful to add after the first 24 hours. In addition, “I always call my patients the day after surgery to see how they’re doing. This helps identify any issues and questions early and is comforting to the patient,” she added.

Dr. Hinshaw disclosed that she has an ownership stake in and sits on the board of directors of Accure Medical.

koakes@mdedge.com

CHICAGO – In a busy clinic it can be hard to find the time to stop, talk, and listen. But doing so will “pay dividends in time spent later – and in reduced complications” of nail surgery, according to Molly A. Hinshaw, MD.

Dr. Hinshaw, director of the nail clinic at the University of Wisconsin–Madison, shared her clinical pearls for patient care through the entire nail surgery process at the American Academy of Dermatology summer meeting.

“One pearl is the importance of patient education before we start,” Dr. Hinshaw said. Preoperatively, she takes time to talk through the entire surgery and expected postoperative course. Critically, she reassures patients that pain will be controlled; she also reviews in detail what the pharmacologic and nonpharmacologic pain control strategies will be.

In addition, it’s important to address patients’ natural anxiety about what the surgical site will look and feel like and how healing will progress, particularly in those first few days after surgery. “I offer a first dressing change in my practice, either at 24 or 48 hours. This can be very anxiolytic for the patient,” she said.

At the preoperative stage, Dr. Hinshaw also tells patients that, from a healing and pain management standpoint, to make sure they plan “to have a restful 48 hours after surgery.” Her patient instructions for the immediate postoperative period include keeping the limb elevated and avoiding unnecessary activity with the affected limb while the digit, whether a finger or toe, is still anesthetized. To stay on top of the pain, the appropriate oral pain medication should be started once sensation starts to return to the digit. She recommends patients also take a dose of their pain medication at bedtime, as this will help them get a restful night of sleep.

“One thing that I’ve learned over the years is that throbbing and a little bit of swelling after surgery is not uncommon,” said Dr. Hinshaw, who uses elastic self-adherent wrap for the top layer of wound dressings after nail surgery. She tells her patients, “if you’re feeling throbbing, you’re welcome to unwrap it and rewrap it more loosely.” Just giving the patient the ability to find a comfortable level of pressure on the affected digit is often enough to alleviate the throbbing, as opposed to treating that throbbing with pain medication.

Dr. Hinshaw said she’s learned to tailor her postoperative analgesia to the surgery and to the patient. With all patients, she is sure to make medication and dosing choices that take comorbidities and potential drug-drug interactions into account. She does not ask patients to stop anticoagulation before nail procedures.

For phenolization procedures and punch biopsies, she’ll advise patients to use acetaminophen or NSAIDs. Some procedures are going to have a more painful recovery course, said Dr. Hinshaw, so she’ll use an opioid such as hydrocodone with acetaminophen for shave excisions and fusiform longitudinal excisions.

The physician and patient can also plan ahead for a brief course of more potent opioids for some procedures. “Certainly for lateral longitudinal excisions, they will need narcotic pain management for at least 48 hours after surgery,” she noted. “It’s a painful surgery.”

Other procedures that will need more postoperative analgesia include flaps and nail unit grafts, she said. In general, NSAIDs are useful to add after the first 24 hours. In addition, “I always call my patients the day after surgery to see how they’re doing. This helps identify any issues and questions early and is comforting to the patient,” she added.

Dr. Hinshaw disclosed that she has an ownership stake in and sits on the board of directors of Accure Medical.

koakes@mdedge.com

CHICAGO – In a busy clinic it can be hard to find the time to stop, talk, and listen. But doing so will “pay dividends in time spent later – and in reduced complications” of nail surgery, according to Molly A. Hinshaw, MD.

Dr. Hinshaw, director of the nail clinic at the University of Wisconsin–Madison, shared her clinical pearls for patient care through the entire nail surgery process at the American Academy of Dermatology summer meeting.

“One pearl is the importance of patient education before we start,” Dr. Hinshaw said. Preoperatively, she takes time to talk through the entire surgery and expected postoperative course. Critically, she reassures patients that pain will be controlled; she also reviews in detail what the pharmacologic and nonpharmacologic pain control strategies will be.

In addition, it’s important to address patients’ natural anxiety about what the surgical site will look and feel like and how healing will progress, particularly in those first few days after surgery. “I offer a first dressing change in my practice, either at 24 or 48 hours. This can be very anxiolytic for the patient,” she said.

At the preoperative stage, Dr. Hinshaw also tells patients that, from a healing and pain management standpoint, to make sure they plan “to have a restful 48 hours after surgery.” Her patient instructions for the immediate postoperative period include keeping the limb elevated and avoiding unnecessary activity with the affected limb while the digit, whether a finger or toe, is still anesthetized. To stay on top of the pain, the appropriate oral pain medication should be started once sensation starts to return to the digit. She recommends patients also take a dose of their pain medication at bedtime, as this will help them get a restful night of sleep.

“One thing that I’ve learned over the years is that throbbing and a little bit of swelling after surgery is not uncommon,” said Dr. Hinshaw, who uses elastic self-adherent wrap for the top layer of wound dressings after nail surgery. She tells her patients, “if you’re feeling throbbing, you’re welcome to unwrap it and rewrap it more loosely.” Just giving the patient the ability to find a comfortable level of pressure on the affected digit is often enough to alleviate the throbbing, as opposed to treating that throbbing with pain medication.

Dr. Hinshaw said she’s learned to tailor her postoperative analgesia to the surgery and to the patient. With all patients, she is sure to make medication and dosing choices that take comorbidities and potential drug-drug interactions into account. She does not ask patients to stop anticoagulation before nail procedures.

For phenolization procedures and punch biopsies, she’ll advise patients to use acetaminophen or NSAIDs. Some procedures are going to have a more painful recovery course, said Dr. Hinshaw, so she’ll use an opioid such as hydrocodone with acetaminophen for shave excisions and fusiform longitudinal excisions.

The physician and patient can also plan ahead for a brief course of more potent opioids for some procedures. “Certainly for lateral longitudinal excisions, they will need narcotic pain management for at least 48 hours after surgery,” she noted. “It’s a painful surgery.”

Other procedures that will need more postoperative analgesia include flaps and nail unit grafts, she said. In general, NSAIDs are useful to add after the first 24 hours. In addition, “I always call my patients the day after surgery to see how they’re doing. This helps identify any issues and questions early and is comforting to the patient,” she added.

Dr. Hinshaw disclosed that she has an ownership stake in and sits on the board of directors of Accure Medical.

koakes@mdedge.com

Case

An 85-year-old man with long-standing chronic obstructive pulmonary disease (COPD) has a witnessed aspiration event while undergoing an outpatient procedure requiring conscious sedation. He is admitted to the hospital for observation overnight. The next morning, he feels well, but his oxygen saturation dips to 85% with ambulation. He reports this is not new for him, but he vehemently does not want supplemental oxygen.

Background

Patients with COPD and severe resting hypoxemia – arterial oxygen partial pressure less than or equal to 55 mm Hg or peripheral capillary oxygen saturation (SpO₂₎ less than or equal to 88% – commonly are prescribed supplemental oxygen. The evidence supporting this practice is limited to two small trials from the 1970s that showed a survival benefit of long-term oxygen therapy (LTOT) in this population,^1,2 but these trials may not be generalizable to patients today.

For patients with COPD and mild to moderate resting hypoxemia (SpO_2, 89%-93%) or patients with exercise-induced hypoxemia, LTOT has not been shown to improve survival, although it may improve symptoms of dyspnea, exercise tolerance, and other patient reported outcomes. Given the costs, risks, and burdens associated with LTOT, a high-quality clinical trial assessing the effects of LTOT on clinically meaningful outcomes, such as survival or hospitalization, in patients with COPD and moderate hypoxemia has been long overdue.
 

Overview of the data

The utility of long-term treatment with supplemental oxygen in patients with stable COPD and moderate resting or exercise-induced desaturation was examined by the Long-Term Oxygen Treatment Trial (LOTT) Research Group. Results were published in the New England Journal of Medicine in October 2016 in the article, “A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation.”³

The study was initially designed to test whether the use of supplemental oxygen would lead to longer time until death as compared with no supplemental oxygen in the subgroup of COPD patients with stable disease and moderate resting desaturation (defined as resting SpO₂ of 89%-93%). However, because of an enrollment of only 34 patients after 7 months, the trial was redesigned to include exercise-induced desaturation (defined as SpO₂ of greater than or equal to 80% for at least 5 minutes, and less than 90% for at least 10 seconds, on a 6-minute walk test) and the secondary outcome of all-cause hospitalization. Hospitalization for any cause was combined with mortality into a new composite primary outcome.

This study was a randomized, controlled trial which enrolled patients at a total of 14 regional clinical centers and their associated sites for a total of 42 centers in the United States. The experimental arm consisted of a long term supplemental oxygen group, and the control group did not receive long term supplemental oxygen. Patients were assigned to groups in a 1:1 ratio and the study was not blinded. Patients with moderate resting desaturation were prescribed 24 hour oxygen at 2 L/min, and patients with moderate exercise-induced desaturation were prescribed oxygen at 2 L/min during exercise and sleep only. The primary outcome was a composite outcome of time until death or time until first hospitalization for any cause. There were multiple secondary outcomes, including incidence of COPD exacerbation, incidence of severe resting desaturation and severe exercise-induced desaturation, quality of life, sleep quality, depression and anxiety, adherence to regimen, 6-minute walk distance, spirometric measurements, risk of cardiovascular disease, and neurocognitive function.

Data were gathered via yearly visits, biannual telephone interviews, and questionnaires mailed at 4 months and 16 months. Adherence was assessed by inquiring about oxygen use every 4 months. If patients in the supplemental oxygen group used stationary oxygen concentrators, logs of meter readings were kept as well. The necessary final sample size was calculated using a time to composite event survival model with the use of the log-rank test statistic.

A total of 738 patients were enrolled in the trial between January 2009 and September 2015 and were followed for 1-6 years. A total of 97% of participants had at least 1 year of follow-up. Out of the 738 randomized patients, 133 (18%) had only resting desaturations, 319 (43%) had only exercise-induced desaturations, and 286 (39%) had both resting and exercise-induced desaturations. Baseline characteristics including age, sex, race, smoking status, quality of life scores, resting SpO_2, and nadir SpO₂ during the 6-minute walk test were similar between the two groups. The only significant difference noted by the authors between the two groups was a lower BODE (body mass index, airflow obstruction, dyspnea, and exercise) index, which was lower in the group with no supplemental oxygen.

In the time-to-event analysis, there was no significant difference between the two groups in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval, 0.79-1.12; P = .52). There were no significant differences in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91-1.13), COPD exacerbations (RR 1.08; 95% CI, 0.98-1.19), and COPD related hospitalizations (RR, 0.99; 95% CI, 0.83-1.17). There were also no differences between the experimental and control groups in quality of life, lung function, and 6-minute walk distance. There were no significant differences in the subgroups classified by desaturation profile, sex, race, nadir SpO₂ during the 6-minute walk test, and forced expiratory volume in 1 second.

The findings in this study show that, in the subgroup of chronic obstructive pulmonary disease patients with stable COPD and moderate resting or exercise-induced desaturation, supplemental oxygen did not affect the time to death or first hospitalization, time to death, time to first hospitalization, time to first COPD exacerbation, time to first hospitalization for a COPD exacerbation, rate of all hospitalizations, rate of all COPD exacerbations, or changes in metrics surrounding quality of life, anxiety/depression, or functional status. This supports earlier studies that demonstrated that long-term treatment with oxygen does not result in longer survival than does no long-term treatment with oxygen in patients with COPD and resting SpO₂ of more than 88%.

The results of this study are a departure from previous studies that had shown improved mortality in patients with COPD and severe desaturation who were treated with LTOT. The authors hypothesized that this may have been caused by physiological effects of oxygen saturation on pulmonary vasoconstriction, release of mediators, and ventilator drive, which occur at an O₂ saturation of 88% or less and may be more significant in patients with chronic hypoxemia. This trial also contrasted previous studies that had shown that oxygen therapy may reduce dyspnea in COPD patients with mild or no hypoxia because the LOTT trial showed no improvement in quality of life, anxiety, and depression measures in patients treated with long-term oxygen as compared with those treated with no oxygen.

Some limitations of the study included the absence of highly symptomatic patients or patients who the providers believed were too ill to participate, the effect of the unblinded nature of the study on outcomes that were patient reported, the lack of assessment of immediate effects of oxygen on exercise performance or symptoms, possible variability in amount of oxygen delivered, and the fact that patients may have overestimated their oxygen use.

In patients with stable COPD and moderate resting or exercise induced desaturation, long-term supplemental oxygen did not provide any benefit in regard to time until death or first hospitalization or any of the other measured outcomes.

Application of data to the case

Our patient has stable COPD and had only moderate exercise-induced desaturation. Long-term supplemental oxygen would not produce a benefit for him.

This study shows us that it would not increase his survival at this point; however, if he were to have worsening exercise-induced or new resting desaturation at some point in the future, supplemental oxygen would then be beneficial. At this point supplemental oxygen would not even affect his rate of hospitalization for COPD- or non-COPD–related reasons. Perhaps most importantly, adding oxygen therapy would not affect his overall quality of life, including his functional status and mood.
 

Bottom line

The addition of supplemental oxygen is not helpful for patients with COPD who have chronic stable moderate hypoxia.

Dr. Farber is a medical instructor in the Duke University Health System in Durham, N.C. Dr. Sata is a medical instructor in the Duke University Hospital. Dr. Wachter is an assistant professor of medicine at Duke University. Dr. Sharma is associate medical director for clinical education in hospital medicine at Duke Regional Hospital and an assistant professor of medicine at Duke University.

References

1. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: A clinical trial. Ann Intern Med. 1980 Sep;93(3):391-8.

2. Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: Report of the Medical Research Council Working Party. Lancet 1981 Mar 28;1(8222):681-6.

3. Long-term oxygen treatment trial research group et al. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med. 2016 Oct 27;375(17):1617-27.

Additional reading

Stoller JK et al. Oxygen therapy for patients with COPD: Current evidence and the Long-term Oxygen Treatment Trial. Chest. 2010 July;138:179-87.

Qaseem A et al. Diagnosis and management of stable chronic obstructive pulmonary disease: A clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011 Aug 2;155(3):179-91.

Ameer F et al. Ambulatory oxygen for people with chronic obstructive pulmonary disease who are not hypoxaemic at rest. Cochrane Database Syst Rev. 2014 Jun 24;(6):CD000238.

Vestbo J et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65.

Quiz: Does this patient need oxygen?

You are caring for a 72-year-old man with stable COPD who was admitted for cellulitis. He is improving clinically on appropriate antibiotics, and he has been stable on room air every time you examine him. The nurse pages you on the day of discharge – a Sunday – informing you that his oxygen saturation dropped to 88% while he was walking the halls this morning. She asks whether he needs to stay in the hospital so you can arrange home supplemental oxygen therapy. What should you do?

A. Keep him in the hospital until you can arrange home oxygen therapy.

B. Discharge him home Sunday but have the oxygen company go out to his house first thing on Monday.

C. Discharge him home without supplemental oxygen therapy.

D. Check an arterial blood gas to help decide if you should set up oxygen therapy.

The answer is C. He meets the description of stable COPD with mild to moderate exercise-induced desaturation. The LOTT trial supports our clinical decision that he would not benefit from supplemental oxygen therapy at this point.

Key Points

• Long-term oxygen therapy (LTOT) is beneficial in patients with COPD and severe resting hypoxemia (arterial oxygen partial pressure ≤ 55 mm Hg or SpO₂ ≤ 88%) and should be prescribed to improve survival in this population.
• Patients with COPD and mild to moderate resting hypoxemia or exercised-induced hypoxemia should not be routinely prescribed LTOT given the associated costs, risks, and burdens and the lack of evidence of benefit.

Case

An 85-year-old man with long-standing chronic obstructive pulmonary disease (COPD) has a witnessed aspiration event while undergoing an outpatient procedure requiring conscious sedation. He is admitted to the hospital for observation overnight. The next morning, he feels well, but his oxygen saturation dips to 85% with ambulation. He reports this is not new for him, but he vehemently does not want supplemental oxygen.

Background

Patients with COPD and severe resting hypoxemia – arterial oxygen partial pressure less than or equal to 55 mm Hg or peripheral capillary oxygen saturation (SpO₂₎ less than or equal to 88% – commonly are prescribed supplemental oxygen. The evidence supporting this practice is limited to two small trials from the 1970s that showed a survival benefit of long-term oxygen therapy (LTOT) in this population,^1,2 but these trials may not be generalizable to patients today.

For patients with COPD and mild to moderate resting hypoxemia (SpO_2, 89%-93%) or patients with exercise-induced hypoxemia, LTOT has not been shown to improve survival, although it may improve symptoms of dyspnea, exercise tolerance, and other patient reported outcomes. Given the costs, risks, and burdens associated with LTOT, a high-quality clinical trial assessing the effects of LTOT on clinically meaningful outcomes, such as survival or hospitalization, in patients with COPD and moderate hypoxemia has been long overdue.
 

Overview of the data

The utility of long-term treatment with supplemental oxygen in patients with stable COPD and moderate resting or exercise-induced desaturation was examined by the Long-Term Oxygen Treatment Trial (LOTT) Research Group. Results were published in the New England Journal of Medicine in October 2016 in the article, “A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation.”³

The study was initially designed to test whether the use of supplemental oxygen would lead to longer time until death as compared with no supplemental oxygen in the subgroup of COPD patients with stable disease and moderate resting desaturation (defined as resting SpO₂ of 89%-93%). However, because of an enrollment of only 34 patients after 7 months, the trial was redesigned to include exercise-induced desaturation (defined as SpO₂ of greater than or equal to 80% for at least 5 minutes, and less than 90% for at least 10 seconds, on a 6-minute walk test) and the secondary outcome of all-cause hospitalization. Hospitalization for any cause was combined with mortality into a new composite primary outcome.

This study was a randomized, controlled trial which enrolled patients at a total of 14 regional clinical centers and their associated sites for a total of 42 centers in the United States. The experimental arm consisted of a long term supplemental oxygen group, and the control group did not receive long term supplemental oxygen. Patients were assigned to groups in a 1:1 ratio and the study was not blinded. Patients with moderate resting desaturation were prescribed 24 hour oxygen at 2 L/min, and patients with moderate exercise-induced desaturation were prescribed oxygen at 2 L/min during exercise and sleep only. The primary outcome was a composite outcome of time until death or time until first hospitalization for any cause. There were multiple secondary outcomes, including incidence of COPD exacerbation, incidence of severe resting desaturation and severe exercise-induced desaturation, quality of life, sleep quality, depression and anxiety, adherence to regimen, 6-minute walk distance, spirometric measurements, risk of cardiovascular disease, and neurocognitive function.

Data were gathered via yearly visits, biannual telephone interviews, and questionnaires mailed at 4 months and 16 months. Adherence was assessed by inquiring about oxygen use every 4 months. If patients in the supplemental oxygen group used stationary oxygen concentrators, logs of meter readings were kept as well. The necessary final sample size was calculated using a time to composite event survival model with the use of the log-rank test statistic.

A total of 738 patients were enrolled in the trial between January 2009 and September 2015 and were followed for 1-6 years. A total of 97% of participants had at least 1 year of follow-up. Out of the 738 randomized patients, 133 (18%) had only resting desaturations, 319 (43%) had only exercise-induced desaturations, and 286 (39%) had both resting and exercise-induced desaturations. Baseline characteristics including age, sex, race, smoking status, quality of life scores, resting SpO_2, and nadir SpO₂ during the 6-minute walk test were similar between the two groups. The only significant difference noted by the authors between the two groups was a lower BODE (body mass index, airflow obstruction, dyspnea, and exercise) index, which was lower in the group with no supplemental oxygen.

In the time-to-event analysis, there was no significant difference between the two groups in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval, 0.79-1.12; P = .52). There were no significant differences in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91-1.13), COPD exacerbations (RR 1.08; 95% CI, 0.98-1.19), and COPD related hospitalizations (RR, 0.99; 95% CI, 0.83-1.17). There were also no differences between the experimental and control groups in quality of life, lung function, and 6-minute walk distance. There were no significant differences in the subgroups classified by desaturation profile, sex, race, nadir SpO₂ during the 6-minute walk test, and forced expiratory volume in 1 second.

The findings in this study show that, in the subgroup of chronic obstructive pulmonary disease patients with stable COPD and moderate resting or exercise-induced desaturation, supplemental oxygen did not affect the time to death or first hospitalization, time to death, time to first hospitalization, time to first COPD exacerbation, time to first hospitalization for a COPD exacerbation, rate of all hospitalizations, rate of all COPD exacerbations, or changes in metrics surrounding quality of life, anxiety/depression, or functional status. This supports earlier studies that demonstrated that long-term treatment with oxygen does not result in longer survival than does no long-term treatment with oxygen in patients with COPD and resting SpO₂ of more than 88%.

The results of this study are a departure from previous studies that had shown improved mortality in patients with COPD and severe desaturation who were treated with LTOT. The authors hypothesized that this may have been caused by physiological effects of oxygen saturation on pulmonary vasoconstriction, release of mediators, and ventilator drive, which occur at an O₂ saturation of 88% or less and may be more significant in patients with chronic hypoxemia. This trial also contrasted previous studies that had shown that oxygen therapy may reduce dyspnea in COPD patients with mild or no hypoxia because the LOTT trial showed no improvement in quality of life, anxiety, and depression measures in patients treated with long-term oxygen as compared with those treated with no oxygen.

Some limitations of the study included the absence of highly symptomatic patients or patients who the providers believed were too ill to participate, the effect of the unblinded nature of the study on outcomes that were patient reported, the lack of assessment of immediate effects of oxygen on exercise performance or symptoms, possible variability in amount of oxygen delivered, and the fact that patients may have overestimated their oxygen use.

In patients with stable COPD and moderate resting or exercise induced desaturation, long-term supplemental oxygen did not provide any benefit in regard to time until death or first hospitalization or any of the other measured outcomes.

Application of data to the case

Our patient has stable COPD and had only moderate exercise-induced desaturation. Long-term supplemental oxygen would not produce a benefit for him.

This study shows us that it would not increase his survival at this point; however, if he were to have worsening exercise-induced or new resting desaturation at some point in the future, supplemental oxygen would then be beneficial. At this point supplemental oxygen would not even affect his rate of hospitalization for COPD- or non-COPD–related reasons. Perhaps most importantly, adding oxygen therapy would not affect his overall quality of life, including his functional status and mood.
 

Bottom line

The addition of supplemental oxygen is not helpful for patients with COPD who have chronic stable moderate hypoxia.

Dr. Farber is a medical instructor in the Duke University Health System in Durham, N.C. Dr. Sata is a medical instructor in the Duke University Hospital. Dr. Wachter is an assistant professor of medicine at Duke University. Dr. Sharma is associate medical director for clinical education in hospital medicine at Duke Regional Hospital and an assistant professor of medicine at Duke University.

References

1. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: A clinical trial. Ann Intern Med. 1980 Sep;93(3):391-8.

2. Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: Report of the Medical Research Council Working Party. Lancet 1981 Mar 28;1(8222):681-6.

3. Long-term oxygen treatment trial research group et al. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med. 2016 Oct 27;375(17):1617-27.

Additional reading

Stoller JK et al. Oxygen therapy for patients with COPD: Current evidence and the Long-term Oxygen Treatment Trial. Chest. 2010 July;138:179-87.

Qaseem A et al. Diagnosis and management of stable chronic obstructive pulmonary disease: A clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011 Aug 2;155(3):179-91.

Ameer F et al. Ambulatory oxygen for people with chronic obstructive pulmonary disease who are not hypoxaemic at rest. Cochrane Database Syst Rev. 2014 Jun 24;(6):CD000238.

Vestbo J et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65.

Quiz: Does this patient need oxygen?

You are caring for a 72-year-old man with stable COPD who was admitted for cellulitis. He is improving clinically on appropriate antibiotics, and he has been stable on room air every time you examine him. The nurse pages you on the day of discharge – a Sunday – informing you that his oxygen saturation dropped to 88% while he was walking the halls this morning. She asks whether he needs to stay in the hospital so you can arrange home supplemental oxygen therapy. What should you do?

A. Keep him in the hospital until you can arrange home oxygen therapy.

B. Discharge him home Sunday but have the oxygen company go out to his house first thing on Monday.

C. Discharge him home without supplemental oxygen therapy.

D. Check an arterial blood gas to help decide if you should set up oxygen therapy.

The answer is C. He meets the description of stable COPD with mild to moderate exercise-induced desaturation. The LOTT trial supports our clinical decision that he would not benefit from supplemental oxygen therapy at this point.

Key Points

• Long-term oxygen therapy (LTOT) is beneficial in patients with COPD and severe resting hypoxemia (arterial oxygen partial pressure ≤ 55 mm Hg or SpO₂ ≤ 88%) and should be prescribed to improve survival in this population.
• Patients with COPD and mild to moderate resting hypoxemia or exercised-induced hypoxemia should not be routinely prescribed LTOT given the associated costs, risks, and burdens and the lack of evidence of benefit.

Case

An 85-year-old man with long-standing chronic obstructive pulmonary disease (COPD) has a witnessed aspiration event while undergoing an outpatient procedure requiring conscious sedation. He is admitted to the hospital for observation overnight. The next morning, he feels well, but his oxygen saturation dips to 85% with ambulation. He reports this is not new for him, but he vehemently does not want supplemental oxygen.

Background

Patients with COPD and severe resting hypoxemia – arterial oxygen partial pressure less than or equal to 55 mm Hg or peripheral capillary oxygen saturation (SpO₂₎ less than or equal to 88% – commonly are prescribed supplemental oxygen. The evidence supporting this practice is limited to two small trials from the 1970s that showed a survival benefit of long-term oxygen therapy (LTOT) in this population,^1,2 but these trials may not be generalizable to patients today.

For patients with COPD and mild to moderate resting hypoxemia (SpO_2, 89%-93%) or patients with exercise-induced hypoxemia, LTOT has not been shown to improve survival, although it may improve symptoms of dyspnea, exercise tolerance, and other patient reported outcomes. Given the costs, risks, and burdens associated with LTOT, a high-quality clinical trial assessing the effects of LTOT on clinically meaningful outcomes, such as survival or hospitalization, in patients with COPD and moderate hypoxemia has been long overdue.
 

Overview of the data

The utility of long-term treatment with supplemental oxygen in patients with stable COPD and moderate resting or exercise-induced desaturation was examined by the Long-Term Oxygen Treatment Trial (LOTT) Research Group. Results were published in the New England Journal of Medicine in October 2016 in the article, “A Randomized Trial of Long-Term Oxygen for COPD with Moderate Desaturation.”³

The study was initially designed to test whether the use of supplemental oxygen would lead to longer time until death as compared with no supplemental oxygen in the subgroup of COPD patients with stable disease and moderate resting desaturation (defined as resting SpO₂ of 89%-93%). However, because of an enrollment of only 34 patients after 7 months, the trial was redesigned to include exercise-induced desaturation (defined as SpO₂ of greater than or equal to 80% for at least 5 minutes, and less than 90% for at least 10 seconds, on a 6-minute walk test) and the secondary outcome of all-cause hospitalization. Hospitalization for any cause was combined with mortality into a new composite primary outcome.

This study was a randomized, controlled trial which enrolled patients at a total of 14 regional clinical centers and their associated sites for a total of 42 centers in the United States. The experimental arm consisted of a long term supplemental oxygen group, and the control group did not receive long term supplemental oxygen. Patients were assigned to groups in a 1:1 ratio and the study was not blinded. Patients with moderate resting desaturation were prescribed 24 hour oxygen at 2 L/min, and patients with moderate exercise-induced desaturation were prescribed oxygen at 2 L/min during exercise and sleep only. The primary outcome was a composite outcome of time until death or time until first hospitalization for any cause. There were multiple secondary outcomes, including incidence of COPD exacerbation, incidence of severe resting desaturation and severe exercise-induced desaturation, quality of life, sleep quality, depression and anxiety, adherence to regimen, 6-minute walk distance, spirometric measurements, risk of cardiovascular disease, and neurocognitive function.

Data were gathered via yearly visits, biannual telephone interviews, and questionnaires mailed at 4 months and 16 months. Adherence was assessed by inquiring about oxygen use every 4 months. If patients in the supplemental oxygen group used stationary oxygen concentrators, logs of meter readings were kept as well. The necessary final sample size was calculated using a time to composite event survival model with the use of the log-rank test statistic.

A total of 738 patients were enrolled in the trial between January 2009 and September 2015 and were followed for 1-6 years. A total of 97% of participants had at least 1 year of follow-up. Out of the 738 randomized patients, 133 (18%) had only resting desaturations, 319 (43%) had only exercise-induced desaturations, and 286 (39%) had both resting and exercise-induced desaturations. Baseline characteristics including age, sex, race, smoking status, quality of life scores, resting SpO_2, and nadir SpO₂ during the 6-minute walk test were similar between the two groups. The only significant difference noted by the authors between the two groups was a lower BODE (body mass index, airflow obstruction, dyspnea, and exercise) index, which was lower in the group with no supplemental oxygen.

In the time-to-event analysis, there was no significant difference between the two groups in the time to death or first hospitalization (hazard ratio, 0.94; 95% confidence interval, 0.79-1.12; P = .52). There were no significant differences in the rates of all hospitalizations (rate ratio, 1.01; 95% CI, 0.91-1.13), COPD exacerbations (RR 1.08; 95% CI, 0.98-1.19), and COPD related hospitalizations (RR, 0.99; 95% CI, 0.83-1.17). There were also no differences between the experimental and control groups in quality of life, lung function, and 6-minute walk distance. There were no significant differences in the subgroups classified by desaturation profile, sex, race, nadir SpO₂ during the 6-minute walk test, and forced expiratory volume in 1 second.

The findings in this study show that, in the subgroup of chronic obstructive pulmonary disease patients with stable COPD and moderate resting or exercise-induced desaturation, supplemental oxygen did not affect the time to death or first hospitalization, time to death, time to first hospitalization, time to first COPD exacerbation, time to first hospitalization for a COPD exacerbation, rate of all hospitalizations, rate of all COPD exacerbations, or changes in metrics surrounding quality of life, anxiety/depression, or functional status. This supports earlier studies that demonstrated that long-term treatment with oxygen does not result in longer survival than does no long-term treatment with oxygen in patients with COPD and resting SpO₂ of more than 88%.

The results of this study are a departure from previous studies that had shown improved mortality in patients with COPD and severe desaturation who were treated with LTOT. The authors hypothesized that this may have been caused by physiological effects of oxygen saturation on pulmonary vasoconstriction, release of mediators, and ventilator drive, which occur at an O₂ saturation of 88% or less and may be more significant in patients with chronic hypoxemia. This trial also contrasted previous studies that had shown that oxygen therapy may reduce dyspnea in COPD patients with mild or no hypoxia because the LOTT trial showed no improvement in quality of life, anxiety, and depression measures in patients treated with long-term oxygen as compared with those treated with no oxygen.

Some limitations of the study included the absence of highly symptomatic patients or patients who the providers believed were too ill to participate, the effect of the unblinded nature of the study on outcomes that were patient reported, the lack of assessment of immediate effects of oxygen on exercise performance or symptoms, possible variability in amount of oxygen delivered, and the fact that patients may have overestimated their oxygen use.

In patients with stable COPD and moderate resting or exercise induced desaturation, long-term supplemental oxygen did not provide any benefit in regard to time until death or first hospitalization or any of the other measured outcomes.

Application of data to the case

Our patient has stable COPD and had only moderate exercise-induced desaturation. Long-term supplemental oxygen would not produce a benefit for him.

This study shows us that it would not increase his survival at this point; however, if he were to have worsening exercise-induced or new resting desaturation at some point in the future, supplemental oxygen would then be beneficial. At this point supplemental oxygen would not even affect his rate of hospitalization for COPD- or non-COPD–related reasons. Perhaps most importantly, adding oxygen therapy would not affect his overall quality of life, including his functional status and mood.
 

Bottom line

The addition of supplemental oxygen is not helpful for patients with COPD who have chronic stable moderate hypoxia.

Dr. Farber is a medical instructor in the Duke University Health System in Durham, N.C. Dr. Sata is a medical instructor in the Duke University Hospital. Dr. Wachter is an assistant professor of medicine at Duke University. Dr. Sharma is associate medical director for clinical education in hospital medicine at Duke Regional Hospital and an assistant professor of medicine at Duke University.

References

1. Nocturnal Oxygen Therapy Trial Group. Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: A clinical trial. Ann Intern Med. 1980 Sep;93(3):391-8.

2. Medical Research Council Working Party. Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema: Report of the Medical Research Council Working Party. Lancet 1981 Mar 28;1(8222):681-6.

3. Long-term oxygen treatment trial research group et al. A randomized trial of long-term oxygen for COPD with moderate desaturation. N Engl J Med. 2016 Oct 27;375(17):1617-27.

Additional reading

Stoller JK et al. Oxygen therapy for patients with COPD: Current evidence and the Long-term Oxygen Treatment Trial. Chest. 2010 July;138:179-87.

Qaseem A et al. Diagnosis and management of stable chronic obstructive pulmonary disease: A clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and European Respiratory Society. Ann Intern Med. 2011 Aug 2;155(3):179-91.

Ameer F et al. Ambulatory oxygen for people with chronic obstructive pulmonary disease who are not hypoxaemic at rest. Cochrane Database Syst Rev. 2014 Jun 24;(6):CD000238.

Vestbo J et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2013 Feb 15;187(4):347-65.

Quiz: Does this patient need oxygen?

You are caring for a 72-year-old man with stable COPD who was admitted for cellulitis. He is improving clinically on appropriate antibiotics, and he has been stable on room air every time you examine him. The nurse pages you on the day of discharge – a Sunday – informing you that his oxygen saturation dropped to 88% while he was walking the halls this morning. She asks whether he needs to stay in the hospital so you can arrange home supplemental oxygen therapy. What should you do?

A. Keep him in the hospital until you can arrange home oxygen therapy.

B. Discharge him home Sunday but have the oxygen company go out to his house first thing on Monday.

C. Discharge him home without supplemental oxygen therapy.

D. Check an arterial blood gas to help decide if you should set up oxygen therapy.

The answer is C. He meets the description of stable COPD with mild to moderate exercise-induced desaturation. The LOTT trial supports our clinical decision that he would not benefit from supplemental oxygen therapy at this point.

Key Points

• Long-term oxygen therapy (LTOT) is beneficial in patients with COPD and severe resting hypoxemia (arterial oxygen partial pressure ≤ 55 mm Hg or SpO₂ ≤ 88%) and should be prescribed to improve survival in this population.
• Patients with COPD and mild to moderate resting hypoxemia or exercised-induced hypoxemia should not be routinely prescribed LTOT given the associated costs, risks, and burdens and the lack of evidence of benefit.

Astrocyte glutamine synthetase may play an important role in the etiology of mesial temporal lobe epilepsy suggests a recent review in the Journal of Neuroscience Research.

• Investigators from the Yale School of Medicine and Southern Illinois School of Medicine believe that inhibition, loss, or dysfunction of the enzyme in astrocytes may be one of the causative factors responsible for mesial temporal lobe epilepsy.
• Their review of the scientific evidence included a study of astrocyte abnormalities related to aquaporin 4, potassium channel Kir4.1, monocarboxylate transporters MCT1 and MCT2, amino acid transporters EAAT1 and EAA2, and glutamine synthetase.
• Their theory on the role of glutamine synthetase prompted the researchers to suggest that the mechanisms that control the enzyme may be worth consideration as targets for new antiepileptic drugs.

Eid T, Lee TW, Patrylo P, Zaveri HP. Astrocytes and glutamine synthetase in epileptogenesis [published online ahead of print July 18, 2018]. J Neurosci Res. 2018: doi: 10.1002/jnr.24267.   

Astrocyte glutamine synthetase may play an important role in the etiology of mesial temporal lobe epilepsy suggests a recent review in the Journal of Neuroscience Research.

• Investigators from the Yale School of Medicine and Southern Illinois School of Medicine believe that inhibition, loss, or dysfunction of the enzyme in astrocytes may be one of the causative factors responsible for mesial temporal lobe epilepsy.
• Their review of the scientific evidence included a study of astrocyte abnormalities related to aquaporin 4, potassium channel Kir4.1, monocarboxylate transporters MCT1 and MCT2, amino acid transporters EAAT1 and EAA2, and glutamine synthetase.
• Their theory on the role of glutamine synthetase prompted the researchers to suggest that the mechanisms that control the enzyme may be worth consideration as targets for new antiepileptic drugs.

Eid T, Lee TW, Patrylo P, Zaveri HP. Astrocytes and glutamine synthetase in epileptogenesis [published online ahead of print July 18, 2018]. J Neurosci Res. 2018: doi: 10.1002/jnr.24267.   

Astrocyte glutamine synthetase may play an important role in the etiology of mesial temporal lobe epilepsy suggests a recent review in the Journal of Neuroscience Research.

• Investigators from the Yale School of Medicine and Southern Illinois School of Medicine believe that inhibition, loss, or dysfunction of the enzyme in astrocytes may be one of the causative factors responsible for mesial temporal lobe epilepsy.
• Their review of the scientific evidence included a study of astrocyte abnormalities related to aquaporin 4, potassium channel Kir4.1, monocarboxylate transporters MCT1 and MCT2, amino acid transporters EAAT1 and EAA2, and glutamine synthetase.
• Their theory on the role of glutamine synthetase prompted the researchers to suggest that the mechanisms that control the enzyme may be worth consideration as targets for new antiepileptic drugs.

Eid T, Lee TW, Patrylo P, Zaveri HP. Astrocytes and glutamine synthetase in epileptogenesis [published online ahead of print July 18, 2018]. J Neurosci Res. 2018: doi: 10.1002/jnr.24267.   

The presence of interictal ripples in an intracranial EEG may serve as useful biomarkers suggests an analysis of data from 27 children who underwent epilepsy surgery.

• The average rate of onset ripples located inside a resected area of the brain predicted a patient’s outcome (odds ratio, 5.37, P=.02)
• Mean onset ripple rate was associated with the Engel class metric for measuring outcomes.
• Resection of the onset ripple zone was linked to good surgical outcomes (P=.047).
• On the other hand, there was no correlation between spread ripple zone, isolated-ripple zone, or spike zones and outcomes.

Tamilia E, Park EH, Percivati S, et al. Surgical resection of ripple onset predicts outcome in pediatric epilepsy [published online ahead of print July 18, 2018]. Ann Neurol.  2018: doi: 10.1002/ana.25295

The presence of interictal ripples in an intracranial EEG may serve as useful biomarkers suggests an analysis of data from 27 children who underwent epilepsy surgery.

• The average rate of onset ripples located inside a resected area of the brain predicted a patient’s outcome (odds ratio, 5.37, P=.02)
• Mean onset ripple rate was associated with the Engel class metric for measuring outcomes.
• Resection of the onset ripple zone was linked to good surgical outcomes (P=.047).
• On the other hand, there was no correlation between spread ripple zone, isolated-ripple zone, or spike zones and outcomes.

Tamilia E, Park EH, Percivati S, et al. Surgical resection of ripple onset predicts outcome in pediatric epilepsy [published online ahead of print July 18, 2018]. Ann Neurol.  2018: doi: 10.1002/ana.25295

The presence of interictal ripples in an intracranial EEG may serve as useful biomarkers suggests an analysis of data from 27 children who underwent epilepsy surgery.

• The average rate of onset ripples located inside a resected area of the brain predicted a patient’s outcome (odds ratio, 5.37, P=.02)
• Mean onset ripple rate was associated with the Engel class metric for measuring outcomes.
• Resection of the onset ripple zone was linked to good surgical outcomes (P=.047).
• On the other hand, there was no correlation between spread ripple zone, isolated-ripple zone, or spike zones and outcomes.

Tamilia E, Park EH, Percivati S, et al. Surgical resection of ripple onset predicts outcome in pediatric epilepsy [published online ahead of print July 18, 2018]. Ann Neurol.  2018: doi: 10.1002/ana.25295

Magnetoencephalography (MEG) and network-based analyses can help characterize absence epilepsy in children according to a study that looked at 16 patients between ages 6 and 12 years who had absence epilepsy.

• Researchers found functional/anatomical hubs in a network that contained bilateral precuneus, left thalamus, three anterior cerebellar subunits of lobule IV-V, vermis, and lobule III.
• Their analysis suggests that these hubs, which are highly connected brain areas, exist in focal cortical, subcortical, and cerebellar areas during absence seizures.
• The existence of hubs in thalami, precuneus and cingulate cortex suggest bilaterally distributed networks of cortical and subcortical regions that may be responsible for seizures.
• Hubs in the anterior cerebellum may be related to terminating motor automatism seen in absence seizures.

Youssofzadeh, V, Agler W, Tenney JF, Kadis DS. Whole-brain MEG connectivity-based analyses reveals critical hubs in childhood absence epilepsy. Epilepsy Res. 2018;145:102-109.

Magnetoencephalography (MEG) and network-based analyses can help characterize absence epilepsy in children according to a study that looked at 16 patients between ages 6 and 12 years who had absence epilepsy.

• Researchers found functional/anatomical hubs in a network that contained bilateral precuneus, left thalamus, three anterior cerebellar subunits of lobule IV-V, vermis, and lobule III.
• Their analysis suggests that these hubs, which are highly connected brain areas, exist in focal cortical, subcortical, and cerebellar areas during absence seizures.
• The existence of hubs in thalami, precuneus and cingulate cortex suggest bilaterally distributed networks of cortical and subcortical regions that may be responsible for seizures.
• Hubs in the anterior cerebellum may be related to terminating motor automatism seen in absence seizures.

Youssofzadeh, V, Agler W, Tenney JF, Kadis DS. Whole-brain MEG connectivity-based analyses reveals critical hubs in childhood absence epilepsy. Epilepsy Res. 2018;145:102-109.

Magnetoencephalography (MEG) and network-based analyses can help characterize absence epilepsy in children according to a study that looked at 16 patients between ages 6 and 12 years who had absence epilepsy.

• Researchers found functional/anatomical hubs in a network that contained bilateral precuneus, left thalamus, three anterior cerebellar subunits of lobule IV-V, vermis, and lobule III.
• Their analysis suggests that these hubs, which are highly connected brain areas, exist in focal cortical, subcortical, and cerebellar areas during absence seizures.
• The existence of hubs in thalami, precuneus and cingulate cortex suggest bilaterally distributed networks of cortical and subcortical regions that may be responsible for seizures.
• Hubs in the anterior cerebellum may be related to terminating motor automatism seen in absence seizures.

Youssofzadeh, V, Agler W, Tenney JF, Kadis DS. Whole-brain MEG connectivity-based analyses reveals critical hubs in childhood absence epilepsy. Epilepsy Res. 2018;145:102-109.

K. Rajender Reddy, MD, discussed the management of hepatitis B virus reactivation (HBVr), which can occur in the setting of treatment with immunosuppressive or direct-acting antiviral agents, HIV, or organ transplant. He discussed the mechanisms by which HBVr occurs despite serologic evidence of viral clearance, and he reviewed the American Gastroenterological Association Institute’s 2015 Clinical Decision Support Tool on managing HBVr. In patients treated with anti-TNF therapy, HBVr was seen almost exclusively in HBsAg+ patients and not HBsAg–/anti-HBc+ patients. Data supports HBV screening prior to starting anti–tumor necrosis factor therapy and prophylactic antiviral therapy for HBsAg-positive patients, Dr. Reddy explained.

Allison R. Schulman, MD, MPH then discussed endoscopic bariatric therapy for obesity. When he spoke about gastric interventions, he said that, although space-occupying devices have been shown to reduce weight and resolve comorbidities, they are more likely to be removed early because of intolerance and can be associated with serious adverse events (in less than 0.1%). He also said that endoscopic sleeve gastroplasty has been associated with significant weight loss and a beneficial effect on comorbidities and aspiration therapy has been associated with a 20%-25% total body weight loss over 1-2 years. With regard to small-bowel interventions, Dr. Schulman discussed sleeves and liners, mucosal resurfacing therapy, anastomosis and enteral diversion, and flow-altering therapy, none of which are Food and Drug Administration–approved. Endoscopic bariatric therapy options of both types fill a gap between medications and surgery, Dr. Schulman concluded, and are reversible, repeatable, and cost-effective and can be used in combination.

Neil H. Stollman, MD, AGAF, reviewed the role of fecal microbial transplantation (FMT) in gastrointestinal disorders and the variety of ways in which FMT can be administered. One of its main uses is for recurrent Clostridium difficile infection (rCDI); this is the only indication for which the FDA will not require an investigational new drug permit. Dr. Stollman discussed current guidelines for FMT and said that systematic reviews have demonstrated that FMT has an overall cure rate of 85%-90% for rCDI with no or few adverse events. He recommended not resuming vancomycin after FMT and not retesting for rCDI unless the patient has suggestive symptoms. Currently, he noted, more than 180 clinical trials are studying the efficacy of FMT in other diseases, including inflammatory bowel disease, irritable bowel syndrome, and liver disease.

Fasiha Kanwal, MD, MSHS, AGAF, who is editor in chief of Clinical Gastroenterology and Hepatology, presented the top three clinical papers published in that journal or in the journal Gastroenterology. The first paper, titled “Chromoendoscopy for surveillance in ulcerative colitis and Crohn’s disease: A systematic review of randomized trials” (Clin Gastroenterol Hepatol. 2017 Nov;15[11]:1684-97), found that chromoendoscopy identifies more patients with dysplasia when compared with standard-definition, white-light endoscopy. There was no direct evidence, however, of an effect on all-cause or cancer-specific mortality.

The second paper, “Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis” (Clin Gastroenterol Hepatol. 2017 Dec;15[12]:1950-6), showed that both agents were generally well tolerated and that they were equally effective in patients who had responded completely to standard therapy but could not tolerate it. In nonresponders to standard therapy, tacrolimus was more effective.

Dr. Kanwal’s study entitled, “Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents” (Gastroenterology. 2017 Oct;153[4]:996-1005) was the third paper. This study found that sustained virologic response (SVR) resulted in a considerable reduction in the risk of HCC. However, the absolute risk of HCC was high in some patients who achieved sustained virologic response, including about 40% who had already progressed to cirrhosis, she said.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2018. Dr. Chang is the vice-chief of the Vatche and Tamar Manounkian division of digestive diseases, the program director of University of California, Los Angeles, GI fellowship program, the codirector of G. Oppenheimer Center for Neurobiology of Stress and Resilience, and a professor of medicine at UCLA. She is on the advisory board for Synergy, IM HealthSciences, and Salix; an adviser for Metameconnect.com and ModifyHealth; and a speaker for Allergan and Takeda.

K. Rajender Reddy, MD, discussed the management of hepatitis B virus reactivation (HBVr), which can occur in the setting of treatment with immunosuppressive or direct-acting antiviral agents, HIV, or organ transplant. He discussed the mechanisms by which HBVr occurs despite serologic evidence of viral clearance, and he reviewed the American Gastroenterological Association Institute’s 2015 Clinical Decision Support Tool on managing HBVr. In patients treated with anti-TNF therapy, HBVr was seen almost exclusively in HBsAg+ patients and not HBsAg–/anti-HBc+ patients. Data supports HBV screening prior to starting anti–tumor necrosis factor therapy and prophylactic antiviral therapy for HBsAg-positive patients, Dr. Reddy explained.

Allison R. Schulman, MD, MPH then discussed endoscopic bariatric therapy for obesity. When he spoke about gastric interventions, he said that, although space-occupying devices have been shown to reduce weight and resolve comorbidities, they are more likely to be removed early because of intolerance and can be associated with serious adverse events (in less than 0.1%). He also said that endoscopic sleeve gastroplasty has been associated with significant weight loss and a beneficial effect on comorbidities and aspiration therapy has been associated with a 20%-25% total body weight loss over 1-2 years. With regard to small-bowel interventions, Dr. Schulman discussed sleeves and liners, mucosal resurfacing therapy, anastomosis and enteral diversion, and flow-altering therapy, none of which are Food and Drug Administration–approved. Endoscopic bariatric therapy options of both types fill a gap between medications and surgery, Dr. Schulman concluded, and are reversible, repeatable, and cost-effective and can be used in combination.

Neil H. Stollman, MD, AGAF, reviewed the role of fecal microbial transplantation (FMT) in gastrointestinal disorders and the variety of ways in which FMT can be administered. One of its main uses is for recurrent Clostridium difficile infection (rCDI); this is the only indication for which the FDA will not require an investigational new drug permit. Dr. Stollman discussed current guidelines for FMT and said that systematic reviews have demonstrated that FMT has an overall cure rate of 85%-90% for rCDI with no or few adverse events. He recommended not resuming vancomycin after FMT and not retesting for rCDI unless the patient has suggestive symptoms. Currently, he noted, more than 180 clinical trials are studying the efficacy of FMT in other diseases, including inflammatory bowel disease, irritable bowel syndrome, and liver disease.

Fasiha Kanwal, MD, MSHS, AGAF, who is editor in chief of Clinical Gastroenterology and Hepatology, presented the top three clinical papers published in that journal or in the journal Gastroenterology. The first paper, titled “Chromoendoscopy for surveillance in ulcerative colitis and Crohn’s disease: A systematic review of randomized trials” (Clin Gastroenterol Hepatol. 2017 Nov;15[11]:1684-97), found that chromoendoscopy identifies more patients with dysplasia when compared with standard-definition, white-light endoscopy. There was no direct evidence, however, of an effect on all-cause or cancer-specific mortality.

The second paper, “Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis” (Clin Gastroenterol Hepatol. 2017 Dec;15[12]:1950-6), showed that both agents were generally well tolerated and that they were equally effective in patients who had responded completely to standard therapy but could not tolerate it. In nonresponders to standard therapy, tacrolimus was more effective.

Dr. Kanwal’s study entitled, “Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents” (Gastroenterology. 2017 Oct;153[4]:996-1005) was the third paper. This study found that sustained virologic response (SVR) resulted in a considerable reduction in the risk of HCC. However, the absolute risk of HCC was high in some patients who achieved sustained virologic response, including about 40% who had already progressed to cirrhosis, she said.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2018. Dr. Chang is the vice-chief of the Vatche and Tamar Manounkian division of digestive diseases, the program director of University of California, Los Angeles, GI fellowship program, the codirector of G. Oppenheimer Center for Neurobiology of Stress and Resilience, and a professor of medicine at UCLA. She is on the advisory board for Synergy, IM HealthSciences, and Salix; an adviser for Metameconnect.com and ModifyHealth; and a speaker for Allergan and Takeda.

K. Rajender Reddy, MD, discussed the management of hepatitis B virus reactivation (HBVr), which can occur in the setting of treatment with immunosuppressive or direct-acting antiviral agents, HIV, or organ transplant. He discussed the mechanisms by which HBVr occurs despite serologic evidence of viral clearance, and he reviewed the American Gastroenterological Association Institute’s 2015 Clinical Decision Support Tool on managing HBVr. In patients treated with anti-TNF therapy, HBVr was seen almost exclusively in HBsAg+ patients and not HBsAg–/anti-HBc+ patients. Data supports HBV screening prior to starting anti–tumor necrosis factor therapy and prophylactic antiviral therapy for HBsAg-positive patients, Dr. Reddy explained.

Allison R. Schulman, MD, MPH then discussed endoscopic bariatric therapy for obesity. When he spoke about gastric interventions, he said that, although space-occupying devices have been shown to reduce weight and resolve comorbidities, they are more likely to be removed early because of intolerance and can be associated with serious adverse events (in less than 0.1%). He also said that endoscopic sleeve gastroplasty has been associated with significant weight loss and a beneficial effect on comorbidities and aspiration therapy has been associated with a 20%-25% total body weight loss over 1-2 years. With regard to small-bowel interventions, Dr. Schulman discussed sleeves and liners, mucosal resurfacing therapy, anastomosis and enteral diversion, and flow-altering therapy, none of which are Food and Drug Administration–approved. Endoscopic bariatric therapy options of both types fill a gap between medications and surgery, Dr. Schulman concluded, and are reversible, repeatable, and cost-effective and can be used in combination.

Neil H. Stollman, MD, AGAF, reviewed the role of fecal microbial transplantation (FMT) in gastrointestinal disorders and the variety of ways in which FMT can be administered. One of its main uses is for recurrent Clostridium difficile infection (rCDI); this is the only indication for which the FDA will not require an investigational new drug permit. Dr. Stollman discussed current guidelines for FMT and said that systematic reviews have demonstrated that FMT has an overall cure rate of 85%-90% for rCDI with no or few adverse events. He recommended not resuming vancomycin after FMT and not retesting for rCDI unless the patient has suggestive symptoms. Currently, he noted, more than 180 clinical trials are studying the efficacy of FMT in other diseases, including inflammatory bowel disease, irritable bowel syndrome, and liver disease.

Fasiha Kanwal, MD, MSHS, AGAF, who is editor in chief of Clinical Gastroenterology and Hepatology, presented the top three clinical papers published in that journal or in the journal Gastroenterology. The first paper, titled “Chromoendoscopy for surveillance in ulcerative colitis and Crohn’s disease: A systematic review of randomized trials” (Clin Gastroenterol Hepatol. 2017 Nov;15[11]:1684-97), found that chromoendoscopy identifies more patients with dysplasia when compared with standard-definition, white-light endoscopy. There was no direct evidence, however, of an effect on all-cause or cancer-specific mortality.

The second paper, “Efficacy and safety of mycophenolate mofetil and tacrolimus as second-line therapy for patients with autoimmune hepatitis” (Clin Gastroenterol Hepatol. 2017 Dec;15[12]:1950-6), showed that both agents were generally well tolerated and that they were equally effective in patients who had responded completely to standard therapy but could not tolerate it. In nonresponders to standard therapy, tacrolimus was more effective.

Dr. Kanwal’s study entitled, “Risk of hepatocellular cancer in HCV patients treated with direct-acting antiviral agents” (Gastroenterology. 2017 Oct;153[4]:996-1005) was the third paper. This study found that sustained virologic response (SVR) resulted in a considerable reduction in the risk of HCC. However, the absolute risk of HCC was high in some patients who achieved sustained virologic response, including about 40% who had already progressed to cirrhosis, she said.
 

This is a summary provided by the moderator of one of the AGA Postgraduate Course sessions held at DDW 2018. Dr. Chang is the vice-chief of the Vatche and Tamar Manounkian division of digestive diseases, the program director of University of California, Los Angeles, GI fellowship program, the codirector of G. Oppenheimer Center for Neurobiology of Stress and Resilience, and a professor of medicine at UCLA. She is on the advisory board for Synergy, IM HealthSciences, and Salix; an adviser for Metameconnect.com and ModifyHealth; and a speaker for Allergan and Takeda.

The Food and Drug Administration has approved lusutrombopag (Mulpleta) for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo medical or dental procedures. The drug is expected to be available in the United States in September 2018.

The most common adverse event was headache, and the recommended dosage for lusutrombopag is 3 mg orally once daily with or without food for 7 days. Lusutrombopag is not indicated for general platelet normalization in patients with chronic liver disease and thrombocytopenia. Full prescribing information and further information about the approval can be found on the FDA website.

Lusutrombopag was approved in Japan in 2015 for this indication and is slated to be evaluated by the European Medicines Agency in 2019. The drug is marketed by Shionogi.

cpalmer@mdedge.com

The Food and Drug Administration has approved lusutrombopag (Mulpleta) for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo medical or dental procedures. The drug is expected to be available in the United States in September 2018.

The most common adverse event was headache, and the recommended dosage for lusutrombopag is 3 mg orally once daily with or without food for 7 days. Lusutrombopag is not indicated for general platelet normalization in patients with chronic liver disease and thrombocytopenia. Full prescribing information and further information about the approval can be found on the FDA website.

Lusutrombopag was approved in Japan in 2015 for this indication and is slated to be evaluated by the European Medicines Agency in 2019. The drug is marketed by Shionogi.

cpalmer@mdedge.com

The Food and Drug Administration has approved lusutrombopag (Mulpleta) for the treatment of thrombocytopenia in patients with chronic liver disease who are scheduled to undergo medical or dental procedures. The drug is expected to be available in the United States in September 2018.

The most common adverse event was headache, and the recommended dosage for lusutrombopag is 3 mg orally once daily with or without food for 7 days. Lusutrombopag is not indicated for general platelet normalization in patients with chronic liver disease and thrombocytopenia. Full prescribing information and further information about the approval can be found on the FDA website.

Lusutrombopag was approved in Japan in 2015 for this indication and is slated to be evaluated by the European Medicines Agency in 2019. The drug is marketed by Shionogi.

cpalmer@mdedge.com

A behavioral “nudge” intervention, targeting primary care prescribers who have particularly high off-label prescription rates of the antipsychotic quetiapine fumarate to older and disabled adults, has shown significant and long-lasting reductions in prescriptions.

A study, published Aug. 1 online by JAMA Psychiatry, looked at the effect of a “peer-comparison” letter, compared with a placebo letter, sent to 5,055 high quetiapine-prescribing primary care physicians in the Medicare program.

The letters said that the physicians’ quetiapine prescribing was extremely high, compared with their peers’ prescribing in the same state. Furthermore, the letters said the high-volume prescribers’ practices were under review because of concerns over medically unjustified use. They also encouraged the doctors to review their prescribing habits, while the placebo letter simply discussed an unrelated Medicare enrollment regulation.

Over the 9-month study, researchers saw a significant 11.1% reduction in the total number days of quetiapine prescribing among physicians who received the intervention letter, compared with those who received the control letter (95% confidence interval, –13.1 to –9.2 days; P less than .001; adjusted difference, –319 days; 95% CI, –374 to –263 days; P less than .001). At 2 years, the cumulative reduction was 15.6% fewer days in the intervention group (95% CI, –18.1 to –13.0; P less than .001), compared with the control group.

The study also used Medicare data to look at the impact on patients and found that individuals whose physicians were in the intervention arm had 3.9% fewer days of quetiapine usage over the 9 months (95% CI, –5.0 to –2.9; P less than 0.11), compared with those in the control arm. The reduction was even greater among patients whose indications for quetiapine were deemed to be of “low value,” as opposed to those who were prescribed for guideline-concordant indications, reported Adam Sacarny, PhD, of Columbia University, New York, and his coauthors.

When researchers looked in more detail at the reductions in prescriptions for guideline-concordant patients, they found that much of this was offset by prescriptions from other prescribers; in particular, physicians with psychiatric specialization or other study prescribers who the patient had not previously received a quetiapine prescription from.

The authors noted that the reductions for guideline-concordant patients could have negative effects if prescribers were reducing their quetiapine prescriptions indiscriminately.

“If this represented a harmful change for patients, we may have expected to see higher rates of adverse outcomes in the guideline-concordant patient group as prescribing rates decreased,” wrote Dr. Sacarny, and his coauthors. “However, if anything, guideline-concordant patients experienced lower rates of hospital encounters after the intervention.”

The study did not see any evidence of substitution to other antipsychotics, nor was any significant difference found in hospital use or mortality between the two arms of the study.

Dr. Sacarny and his coauthors cited several limitations. One is that the analysis looked at prescribing covered by Medicare Part D only. Nevertheless, they said, the results show the impact that peer comparison letters can have on prescribing patterns.

“These results provide encouraging evidence that high prescribers of antipsychotics can decrease quetiapine prescribing, without adverse clinical consequences, in response to a letter highlighting their overall high rates of prescribing,” the authors wrote.

The study was supported by the Robert Wood Johnson Foundation, Abdul Latif Jameel Poverty Action Lab North America, and the Laura and John Arnold Foundation. No conflicts of interest were reported.

SOURCE: Sacarny A et al. JAMA Psychiatry. 2018 Aug 1. doi: 10.1001/jamapsychiatry.2018.1867.


 

A behavioral “nudge” intervention, targeting primary care prescribers who have particularly high off-label prescription rates of the antipsychotic quetiapine fumarate to older and disabled adults, has shown significant and long-lasting reductions in prescriptions.

A study, published Aug. 1 online by JAMA Psychiatry, looked at the effect of a “peer-comparison” letter, compared with a placebo letter, sent to 5,055 high quetiapine-prescribing primary care physicians in the Medicare program.

The letters said that the physicians’ quetiapine prescribing was extremely high, compared with their peers’ prescribing in the same state. Furthermore, the letters said the high-volume prescribers’ practices were under review because of concerns over medically unjustified use. They also encouraged the doctors to review their prescribing habits, while the placebo letter simply discussed an unrelated Medicare enrollment regulation.

Over the 9-month study, researchers saw a significant 11.1% reduction in the total number days of quetiapine prescribing among physicians who received the intervention letter, compared with those who received the control letter (95% confidence interval, –13.1 to –9.2 days; P less than .001; adjusted difference, –319 days; 95% CI, –374 to –263 days; P less than .001). At 2 years, the cumulative reduction was 15.6% fewer days in the intervention group (95% CI, –18.1 to –13.0; P less than .001), compared with the control group.

The study also used Medicare data to look at the impact on patients and found that individuals whose physicians were in the intervention arm had 3.9% fewer days of quetiapine usage over the 9 months (95% CI, –5.0 to –2.9; P less than 0.11), compared with those in the control arm. The reduction was even greater among patients whose indications for quetiapine were deemed to be of “low value,” as opposed to those who were prescribed for guideline-concordant indications, reported Adam Sacarny, PhD, of Columbia University, New York, and his coauthors.

When researchers looked in more detail at the reductions in prescriptions for guideline-concordant patients, they found that much of this was offset by prescriptions from other prescribers; in particular, physicians with psychiatric specialization or other study prescribers who the patient had not previously received a quetiapine prescription from.

The authors noted that the reductions for guideline-concordant patients could have negative effects if prescribers were reducing their quetiapine prescriptions indiscriminately.

“If this represented a harmful change for patients, we may have expected to see higher rates of adverse outcomes in the guideline-concordant patient group as prescribing rates decreased,” wrote Dr. Sacarny, and his coauthors. “However, if anything, guideline-concordant patients experienced lower rates of hospital encounters after the intervention.”

The study did not see any evidence of substitution to other antipsychotics, nor was any significant difference found in hospital use or mortality between the two arms of the study.

Dr. Sacarny and his coauthors cited several limitations. One is that the analysis looked at prescribing covered by Medicare Part D only. Nevertheless, they said, the results show the impact that peer comparison letters can have on prescribing patterns.

“These results provide encouraging evidence that high prescribers of antipsychotics can decrease quetiapine prescribing, without adverse clinical consequences, in response to a letter highlighting their overall high rates of prescribing,” the authors wrote.

The study was supported by the Robert Wood Johnson Foundation, Abdul Latif Jameel Poverty Action Lab North America, and the Laura and John Arnold Foundation. No conflicts of interest were reported.

SOURCE: Sacarny A et al. JAMA Psychiatry. 2018 Aug 1. doi: 10.1001/jamapsychiatry.2018.1867.


 

A behavioral “nudge” intervention, targeting primary care prescribers who have particularly high off-label prescription rates of the antipsychotic quetiapine fumarate to older and disabled adults, has shown significant and long-lasting reductions in prescriptions.

A study, published Aug. 1 online by JAMA Psychiatry, looked at the effect of a “peer-comparison” letter, compared with a placebo letter, sent to 5,055 high quetiapine-prescribing primary care physicians in the Medicare program.

The letters said that the physicians’ quetiapine prescribing was extremely high, compared with their peers’ prescribing in the same state. Furthermore, the letters said the high-volume prescribers’ practices were under review because of concerns over medically unjustified use. They also encouraged the doctors to review their prescribing habits, while the placebo letter simply discussed an unrelated Medicare enrollment regulation.

Over the 9-month study, researchers saw a significant 11.1% reduction in the total number days of quetiapine prescribing among physicians who received the intervention letter, compared with those who received the control letter (95% confidence interval, –13.1 to –9.2 days; P less than .001; adjusted difference, –319 days; 95% CI, –374 to –263 days; P less than .001). At 2 years, the cumulative reduction was 15.6% fewer days in the intervention group (95% CI, –18.1 to –13.0; P less than .001), compared with the control group.

The study also used Medicare data to look at the impact on patients and found that individuals whose physicians were in the intervention arm had 3.9% fewer days of quetiapine usage over the 9 months (95% CI, –5.0 to –2.9; P less than 0.11), compared with those in the control arm. The reduction was even greater among patients whose indications for quetiapine were deemed to be of “low value,” as opposed to those who were prescribed for guideline-concordant indications, reported Adam Sacarny, PhD, of Columbia University, New York, and his coauthors.

When researchers looked in more detail at the reductions in prescriptions for guideline-concordant patients, they found that much of this was offset by prescriptions from other prescribers; in particular, physicians with psychiatric specialization or other study prescribers who the patient had not previously received a quetiapine prescription from.

The authors noted that the reductions for guideline-concordant patients could have negative effects if prescribers were reducing their quetiapine prescriptions indiscriminately.

“If this represented a harmful change for patients, we may have expected to see higher rates of adverse outcomes in the guideline-concordant patient group as prescribing rates decreased,” wrote Dr. Sacarny, and his coauthors. “However, if anything, guideline-concordant patients experienced lower rates of hospital encounters after the intervention.”

The study did not see any evidence of substitution to other antipsychotics, nor was any significant difference found in hospital use or mortality between the two arms of the study.

Dr. Sacarny and his coauthors cited several limitations. One is that the analysis looked at prescribing covered by Medicare Part D only. Nevertheless, they said, the results show the impact that peer comparison letters can have on prescribing patterns.

“These results provide encouraging evidence that high prescribers of antipsychotics can decrease quetiapine prescribing, without adverse clinical consequences, in response to a letter highlighting their overall high rates of prescribing,” the authors wrote.

The study was supported by the Robert Wood Johnson Foundation, Abdul Latif Jameel Poverty Action Lab North America, and the Laura and John Arnold Foundation. No conflicts of interest were reported.

SOURCE: Sacarny A et al. JAMA Psychiatry. 2018 Aug 1. doi: 10.1001/jamapsychiatry.2018.1867.


 

Surveillance endoscopy should be spaced at 1 and 3 years after complete eradication of low-grade intestinal metaplasia and at 3 months, 6 months, 1 year, and then annually in cases of high-grade dysplasia, researchers wrote in Gastroenterology.

This “much-attenuated schedule of surveillance endoscopy would provide protection from invasive adenocarcinoma,” wrote Cary C. Cotton, MD, of the department of medicine at the University of North Carolina at Chapel Hill, with his associates. Following this schedule could prevent unnecessary endoscopies while still detecting unresectable cancers at rates under 1 in 1,000 endoscopies, they added.

Barrett’s esophagus recurs in at least one in four cases after successful radiofrequency ablation, the researchers noted. Therefore, surveillance endoscopy is recommended after complete eradication of intestinal metaplasia, but only expert opinion informs the frequency of surveillance. This study modeled and validated rates of neoplastic recurrence by using data from the United States Radiofrequency Ablation Registry during 2004-2013 and from the United Kingdom National Halo Registry during 2007-2015.

In line with prior research, predictors of neoplastic recurrence included baseline histologic grade, age, sex, endoscopic mucosal resection, and baseline length of Barrett’s esophagus, the researchers said. The strongest predictor of recurrence was the most severe histologic grade identified before complete eradication of intestinal metaplasia. After controlling for covariates, a model based only on most-severe baseline histology predicted neoplastic recurrence with a C statistic of 0.892 (95% confidence interval, 0.86-0.92) in the United States Radiofrequency Ablation Registry.

Dysplasia recurred at similar rates regardless of whether patients had nondysplastic Barrett’s esophagus or indeterminate dysplasia. Recurrence rates also were similar between patients with high-grade dysplasia and patients with intramucosal carcinoma. Thus, the researchers identified three risk groups based on most-severe baseline histology: dysplastic Barrett’s esophagus or indefinite for dysplasia, low-grade dysplasia, and high-grade lesions or intramucosal adenocarcinoma.

The annual rate of any-grade neoplastic recurrence was 0.19% in the lowest-risk group, 1.98% in the intermediate-risk group, and 5.93% in the highest-risk group. “In the higher-risk groups, neoplastic recurrence occurred at a higher rate in the first year, but at a constant estimated rate thereafter,” the investigators wrote. Among 114 initial cases of neoplastic recurrence, 1.8% were esophageal adenocarcinoma and another 1.8% of patients developed esophageal adenocarcinoma within 6 months.

The researchers then modeled surveillance intervals by assuming a 2.9% rate of neoplastic recurrence per visit, which yielded a 0.1% rate of invasive adenocarcinoma. “This level of risk tolerance was chosen so that the risk of complications from surveillance endoscopy – approximately one in 1,000 in this patient population – would roughly approximate the risk of invasive carcinoma discovered at the exam,” they wrote. For patients at higher risk of endoscopic complications, they set the rate of neoplastic recurrence at 5.7%, which yielded a 0.2% rate of invasive cancer. “As would be expected, the higher the risk tolerance, the longer the period between endoscopic surveillance intervals.”

Based on the model, the researchers proposed surveillance intervals of 1 year, followed by 3 years, followed by more than 5 years for patients with completely eradicated low-grade dysplasia. For cases of high-grade dysplasia or carcinoma in situ, the proposed surveillance intervals were 3 months, 6 months, 1 year, and then annually. The model also performed well when applied to data from the United Kingdom National Halo Registry, the investigators said, noting that their approach was the first to directly establish an evidence base for surveillance practices in Barrett’s esophagus.

SOURCE: Cotton CC et al. Gastroenterology. 2018 Apr 12. doi: 10.1053/j.gastro.2018.04.011.

Surveillance endoscopy should be spaced at 1 and 3 years after complete eradication of low-grade intestinal metaplasia and at 3 months, 6 months, 1 year, and then annually in cases of high-grade dysplasia, researchers wrote in Gastroenterology.

This “much-attenuated schedule of surveillance endoscopy would provide protection from invasive adenocarcinoma,” wrote Cary C. Cotton, MD, of the department of medicine at the University of North Carolina at Chapel Hill, with his associates. Following this schedule could prevent unnecessary endoscopies while still detecting unresectable cancers at rates under 1 in 1,000 endoscopies, they added.

Barrett’s esophagus recurs in at least one in four cases after successful radiofrequency ablation, the researchers noted. Therefore, surveillance endoscopy is recommended after complete eradication of intestinal metaplasia, but only expert opinion informs the frequency of surveillance. This study modeled and validated rates of neoplastic recurrence by using data from the United States Radiofrequency Ablation Registry during 2004-2013 and from the United Kingdom National Halo Registry during 2007-2015.

In line with prior research, predictors of neoplastic recurrence included baseline histologic grade, age, sex, endoscopic mucosal resection, and baseline length of Barrett’s esophagus, the researchers said. The strongest predictor of recurrence was the most severe histologic grade identified before complete eradication of intestinal metaplasia. After controlling for covariates, a model based only on most-severe baseline histology predicted neoplastic recurrence with a C statistic of 0.892 (95% confidence interval, 0.86-0.92) in the United States Radiofrequency Ablation Registry.

Dysplasia recurred at similar rates regardless of whether patients had nondysplastic Barrett’s esophagus or indeterminate dysplasia. Recurrence rates also were similar between patients with high-grade dysplasia and patients with intramucosal carcinoma. Thus, the researchers identified three risk groups based on most-severe baseline histology: dysplastic Barrett’s esophagus or indefinite for dysplasia, low-grade dysplasia, and high-grade lesions or intramucosal adenocarcinoma.

The annual rate of any-grade neoplastic recurrence was 0.19% in the lowest-risk group, 1.98% in the intermediate-risk group, and 5.93% in the highest-risk group. “In the higher-risk groups, neoplastic recurrence occurred at a higher rate in the first year, but at a constant estimated rate thereafter,” the investigators wrote. Among 114 initial cases of neoplastic recurrence, 1.8% were esophageal adenocarcinoma and another 1.8% of patients developed esophageal adenocarcinoma within 6 months.

The researchers then modeled surveillance intervals by assuming a 2.9% rate of neoplastic recurrence per visit, which yielded a 0.1% rate of invasive adenocarcinoma. “This level of risk tolerance was chosen so that the risk of complications from surveillance endoscopy – approximately one in 1,000 in this patient population – would roughly approximate the risk of invasive carcinoma discovered at the exam,” they wrote. For patients at higher risk of endoscopic complications, they set the rate of neoplastic recurrence at 5.7%, which yielded a 0.2% rate of invasive cancer. “As would be expected, the higher the risk tolerance, the longer the period between endoscopic surveillance intervals.”

Based on the model, the researchers proposed surveillance intervals of 1 year, followed by 3 years, followed by more than 5 years for patients with completely eradicated low-grade dysplasia. For cases of high-grade dysplasia or carcinoma in situ, the proposed surveillance intervals were 3 months, 6 months, 1 year, and then annually. The model also performed well when applied to data from the United Kingdom National Halo Registry, the investigators said, noting that their approach was the first to directly establish an evidence base for surveillance practices in Barrett’s esophagus.

SOURCE: Cotton CC et al. Gastroenterology. 2018 Apr 12. doi: 10.1053/j.gastro.2018.04.011.

Surveillance endoscopy should be spaced at 1 and 3 years after complete eradication of low-grade intestinal metaplasia and at 3 months, 6 months, 1 year, and then annually in cases of high-grade dysplasia, researchers wrote in Gastroenterology.

This “much-attenuated schedule of surveillance endoscopy would provide protection from invasive adenocarcinoma,” wrote Cary C. Cotton, MD, of the department of medicine at the University of North Carolina at Chapel Hill, with his associates. Following this schedule could prevent unnecessary endoscopies while still detecting unresectable cancers at rates under 1 in 1,000 endoscopies, they added.

Barrett’s esophagus recurs in at least one in four cases after successful radiofrequency ablation, the researchers noted. Therefore, surveillance endoscopy is recommended after complete eradication of intestinal metaplasia, but only expert opinion informs the frequency of surveillance. This study modeled and validated rates of neoplastic recurrence by using data from the United States Radiofrequency Ablation Registry during 2004-2013 and from the United Kingdom National Halo Registry during 2007-2015.

In line with prior research, predictors of neoplastic recurrence included baseline histologic grade, age, sex, endoscopic mucosal resection, and baseline length of Barrett’s esophagus, the researchers said. The strongest predictor of recurrence was the most severe histologic grade identified before complete eradication of intestinal metaplasia. After controlling for covariates, a model based only on most-severe baseline histology predicted neoplastic recurrence with a C statistic of 0.892 (95% confidence interval, 0.86-0.92) in the United States Radiofrequency Ablation Registry.

Dysplasia recurred at similar rates regardless of whether patients had nondysplastic Barrett’s esophagus or indeterminate dysplasia. Recurrence rates also were similar between patients with high-grade dysplasia and patients with intramucosal carcinoma. Thus, the researchers identified three risk groups based on most-severe baseline histology: dysplastic Barrett’s esophagus or indefinite for dysplasia, low-grade dysplasia, and high-grade lesions or intramucosal adenocarcinoma.

The annual rate of any-grade neoplastic recurrence was 0.19% in the lowest-risk group, 1.98% in the intermediate-risk group, and 5.93% in the highest-risk group. “In the higher-risk groups, neoplastic recurrence occurred at a higher rate in the first year, but at a constant estimated rate thereafter,” the investigators wrote. Among 114 initial cases of neoplastic recurrence, 1.8% were esophageal adenocarcinoma and another 1.8% of patients developed esophageal adenocarcinoma within 6 months.

The researchers then modeled surveillance intervals by assuming a 2.9% rate of neoplastic recurrence per visit, which yielded a 0.1% rate of invasive adenocarcinoma. “This level of risk tolerance was chosen so that the risk of complications from surveillance endoscopy – approximately one in 1,000 in this patient population – would roughly approximate the risk of invasive carcinoma discovered at the exam,” they wrote. For patients at higher risk of endoscopic complications, they set the rate of neoplastic recurrence at 5.7%, which yielded a 0.2% rate of invasive cancer. “As would be expected, the higher the risk tolerance, the longer the period between endoscopic surveillance intervals.”

Based on the model, the researchers proposed surveillance intervals of 1 year, followed by 3 years, followed by more than 5 years for patients with completely eradicated low-grade dysplasia. For cases of high-grade dysplasia or carcinoma in situ, the proposed surveillance intervals were 3 months, 6 months, 1 year, and then annually. The model also performed well when applied to data from the United Kingdom National Halo Registry, the investigators said, noting that their approach was the first to directly establish an evidence base for surveillance practices in Barrett’s esophagus.

SOURCE: Cotton CC et al. Gastroenterology. 2018 Apr 12. doi: 10.1053/j.gastro.2018.04.011.

LOS ANGELES—Laterality is an independent predictor of endovascular thrombectomy in patients with an NIH Stroke Scale (NIHSS) score of 12 or lower, according to research described at the 70th Annual Meeting of the American Academy of Neurology. “There may be a need for a laterality-based NIHSS score or at least a conscious effort to look for right-hemisphere strokes with a large-vessel occlusion,” said Shashvat Desai, MD, a neurology trainee at the University of Pittsburgh.

Endovascular thrombectomy is the standard of care for acute ischemic stroke resulting from a large-vessel occlusion. Among the eligibility criteria for thrombectomy is an NIHSS score of 6 or higher.

“The NIHSS score is biased and will allow a higher score for dominant-hemisphere strokes, as compared with nondominant-hemisphere strokes,” said Dr. Desai. “Seven points on this scale are directly related to language, which is a dominant-hemisphere function, and only two points are for neglect, which occurs during nondominant-hemisphere strokes.”

A Retrospective Data Analysis

To test their hypothesis that NIHSS score hemispheric lateralization bias affects stroke patient selection for acute endovascular thrombectomy, Dr. Desai and colleagues analyzed data from consecutive patients with acute ischemic stroke resulting from large-vessel occlusion who were admitted to a comprehensive stroke center between June 2015 and December 2016. Eligible patients were identified within 24 hours of when they were last known to be well, were functionally independent at baseline, had an Alberta Stroke Program Early CT (ASPECT) score of 6 or higher, and had an NIHSS score of 6 or higher. The investigators included 211 patients in their study. They examined variables such as age, NIHSS score, occlusion location, baseline modified Rankin Scale (mRS) score, time to presentation, and treatment received. When they separated patients with left-hemisphere strokes from those with right-hemisphere strokes, they found that the two groups were well matched in terms of age, gender, and site of occlusion. The median admission NIHSS score was 19 for left-hemisphere strokes and 15 for right-hemisphere strokes, and the difference between groups was statistically significant.

Thrombectomy Was More Common for Left-Hemisphere Strokes

Endovascular thrombectomy was performed for 87% of left-hemisphere strokes, compared with 78% of right-hemisphere strokes, and the difference between groups was statistically significant. When the researchers examined only participants with a low NIHSS score (ie, 12 or lower), they found that thrombectomy was performed in 81% of left-hemisphere strokes, compared with 52% of right-hemisphere strokes. The difference in the rate of treatment was statistically significant. Among patients with a high NIHSS score (ie, higher than 12), endovascular therapy was performed in 88% of participants, regardless of laterality.

A regression analysis that included variables such as age, sex, occlusion location, time to presentation, ASPECT score, IV t-PA, and laterality indicated that laterality was the sole and independent predictor of receiving endovascular thrombectomy in patients with low NIHSS score. “The preservation of language in right-hemisphere strokes with low NIHSS score reduces the chances of receiving endovascular thrombectomy,” said Dr. Desai.

Among patients with low NIHSS scores who received thrombectomy, the rate of good outcome (ie, an mRS score of 0 to 2) at three months was 88% for left-hemisphere strokes and 71% for right-hemisphere strokes. This difference was not statistically significant. Among all patients with low NIHSS scores, irrespective of treatment, 86% of left-hemisphere strokes had a good outcome, compared with 48% of right-hemisphere strokes. This difference was statistically significant.

—Erik Greb

LOS ANGELES—Laterality is an independent predictor of endovascular thrombectomy in patients with an NIH Stroke Scale (NIHSS) score of 12 or lower, according to research described at the 70th Annual Meeting of the American Academy of Neurology. “There may be a need for a laterality-based NIHSS score or at least a conscious effort to look for right-hemisphere strokes with a large-vessel occlusion,” said Shashvat Desai, MD, a neurology trainee at the University of Pittsburgh.

Endovascular thrombectomy is the standard of care for acute ischemic stroke resulting from a large-vessel occlusion. Among the eligibility criteria for thrombectomy is an NIHSS score of 6 or higher.

“The NIHSS score is biased and will allow a higher score for dominant-hemisphere strokes, as compared with nondominant-hemisphere strokes,” said Dr. Desai. “Seven points on this scale are directly related to language, which is a dominant-hemisphere function, and only two points are for neglect, which occurs during nondominant-hemisphere strokes.”

A Retrospective Data Analysis

To test their hypothesis that NIHSS score hemispheric lateralization bias affects stroke patient selection for acute endovascular thrombectomy, Dr. Desai and colleagues analyzed data from consecutive patients with acute ischemic stroke resulting from large-vessel occlusion who were admitted to a comprehensive stroke center between June 2015 and December 2016. Eligible patients were identified within 24 hours of when they were last known to be well, were functionally independent at baseline, had an Alberta Stroke Program Early CT (ASPECT) score of 6 or higher, and had an NIHSS score of 6 or higher. The investigators included 211 patients in their study. They examined variables such as age, NIHSS score, occlusion location, baseline modified Rankin Scale (mRS) score, time to presentation, and treatment received. When they separated patients with left-hemisphere strokes from those with right-hemisphere strokes, they found that the two groups were well matched in terms of age, gender, and site of occlusion. The median admission NIHSS score was 19 for left-hemisphere strokes and 15 for right-hemisphere strokes, and the difference between groups was statistically significant.

Thrombectomy Was More Common for Left-Hemisphere Strokes

Endovascular thrombectomy was performed for 87% of left-hemisphere strokes, compared with 78% of right-hemisphere strokes, and the difference between groups was statistically significant. When the researchers examined only participants with a low NIHSS score (ie, 12 or lower), they found that thrombectomy was performed in 81% of left-hemisphere strokes, compared with 52% of right-hemisphere strokes. The difference in the rate of treatment was statistically significant. Among patients with a high NIHSS score (ie, higher than 12), endovascular therapy was performed in 88% of participants, regardless of laterality.

A regression analysis that included variables such as age, sex, occlusion location, time to presentation, ASPECT score, IV t-PA, and laterality indicated that laterality was the sole and independent predictor of receiving endovascular thrombectomy in patients with low NIHSS score. “The preservation of language in right-hemisphere strokes with low NIHSS score reduces the chances of receiving endovascular thrombectomy,” said Dr. Desai.

Among patients with low NIHSS scores who received thrombectomy, the rate of good outcome (ie, an mRS score of 0 to 2) at three months was 88% for left-hemisphere strokes and 71% for right-hemisphere strokes. This difference was not statistically significant. Among all patients with low NIHSS scores, irrespective of treatment, 86% of left-hemisphere strokes had a good outcome, compared with 48% of right-hemisphere strokes. This difference was statistically significant.

—Erik Greb

LOS ANGELES—Laterality is an independent predictor of endovascular thrombectomy in patients with an NIH Stroke Scale (NIHSS) score of 12 or lower, according to research described at the 70th Annual Meeting of the American Academy of Neurology. “There may be a need for a laterality-based NIHSS score or at least a conscious effort to look for right-hemisphere strokes with a large-vessel occlusion,” said Shashvat Desai, MD, a neurology trainee at the University of Pittsburgh.

Endovascular thrombectomy is the standard of care for acute ischemic stroke resulting from a large-vessel occlusion. Among the eligibility criteria for thrombectomy is an NIHSS score of 6 or higher.

“The NIHSS score is biased and will allow a higher score for dominant-hemisphere strokes, as compared with nondominant-hemisphere strokes,” said Dr. Desai. “Seven points on this scale are directly related to language, which is a dominant-hemisphere function, and only two points are for neglect, which occurs during nondominant-hemisphere strokes.”

A Retrospective Data Analysis

To test their hypothesis that NIHSS score hemispheric lateralization bias affects stroke patient selection for acute endovascular thrombectomy, Dr. Desai and colleagues analyzed data from consecutive patients with acute ischemic stroke resulting from large-vessel occlusion who were admitted to a comprehensive stroke center between June 2015 and December 2016. Eligible patients were identified within 24 hours of when they were last known to be well, were functionally independent at baseline, had an Alberta Stroke Program Early CT (ASPECT) score of 6 or higher, and had an NIHSS score of 6 or higher. The investigators included 211 patients in their study. They examined variables such as age, NIHSS score, occlusion location, baseline modified Rankin Scale (mRS) score, time to presentation, and treatment received. When they separated patients with left-hemisphere strokes from those with right-hemisphere strokes, they found that the two groups were well matched in terms of age, gender, and site of occlusion. The median admission NIHSS score was 19 for left-hemisphere strokes and 15 for right-hemisphere strokes, and the difference between groups was statistically significant.

Thrombectomy Was More Common for Left-Hemisphere Strokes

Endovascular thrombectomy was performed for 87% of left-hemisphere strokes, compared with 78% of right-hemisphere strokes, and the difference between groups was statistically significant. When the researchers examined only participants with a low NIHSS score (ie, 12 or lower), they found that thrombectomy was performed in 81% of left-hemisphere strokes, compared with 52% of right-hemisphere strokes. The difference in the rate of treatment was statistically significant. Among patients with a high NIHSS score (ie, higher than 12), endovascular therapy was performed in 88% of participants, regardless of laterality.

A regression analysis that included variables such as age, sex, occlusion location, time to presentation, ASPECT score, IV t-PA, and laterality indicated that laterality was the sole and independent predictor of receiving endovascular thrombectomy in patients with low NIHSS score. “The preservation of language in right-hemisphere strokes with low NIHSS score reduces the chances of receiving endovascular thrombectomy,” said Dr. Desai.

Among patients with low NIHSS scores who received thrombectomy, the rate of good outcome (ie, an mRS score of 0 to 2) at three months was 88% for left-hemisphere strokes and 71% for right-hemisphere strokes. This difference was not statistically significant. Among all patients with low NIHSS scores, irrespective of treatment, 86% of left-hemisphere strokes had a good outcome, compared with 48% of right-hemisphere strokes. This difference was statistically significant.

—Erik Greb