A 46-year-old man with no significant medical history presents to the emergency department (ED) with right flank pain and nausea. CT reveals a 5-mm ureteral stone with no obstruction or hydronephrosis. You are planning to start him on IV ketorolac for pain. What is the most appropriate dose?

Ketorolac tromethamine is a highly effective NSAID. As a nonopiate analgesic, it is often the first choice for the treatment of acute pain in the flank, abdomen, musculoskeletal system, or head.² While it is not associated with euphoria, withdrawal effects, or respiratory depression (like its opiate analgesic counterparts), ketorolac carries an FDA black-box warning for gastrointestinal, cardiovascular, renal, and bleeding risks.³

NSAIDs are known to have a “ceiling dose” at which maximum analgesic benefit is achieved; higher doses will not provide further pain relief. Higher doses of ketorolac may be used when the anti-inflammatory effects of NSAIDs are desired, but they are likely to cause more adverse effects.⁴ Available data describe the ceiling dose of ketorolac as 10 mg across dosage forms—yet the majority of research and most health care providers in current practice use higher doses (20 to 60 mg).^4,5 The FDA-approved labeling provides for a maximum dose of 60 mg/d.³

In one recent study, ketorolac was prescribed above its ceiling dose in at least 97% of patients who received IV doses and at least 96% of those who received intramuscular (IM) doses in a US ED.⁶ If 10 mg of ketorolac is an effective analgesic dose, current practice exceeds the label recommendation to use the lowest effective dose. This study sought to determine the comparative efficacy of 3 different doses of IV ketorolac for acute pain management in an ED.

STUDY SUMMARY

10 mg of ketorolac is enough for pain

This randomized double-blind trial evaluated the effectiveness of ketorolac in 240 adult patients (ages 18 to 65) presenting to an ED with acute flank, abdominal, musculoskeletal, or headache pain.¹ Acute pain was defined as onset within the past 30 days.

Patients were randomly assigned to receive either 10, 15, or 30 mg of IV ketorolac in 10 mL of normal saline. A pharmacist prepared the medication in identical syringes, which were delivered in a blinded manner to the nurses caring for the patients. Pain (measured using a 0-to-10 scale), vital signs, and adverse effects were assessed at baseline and at 15, 30, 60, 90, and 120 minutes. If patients were still in pain at 30 minutes, IV morphine (0.1 mg/kg) was offered. The primary outcome was a numerical pain score at 30 minutes after ketorolac administration; secondary outcomes included the occurrence of adverse events and the use of rescue medication (morphine).

The treatment groups were similar in terms of demographics and baseline vital signs. Mean age was 39 to 42. Across the 3 groups, 36% to 40% of patients had abdominal pain, 26% to 39% had flank pain, 20% to 26% had musculoskeletal pain, and 1% to 11% had headache pain. Patients had experienced pain for an average of 1.5 to 3.5 days.

Continue to: Baseline pain scores...

Baseline pain scores were similar for all 3 groups (7.5-7.8 on a 10-point scale). In the intention-to-treat analysis, all 3 doses of ketorolac decreased pain significantly at 30 minutes, with no difference between the groups: mean pain scores postintervention were 5.1 for the 10- and 15-mg group and 4.8 for the 30-mg group. There was no difference between the groups at any other time intervals. There was also no difference between groups in the number of patients who needed rescue medication at 30 minutes (4 patients in the 10-mg group, 3 patients in the 15-mg group, and 4 patients in the 30-mg group). In addition, adverse events (eg, dizziness, nausea, headache, itching, flushing) did not differ between the groups.

WHAT’S NEW

10 mg is just as effective as 30 mg

This trial confirms that a low dose of IV ketorolac is just as effective as higher doses for acute pain control.

CAVEATS

2-hour limit; no look at long-term effects

It isn’t known whether the higher dose would have provided greater pain relief beyond the 120 minutes evaluated in this trial, or if alternative dosage forms (oral or IM) would result in different outcomes. This study was not designed to compare serious long-term adverse effects such as bleeding, renal impairment, or cardiovascular events. Additionally, this study was not powered to look at specific therapeutic indications or anti-inflammatory response.

CHALLENGES TO IMPLEMENTATION

10-mg single-dose vial not readily available

Ketorolac tromethamine for injection is available in the United States in 15-, 30-, and 60-mg single-dose vials. Because a 10-mg dose is not available as a single-dose vial, it would need to be specially prepared (as it was in this study). However, this study should reassure providers that using the lowest available dose (eg, 15 mg IV if that is what is available) will relieve acute pain as well as higher doses will. CR

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[1]:41-42).

A 46-year-old man with no significant medical history presents to the emergency department (ED) with right flank pain and nausea. CT reveals a 5-mm ureteral stone with no obstruction or hydronephrosis. You are planning to start him on IV ketorolac for pain. What is the most appropriate dose?

Ketorolac tromethamine is a highly effective NSAID. As a nonopiate analgesic, it is often the first choice for the treatment of acute pain in the flank, abdomen, musculoskeletal system, or head.² While it is not associated with euphoria, withdrawal effects, or respiratory depression (like its opiate analgesic counterparts), ketorolac carries an FDA black-box warning for gastrointestinal, cardiovascular, renal, and bleeding risks.³

NSAIDs are known to have a “ceiling dose” at which maximum analgesic benefit is achieved; higher doses will not provide further pain relief. Higher doses of ketorolac may be used when the anti-inflammatory effects of NSAIDs are desired, but they are likely to cause more adverse effects.⁴ Available data describe the ceiling dose of ketorolac as 10 mg across dosage forms—yet the majority of research and most health care providers in current practice use higher doses (20 to 60 mg).^4,5 The FDA-approved labeling provides for a maximum dose of 60 mg/d.³

In one recent study, ketorolac was prescribed above its ceiling dose in at least 97% of patients who received IV doses and at least 96% of those who received intramuscular (IM) doses in a US ED.⁶ If 10 mg of ketorolac is an effective analgesic dose, current practice exceeds the label recommendation to use the lowest effective dose. This study sought to determine the comparative efficacy of 3 different doses of IV ketorolac for acute pain management in an ED.

STUDY SUMMARY

10 mg of ketorolac is enough for pain

This randomized double-blind trial evaluated the effectiveness of ketorolac in 240 adult patients (ages 18 to 65) presenting to an ED with acute flank, abdominal, musculoskeletal, or headache pain.¹ Acute pain was defined as onset within the past 30 days.

Patients were randomly assigned to receive either 10, 15, or 30 mg of IV ketorolac in 10 mL of normal saline. A pharmacist prepared the medication in identical syringes, which were delivered in a blinded manner to the nurses caring for the patients. Pain (measured using a 0-to-10 scale), vital signs, and adverse effects were assessed at baseline and at 15, 30, 60, 90, and 120 minutes. If patients were still in pain at 30 minutes, IV morphine (0.1 mg/kg) was offered. The primary outcome was a numerical pain score at 30 minutes after ketorolac administration; secondary outcomes included the occurrence of adverse events and the use of rescue medication (morphine).

The treatment groups were similar in terms of demographics and baseline vital signs. Mean age was 39 to 42. Across the 3 groups, 36% to 40% of patients had abdominal pain, 26% to 39% had flank pain, 20% to 26% had musculoskeletal pain, and 1% to 11% had headache pain. Patients had experienced pain for an average of 1.5 to 3.5 days.

Continue to: Baseline pain scores...

Baseline pain scores were similar for all 3 groups (7.5-7.8 on a 10-point scale). In the intention-to-treat analysis, all 3 doses of ketorolac decreased pain significantly at 30 minutes, with no difference between the groups: mean pain scores postintervention were 5.1 for the 10- and 15-mg group and 4.8 for the 30-mg group. There was no difference between the groups at any other time intervals. There was also no difference between groups in the number of patients who needed rescue medication at 30 minutes (4 patients in the 10-mg group, 3 patients in the 15-mg group, and 4 patients in the 30-mg group). In addition, adverse events (eg, dizziness, nausea, headache, itching, flushing) did not differ between the groups.

WHAT’S NEW

10 mg is just as effective as 30 mg

This trial confirms that a low dose of IV ketorolac is just as effective as higher doses for acute pain control.

CAVEATS

2-hour limit; no look at long-term effects

It isn’t known whether the higher dose would have provided greater pain relief beyond the 120 minutes evaluated in this trial, or if alternative dosage forms (oral or IM) would result in different outcomes. This study was not designed to compare serious long-term adverse effects such as bleeding, renal impairment, or cardiovascular events. Additionally, this study was not powered to look at specific therapeutic indications or anti-inflammatory response.

CHALLENGES TO IMPLEMENTATION

10-mg single-dose vial not readily available

Ketorolac tromethamine for injection is available in the United States in 15-, 30-, and 60-mg single-dose vials. Because a 10-mg dose is not available as a single-dose vial, it would need to be specially prepared (as it was in this study). However, this study should reassure providers that using the lowest available dose (eg, 15 mg IV if that is what is available) will relieve acute pain as well as higher doses will. CR

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[1]:41-42).

A 46-year-old man with no significant medical history presents to the emergency department (ED) with right flank pain and nausea. CT reveals a 5-mm ureteral stone with no obstruction or hydronephrosis. You are planning to start him on IV ketorolac for pain. What is the most appropriate dose?

Ketorolac tromethamine is a highly effective NSAID. As a nonopiate analgesic, it is often the first choice for the treatment of acute pain in the flank, abdomen, musculoskeletal system, or head.² While it is not associated with euphoria, withdrawal effects, or respiratory depression (like its opiate analgesic counterparts), ketorolac carries an FDA black-box warning for gastrointestinal, cardiovascular, renal, and bleeding risks.³

NSAIDs are known to have a “ceiling dose” at which maximum analgesic benefit is achieved; higher doses will not provide further pain relief. Higher doses of ketorolac may be used when the anti-inflammatory effects of NSAIDs are desired, but they are likely to cause more adverse effects.⁴ Available data describe the ceiling dose of ketorolac as 10 mg across dosage forms—yet the majority of research and most health care providers in current practice use higher doses (20 to 60 mg).^4,5 The FDA-approved labeling provides for a maximum dose of 60 mg/d.³

In one recent study, ketorolac was prescribed above its ceiling dose in at least 97% of patients who received IV doses and at least 96% of those who received intramuscular (IM) doses in a US ED.⁶ If 10 mg of ketorolac is an effective analgesic dose, current practice exceeds the label recommendation to use the lowest effective dose. This study sought to determine the comparative efficacy of 3 different doses of IV ketorolac for acute pain management in an ED.

STUDY SUMMARY

10 mg of ketorolac is enough for pain

This randomized double-blind trial evaluated the effectiveness of ketorolac in 240 adult patients (ages 18 to 65) presenting to an ED with acute flank, abdominal, musculoskeletal, or headache pain.¹ Acute pain was defined as onset within the past 30 days.

Patients were randomly assigned to receive either 10, 15, or 30 mg of IV ketorolac in 10 mL of normal saline. A pharmacist prepared the medication in identical syringes, which were delivered in a blinded manner to the nurses caring for the patients. Pain (measured using a 0-to-10 scale), vital signs, and adverse effects were assessed at baseline and at 15, 30, 60, 90, and 120 minutes. If patients were still in pain at 30 minutes, IV morphine (0.1 mg/kg) was offered. The primary outcome was a numerical pain score at 30 minutes after ketorolac administration; secondary outcomes included the occurrence of adverse events and the use of rescue medication (morphine).

The treatment groups were similar in terms of demographics and baseline vital signs. Mean age was 39 to 42. Across the 3 groups, 36% to 40% of patients had abdominal pain, 26% to 39% had flank pain, 20% to 26% had musculoskeletal pain, and 1% to 11% had headache pain. Patients had experienced pain for an average of 1.5 to 3.5 days.

Continue to: Baseline pain scores...

Baseline pain scores were similar for all 3 groups (7.5-7.8 on a 10-point scale). In the intention-to-treat analysis, all 3 doses of ketorolac decreased pain significantly at 30 minutes, with no difference between the groups: mean pain scores postintervention were 5.1 for the 10- and 15-mg group and 4.8 for the 30-mg group. There was no difference between the groups at any other time intervals. There was also no difference between groups in the number of patients who needed rescue medication at 30 minutes (4 patients in the 10-mg group, 3 patients in the 15-mg group, and 4 patients in the 30-mg group). In addition, adverse events (eg, dizziness, nausea, headache, itching, flushing) did not differ between the groups.

WHAT’S NEW

10 mg is just as effective as 30 mg

This trial confirms that a low dose of IV ketorolac is just as effective as higher doses for acute pain control.

CAVEATS

2-hour limit; no look at long-term effects

It isn’t known whether the higher dose would have provided greater pain relief beyond the 120 minutes evaluated in this trial, or if alternative dosage forms (oral or IM) would result in different outcomes. This study was not designed to compare serious long-term adverse effects such as bleeding, renal impairment, or cardiovascular events. Additionally, this study was not powered to look at specific therapeutic indications or anti-inflammatory response.

CHALLENGES TO IMPLEMENTATION

10-mg single-dose vial not readily available

Ketorolac tromethamine for injection is available in the United States in 15-, 30-, and 60-mg single-dose vials. Because a 10-mg dose is not available as a single-dose vial, it would need to be specially prepared (as it was in this study). However, this study should reassure providers that using the lowest available dose (eg, 15 mg IV if that is what is available) will relieve acute pain as well as higher doses will. CR

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2019. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2019;68[1]:41-42).

The estimated prevalence of obstructive sleep apnea in North and South America stands at 170 million, results from a novel epidemiologic analysis showed.

“I would not have thought that there are 170 million people in the Americas with clinically important sleep apnea based on our conservative estimates,” the study’s first author, Atul Malhotra, MD, said in an interview in advance of the annual meeting of the Associated Professional Sleep Societies. “Even if we restrict the conversation to moderate to severe sleep apnea, we still see 81 million people afflicted in the Americas alone. We have recently estimated almost 1 billion patients afflicted with OSA worldwide.”

In an effort to estimate the Americas’ prevalence of adult OSA using existing data from epidemiologic studies, Dr. Malhotra, director of sleep medicine at the University of California, San Diego, senior author Adam V. Benjafield, PhD, and their colleagues contacted authors of important analyses on the topic following an exhaustive review of the literature. For countries where no measurement had been made, they used publicly available data to obtain estimates of age, sex, race, and body mass index. Next, they developed an algorithm to match countries without prevalence estimates with countries from which OSA epidemiologic studies exist. “The situation was complicated given the variable age of the existing studies, the differences in technology used (e.g., nasal pressure vs. thermistor), the changing scoring criteria, and other sources of variability,” the researchers wrote in their abstract.

Dr. Malhotra reported on data from 38 of 40 countries in the Americas. Drawing from American Academy of Sleep Medicine 2012 criteria and using what they characterized as a “somewhat conservative” approach, the researchers estimated the prevalence of adult OSA in the Americas to be 170 million, or 37% of the population. In addition, they estimate that 81 million adults, or 18% of the population, suffer from moderate to severe OSA based on an apnea hypopnea index of 15 or more per hour. The countries with the greatest burden of OSA are the United States (54 million), Brazil (49 million), and Colombia (11 million).

“The findings will hopefully help to raise awareness about the disease but also encourage a strategic conversation regarding how best to address this large burden,” Dr. Malhotra said. “We are unaware of prior efforts to estimate OSA prevalence on a large scale.”

He acknowledged certain limitations of the study, including that the methods, equipment, definitions, and criteria used in existing studies in the medial literature varied widely. “We did our best to harmonize these methods across studies but obviously we can’t change the equipment that was used in previous studies,” he said. “Thus, we view our findings as an estimate requiring further efforts to corroborate.”

The research stemmed from an academic/industry partnership with ResMed, which provided a donation the UCSD Sleep Medicine Center. Dr. Malhotra reported having no financial disclosures. Dr. Benjafield is an employee of ResMed, a medical equipment company that specializes in sleep-related breathing devices.

dbrunk@mdedge.com

SOURCE: Malhotra A et al. SLEEP 2019, Abstract 0477.

The estimated prevalence of obstructive sleep apnea in North and South America stands at 170 million, results from a novel epidemiologic analysis showed.

“I would not have thought that there are 170 million people in the Americas with clinically important sleep apnea based on our conservative estimates,” the study’s first author, Atul Malhotra, MD, said in an interview in advance of the annual meeting of the Associated Professional Sleep Societies. “Even if we restrict the conversation to moderate to severe sleep apnea, we still see 81 million people afflicted in the Americas alone. We have recently estimated almost 1 billion patients afflicted with OSA worldwide.”

In an effort to estimate the Americas’ prevalence of adult OSA using existing data from epidemiologic studies, Dr. Malhotra, director of sleep medicine at the University of California, San Diego, senior author Adam V. Benjafield, PhD, and their colleagues contacted authors of important analyses on the topic following an exhaustive review of the literature. For countries where no measurement had been made, they used publicly available data to obtain estimates of age, sex, race, and body mass index. Next, they developed an algorithm to match countries without prevalence estimates with countries from which OSA epidemiologic studies exist. “The situation was complicated given the variable age of the existing studies, the differences in technology used (e.g., nasal pressure vs. thermistor), the changing scoring criteria, and other sources of variability,” the researchers wrote in their abstract.

Dr. Malhotra reported on data from 38 of 40 countries in the Americas. Drawing from American Academy of Sleep Medicine 2012 criteria and using what they characterized as a “somewhat conservative” approach, the researchers estimated the prevalence of adult OSA in the Americas to be 170 million, or 37% of the population. In addition, they estimate that 81 million adults, or 18% of the population, suffer from moderate to severe OSA based on an apnea hypopnea index of 15 or more per hour. The countries with the greatest burden of OSA are the United States (54 million), Brazil (49 million), and Colombia (11 million).

“The findings will hopefully help to raise awareness about the disease but also encourage a strategic conversation regarding how best to address this large burden,” Dr. Malhotra said. “We are unaware of prior efforts to estimate OSA prevalence on a large scale.”

He acknowledged certain limitations of the study, including that the methods, equipment, definitions, and criteria used in existing studies in the medial literature varied widely. “We did our best to harmonize these methods across studies but obviously we can’t change the equipment that was used in previous studies,” he said. “Thus, we view our findings as an estimate requiring further efforts to corroborate.”

The research stemmed from an academic/industry partnership with ResMed, which provided a donation the UCSD Sleep Medicine Center. Dr. Malhotra reported having no financial disclosures. Dr. Benjafield is an employee of ResMed, a medical equipment company that specializes in sleep-related breathing devices.

dbrunk@mdedge.com

SOURCE: Malhotra A et al. SLEEP 2019, Abstract 0477.

The estimated prevalence of obstructive sleep apnea in North and South America stands at 170 million, results from a novel epidemiologic analysis showed.

“I would not have thought that there are 170 million people in the Americas with clinically important sleep apnea based on our conservative estimates,” the study’s first author, Atul Malhotra, MD, said in an interview in advance of the annual meeting of the Associated Professional Sleep Societies. “Even if we restrict the conversation to moderate to severe sleep apnea, we still see 81 million people afflicted in the Americas alone. We have recently estimated almost 1 billion patients afflicted with OSA worldwide.”

In an effort to estimate the Americas’ prevalence of adult OSA using existing data from epidemiologic studies, Dr. Malhotra, director of sleep medicine at the University of California, San Diego, senior author Adam V. Benjafield, PhD, and their colleagues contacted authors of important analyses on the topic following an exhaustive review of the literature. For countries where no measurement had been made, they used publicly available data to obtain estimates of age, sex, race, and body mass index. Next, they developed an algorithm to match countries without prevalence estimates with countries from which OSA epidemiologic studies exist. “The situation was complicated given the variable age of the existing studies, the differences in technology used (e.g., nasal pressure vs. thermistor), the changing scoring criteria, and other sources of variability,” the researchers wrote in their abstract.

Dr. Malhotra reported on data from 38 of 40 countries in the Americas. Drawing from American Academy of Sleep Medicine 2012 criteria and using what they characterized as a “somewhat conservative” approach, the researchers estimated the prevalence of adult OSA in the Americas to be 170 million, or 37% of the population. In addition, they estimate that 81 million adults, or 18% of the population, suffer from moderate to severe OSA based on an apnea hypopnea index of 15 or more per hour. The countries with the greatest burden of OSA are the United States (54 million), Brazil (49 million), and Colombia (11 million).

“The findings will hopefully help to raise awareness about the disease but also encourage a strategic conversation regarding how best to address this large burden,” Dr. Malhotra said. “We are unaware of prior efforts to estimate OSA prevalence on a large scale.”

He acknowledged certain limitations of the study, including that the methods, equipment, definitions, and criteria used in existing studies in the medial literature varied widely. “We did our best to harmonize these methods across studies but obviously we can’t change the equipment that was used in previous studies,” he said. “Thus, we view our findings as an estimate requiring further efforts to corroborate.”

The research stemmed from an academic/industry partnership with ResMed, which provided a donation the UCSD Sleep Medicine Center. Dr. Malhotra reported having no financial disclosures. Dr. Benjafield is an employee of ResMed, a medical equipment company that specializes in sleep-related breathing devices.

dbrunk@mdedge.com

SOURCE: Malhotra A et al. SLEEP 2019, Abstract 0477.

The monoclonal antibody teplizumab may delay the onset of type 1 diabetes in individuals at high risk, according to research presented at the annual scientific sessions of the American Diabetes Association.

In this study, 76 first-degree relatives of individuals with type 1 diabetes – who did not themselves have the disease but were considered at high risk because of antibodies and abnormal glucose tolerance tests – were randomized to a single two-week outpatient course of intravenous teplizumab or saline placebo. The patients, of whom 72% were 18 years of age or younger, were followed for a median of 745 days and had twice-yearly oral glucose tolerance testing.

Overall, 43% of the 44 patients who received teplizumab were diagnosed with type 1 diabetes during the course of the study, compared with 72% of the 32 who received the placebo. The treatment was associated with a 59% reduction in the hazard ratio for type 1 diabetes, even after adjusting for age, the results of a second oral glucose-tolerance testing before randomization, or the presence of anti-GAD65 antibodies.

The median time to diagnosis was 48.4 months in the teplizumab group and 24.4 months in the placebo group. The greatest effect was seen in the first year after randomization, during which only 7% of the teplizumab group were diagnosed with type 1 diabetes, compared with 44% of the placebo group. The findings were published simultaneously in the New England Journal of Medicine.

“The delay of progression to type 1 diabetes is of clinical importance, particularly for children, in whom the diagnosis is associated with adverse outcomes, and given the challenges of daily management of the condition,” said Dr. Kevan C. Herold, professor of immunobiology and medicine at Yale University, New Haven, Conn., and coauthors.

There were significantly more adverse events in the teplizumab group, compared with placebo, with three-quarters of the 20 grade 3 adverse events being lymphopenia during the first 30 days. In all but one participant, however, the lymphopenia resolved by day 45. Participants receiving teplizumab also reported a higher incidence of dermatologic adverse events, such as a spontaneously-resolving rash that was experienced by just over one-third of the group.

The researchers also looked for evidence of T-cell unresponsiveness, which has been previously seen in patients with new-onset type 1 diabetes who received treatment with teplizumab. They noted an increase in a particular type of CD8+ T cell associated with T-cell unresponsiveness at months 3 and 6 in participants treated with teplizumab.

Teplizumab is an Fc receptor-nonbinding monoclonal antibody that has been shown to reduce the loss of beta-cell function in patients with type 1 diabetes (Diabetes. 2013 Nov;62(11):3766-74).

The study was supported by the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the American Diabetes Association, with the study drug and additional site monitoring provided by MacroGenics. Eight authors declared grants, personal fees, and other support from private industry, with one also declaring income and stock options from MacroGenics.

SOURCE: Herold K et al. NEJM. 2019 Jun 9. doi: 10.1056/NEJMoa1902226*

*Correction, 6/9/2019: An earlier version of this story misstated the doi number for the journal article. The number is 10.1056/NEJMoa1902226.

The monoclonal antibody teplizumab may delay the onset of type 1 diabetes in individuals at high risk, according to research presented at the annual scientific sessions of the American Diabetes Association.

In this study, 76 first-degree relatives of individuals with type 1 diabetes – who did not themselves have the disease but were considered at high risk because of antibodies and abnormal glucose tolerance tests – were randomized to a single two-week outpatient course of intravenous teplizumab or saline placebo. The patients, of whom 72% were 18 years of age or younger, were followed for a median of 745 days and had twice-yearly oral glucose tolerance testing.

Overall, 43% of the 44 patients who received teplizumab were diagnosed with type 1 diabetes during the course of the study, compared with 72% of the 32 who received the placebo. The treatment was associated with a 59% reduction in the hazard ratio for type 1 diabetes, even after adjusting for age, the results of a second oral glucose-tolerance testing before randomization, or the presence of anti-GAD65 antibodies.

The median time to diagnosis was 48.4 months in the teplizumab group and 24.4 months in the placebo group. The greatest effect was seen in the first year after randomization, during which only 7% of the teplizumab group were diagnosed with type 1 diabetes, compared with 44% of the placebo group. The findings were published simultaneously in the New England Journal of Medicine.

“The delay of progression to type 1 diabetes is of clinical importance, particularly for children, in whom the diagnosis is associated with adverse outcomes, and given the challenges of daily management of the condition,” said Dr. Kevan C. Herold, professor of immunobiology and medicine at Yale University, New Haven, Conn., and coauthors.

There were significantly more adverse events in the teplizumab group, compared with placebo, with three-quarters of the 20 grade 3 adverse events being lymphopenia during the first 30 days. In all but one participant, however, the lymphopenia resolved by day 45. Participants receiving teplizumab also reported a higher incidence of dermatologic adverse events, such as a spontaneously-resolving rash that was experienced by just over one-third of the group.

The researchers also looked for evidence of T-cell unresponsiveness, which has been previously seen in patients with new-onset type 1 diabetes who received treatment with teplizumab. They noted an increase in a particular type of CD8+ T cell associated with T-cell unresponsiveness at months 3 and 6 in participants treated with teplizumab.

Teplizumab is an Fc receptor-nonbinding monoclonal antibody that has been shown to reduce the loss of beta-cell function in patients with type 1 diabetes (Diabetes. 2013 Nov;62(11):3766-74).

The study was supported by the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the American Diabetes Association, with the study drug and additional site monitoring provided by MacroGenics. Eight authors declared grants, personal fees, and other support from private industry, with one also declaring income and stock options from MacroGenics.

SOURCE: Herold K et al. NEJM. 2019 Jun 9. doi: 10.1056/NEJMoa1902226*

*Correction, 6/9/2019: An earlier version of this story misstated the doi number for the journal article. The number is 10.1056/NEJMoa1902226.

The monoclonal antibody teplizumab may delay the onset of type 1 diabetes in individuals at high risk, according to research presented at the annual scientific sessions of the American Diabetes Association.

In this study, 76 first-degree relatives of individuals with type 1 diabetes – who did not themselves have the disease but were considered at high risk because of antibodies and abnormal glucose tolerance tests – were randomized to a single two-week outpatient course of intravenous teplizumab or saline placebo. The patients, of whom 72% were 18 years of age or younger, were followed for a median of 745 days and had twice-yearly oral glucose tolerance testing.

Overall, 43% of the 44 patients who received teplizumab were diagnosed with type 1 diabetes during the course of the study, compared with 72% of the 32 who received the placebo. The treatment was associated with a 59% reduction in the hazard ratio for type 1 diabetes, even after adjusting for age, the results of a second oral glucose-tolerance testing before randomization, or the presence of anti-GAD65 antibodies.

The median time to diagnosis was 48.4 months in the teplizumab group and 24.4 months in the placebo group. The greatest effect was seen in the first year after randomization, during which only 7% of the teplizumab group were diagnosed with type 1 diabetes, compared with 44% of the placebo group. The findings were published simultaneously in the New England Journal of Medicine.

“The delay of progression to type 1 diabetes is of clinical importance, particularly for children, in whom the diagnosis is associated with adverse outcomes, and given the challenges of daily management of the condition,” said Dr. Kevan C. Herold, professor of immunobiology and medicine at Yale University, New Haven, Conn., and coauthors.

There were significantly more adverse events in the teplizumab group, compared with placebo, with three-quarters of the 20 grade 3 adverse events being lymphopenia during the first 30 days. In all but one participant, however, the lymphopenia resolved by day 45. Participants receiving teplizumab also reported a higher incidence of dermatologic adverse events, such as a spontaneously-resolving rash that was experienced by just over one-third of the group.

The researchers also looked for evidence of T-cell unresponsiveness, which has been previously seen in patients with new-onset type 1 diabetes who received treatment with teplizumab. They noted an increase in a particular type of CD8+ T cell associated with T-cell unresponsiveness at months 3 and 6 in participants treated with teplizumab.

Teplizumab is an Fc receptor-nonbinding monoclonal antibody that has been shown to reduce the loss of beta-cell function in patients with type 1 diabetes (Diabetes. 2013 Nov;62(11):3766-74).

The study was supported by the National Institutes of Health, the Juvenile Diabetes Research Foundation, and the American Diabetes Association, with the study drug and additional site monitoring provided by MacroGenics. Eight authors declared grants, personal fees, and other support from private industry, with one also declaring income and stock options from MacroGenics.

SOURCE: Herold K et al. NEJM. 2019 Jun 9. doi: 10.1056/NEJMoa1902226*

*Correction, 6/9/2019: An earlier version of this story misstated the doi number for the journal article. The number is 10.1056/NEJMoa1902226.

FORT LAUDERDALE, FLA. — A multicenter pilot study of a prophylactic regimen for both matched sibling donor and unrelated donor bone marrow transplantation in adults with severe sickle cell disease has found similar overall and event-free survival rates between the two approaches, exceeding 90% and 85%, respectively, at one year, according to preliminary results presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

The results have led to a Phase 2 single-arm, multicenter trial, known as STRIDE , to evaluate a reduced toxicity preparative regimen consisting of busulfan (13.2 mg/kg), fludarabine (175   mg/m ² ) and antithymocyte globulin (ATG, 6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis in adults with sickle cell disease (SCD), said Lakshmanan Krishnamurti, MD, of Children’s Healthcare of Atlanta/Emory University. “The data are similar with 91% overall survival and 86% event-free survival,” he said.

The pilot study, published recently ( Am J Hematol. 2019;94:446-54 ), indicated the effectiveness of non-myeloablative conditioning in SCD patients with matched-sibling bone marrow transplant (BMT), with a higher intensity regimen of busulfan/fludarabine/ATG effective in unrelated donor BMT for other conditions, Dr. Krishnamurti said.

The pilot study also found that three-year event-free survival (EFS) of 82%, and statistically significant improvements in pain and health-related quality of life.

STRIDE is the first comparative study of BMT vs. standard of care in severe SCD, Dr. Krishnamurti added. The primary endpoint is overall survival at two years after biologic assignment, with longer-term outcomes including survival at three to 10 years post-hematopoietic stem cell transplantation (HSCT), and impact of BMT on sickle-related events, organ function, health-related quality of life and chronic pain.  

The pilot study included 22 patients between the ages of 17 and 36 who had BMT at eight centers. Seventeen patients received marrow from a sibling-matched donor and five patients received marrow from an unrelated donor. 

Dr. Krishnamurti referenced a recent study out of France that showed chimerism levels after transplant may be a determining physiological factor for outcomes (Haematologica. doi:10.3324/haematol.2018.213207 ). “So if chimerism is stable, somewhere in the 25% to 50% or better range, and hemoglobin levels are improved, this decrease hemolysis,” he said. “This is very important in understanding how to manage these patients.”

That study showed that rates of chronic GVHD up to 10 years post-transplant have steadily improved over the past three decades in patients with SCD who’ve had BMT, Dr. Krishnamurti noted. “But chronic GVHD is higher in patients age 16 to 30 vs. patients 15 and younger,” he said, “so that’s the reason to consider transplantation sooner in patients who have a matched sibling donor.”

The French study shows that BMT with sibling-matched donors has excellent outcomes in young children, Dr. Krishnamurti said. “Outcomes for adults with transplantation is becoming similar to that in children,” he added. “Age is an important predictor of outcomes and the risk for progressive morbidity-impaired quality of life and risk of mortality still exists in adults with sickle cell disease.”

The bottom line, he said, is that patients and caregivers must be given the opportunity to consider transplantation as an option at younger ages.

Dr. Krishnamurti did not disclose any financial relationships.

SOURCE: Krishnamurti L et al. FSCDR 2019

FORT LAUDERDALE, FLA. — A multicenter pilot study of a prophylactic regimen for both matched sibling donor and unrelated donor bone marrow transplantation in adults with severe sickle cell disease has found similar overall and event-free survival rates between the two approaches, exceeding 90% and 85%, respectively, at one year, according to preliminary results presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

The results have led to a Phase 2 single-arm, multicenter trial, known as STRIDE , to evaluate a reduced toxicity preparative regimen consisting of busulfan (13.2 mg/kg), fludarabine (175   mg/m ² ) and antithymocyte globulin (ATG, 6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis in adults with sickle cell disease (SCD), said Lakshmanan Krishnamurti, MD, of Children’s Healthcare of Atlanta/Emory University. “The data are similar with 91% overall survival and 86% event-free survival,” he said.

The pilot study, published recently ( Am J Hematol. 2019;94:446-54 ), indicated the effectiveness of non-myeloablative conditioning in SCD patients with matched-sibling bone marrow transplant (BMT), with a higher intensity regimen of busulfan/fludarabine/ATG effective in unrelated donor BMT for other conditions, Dr. Krishnamurti said.

The pilot study also found that three-year event-free survival (EFS) of 82%, and statistically significant improvements in pain and health-related quality of life.

STRIDE is the first comparative study of BMT vs. standard of care in severe SCD, Dr. Krishnamurti added. The primary endpoint is overall survival at two years after biologic assignment, with longer-term outcomes including survival at three to 10 years post-hematopoietic stem cell transplantation (HSCT), and impact of BMT on sickle-related events, organ function, health-related quality of life and chronic pain.  

The pilot study included 22 patients between the ages of 17 and 36 who had BMT at eight centers. Seventeen patients received marrow from a sibling-matched donor and five patients received marrow from an unrelated donor. 

Dr. Krishnamurti referenced a recent study out of France that showed chimerism levels after transplant may be a determining physiological factor for outcomes (Haematologica. doi:10.3324/haematol.2018.213207 ). “So if chimerism is stable, somewhere in the 25% to 50% or better range, and hemoglobin levels are improved, this decrease hemolysis,” he said. “This is very important in understanding how to manage these patients.”

That study showed that rates of chronic GVHD up to 10 years post-transplant have steadily improved over the past three decades in patients with SCD who’ve had BMT, Dr. Krishnamurti noted. “But chronic GVHD is higher in patients age 16 to 30 vs. patients 15 and younger,” he said, “so that’s the reason to consider transplantation sooner in patients who have a matched sibling donor.”

The French study shows that BMT with sibling-matched donors has excellent outcomes in young children, Dr. Krishnamurti said. “Outcomes for adults with transplantation is becoming similar to that in children,” he added. “Age is an important predictor of outcomes and the risk for progressive morbidity-impaired quality of life and risk of mortality still exists in adults with sickle cell disease.”

The bottom line, he said, is that patients and caregivers must be given the opportunity to consider transplantation as an option at younger ages.

Dr. Krishnamurti did not disclose any financial relationships.

SOURCE: Krishnamurti L et al. FSCDR 2019

FORT LAUDERDALE, FLA. — A multicenter pilot study of a prophylactic regimen for both matched sibling donor and unrelated donor bone marrow transplantation in adults with severe sickle cell disease has found similar overall and event-free survival rates between the two approaches, exceeding 90% and 85%, respectively, at one year, according to preliminary results presented at the annual meeting of the Foundation for Sickle Cell Disease Research.

The results have led to a Phase 2 single-arm, multicenter trial, known as STRIDE , to evaluate a reduced toxicity preparative regimen consisting of busulfan (13.2 mg/kg), fludarabine (175   mg/m ² ) and antithymocyte globulin (ATG, 6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis in adults with sickle cell disease (SCD), said Lakshmanan Krishnamurti, MD, of Children’s Healthcare of Atlanta/Emory University. “The data are similar with 91% overall survival and 86% event-free survival,” he said.

The pilot study, published recently ( Am J Hematol. 2019;94:446-54 ), indicated the effectiveness of non-myeloablative conditioning in SCD patients with matched-sibling bone marrow transplant (BMT), with a higher intensity regimen of busulfan/fludarabine/ATG effective in unrelated donor BMT for other conditions, Dr. Krishnamurti said.

The pilot study also found that three-year event-free survival (EFS) of 82%, and statistically significant improvements in pain and health-related quality of life.

STRIDE is the first comparative study of BMT vs. standard of care in severe SCD, Dr. Krishnamurti added. The primary endpoint is overall survival at two years after biologic assignment, with longer-term outcomes including survival at three to 10 years post-hematopoietic stem cell transplantation (HSCT), and impact of BMT on sickle-related events, organ function, health-related quality of life and chronic pain.  

The pilot study included 22 patients between the ages of 17 and 36 who had BMT at eight centers. Seventeen patients received marrow from a sibling-matched donor and five patients received marrow from an unrelated donor. 

Dr. Krishnamurti referenced a recent study out of France that showed chimerism levels after transplant may be a determining physiological factor for outcomes (Haematologica. doi:10.3324/haematol.2018.213207 ). “So if chimerism is stable, somewhere in the 25% to 50% or better range, and hemoglobin levels are improved, this decrease hemolysis,” he said. “This is very important in understanding how to manage these patients.”

That study showed that rates of chronic GVHD up to 10 years post-transplant have steadily improved over the past three decades in patients with SCD who’ve had BMT, Dr. Krishnamurti noted. “But chronic GVHD is higher in patients age 16 to 30 vs. patients 15 and younger,” he said, “so that’s the reason to consider transplantation sooner in patients who have a matched sibling donor.”

The French study shows that BMT with sibling-matched donors has excellent outcomes in young children, Dr. Krishnamurti said. “Outcomes for adults with transplantation is becoming similar to that in children,” he added. “Age is an important predictor of outcomes and the risk for progressive morbidity-impaired quality of life and risk of mortality still exists in adults with sickle cell disease.”

The bottom line, he said, is that patients and caregivers must be given the opportunity to consider transplantation as an option at younger ages.

Dr. Krishnamurti did not disclose any financial relationships.

SOURCE: Krishnamurti L et al. FSCDR 2019

The introduction of separate payment for the immediate postpartum implantation of long-acting reversible contraception was associated with increased use and a slow-down in the number of short-interval births in patients covered by South Carolina’s Medicaid program.

Immediate postpartum long-acting reversible contraception (IPP-LARC) is recommended to reduce the incidence of short pregnancy intervals – pregnancies within 6-24 months of each other. The global payment for hospital labor and delivery, however, may act as a disincentive to providing IPP-LARC, according to Maria W. Steenland of Brown University, Providence, R.I., and co-authors.

They looked at inpatient Medicaid claims data for 242,825 childbirth hospitalizations in South Carolina from 2010-2017; during that time the state Medicaid program began to provide an additional payment for IPP-LARC.

At the start of the study, just 0.07% of women received an IPP-LARC. After the change in reimbursement policy in March 2012, there was a steady 0.07 percentage point monthly increase in their use in adults and 0.1 percentage point increase per month in adolescents. In December 2017, 5.65% of adults and 10.48% of adolescents received an IPP-LARC (JAMA. 2019; doi: 10.1001/jama.2019.6854).

There was a corresponding, significant change in the trend of short-interval births among adolescents. Before the policy change, adolescent short-interval births had been increasing, but by March 2016 – 4 years after the payment change – the adolescent short-interval birth rate was 5.28 percentage points lower than what was expected had the increasing trend continued.

There was no significant change in the trend for short-interval births among adults.

“These findings suggest that IPP-LARC reimbursement could increase immediate postpartum contraceptive options and help adolescents avoid short-interval births,” the authors wrote, noting that as of February 2018, 36 other states’ Medicaid programs had began separately reimbursing for IPP-LARC.

They also raised the possibility that there may have been confounding due to other events that occurred at the same time as the policy changes.

The study was supported by the Eric M. Mindich Research Fund and one author was supported by National Institutes of Health. No conflicts of interest were declared.

SOURCE: Steenland M et al. JAMA 2019, DOI:10.1001/jama.2019.6854.

The introduction of separate payment for the immediate postpartum implantation of long-acting reversible contraception was associated with increased use and a slow-down in the number of short-interval births in patients covered by South Carolina’s Medicaid program.

Immediate postpartum long-acting reversible contraception (IPP-LARC) is recommended to reduce the incidence of short pregnancy intervals – pregnancies within 6-24 months of each other. The global payment for hospital labor and delivery, however, may act as a disincentive to providing IPP-LARC, according to Maria W. Steenland of Brown University, Providence, R.I., and co-authors.

They looked at inpatient Medicaid claims data for 242,825 childbirth hospitalizations in South Carolina from 2010-2017; during that time the state Medicaid program began to provide an additional payment for IPP-LARC.

At the start of the study, just 0.07% of women received an IPP-LARC. After the change in reimbursement policy in March 2012, there was a steady 0.07 percentage point monthly increase in their use in adults and 0.1 percentage point increase per month in adolescents. In December 2017, 5.65% of adults and 10.48% of adolescents received an IPP-LARC (JAMA. 2019; doi: 10.1001/jama.2019.6854).

There was a corresponding, significant change in the trend of short-interval births among adolescents. Before the policy change, adolescent short-interval births had been increasing, but by March 2016 – 4 years after the payment change – the adolescent short-interval birth rate was 5.28 percentage points lower than what was expected had the increasing trend continued.

There was no significant change in the trend for short-interval births among adults.

“These findings suggest that IPP-LARC reimbursement could increase immediate postpartum contraceptive options and help adolescents avoid short-interval births,” the authors wrote, noting that as of February 2018, 36 other states’ Medicaid programs had began separately reimbursing for IPP-LARC.

They also raised the possibility that there may have been confounding due to other events that occurred at the same time as the policy changes.

The study was supported by the Eric M. Mindich Research Fund and one author was supported by National Institutes of Health. No conflicts of interest were declared.

SOURCE: Steenland M et al. JAMA 2019, DOI:10.1001/jama.2019.6854.

The introduction of separate payment for the immediate postpartum implantation of long-acting reversible contraception was associated with increased use and a slow-down in the number of short-interval births in patients covered by South Carolina’s Medicaid program.

Immediate postpartum long-acting reversible contraception (IPP-LARC) is recommended to reduce the incidence of short pregnancy intervals – pregnancies within 6-24 months of each other. The global payment for hospital labor and delivery, however, may act as a disincentive to providing IPP-LARC, according to Maria W. Steenland of Brown University, Providence, R.I., and co-authors.

They looked at inpatient Medicaid claims data for 242,825 childbirth hospitalizations in South Carolina from 2010-2017; during that time the state Medicaid program began to provide an additional payment for IPP-LARC.

At the start of the study, just 0.07% of women received an IPP-LARC. After the change in reimbursement policy in March 2012, there was a steady 0.07 percentage point monthly increase in their use in adults and 0.1 percentage point increase per month in adolescents. In December 2017, 5.65% of adults and 10.48% of adolescents received an IPP-LARC (JAMA. 2019; doi: 10.1001/jama.2019.6854).

There was a corresponding, significant change in the trend of short-interval births among adolescents. Before the policy change, adolescent short-interval births had been increasing, but by March 2016 – 4 years after the payment change – the adolescent short-interval birth rate was 5.28 percentage points lower than what was expected had the increasing trend continued.

There was no significant change in the trend for short-interval births among adults.

“These findings suggest that IPP-LARC reimbursement could increase immediate postpartum contraceptive options and help adolescents avoid short-interval births,” the authors wrote, noting that as of February 2018, 36 other states’ Medicaid programs had began separately reimbursing for IPP-LARC.

They also raised the possibility that there may have been confounding due to other events that occurred at the same time as the policy changes.

The study was supported by the Eric M. Mindich Research Fund and one author was supported by National Institutes of Health. No conflicts of interest were declared.

SOURCE: Steenland M et al. JAMA 2019, DOI:10.1001/jama.2019.6854.

SAN FRANCISCO – Seventy-percent of type 2 diabetes patients who lost more than 33 pounds on a liquid diet over a few months, and kept it off, were free of the disease at 2 years, according to United Kingdom investigators.

M. Alexander Otto/MDedge News

The odds of remission – meaning a hemoglobin A1c below 6.5% on repeat testing, off all medications – were directly related to the amount of weight patients lost; 60% of subjects who lost 22-33 pounds were free of type 2 disease at 2 years, versus 29% who lost 11-21 pounds, and 5% who lost less than 11 pounds.

“If people lose” around 30 pounds “and keep it off for 2 years, there’s a two-thirds chance of them escaping type 2 [diabetes]. People want to understand their options, and this is an option. This is very good news for people with diabetes,” said senior investigator Roy Taylor, MD, a professor of medicine and metabolism at the University of Newcastle, Newcastle upon Tyne, England, who presented the findings of the Diabetes Remission Clinical Trial (DiRECT) at the annual scientific sessions of the American Diabetes Association (Lancet Diabetes Endocrinol. 2019 May;7(5):344-355).

A subgroup analysis he also presented found that beta cell function rebounds rapidly after weight loss and is pretty much normal at 2 years, so long as people keep the weight off.


The study is rooted in previous work by Dr. Taylor and his colleagues that found that very low-calorie diets normalized fasting plasma glucose in just 7 days in patients with type 2 diabetes due to a rapid fall in liver fat content and subsequent restoration of insulin sensitivity. That and other findings suggested that fast weight loss – instead of the traditional gradual approach – might help.

He and his team randomized 149 volunteers from primary care practices in the United Kingdom to standard care, and 149 others to rapid weight loss; more than a quarter of the patients who were asked agreed to participate.

aotto@mdedge.com
 

SOURCE: Zhyzhneuskaya SV et al., ADA 2019 abstract 66-OR

SAN FRANCISCO – Seventy-percent of type 2 diabetes patients who lost more than 33 pounds on a liquid diet over a few months, and kept it off, were free of the disease at 2 years, according to United Kingdom investigators.

M. Alexander Otto/MDedge News

The odds of remission – meaning a hemoglobin A1c below 6.5% on repeat testing, off all medications – were directly related to the amount of weight patients lost; 60% of subjects who lost 22-33 pounds were free of type 2 disease at 2 years, versus 29% who lost 11-21 pounds, and 5% who lost less than 11 pounds.

“If people lose” around 30 pounds “and keep it off for 2 years, there’s a two-thirds chance of them escaping type 2 [diabetes]. People want to understand their options, and this is an option. This is very good news for people with diabetes,” said senior investigator Roy Taylor, MD, a professor of medicine and metabolism at the University of Newcastle, Newcastle upon Tyne, England, who presented the findings of the Diabetes Remission Clinical Trial (DiRECT) at the annual scientific sessions of the American Diabetes Association (Lancet Diabetes Endocrinol. 2019 May;7(5):344-355).

A subgroup analysis he also presented found that beta cell function rebounds rapidly after weight loss and is pretty much normal at 2 years, so long as people keep the weight off.


The study is rooted in previous work by Dr. Taylor and his colleagues that found that very low-calorie diets normalized fasting plasma glucose in just 7 days in patients with type 2 diabetes due to a rapid fall in liver fat content and subsequent restoration of insulin sensitivity. That and other findings suggested that fast weight loss – instead of the traditional gradual approach – might help.

He and his team randomized 149 volunteers from primary care practices in the United Kingdom to standard care, and 149 others to rapid weight loss; more than a quarter of the patients who were asked agreed to participate.

aotto@mdedge.com
 

SOURCE: Zhyzhneuskaya SV et al., ADA 2019 abstract 66-OR

SAN FRANCISCO – Seventy-percent of type 2 diabetes patients who lost more than 33 pounds on a liquid diet over a few months, and kept it off, were free of the disease at 2 years, according to United Kingdom investigators.

M. Alexander Otto/MDedge News

The odds of remission – meaning a hemoglobin A1c below 6.5% on repeat testing, off all medications – were directly related to the amount of weight patients lost; 60% of subjects who lost 22-33 pounds were free of type 2 disease at 2 years, versus 29% who lost 11-21 pounds, and 5% who lost less than 11 pounds.

“If people lose” around 30 pounds “and keep it off for 2 years, there’s a two-thirds chance of them escaping type 2 [diabetes]. People want to understand their options, and this is an option. This is very good news for people with diabetes,” said senior investigator Roy Taylor, MD, a professor of medicine and metabolism at the University of Newcastle, Newcastle upon Tyne, England, who presented the findings of the Diabetes Remission Clinical Trial (DiRECT) at the annual scientific sessions of the American Diabetes Association (Lancet Diabetes Endocrinol. 2019 May;7(5):344-355).

A subgroup analysis he also presented found that beta cell function rebounds rapidly after weight loss and is pretty much normal at 2 years, so long as people keep the weight off.


The study is rooted in previous work by Dr. Taylor and his colleagues that found that very low-calorie diets normalized fasting plasma glucose in just 7 days in patients with type 2 diabetes due to a rapid fall in liver fat content and subsequent restoration of insulin sensitivity. That and other findings suggested that fast weight loss – instead of the traditional gradual approach – might help.

He and his team randomized 149 volunteers from primary care practices in the United Kingdom to standard care, and 149 others to rapid weight loss; more than a quarter of the patients who were asked agreed to participate.

aotto@mdedge.com
 

SOURCE: Zhyzhneuskaya SV et al., ADA 2019 abstract 66-OR

SEATTLE – Finding a balance between maintaining patient privacy and preventing self-harm is crucial in multiple sclerosis patients at risk for suicide.

“There are some situations where concern for a patient’s safety overrides [confidentiality],” Lauren Sankary, an attorney and neuroethics fellow at the Cleveland Clinic, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “I want to empower you to feel confident to break confidentiality when it makes sense based on your professional judgment.”

It’s not clear whether suicide is more common in patients with MS. A systematic review from 2012 found that most studies reviewed documented a higher rate of suicide in patients with MS, compared with the general population (J Psychosom Res. 2012 Dec;73(6):411-7) while a report from 2017 noted that rates of suicidal intent were elevated in MS (Mult Scler. 2017 Jun;23(7):923-927). Conversely, a French study from 2017 found that excess suicide risk may not be true for MS patients (Mult Scler. 2017 May;23(6):864-871).

When considering breaking confidentiality to seek help for a patient, Ms. Sankary said, “the ethical tension is that on the one hand, disclosing protected health information may protect patient safety. But on the other hand, it may threaten the therapeutic relationship. It’s a true ethical dilemma, and part of what’s difficult is figuring out in which situations are we willing to accept these tradeoffs.”

Consider professional ethical guidelines, federal and local laws, and clinical protocols in the decision making process, she advised.

On the federal level, HIPAA allows the breaking of confidentiality when it “is necessary to prevent or lessen a serious and imminent threat to the health or safety of a person or the public.”

The U.S. Department of Health & Human Services’ Office of Civil Rights notes that “HIPAA permits a covered health care provider to notify a patient’s family members of a serious and imminent threat to the health or safety of the patient or others if those family members are in a position to lessen or avert the threat. Thus, to the extent that a provider determines that there is a serious and imminent threat of a patient physically harming self or others, HIPAA would permit the provider to warn the appropriate person(s) of the threat, consistent with his or her professional ethical obligations and State law requirements.”

Confidential information cannot be disclosed to just anyone, however. HIPAA notes that it must be disclosed only to “a person or persons reasonably able to prevent or lessen the threat, including the target of the threat.”

HIPAA doesn’t require medical professionals to report suicide risk, Ms. Sankary said, but some states require certain professionals to do so. And some states require certain professionals to alert parents if children are suicidal.

The laws mainly affect mental health professionals but may extend to physicians and nurses, according to the National Conference of State Legislators. For example, New Jersey professionals in several fields have a duty to warn in certain situations, including the risk of self-harm.

The American Medical Association’s Code of Medical Ethics suggests physicians must “inform the patient when there has been a significant infringement on privacy of which the patient would otherwise not be aware,” Ms. Sankary said.

Ms. Sankary reported no relevant disclosures.

SEATTLE – Finding a balance between maintaining patient privacy and preventing self-harm is crucial in multiple sclerosis patients at risk for suicide.

“There are some situations where concern for a patient’s safety overrides [confidentiality],” Lauren Sankary, an attorney and neuroethics fellow at the Cleveland Clinic, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “I want to empower you to feel confident to break confidentiality when it makes sense based on your professional judgment.”

It’s not clear whether suicide is more common in patients with MS. A systematic review from 2012 found that most studies reviewed documented a higher rate of suicide in patients with MS, compared with the general population (J Psychosom Res. 2012 Dec;73(6):411-7) while a report from 2017 noted that rates of suicidal intent were elevated in MS (Mult Scler. 2017 Jun;23(7):923-927). Conversely, a French study from 2017 found that excess suicide risk may not be true for MS patients (Mult Scler. 2017 May;23(6):864-871).

When considering breaking confidentiality to seek help for a patient, Ms. Sankary said, “the ethical tension is that on the one hand, disclosing protected health information may protect patient safety. But on the other hand, it may threaten the therapeutic relationship. It’s a true ethical dilemma, and part of what’s difficult is figuring out in which situations are we willing to accept these tradeoffs.”

Consider professional ethical guidelines, federal and local laws, and clinical protocols in the decision making process, she advised.

On the federal level, HIPAA allows the breaking of confidentiality when it “is necessary to prevent or lessen a serious and imminent threat to the health or safety of a person or the public.”

The U.S. Department of Health & Human Services’ Office of Civil Rights notes that “HIPAA permits a covered health care provider to notify a patient’s family members of a serious and imminent threat to the health or safety of the patient or others if those family members are in a position to lessen or avert the threat. Thus, to the extent that a provider determines that there is a serious and imminent threat of a patient physically harming self or others, HIPAA would permit the provider to warn the appropriate person(s) of the threat, consistent with his or her professional ethical obligations and State law requirements.”

Confidential information cannot be disclosed to just anyone, however. HIPAA notes that it must be disclosed only to “a person or persons reasonably able to prevent or lessen the threat, including the target of the threat.”

HIPAA doesn’t require medical professionals to report suicide risk, Ms. Sankary said, but some states require certain professionals to do so. And some states require certain professionals to alert parents if children are suicidal.

The laws mainly affect mental health professionals but may extend to physicians and nurses, according to the National Conference of State Legislators. For example, New Jersey professionals in several fields have a duty to warn in certain situations, including the risk of self-harm.

The American Medical Association’s Code of Medical Ethics suggests physicians must “inform the patient when there has been a significant infringement on privacy of which the patient would otherwise not be aware,” Ms. Sankary said.

Ms. Sankary reported no relevant disclosures.

SEATTLE – Finding a balance between maintaining patient privacy and preventing self-harm is crucial in multiple sclerosis patients at risk for suicide.

“There are some situations where concern for a patient’s safety overrides [confidentiality],” Lauren Sankary, an attorney and neuroethics fellow at the Cleveland Clinic, said at the annual meeting of the Consortium of Multiple Sclerosis Centers. “I want to empower you to feel confident to break confidentiality when it makes sense based on your professional judgment.”

It’s not clear whether suicide is more common in patients with MS. A systematic review from 2012 found that most studies reviewed documented a higher rate of suicide in patients with MS, compared with the general population (J Psychosom Res. 2012 Dec;73(6):411-7) while a report from 2017 noted that rates of suicidal intent were elevated in MS (Mult Scler. 2017 Jun;23(7):923-927). Conversely, a French study from 2017 found that excess suicide risk may not be true for MS patients (Mult Scler. 2017 May;23(6):864-871).

When considering breaking confidentiality to seek help for a patient, Ms. Sankary said, “the ethical tension is that on the one hand, disclosing protected health information may protect patient safety. But on the other hand, it may threaten the therapeutic relationship. It’s a true ethical dilemma, and part of what’s difficult is figuring out in which situations are we willing to accept these tradeoffs.”

Consider professional ethical guidelines, federal and local laws, and clinical protocols in the decision making process, she advised.

On the federal level, HIPAA allows the breaking of confidentiality when it “is necessary to prevent or lessen a serious and imminent threat to the health or safety of a person or the public.”

The U.S. Department of Health & Human Services’ Office of Civil Rights notes that “HIPAA permits a covered health care provider to notify a patient’s family members of a serious and imminent threat to the health or safety of the patient or others if those family members are in a position to lessen or avert the threat. Thus, to the extent that a provider determines that there is a serious and imminent threat of a patient physically harming self or others, HIPAA would permit the provider to warn the appropriate person(s) of the threat, consistent with his or her professional ethical obligations and State law requirements.”

Confidential information cannot be disclosed to just anyone, however. HIPAA notes that it must be disclosed only to “a person or persons reasonably able to prevent or lessen the threat, including the target of the threat.”

HIPAA doesn’t require medical professionals to report suicide risk, Ms. Sankary said, but some states require certain professionals to do so. And some states require certain professionals to alert parents if children are suicidal.

The laws mainly affect mental health professionals but may extend to physicians and nurses, according to the National Conference of State Legislators. For example, New Jersey professionals in several fields have a duty to warn in certain situations, including the risk of self-harm.

The American Medical Association’s Code of Medical Ethics suggests physicians must “inform the patient when there has been a significant infringement on privacy of which the patient would otherwise not be aware,” Ms. Sankary said.

Ms. Sankary reported no relevant disclosures.

Frailty increasingly has been seen as a factor in procedural outcomes, including vascular surgery. Nutrition factors among older adults have also become an issue of concern, and older adults undergoing interventions for peripheral arterial disease (PAD) may be at risk for malnutrition. In Friday’s Scientific Session 6, Laura Drudi, MD, of McGill University, Montreal, will report on a study that she and her colleagues performed to determine the association between preprocedural nutritional status and all-cause mortality in patients being treated for PAD.

Dr. Drudi will report on their post hoc analysis of the FRAILED (Frailty Assessment in Lower Extremity arterial Disease) prospective cohort, which comprised two centers recruiting patients during July 1, 2015–Oct.1, 2016. Individuals who underwent vascular interventions for Rutherford class 3 or higher PAD were enrolled.

Trained observers used the Mini Nutritional Assessment (MNA)–Short Form to assess the patients before their procedures. Scores less than or equal to 7 on a 14-point scale were considered malnourished, with scores of 8-11 indicated that patients were at risk for malnutrition.

The modified Essential Frailty Toolset (mEFT) was simultaneously used to measure frailty, with scores of 3 or less on a 5-point scale considered frail. The primary endpoint of the study was all-cause mortality at 12 months after the procedure. Dr. Drudi will report on the results of the cohort of 148 patients (39.2% women) with a mean age of 70 years, and a mean body mass index of 26.7 kg/m². Among these patients, 59 (40%) had claudication and 89 (60%) had chronic limb-threatening ischemia. A total of 98 (66%) patients underwent endovascular revascularization and 50 (34%) underwent open or hybrid revascularization.

Overall, 3% of subjects were classified as malnourished and 33% were at risk for malnutrition. There were 9 (6%) deaths at 12 months. Mini Nutritional Assessment–Short Form scores were modestly but significantly correlated with the mEFT scores (Pearson’s R = –0.48; P less than .001).

”We found that patients with malnourishment or at risk of malnourishment had a 2.5-fold higher crude 1-year mortality, compared with those with normal nutritional status,” said Dr. Drudi.

In the 41% of patients deemed frail, malnutrition was associated with all-cause mortality (adjusted odds ratio, 2.08 per point decrease in MNA scores); whereas in the nonfrail patients, MNA scores had little or no effect on mortality (adjusted OR, 1.05).

“Preprocedural nutritional status is associated with mortality in frail older adults undergoing interventions for PAD. Clinical trials are needed to determine whether pre- and postprocedural nutritional interventions can improve clinical outcomes in these vulnerable individuals,” Dr. Drudi concluded. 

Friday, June 21
1:30-3:00 p.m.
Gaylord National, Potomac A/B
S6: Scientific Session 6: RS16

Frailty increasingly has been seen as a factor in procedural outcomes, including vascular surgery. Nutrition factors among older adults have also become an issue of concern, and older adults undergoing interventions for peripheral arterial disease (PAD) may be at risk for malnutrition. In Friday’s Scientific Session 6, Laura Drudi, MD, of McGill University, Montreal, will report on a study that she and her colleagues performed to determine the association between preprocedural nutritional status and all-cause mortality in patients being treated for PAD.

Dr. Drudi will report on their post hoc analysis of the FRAILED (Frailty Assessment in Lower Extremity arterial Disease) prospective cohort, which comprised two centers recruiting patients during July 1, 2015–Oct.1, 2016. Individuals who underwent vascular interventions for Rutherford class 3 or higher PAD were enrolled.

Trained observers used the Mini Nutritional Assessment (MNA)–Short Form to assess the patients before their procedures. Scores less than or equal to 7 on a 14-point scale were considered malnourished, with scores of 8-11 indicated that patients were at risk for malnutrition.

The modified Essential Frailty Toolset (mEFT) was simultaneously used to measure frailty, with scores of 3 or less on a 5-point scale considered frail. The primary endpoint of the study was all-cause mortality at 12 months after the procedure. Dr. Drudi will report on the results of the cohort of 148 patients (39.2% women) with a mean age of 70 years, and a mean body mass index of 26.7 kg/m². Among these patients, 59 (40%) had claudication and 89 (60%) had chronic limb-threatening ischemia. A total of 98 (66%) patients underwent endovascular revascularization and 50 (34%) underwent open or hybrid revascularization.

Overall, 3% of subjects were classified as malnourished and 33% were at risk for malnutrition. There were 9 (6%) deaths at 12 months. Mini Nutritional Assessment–Short Form scores were modestly but significantly correlated with the mEFT scores (Pearson’s R = –0.48; P less than .001).

”We found that patients with malnourishment or at risk of malnourishment had a 2.5-fold higher crude 1-year mortality, compared with those with normal nutritional status,” said Dr. Drudi.

In the 41% of patients deemed frail, malnutrition was associated with all-cause mortality (adjusted odds ratio, 2.08 per point decrease in MNA scores); whereas in the nonfrail patients, MNA scores had little or no effect on mortality (adjusted OR, 1.05).

“Preprocedural nutritional status is associated with mortality in frail older adults undergoing interventions for PAD. Clinical trials are needed to determine whether pre- and postprocedural nutritional interventions can improve clinical outcomes in these vulnerable individuals,” Dr. Drudi concluded. 

Friday, June 21
1:30-3:00 p.m.
Gaylord National, Potomac A/B
S6: Scientific Session 6: RS16

Frailty increasingly has been seen as a factor in procedural outcomes, including vascular surgery. Nutrition factors among older adults have also become an issue of concern, and older adults undergoing interventions for peripheral arterial disease (PAD) may be at risk for malnutrition. In Friday’s Scientific Session 6, Laura Drudi, MD, of McGill University, Montreal, will report on a study that she and her colleagues performed to determine the association between preprocedural nutritional status and all-cause mortality in patients being treated for PAD.

Dr. Drudi will report on their post hoc analysis of the FRAILED (Frailty Assessment in Lower Extremity arterial Disease) prospective cohort, which comprised two centers recruiting patients during July 1, 2015–Oct.1, 2016. Individuals who underwent vascular interventions for Rutherford class 3 or higher PAD were enrolled.

Trained observers used the Mini Nutritional Assessment (MNA)–Short Form to assess the patients before their procedures. Scores less than or equal to 7 on a 14-point scale were considered malnourished, with scores of 8-11 indicated that patients were at risk for malnutrition.

The modified Essential Frailty Toolset (mEFT) was simultaneously used to measure frailty, with scores of 3 or less on a 5-point scale considered frail. The primary endpoint of the study was all-cause mortality at 12 months after the procedure. Dr. Drudi will report on the results of the cohort of 148 patients (39.2% women) with a mean age of 70 years, and a mean body mass index of 26.7 kg/m². Among these patients, 59 (40%) had claudication and 89 (60%) had chronic limb-threatening ischemia. A total of 98 (66%) patients underwent endovascular revascularization and 50 (34%) underwent open or hybrid revascularization.

Overall, 3% of subjects were classified as malnourished and 33% were at risk for malnutrition. There were 9 (6%) deaths at 12 months. Mini Nutritional Assessment–Short Form scores were modestly but significantly correlated with the mEFT scores (Pearson’s R = –0.48; P less than .001).

”We found that patients with malnourishment or at risk of malnourishment had a 2.5-fold higher crude 1-year mortality, compared with those with normal nutritional status,” said Dr. Drudi.

In the 41% of patients deemed frail, malnutrition was associated with all-cause mortality (adjusted odds ratio, 2.08 per point decrease in MNA scores); whereas in the nonfrail patients, MNA scores had little or no effect on mortality (adjusted OR, 1.05).

“Preprocedural nutritional status is associated with mortality in frail older adults undergoing interventions for PAD. Clinical trials are needed to determine whether pre- and postprocedural nutritional interventions can improve clinical outcomes in these vulnerable individuals,” Dr. Drudi concluded. 

Friday, June 21
1:30-3:00 p.m.
Gaylord National, Potomac A/B
S6: Scientific Session 6: RS16

After months of planning, the day is finally here! Friday evening, 500 people will be living the high life at the  “Vascular Spectacular” gala, celebrating the specialty and each other.

RUSSELLTATEdotCOM/DigitalVision Vectors

But everyone, no matter where they are in the world, may participate in the gala’s Silent Auction, right until it closes this evening.

In fact, bidding on nearly 70 items began in late May. Here’s how to join in the fun:

• Sign up on vam19gala.givesmart.com and peruse the selections.

• Place a bid. All bidders will be identified by name.

• If desired, monitor the bidding, by setting up notifications to learn when someone else ups the ante.

• Continue to bid until the auction closes during the gala itself.

• Wait for your prizes to be mailed to you — and know you have contributed to continuing the important work of the SVS Foundation.

The live auction takes place at the gala in its entirety and only those present can bid.

The Gala Committee is comprised of Drs. Cynthia Shortell and Benjamin Starnes, cochairs; and Enrico Ascher, William Jordan Jr., Melina Kibbe, Richard Lynn, Matthew Mell, Ben Pearce, Amy Reed, Russell Samson, William Shutze, Mal Sheahan, Maureen Sheehan and Anton Sidawy. 

What’s available? Dr. Clem Darling’s “Darling Magical Whiskery Tour” to sample top-tier whiskey in the mutually agreed-upon city; a stay in Lake Tahoe, a beach-front condo in Florida and a spacious townhome at the entrance to Rehoboth Beach, Del.; wildlife photos; fine art; jewelry; fine wine; portraits for people and pets; sports-related items; Maui Jim sunglasses; free admission to attractions from coast to coast and more. There are even one-on-one sessions with a number of vascular surgeons. 

In addition, Cydar Medical is offering a one-year subscription to Cydar EV Fusion Imaging, the world’s first AI-powered image fusion platform, valued at $50,000.  

All proceeds benefit the SVS Foundation.
 

After months of planning, the day is finally here! Friday evening, 500 people will be living the high life at the  “Vascular Spectacular” gala, celebrating the specialty and each other.

RUSSELLTATEdotCOM/DigitalVision Vectors

But everyone, no matter where they are in the world, may participate in the gala’s Silent Auction, right until it closes this evening.

In fact, bidding on nearly 70 items began in late May. Here’s how to join in the fun:

• Sign up on vam19gala.givesmart.com and peruse the selections.

• Place a bid. All bidders will be identified by name.

• If desired, monitor the bidding, by setting up notifications to learn when someone else ups the ante.

• Continue to bid until the auction closes during the gala itself.

• Wait for your prizes to be mailed to you — and know you have contributed to continuing the important work of the SVS Foundation.

The live auction takes place at the gala in its entirety and only those present can bid.

The Gala Committee is comprised of Drs. Cynthia Shortell and Benjamin Starnes, cochairs; and Enrico Ascher, William Jordan Jr., Melina Kibbe, Richard Lynn, Matthew Mell, Ben Pearce, Amy Reed, Russell Samson, William Shutze, Mal Sheahan, Maureen Sheehan and Anton Sidawy. 

What’s available? Dr. Clem Darling’s “Darling Magical Whiskery Tour” to sample top-tier whiskey in the mutually agreed-upon city; a stay in Lake Tahoe, a beach-front condo in Florida and a spacious townhome at the entrance to Rehoboth Beach, Del.; wildlife photos; fine art; jewelry; fine wine; portraits for people and pets; sports-related items; Maui Jim sunglasses; free admission to attractions from coast to coast and more. There are even one-on-one sessions with a number of vascular surgeons. 

In addition, Cydar Medical is offering a one-year subscription to Cydar EV Fusion Imaging, the world’s first AI-powered image fusion platform, valued at $50,000.  

All proceeds benefit the SVS Foundation.
 

After months of planning, the day is finally here! Friday evening, 500 people will be living the high life at the  “Vascular Spectacular” gala, celebrating the specialty and each other.

RUSSELLTATEdotCOM/DigitalVision Vectors

But everyone, no matter where they are in the world, may participate in the gala’s Silent Auction, right until it closes this evening.

In fact, bidding on nearly 70 items began in late May. Here’s how to join in the fun:

• Sign up on vam19gala.givesmart.com and peruse the selections.

• Place a bid. All bidders will be identified by name.

• If desired, monitor the bidding, by setting up notifications to learn when someone else ups the ante.

• Continue to bid until the auction closes during the gala itself.

• Wait for your prizes to be mailed to you — and know you have contributed to continuing the important work of the SVS Foundation.

The live auction takes place at the gala in its entirety and only those present can bid.

The Gala Committee is comprised of Drs. Cynthia Shortell and Benjamin Starnes, cochairs; and Enrico Ascher, William Jordan Jr., Melina Kibbe, Richard Lynn, Matthew Mell, Ben Pearce, Amy Reed, Russell Samson, William Shutze, Mal Sheahan, Maureen Sheehan and Anton Sidawy. 

What’s available? Dr. Clem Darling’s “Darling Magical Whiskery Tour” to sample top-tier whiskey in the mutually agreed-upon city; a stay in Lake Tahoe, a beach-front condo in Florida and a spacious townhome at the entrance to Rehoboth Beach, Del.; wildlife photos; fine art; jewelry; fine wine; portraits for people and pets; sports-related items; Maui Jim sunglasses; free admission to attractions from coast to coast and more. There are even one-on-one sessions with a number of vascular surgeons. 

In addition, Cydar Medical is offering a one-year subscription to Cydar EV Fusion Imaging, the world’s first AI-powered image fusion platform, valued at $50,000.  

All proceeds benefit the SVS Foundation.
 

Starting a vascular surgery integrated program or fellowship can be a daunting process. There exist a number of misconceptions about required case volume, program affiliations, and required number of faculty.

Requirements for creating such programs have recently been lightened. And the SVS and the Association of Program Directors in Vascular Surgery have a number of initiatives in place to help.

SVS will host an informational session for anyone interested in starting a program from 9:30 to 10:30 a.m. Friday, June 14, in National Harbor 4. Most of the session will be interactive, with experienced program directors offering participants useful information and practical advice. 

Starting a vascular surgery integrated program or fellowship can be a daunting process. There exist a number of misconceptions about required case volume, program affiliations, and required number of faculty.

Requirements for creating such programs have recently been lightened. And the SVS and the Association of Program Directors in Vascular Surgery have a number of initiatives in place to help.

SVS will host an informational session for anyone interested in starting a program from 9:30 to 10:30 a.m. Friday, June 14, in National Harbor 4. Most of the session will be interactive, with experienced program directors offering participants useful information and practical advice. 

Starting a vascular surgery integrated program or fellowship can be a daunting process. There exist a number of misconceptions about required case volume, program affiliations, and required number of faculty.

Requirements for creating such programs have recently been lightened. And the SVS and the Association of Program Directors in Vascular Surgery have a number of initiatives in place to help.

SVS will host an informational session for anyone interested in starting a program from 9:30 to 10:30 a.m. Friday, June 14, in National Harbor 4. Most of the session will be interactive, with experienced program directors offering participants useful information and practical advice.