Kernohan’s notch false localizing sign. PPRF. The 7th nerve fascicle wraps around the 6th nerve nucleus. (Or is it the other way around?)
 

Yes, I’m studying for my 10-year boards.

It’s funny how many of these details you forget over time. I used to be able to rattle off names, syndromes, and pathways at the dreaded Thursday morning differential conference in residency. To not know them would get you a dreaded glare from the chairman. Now ... not as much.

Granted, the names of such things become less important over time. What’s important is the instinctive understanding of them that comes with experience. Remembering the specific name of a neural pathway becomes less relevant compared to recognizing where the problem is when you see that patient, and translating that into appropriate testing and treatment.

But, every 10 years, I have to go back to the books. Relearn the faded details of enzyme pathways, miscellaneous receptor actions, and courses of nerve tracts.

A lot of it is done on my iPad, a gadget I never imagined back in medical school, but it’s still the same routine I knew so well back then: Reading a page, staring blankly off to commit some point to memory, taking a practice test, and reviewing the answers. Occasionally, wandering off to get a can of soda or make tea.

Of course, today I have to work that around my family and job, concerns I didn’t have to split my time with in medical school. I had classmates who were married and had kids, and this always gives me a new respect for how they managed it.

Does knowing these details again make me a better doctor? I have no idea. I understand the idea that we need some way of showing we’re still on top of things after 20 years in the field. I’m not sure the current maintenance of certification practices are the best way to do that, but admittedly I don’t have any better ideas.
 

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

Kernohan’s notch false localizing sign. PPRF. The 7th nerve fascicle wraps around the 6th nerve nucleus. (Or is it the other way around?)
 

Yes, I’m studying for my 10-year boards.

It’s funny how many of these details you forget over time. I used to be able to rattle off names, syndromes, and pathways at the dreaded Thursday morning differential conference in residency. To not know them would get you a dreaded glare from the chairman. Now ... not as much.

Granted, the names of such things become less important over time. What’s important is the instinctive understanding of them that comes with experience. Remembering the specific name of a neural pathway becomes less relevant compared to recognizing where the problem is when you see that patient, and translating that into appropriate testing and treatment.

But, every 10 years, I have to go back to the books. Relearn the faded details of enzyme pathways, miscellaneous receptor actions, and courses of nerve tracts.

A lot of it is done on my iPad, a gadget I never imagined back in medical school, but it’s still the same routine I knew so well back then: Reading a page, staring blankly off to commit some point to memory, taking a practice test, and reviewing the answers. Occasionally, wandering off to get a can of soda or make tea.

Of course, today I have to work that around my family and job, concerns I didn’t have to split my time with in medical school. I had classmates who were married and had kids, and this always gives me a new respect for how they managed it.

Does knowing these details again make me a better doctor? I have no idea. I understand the idea that we need some way of showing we’re still on top of things after 20 years in the field. I’m not sure the current maintenance of certification practices are the best way to do that, but admittedly I don’t have any better ideas.
 

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

Kernohan’s notch false localizing sign. PPRF. The 7th nerve fascicle wraps around the 6th nerve nucleus. (Or is it the other way around?)
 

Yes, I’m studying for my 10-year boards.

It’s funny how many of these details you forget over time. I used to be able to rattle off names, syndromes, and pathways at the dreaded Thursday morning differential conference in residency. To not know them would get you a dreaded glare from the chairman. Now ... not as much.

Granted, the names of such things become less important over time. What’s important is the instinctive understanding of them that comes with experience. Remembering the specific name of a neural pathway becomes less relevant compared to recognizing where the problem is when you see that patient, and translating that into appropriate testing and treatment.

But, every 10 years, I have to go back to the books. Relearn the faded details of enzyme pathways, miscellaneous receptor actions, and courses of nerve tracts.

A lot of it is done on my iPad, a gadget I never imagined back in medical school, but it’s still the same routine I knew so well back then: Reading a page, staring blankly off to commit some point to memory, taking a practice test, and reviewing the answers. Occasionally, wandering off to get a can of soda or make tea.

Of course, today I have to work that around my family and job, concerns I didn’t have to split my time with in medical school. I had classmates who were married and had kids, and this always gives me a new respect for how they managed it.

Does knowing these details again make me a better doctor? I have no idea. I understand the idea that we need some way of showing we’re still on top of things after 20 years in the field. I’m not sure the current maintenance of certification practices are the best way to do that, but admittedly I don’t have any better ideas.
 

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

For first-line treatment of patients with fecal incontinence, pelvic floor muscle training (PFMT) is superior to attention-control massage, according to investigators.

Source: American Gastroenterological Association

In a study involving 98 patients, those who combined PFMT with biofeedback and conservative therapy were five times as likely to report improved symptoms than those who used attention-control massage and conservative therapy, reported Anja Ussing, MD, of Copenhagen University Hospital in Hvidovre, Denmark, and colleagues. Patients in the PFMT group also had significantly greater reductions in severity of incontinence, based on Vaizey incontinence score.

“Evidence from randomized controlled trials regarding the effect of PFMT for fecal incontinence is lacking,” the investigators wrote in Clinical Gastroenterology and Hepatology. Although previous trials have evaluated PFMT, none controlled for the effect of interactions with care providers. “To evaluate the effect of PFMT, there is a need for a trial that uses a comparator to control for this nonspecific trial effect associated with the attention given by the health care professional.”

To perform such a trial, the investigators recruited 98 patients with a history of fecal incontinence for at least 6 months. Patients were excluded if they had severe neurologic conditions, pregnancy, diarrhea, rectal prolapse, previous radiotherapy or cancer surgery in the lower abdomen, cognitive impairment, inadequate fluency in Danish, or a history of at least two PFMT training sessions within the past year. Enrolled patients were randomized in a 1:1 ratio to receive PFMT with biofeedback and conservative treatment, or attention-control massage training and conservative therapy. The primary outcome was symptom improvement, determined by the Patient Global Impression of Improvement scale at 16 weeks. Secondary outcome measures included the Fecal Incontinence Severity Index, Vaizey score, and Fecal Incontinence Quality of Life Scale.

Patients were predominantly female, with just three men in the PFMT group and six in the attention-control massage group. The PFMT group also had a slightly higher median age, at 65 years, compared with 58 years in the control group.

At 16 weeks, the difference in self-reported symptoms was dramatic, with 74.5% of patients in the PFMT group reporting improvement, compared with 35.5% in the control group, which translated to an unadjusted odds ratio of 5.16 (P = .0002). When symptom improvements were confined to those who reported being “very much better” or “much better,” the disparity between groups still remained strong, with an unadjusted OR of 2.98 (P = .025). Among the three secondary outcomes, only the Vaizey score showed a significant difference between groups. Patients treated with PFMT had a mean difference in Vaizey score change of –1.83 points, using a scale from 0 to 24, with 24 representing complete incontinence (P = .04).

“We were not able to show any differences between groups in the number of fecal incontinence episodes,” the investigators wrote. “We had much missing data in the bowel diaries and we can only guess what the result would have been if the data had been more complete. Electronic assessment of incontinence episodes could be a way to reduce the amount of missing data in future trials.”

Still, the investigators concluded that PFMT was the superior therapy. “Based on the results, PFMT in combination with conservative treatment should be offered as first-line treatment for adults with fecal incontinence.”

They also highlighted the broad applicability of their findings, regardless of facility type.

“In the current trial, more than one-third of patients had sphincter injuries confirmed at endoanal ultrasound, this reflects the tertiary setting of our trial,” they wrote. “However, our results may be highly relevant in a primary setting because there is an unmet need for treatment of fecal incontinence in primary health care, and the interventions do not necessarily need to be conducted at specialized centers.”

The study was funded by the Danish Foundation for Research in Physiotherapy, The Lundbeck Foundation, the Research Foundation at Copenhagen University Hospital, and the Foundation of Aase and Ejnar Danielsen. The investigators reported additional relationships with Medtronic, Helsefonden, Gynzone, and others.

SOURCE: Ussing A et al. Clin Gastroenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.015.

For first-line treatment of patients with fecal incontinence, pelvic floor muscle training (PFMT) is superior to attention-control massage, according to investigators.

Source: American Gastroenterological Association

In a study involving 98 patients, those who combined PFMT with biofeedback and conservative therapy were five times as likely to report improved symptoms than those who used attention-control massage and conservative therapy, reported Anja Ussing, MD, of Copenhagen University Hospital in Hvidovre, Denmark, and colleagues. Patients in the PFMT group also had significantly greater reductions in severity of incontinence, based on Vaizey incontinence score.

“Evidence from randomized controlled trials regarding the effect of PFMT for fecal incontinence is lacking,” the investigators wrote in Clinical Gastroenterology and Hepatology. Although previous trials have evaluated PFMT, none controlled for the effect of interactions with care providers. “To evaluate the effect of PFMT, there is a need for a trial that uses a comparator to control for this nonspecific trial effect associated with the attention given by the health care professional.”

To perform such a trial, the investigators recruited 98 patients with a history of fecal incontinence for at least 6 months. Patients were excluded if they had severe neurologic conditions, pregnancy, diarrhea, rectal prolapse, previous radiotherapy or cancer surgery in the lower abdomen, cognitive impairment, inadequate fluency in Danish, or a history of at least two PFMT training sessions within the past year. Enrolled patients were randomized in a 1:1 ratio to receive PFMT with biofeedback and conservative treatment, or attention-control massage training and conservative therapy. The primary outcome was symptom improvement, determined by the Patient Global Impression of Improvement scale at 16 weeks. Secondary outcome measures included the Fecal Incontinence Severity Index, Vaizey score, and Fecal Incontinence Quality of Life Scale.

Patients were predominantly female, with just three men in the PFMT group and six in the attention-control massage group. The PFMT group also had a slightly higher median age, at 65 years, compared with 58 years in the control group.

At 16 weeks, the difference in self-reported symptoms was dramatic, with 74.5% of patients in the PFMT group reporting improvement, compared with 35.5% in the control group, which translated to an unadjusted odds ratio of 5.16 (P = .0002). When symptom improvements were confined to those who reported being “very much better” or “much better,” the disparity between groups still remained strong, with an unadjusted OR of 2.98 (P = .025). Among the three secondary outcomes, only the Vaizey score showed a significant difference between groups. Patients treated with PFMT had a mean difference in Vaizey score change of –1.83 points, using a scale from 0 to 24, with 24 representing complete incontinence (P = .04).

“We were not able to show any differences between groups in the number of fecal incontinence episodes,” the investigators wrote. “We had much missing data in the bowel diaries and we can only guess what the result would have been if the data had been more complete. Electronic assessment of incontinence episodes could be a way to reduce the amount of missing data in future trials.”

Still, the investigators concluded that PFMT was the superior therapy. “Based on the results, PFMT in combination with conservative treatment should be offered as first-line treatment for adults with fecal incontinence.”

They also highlighted the broad applicability of their findings, regardless of facility type.

“In the current trial, more than one-third of patients had sphincter injuries confirmed at endoanal ultrasound, this reflects the tertiary setting of our trial,” they wrote. “However, our results may be highly relevant in a primary setting because there is an unmet need for treatment of fecal incontinence in primary health care, and the interventions do not necessarily need to be conducted at specialized centers.”

The study was funded by the Danish Foundation for Research in Physiotherapy, The Lundbeck Foundation, the Research Foundation at Copenhagen University Hospital, and the Foundation of Aase and Ejnar Danielsen. The investigators reported additional relationships with Medtronic, Helsefonden, Gynzone, and others.

SOURCE: Ussing A et al. Clin Gastroenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.015.

For first-line treatment of patients with fecal incontinence, pelvic floor muscle training (PFMT) is superior to attention-control massage, according to investigators.

Source: American Gastroenterological Association

In a study involving 98 patients, those who combined PFMT with biofeedback and conservative therapy were five times as likely to report improved symptoms than those who used attention-control massage and conservative therapy, reported Anja Ussing, MD, of Copenhagen University Hospital in Hvidovre, Denmark, and colleagues. Patients in the PFMT group also had significantly greater reductions in severity of incontinence, based on Vaizey incontinence score.

“Evidence from randomized controlled trials regarding the effect of PFMT for fecal incontinence is lacking,” the investigators wrote in Clinical Gastroenterology and Hepatology. Although previous trials have evaluated PFMT, none controlled for the effect of interactions with care providers. “To evaluate the effect of PFMT, there is a need for a trial that uses a comparator to control for this nonspecific trial effect associated with the attention given by the health care professional.”

To perform such a trial, the investigators recruited 98 patients with a history of fecal incontinence for at least 6 months. Patients were excluded if they had severe neurologic conditions, pregnancy, diarrhea, rectal prolapse, previous radiotherapy or cancer surgery in the lower abdomen, cognitive impairment, inadequate fluency in Danish, or a history of at least two PFMT training sessions within the past year. Enrolled patients were randomized in a 1:1 ratio to receive PFMT with biofeedback and conservative treatment, or attention-control massage training and conservative therapy. The primary outcome was symptom improvement, determined by the Patient Global Impression of Improvement scale at 16 weeks. Secondary outcome measures included the Fecal Incontinence Severity Index, Vaizey score, and Fecal Incontinence Quality of Life Scale.

Patients were predominantly female, with just three men in the PFMT group and six in the attention-control massage group. The PFMT group also had a slightly higher median age, at 65 years, compared with 58 years in the control group.

At 16 weeks, the difference in self-reported symptoms was dramatic, with 74.5% of patients in the PFMT group reporting improvement, compared with 35.5% in the control group, which translated to an unadjusted odds ratio of 5.16 (P = .0002). When symptom improvements were confined to those who reported being “very much better” or “much better,” the disparity between groups still remained strong, with an unadjusted OR of 2.98 (P = .025). Among the three secondary outcomes, only the Vaizey score showed a significant difference between groups. Patients treated with PFMT had a mean difference in Vaizey score change of –1.83 points, using a scale from 0 to 24, with 24 representing complete incontinence (P = .04).

“We were not able to show any differences between groups in the number of fecal incontinence episodes,” the investigators wrote. “We had much missing data in the bowel diaries and we can only guess what the result would have been if the data had been more complete. Electronic assessment of incontinence episodes could be a way to reduce the amount of missing data in future trials.”

Still, the investigators concluded that PFMT was the superior therapy. “Based on the results, PFMT in combination with conservative treatment should be offered as first-line treatment for adults with fecal incontinence.”

They also highlighted the broad applicability of their findings, regardless of facility type.

“In the current trial, more than one-third of patients had sphincter injuries confirmed at endoanal ultrasound, this reflects the tertiary setting of our trial,” they wrote. “However, our results may be highly relevant in a primary setting because there is an unmet need for treatment of fecal incontinence in primary health care, and the interventions do not necessarily need to be conducted at specialized centers.”

The study was funded by the Danish Foundation for Research in Physiotherapy, The Lundbeck Foundation, the Research Foundation at Copenhagen University Hospital, and the Foundation of Aase and Ejnar Danielsen. The investigators reported additional relationships with Medtronic, Helsefonden, Gynzone, and others.

SOURCE: Ussing A et al. Clin Gastroenterol Hepatol. 2018 Dec 20. doi: 10.1016/j.cgh.2018.12.015.

Closing mucosal defects with hemoclips after endoscopic resection of large polyps in the proximal colon may significantly reduce postoperative bleeding risk, according to investigators.

In a prospective study of almost 1,000 patients, this benefit was not influenced by polyp size, electrocautery setting, or concomitant use of antithrombotic medications, reported Heiko Pohl, MD, of Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“Endoscopic resection has replaced surgical resection as the primary treatment for large colon polyps due to a lower morbidity and less need for hospitalization,” the investigators wrote in Gastroenterology. “Postprocedure bleeding is the most common severe complication, occurring in 2%-24% of patients.” This risk is particularly common among patients with large polyps in the proximal colon.

Although previous trials have suggested that closing polyp resection sites with hemoclips could reduce the risk of postoperative bleeding, studies to date have been retrospective or uncontrolled, precluding definitive conclusions.

The prospective, controlled trial involved 44 endoscopists at 18 treatment centers. Enrollment included 919 patients with large, nonpedunculated colorectal polyps of at least 20 mm in diameter. Patients were randomized in an approximate 1:1 ratio into the clip group or control group and followed for at least 30 days after endoscopic polyp resection. The primary outcome was postoperative bleeding, defined as severe bleeding that required invasive intervention such as surgery or blood transfusion during follow-up. Subgroup analysis looked for associations between bleeding and polyp location, size, electrocautery setting, and medications.

Across the entire population, postoperative bleeding was significantly less common among patients who had their resection sites closed with clips, occurring at a rate of 3.5%, compared with 7.1% in the control group (P = .015). Serious adverse events were also less common in the clip group than the control group (4.8% vs. 9.5%; P = .006).

While the reduction of bleeding risk from clip closure was not influenced by polyp size, use of antithrombotic medications, or electrocautery setting, polyp location turned out to be a critical factor. Greatest reduction in risk of postoperative bleeding was seen among the 615 patients who had proximal polyps, based on a bleeding rate of 3.3% when clipped versus 9.6% among those who went without clips (P = .001). In contrast, clips in the distal colon were associated with a higher absolute risk of postoperative bleeding than no clips (4.0% vs. 1.4%); however, this difference was not statistically significant (P = .178).

“[T]his multicenter trial provides strong evidence that endoscopic clip closure of the mucosal defect after resection of large ... nonpedunculated colon polyps in the proximal colon significantly reduces the risk of postprocedure bleeding,” the investigators wrote.

They suggested that their study provides greater confidence in findings than similar trials previously conducted, enough to recommend that endoscopic techniques be altered accordingly. “[O]ur trial was methodologically rigorous, adequately powered, and all polyps were removed by endoscopic mucosal resection, which is considered the standard technique for large colon polyps in Western countries,” they wrote. “The results of the study are therefore broadly applicable to current practice. Furthermore, conduct of the study at different centers with multiple endoscopists strengthens generalizability of the findings.”

The investigators also speculated about why postoperative bleeding risk was increased when clips were used in the distal colon. “Potential explanations include a poorer quality of clipping, a shorter clip retention time, possible related to a thicker colon wall in the distal compared to the proximal colon,” they wrote, adding that “these considerations are worthy of further study.”

Indeed, more work remains to be done. “A formal cost-effectiveness analysis is needed to better understand the value of clip closure,” they wrote. “Such analysis can then also examine possible thresholds, for instance regarding the minimum proportion of polyp resections, for which complete closure should be achieved, or the maximum number of clips to close a defect.”

The study was funded by Boston Scientific. The investigators reported additional relationships with U.S. Endoscopy, Olympus, Medtronic, and others.

SOURCE: Pohl H et al. Gastroenterology. 2019 Mar 15. doi: 10.1053/j.gastro.2019.03.019.

Closing mucosal defects with hemoclips after endoscopic resection of large polyps in the proximal colon may significantly reduce postoperative bleeding risk, according to investigators.

In a prospective study of almost 1,000 patients, this benefit was not influenced by polyp size, electrocautery setting, or concomitant use of antithrombotic medications, reported Heiko Pohl, MD, of Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“Endoscopic resection has replaced surgical resection as the primary treatment for large colon polyps due to a lower morbidity and less need for hospitalization,” the investigators wrote in Gastroenterology. “Postprocedure bleeding is the most common severe complication, occurring in 2%-24% of patients.” This risk is particularly common among patients with large polyps in the proximal colon.

Although previous trials have suggested that closing polyp resection sites with hemoclips could reduce the risk of postoperative bleeding, studies to date have been retrospective or uncontrolled, precluding definitive conclusions.

The prospective, controlled trial involved 44 endoscopists at 18 treatment centers. Enrollment included 919 patients with large, nonpedunculated colorectal polyps of at least 20 mm in diameter. Patients were randomized in an approximate 1:1 ratio into the clip group or control group and followed for at least 30 days after endoscopic polyp resection. The primary outcome was postoperative bleeding, defined as severe bleeding that required invasive intervention such as surgery or blood transfusion during follow-up. Subgroup analysis looked for associations between bleeding and polyp location, size, electrocautery setting, and medications.

Across the entire population, postoperative bleeding was significantly less common among patients who had their resection sites closed with clips, occurring at a rate of 3.5%, compared with 7.1% in the control group (P = .015). Serious adverse events were also less common in the clip group than the control group (4.8% vs. 9.5%; P = .006).

While the reduction of bleeding risk from clip closure was not influenced by polyp size, use of antithrombotic medications, or electrocautery setting, polyp location turned out to be a critical factor. Greatest reduction in risk of postoperative bleeding was seen among the 615 patients who had proximal polyps, based on a bleeding rate of 3.3% when clipped versus 9.6% among those who went without clips (P = .001). In contrast, clips in the distal colon were associated with a higher absolute risk of postoperative bleeding than no clips (4.0% vs. 1.4%); however, this difference was not statistically significant (P = .178).

“[T]his multicenter trial provides strong evidence that endoscopic clip closure of the mucosal defect after resection of large ... nonpedunculated colon polyps in the proximal colon significantly reduces the risk of postprocedure bleeding,” the investigators wrote.

They suggested that their study provides greater confidence in findings than similar trials previously conducted, enough to recommend that endoscopic techniques be altered accordingly. “[O]ur trial was methodologically rigorous, adequately powered, and all polyps were removed by endoscopic mucosal resection, which is considered the standard technique for large colon polyps in Western countries,” they wrote. “The results of the study are therefore broadly applicable to current practice. Furthermore, conduct of the study at different centers with multiple endoscopists strengthens generalizability of the findings.”

The investigators also speculated about why postoperative bleeding risk was increased when clips were used in the distal colon. “Potential explanations include a poorer quality of clipping, a shorter clip retention time, possible related to a thicker colon wall in the distal compared to the proximal colon,” they wrote, adding that “these considerations are worthy of further study.”

Indeed, more work remains to be done. “A formal cost-effectiveness analysis is needed to better understand the value of clip closure,” they wrote. “Such analysis can then also examine possible thresholds, for instance regarding the minimum proportion of polyp resections, for which complete closure should be achieved, or the maximum number of clips to close a defect.”

The study was funded by Boston Scientific. The investigators reported additional relationships with U.S. Endoscopy, Olympus, Medtronic, and others.

SOURCE: Pohl H et al. Gastroenterology. 2019 Mar 15. doi: 10.1053/j.gastro.2019.03.019.

Closing mucosal defects with hemoclips after endoscopic resection of large polyps in the proximal colon may significantly reduce postoperative bleeding risk, according to investigators.

In a prospective study of almost 1,000 patients, this benefit was not influenced by polyp size, electrocautery setting, or concomitant use of antithrombotic medications, reported Heiko Pohl, MD, of Geisel School of Medicine at Dartmouth, Hanover, N.H., and colleagues.

“Endoscopic resection has replaced surgical resection as the primary treatment for large colon polyps due to a lower morbidity and less need for hospitalization,” the investigators wrote in Gastroenterology. “Postprocedure bleeding is the most common severe complication, occurring in 2%-24% of patients.” This risk is particularly common among patients with large polyps in the proximal colon.

Although previous trials have suggested that closing polyp resection sites with hemoclips could reduce the risk of postoperative bleeding, studies to date have been retrospective or uncontrolled, precluding definitive conclusions.

The prospective, controlled trial involved 44 endoscopists at 18 treatment centers. Enrollment included 919 patients with large, nonpedunculated colorectal polyps of at least 20 mm in diameter. Patients were randomized in an approximate 1:1 ratio into the clip group or control group and followed for at least 30 days after endoscopic polyp resection. The primary outcome was postoperative bleeding, defined as severe bleeding that required invasive intervention such as surgery or blood transfusion during follow-up. Subgroup analysis looked for associations between bleeding and polyp location, size, electrocautery setting, and medications.

Across the entire population, postoperative bleeding was significantly less common among patients who had their resection sites closed with clips, occurring at a rate of 3.5%, compared with 7.1% in the control group (P = .015). Serious adverse events were also less common in the clip group than the control group (4.8% vs. 9.5%; P = .006).

While the reduction of bleeding risk from clip closure was not influenced by polyp size, use of antithrombotic medications, or electrocautery setting, polyp location turned out to be a critical factor. Greatest reduction in risk of postoperative bleeding was seen among the 615 patients who had proximal polyps, based on a bleeding rate of 3.3% when clipped versus 9.6% among those who went without clips (P = .001). In contrast, clips in the distal colon were associated with a higher absolute risk of postoperative bleeding than no clips (4.0% vs. 1.4%); however, this difference was not statistically significant (P = .178).

“[T]his multicenter trial provides strong evidence that endoscopic clip closure of the mucosal defect after resection of large ... nonpedunculated colon polyps in the proximal colon significantly reduces the risk of postprocedure bleeding,” the investigators wrote.

They suggested that their study provides greater confidence in findings than similar trials previously conducted, enough to recommend that endoscopic techniques be altered accordingly. “[O]ur trial was methodologically rigorous, adequately powered, and all polyps were removed by endoscopic mucosal resection, which is considered the standard technique for large colon polyps in Western countries,” they wrote. “The results of the study are therefore broadly applicable to current practice. Furthermore, conduct of the study at different centers with multiple endoscopists strengthens generalizability of the findings.”

The investigators also speculated about why postoperative bleeding risk was increased when clips were used in the distal colon. “Potential explanations include a poorer quality of clipping, a shorter clip retention time, possible related to a thicker colon wall in the distal compared to the proximal colon,” they wrote, adding that “these considerations are worthy of further study.”

Indeed, more work remains to be done. “A formal cost-effectiveness analysis is needed to better understand the value of clip closure,” they wrote. “Such analysis can then also examine possible thresholds, for instance regarding the minimum proportion of polyp resections, for which complete closure should be achieved, or the maximum number of clips to close a defect.”

The study was funded by Boston Scientific. The investigators reported additional relationships with U.S. Endoscopy, Olympus, Medtronic, and others.

SOURCE: Pohl H et al. Gastroenterology. 2019 Mar 15. doi: 10.1053/j.gastro.2019.03.019.

CHICAGO – Because gastroparesis and functional dyspepsia share several symptoms (e.g., upper abdominal pain, fullness, and bloating) and pathophysiological abnormalities (e.g., delayed gastric emptying, impaired gastric accommodation, and visceral hypersensitivity), it can be hard to distinguish the two conditions, according to a lecture presented at Freston Conference 2019, sponsored by the American Gastroenterological Association. Additional research into the role of diet in these conditions will improve the treatment of these patients, said Linda Nguyen, MD, director of neurogastroenterology and motility at Stanford (Calif.) University.

Distinguishing the disorders

The accepted definition of gastroparesis is abnormal gastric emptying in the absence of a mechanical obstruction. The condition’s symptoms include nausea, vomiting, bloating, early satiety, abdominal pain, and weight loss. A previous consensus held that if a patient had abdominal pain, he or she did not have gastroparesis. Yet studies indicate that up to 80% of patients with gastroparesis have pain.

Functional dyspepsia is defined as bothersome postprandial fullness, early satiety, and epigastric pain or burning in the absence of structural abnormality. The disorder can be subdivided into postprandial distress (i.e., meal-related symptomatology) and epigastric pain syndrome (i.e., pain or burning that may or may not be related to meals). Either of these alternatives may entail nausea and vomiting.

Comparing the pathophysiologies of gastroparesis and functional dyspepsia helps to distinguish these disorders from each other. A 2019 review described rapid gastric emptying and duodenal eosinophilia in patients with functional dyspepsia, but not in patients with gastroparesis. Patients with epigastric pain syndrome had sensitivity to acid, bile, and fats. Patients with idiopathic gastroparesis, which is the most common type, had a weak antral pump and abnormal duodenal feedback, but patients with functional dyspepsia did not have these characteristics (J Neurogastroenterol Motil. 2019;25[1]:27-35).
 

Examining symptoms and severity

One examination of patients with gastroparesis found that approximately 46% of them had a body mass index of 25 or greater. About 26% of patients had a BMI greater than 30. Yet these patients were eating less than 60% of their recommended daily allowances, based on their age, height, weight, and sex (Clin Gastroenterol Hepatol. 2011;9[12]:1056-64).

Accelerating gastric emptying may not relieve symptoms completely in a patient with gastroparesis, said Dr. Nguyen. A 2007 study of patients with gastroparesis found that 43% had impaired accommodation, and 29% had visceral hypersensitivity (Gut. 2007;56[1]:29-36). The same data indicated that gastric emptying time was not correlated with symptom severity. Impaired accommodation, however, was associated with early satiety and weight loss. Visceral hypersensitivity was associated with pain, early satiety, and weight loss. These data suggest that accommodation and visceral hypersensitivity may influence symptom severity in gastroparesis, said Dr. Nguyen.

Other researchers compared mild, moderate, and severe symptoms of early satiety in patients with gastroparesis. They found that patients with severe symptoms of early satiety have more delayed gastric emptying than do patients with mild or moderate symptoms of early satiety (Neurogastroenterol Motil. 2017;29[4].).

Dr. Nguyen and colleagues examined normal gastric emptying, compared with severely delayed gastric emptying, which they defined as greater than 35% retention at 4 hours. They found that severely delayed gastric emptying was associated with more severe symptoms, particularly nausea and vomiting, as measured by Gastroparesis Cardinal Symptom Index (GCSI). Extreme symptoms may help differentiate between gastroparesis and functional dyspepsia, said Dr. Nguyen.


 

Dietary and pharmacologic treatment

Although clinicians might consider recommending dietary modifications to treat gastroparesis or functional dyspepsia, the literature contains little evidence about their efficacy in these indications, said Dr. Nguyen. Based on a study by Tack and colleagues, some clinicians recommend small, frequent meals that are low in fat and low in fiber to patients with gastroparesis. Such a diet could be harmful, however, to patients with comorbid diabetes, irritable bowel syndrome, or renal failure.

Common dietary recommendations for functional dyspepsia include small, frequent meals; decreased fat consumption; and avoidance of citrus and spicy foods. These recommendations are based on small studies in which patients reported which foods tended to cause their symptoms. Trials of dietary modifications in functional dyspepsia, however, are lacking.

Nevertheless, the literature can guide the selection of pharmacotherapy for these disorders. Talley et al. examined the effects of neuromodulators such as amitriptyline, a tricyclic antidepressant, and escitalopram in functional dyspepsia. About 70% of the sample had postprandial distress syndrome, and 20% met criteria for idiopathic gastroparesis. Amitriptyline provided greater symptomatic relief to these patients than did placebo, but escitalopram did not. Patients who met criteria for idiopathic gastroparesis did not respond well to tricyclic antidepressants, but patients with epigastric pain syndrome did. Furthermore, compared with patients with normal gastric emptying, those with delayed emptying did not respond to tricyclic antidepressants. A separate study found that the tricyclic antidepressant nortriptyline did not improve symptoms of gastroparesis (JAMA. 2013;310[24]:2640-9).

Promotility agents may be beneficial for certain patients. A study published this year suggests that, compared with placebo, prucalopride is effective for nausea, vomiting, fullness, bloating, and gastric emptying in patients with idiopathic gastroparesis (Am J Gastroenterol. 2019;114[8]:1265-74.). A 2017 meta-analysis, however, found that proton pump inhibitors were more effective than promotility agents in patients with functional dyspepsia (Am J Gastroenterol. 2017;112[7]:988-1013.).

Pyloric dysfunction may accompany gastroparesis in some patients. Increased severity of gastric emptying delay is associated with increased pylorospasm. Endoscopists have gained experience in performing pyloric myotomy, and this treatment has become more popular. Uncontrolled studies indicate that the proportion of patients with decreased symptom severity after this procedure is higher than 70% and can be as high as 86% (Gastrointest Endosc. 2017;85[1]:123-8). The predictors of a good response include idiopathic etiology, male sex, moderate symptom severity, and greater delay in gastric emptying.

Functional dyspepsia should perhaps be understood as normal gastric emptying and symptoms of epigastric pain syndrome, said Dr. Nguyen. Those patients may respond to neuromodulators, she added. Idiopathic gastroparesis appears to be characterized by severe delay in gastric emptying, postprandial symptoms, nausea, and vomiting. “In the middle is the gray zone, where you have these patients with postprandial distress with or without delayed gastric emptying,” said Dr. Nguyen. Functional dyspepsia and gastroparesis could be two ends of a spectrum, and the best management for patients with symptoms that occur in both disorders is unclear.

Help educate your patients about gastroparesis, its symptoms and causes, as well as testing and treatment using AGA patient education, which can be found in the GI Patient Center at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroparesis.

[email protected]

CHICAGO – Because gastroparesis and functional dyspepsia share several symptoms (e.g., upper abdominal pain, fullness, and bloating) and pathophysiological abnormalities (e.g., delayed gastric emptying, impaired gastric accommodation, and visceral hypersensitivity), it can be hard to distinguish the two conditions, according to a lecture presented at Freston Conference 2019, sponsored by the American Gastroenterological Association. Additional research into the role of diet in these conditions will improve the treatment of these patients, said Linda Nguyen, MD, director of neurogastroenterology and motility at Stanford (Calif.) University.

Distinguishing the disorders

The accepted definition of gastroparesis is abnormal gastric emptying in the absence of a mechanical obstruction. The condition’s symptoms include nausea, vomiting, bloating, early satiety, abdominal pain, and weight loss. A previous consensus held that if a patient had abdominal pain, he or she did not have gastroparesis. Yet studies indicate that up to 80% of patients with gastroparesis have pain.

Functional dyspepsia is defined as bothersome postprandial fullness, early satiety, and epigastric pain or burning in the absence of structural abnormality. The disorder can be subdivided into postprandial distress (i.e., meal-related symptomatology) and epigastric pain syndrome (i.e., pain or burning that may or may not be related to meals). Either of these alternatives may entail nausea and vomiting.

Comparing the pathophysiologies of gastroparesis and functional dyspepsia helps to distinguish these disorders from each other. A 2019 review described rapid gastric emptying and duodenal eosinophilia in patients with functional dyspepsia, but not in patients with gastroparesis. Patients with epigastric pain syndrome had sensitivity to acid, bile, and fats. Patients with idiopathic gastroparesis, which is the most common type, had a weak antral pump and abnormal duodenal feedback, but patients with functional dyspepsia did not have these characteristics (J Neurogastroenterol Motil. 2019;25[1]:27-35).
 

Examining symptoms and severity

One examination of patients with gastroparesis found that approximately 46% of them had a body mass index of 25 or greater. About 26% of patients had a BMI greater than 30. Yet these patients were eating less than 60% of their recommended daily allowances, based on their age, height, weight, and sex (Clin Gastroenterol Hepatol. 2011;9[12]:1056-64).

Accelerating gastric emptying may not relieve symptoms completely in a patient with gastroparesis, said Dr. Nguyen. A 2007 study of patients with gastroparesis found that 43% had impaired accommodation, and 29% had visceral hypersensitivity (Gut. 2007;56[1]:29-36). The same data indicated that gastric emptying time was not correlated with symptom severity. Impaired accommodation, however, was associated with early satiety and weight loss. Visceral hypersensitivity was associated with pain, early satiety, and weight loss. These data suggest that accommodation and visceral hypersensitivity may influence symptom severity in gastroparesis, said Dr. Nguyen.

Other researchers compared mild, moderate, and severe symptoms of early satiety in patients with gastroparesis. They found that patients with severe symptoms of early satiety have more delayed gastric emptying than do patients with mild or moderate symptoms of early satiety (Neurogastroenterol Motil. 2017;29[4].).

Dr. Nguyen and colleagues examined normal gastric emptying, compared with severely delayed gastric emptying, which they defined as greater than 35% retention at 4 hours. They found that severely delayed gastric emptying was associated with more severe symptoms, particularly nausea and vomiting, as measured by Gastroparesis Cardinal Symptom Index (GCSI). Extreme symptoms may help differentiate between gastroparesis and functional dyspepsia, said Dr. Nguyen.


 

Dietary and pharmacologic treatment

Although clinicians might consider recommending dietary modifications to treat gastroparesis or functional dyspepsia, the literature contains little evidence about their efficacy in these indications, said Dr. Nguyen. Based on a study by Tack and colleagues, some clinicians recommend small, frequent meals that are low in fat and low in fiber to patients with gastroparesis. Such a diet could be harmful, however, to patients with comorbid diabetes, irritable bowel syndrome, or renal failure.

Common dietary recommendations for functional dyspepsia include small, frequent meals; decreased fat consumption; and avoidance of citrus and spicy foods. These recommendations are based on small studies in which patients reported which foods tended to cause their symptoms. Trials of dietary modifications in functional dyspepsia, however, are lacking.

Nevertheless, the literature can guide the selection of pharmacotherapy for these disorders. Talley et al. examined the effects of neuromodulators such as amitriptyline, a tricyclic antidepressant, and escitalopram in functional dyspepsia. About 70% of the sample had postprandial distress syndrome, and 20% met criteria for idiopathic gastroparesis. Amitriptyline provided greater symptomatic relief to these patients than did placebo, but escitalopram did not. Patients who met criteria for idiopathic gastroparesis did not respond well to tricyclic antidepressants, but patients with epigastric pain syndrome did. Furthermore, compared with patients with normal gastric emptying, those with delayed emptying did not respond to tricyclic antidepressants. A separate study found that the tricyclic antidepressant nortriptyline did not improve symptoms of gastroparesis (JAMA. 2013;310[24]:2640-9).

Promotility agents may be beneficial for certain patients. A study published this year suggests that, compared with placebo, prucalopride is effective for nausea, vomiting, fullness, bloating, and gastric emptying in patients with idiopathic gastroparesis (Am J Gastroenterol. 2019;114[8]:1265-74.). A 2017 meta-analysis, however, found that proton pump inhibitors were more effective than promotility agents in patients with functional dyspepsia (Am J Gastroenterol. 2017;112[7]:988-1013.).

Pyloric dysfunction may accompany gastroparesis in some patients. Increased severity of gastric emptying delay is associated with increased pylorospasm. Endoscopists have gained experience in performing pyloric myotomy, and this treatment has become more popular. Uncontrolled studies indicate that the proportion of patients with decreased symptom severity after this procedure is higher than 70% and can be as high as 86% (Gastrointest Endosc. 2017;85[1]:123-8). The predictors of a good response include idiopathic etiology, male sex, moderate symptom severity, and greater delay in gastric emptying.

Functional dyspepsia should perhaps be understood as normal gastric emptying and symptoms of epigastric pain syndrome, said Dr. Nguyen. Those patients may respond to neuromodulators, she added. Idiopathic gastroparesis appears to be characterized by severe delay in gastric emptying, postprandial symptoms, nausea, and vomiting. “In the middle is the gray zone, where you have these patients with postprandial distress with or without delayed gastric emptying,” said Dr. Nguyen. Functional dyspepsia and gastroparesis could be two ends of a spectrum, and the best management for patients with symptoms that occur in both disorders is unclear.

Help educate your patients about gastroparesis, its symptoms and causes, as well as testing and treatment using AGA patient education, which can be found in the GI Patient Center at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroparesis.

[email protected]

CHICAGO – Because gastroparesis and functional dyspepsia share several symptoms (e.g., upper abdominal pain, fullness, and bloating) and pathophysiological abnormalities (e.g., delayed gastric emptying, impaired gastric accommodation, and visceral hypersensitivity), it can be hard to distinguish the two conditions, according to a lecture presented at Freston Conference 2019, sponsored by the American Gastroenterological Association. Additional research into the role of diet in these conditions will improve the treatment of these patients, said Linda Nguyen, MD, director of neurogastroenterology and motility at Stanford (Calif.) University.

Distinguishing the disorders

The accepted definition of gastroparesis is abnormal gastric emptying in the absence of a mechanical obstruction. The condition’s symptoms include nausea, vomiting, bloating, early satiety, abdominal pain, and weight loss. A previous consensus held that if a patient had abdominal pain, he or she did not have gastroparesis. Yet studies indicate that up to 80% of patients with gastroparesis have pain.

Functional dyspepsia is defined as bothersome postprandial fullness, early satiety, and epigastric pain or burning in the absence of structural abnormality. The disorder can be subdivided into postprandial distress (i.e., meal-related symptomatology) and epigastric pain syndrome (i.e., pain or burning that may or may not be related to meals). Either of these alternatives may entail nausea and vomiting.

Comparing the pathophysiologies of gastroparesis and functional dyspepsia helps to distinguish these disorders from each other. A 2019 review described rapid gastric emptying and duodenal eosinophilia in patients with functional dyspepsia, but not in patients with gastroparesis. Patients with epigastric pain syndrome had sensitivity to acid, bile, and fats. Patients with idiopathic gastroparesis, which is the most common type, had a weak antral pump and abnormal duodenal feedback, but patients with functional dyspepsia did not have these characteristics (J Neurogastroenterol Motil. 2019;25[1]:27-35).
 

Examining symptoms and severity

One examination of patients with gastroparesis found that approximately 46% of them had a body mass index of 25 or greater. About 26% of patients had a BMI greater than 30. Yet these patients were eating less than 60% of their recommended daily allowances, based on their age, height, weight, and sex (Clin Gastroenterol Hepatol. 2011;9[12]:1056-64).

Accelerating gastric emptying may not relieve symptoms completely in a patient with gastroparesis, said Dr. Nguyen. A 2007 study of patients with gastroparesis found that 43% had impaired accommodation, and 29% had visceral hypersensitivity (Gut. 2007;56[1]:29-36). The same data indicated that gastric emptying time was not correlated with symptom severity. Impaired accommodation, however, was associated with early satiety and weight loss. Visceral hypersensitivity was associated with pain, early satiety, and weight loss. These data suggest that accommodation and visceral hypersensitivity may influence symptom severity in gastroparesis, said Dr. Nguyen.

Other researchers compared mild, moderate, and severe symptoms of early satiety in patients with gastroparesis. They found that patients with severe symptoms of early satiety have more delayed gastric emptying than do patients with mild or moderate symptoms of early satiety (Neurogastroenterol Motil. 2017;29[4].).

Dr. Nguyen and colleagues examined normal gastric emptying, compared with severely delayed gastric emptying, which they defined as greater than 35% retention at 4 hours. They found that severely delayed gastric emptying was associated with more severe symptoms, particularly nausea and vomiting, as measured by Gastroparesis Cardinal Symptom Index (GCSI). Extreme symptoms may help differentiate between gastroparesis and functional dyspepsia, said Dr. Nguyen.


 

Dietary and pharmacologic treatment

Although clinicians might consider recommending dietary modifications to treat gastroparesis or functional dyspepsia, the literature contains little evidence about their efficacy in these indications, said Dr. Nguyen. Based on a study by Tack and colleagues, some clinicians recommend small, frequent meals that are low in fat and low in fiber to patients with gastroparesis. Such a diet could be harmful, however, to patients with comorbid diabetes, irritable bowel syndrome, or renal failure.

Common dietary recommendations for functional dyspepsia include small, frequent meals; decreased fat consumption; and avoidance of citrus and spicy foods. These recommendations are based on small studies in which patients reported which foods tended to cause their symptoms. Trials of dietary modifications in functional dyspepsia, however, are lacking.

Nevertheless, the literature can guide the selection of pharmacotherapy for these disorders. Talley et al. examined the effects of neuromodulators such as amitriptyline, a tricyclic antidepressant, and escitalopram in functional dyspepsia. About 70% of the sample had postprandial distress syndrome, and 20% met criteria for idiopathic gastroparesis. Amitriptyline provided greater symptomatic relief to these patients than did placebo, but escitalopram did not. Patients who met criteria for idiopathic gastroparesis did not respond well to tricyclic antidepressants, but patients with epigastric pain syndrome did. Furthermore, compared with patients with normal gastric emptying, those with delayed emptying did not respond to tricyclic antidepressants. A separate study found that the tricyclic antidepressant nortriptyline did not improve symptoms of gastroparesis (JAMA. 2013;310[24]:2640-9).

Promotility agents may be beneficial for certain patients. A study published this year suggests that, compared with placebo, prucalopride is effective for nausea, vomiting, fullness, bloating, and gastric emptying in patients with idiopathic gastroparesis (Am J Gastroenterol. 2019;114[8]:1265-74.). A 2017 meta-analysis, however, found that proton pump inhibitors were more effective than promotility agents in patients with functional dyspepsia (Am J Gastroenterol. 2017;112[7]:988-1013.).

Pyloric dysfunction may accompany gastroparesis in some patients. Increased severity of gastric emptying delay is associated with increased pylorospasm. Endoscopists have gained experience in performing pyloric myotomy, and this treatment has become more popular. Uncontrolled studies indicate that the proportion of patients with decreased symptom severity after this procedure is higher than 70% and can be as high as 86% (Gastrointest Endosc. 2017;85[1]:123-8). The predictors of a good response include idiopathic etiology, male sex, moderate symptom severity, and greater delay in gastric emptying.

Functional dyspepsia should perhaps be understood as normal gastric emptying and symptoms of epigastric pain syndrome, said Dr. Nguyen. Those patients may respond to neuromodulators, she added. Idiopathic gastroparesis appears to be characterized by severe delay in gastric emptying, postprandial symptoms, nausea, and vomiting. “In the middle is the gray zone, where you have these patients with postprandial distress with or without delayed gastric emptying,” said Dr. Nguyen. Functional dyspepsia and gastroparesis could be two ends of a spectrum, and the best management for patients with symptoms that occur in both disorders is unclear.

Help educate your patients about gastroparesis, its symptoms and causes, as well as testing and treatment using AGA patient education, which can be found in the GI Patient Center at https://www.gastro.org/practice-guidance/gi-patient-center/topic/gastroparesis.

[email protected]

The FP suspected acute systemic lupus erythematosus (SLE) with an acute cutaneous component. Laboratory testing showed a very high level of antinuclear antibodies. The patient was referred to Rheumatology and Dermatology. The dermatologist was available for a phone consult and suggested starting the patient on prednisone 60 mg/d as the Medrol Dosepak that the patient previously received had insufficient prednisolone for this severe flare of acute cutaneous lupus.

Although the classic description of acute SLE involves a butterfly rash, the rash of acute cutaneous lupus can include other areas of the face and body. As was seen in this case, the nasolabial fold tends to be spared and there are often skin erosions and crusting.

Based on the patient’s lab tests and symptoms, the dermatologist determined that the patient met the criteria for SLE. The patient was started on hydroxychloroquine 400 mg/d. The plan was to taper the patient’s prednisone slowly. By the following week, her skin and fatigue were much improved.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Pye A, Mayeaux EJ, Mishra V, et al. Lupus. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1183-1193.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the 3rd edition of the Color Atlas and Synopsis of Family Medicine as an app by clicking on this link: https://usatinemedia.com/app/color-atlas-of-family-medicine/

The FP suspected acute systemic lupus erythematosus (SLE) with an acute cutaneous component. Laboratory testing showed a very high level of antinuclear antibodies. The patient was referred to Rheumatology and Dermatology. The dermatologist was available for a phone consult and suggested starting the patient on prednisone 60 mg/d as the Medrol Dosepak that the patient previously received had insufficient prednisolone for this severe flare of acute cutaneous lupus.

Although the classic description of acute SLE involves a butterfly rash, the rash of acute cutaneous lupus can include other areas of the face and body. As was seen in this case, the nasolabial fold tends to be spared and there are often skin erosions and crusting.

Based on the patient’s lab tests and symptoms, the dermatologist determined that the patient met the criteria for SLE. The patient was started on hydroxychloroquine 400 mg/d. The plan was to taper the patient’s prednisone slowly. By the following week, her skin and fatigue were much improved.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Pye A, Mayeaux EJ, Mishra V, et al. Lupus. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1183-1193.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the 3rd edition of the Color Atlas and Synopsis of Family Medicine as an app by clicking on this link: https://usatinemedia.com/app/color-atlas-of-family-medicine/

The FP suspected acute systemic lupus erythematosus (SLE) with an acute cutaneous component. Laboratory testing showed a very high level of antinuclear antibodies. The patient was referred to Rheumatology and Dermatology. The dermatologist was available for a phone consult and suggested starting the patient on prednisone 60 mg/d as the Medrol Dosepak that the patient previously received had insufficient prednisolone for this severe flare of acute cutaneous lupus.

Although the classic description of acute SLE involves a butterfly rash, the rash of acute cutaneous lupus can include other areas of the face and body. As was seen in this case, the nasolabial fold tends to be spared and there are often skin erosions and crusting.

Based on the patient’s lab tests and symptoms, the dermatologist determined that the patient met the criteria for SLE. The patient was started on hydroxychloroquine 400 mg/d. The plan was to taper the patient’s prednisone slowly. By the following week, her skin and fatigue were much improved.

‌

Photos and text for Photo Rounds Friday courtesy of Richard P. Usatine, MD. This case was adapted from: Pye A, Mayeaux EJ, Mishra V, et al. Lupus. In: Usatine R, Smith M, Mayeaux EJ, et al, eds. Color Atlas and Synopsis of Family Medicine. 3rd ed. New York, NY: McGraw-Hill; 2019:1183-1193.

To learn more about the newest 3rd edition of the Color Atlas and Synopsis of Family Medicine, see: https://www.amazon.com/Color-Atlas-Synopsis-Family-Medicine/dp/1259862046/

You can get the 3rd edition of the Color Atlas and Synopsis of Family Medicine as an app by clicking on this link: https://usatinemedia.com/app/color-atlas-of-family-medicine/

Survivors of the 2013-2016 Ebola epidemic in West Africa had lingering health effects of the disease. These patients had a much greater mortality in the first year after discharge, compared with the general population. Among those survivors who died, the majority appear to have expired because of renal failure, according to the results of an assessment the by the Guinean national survivors’ monitoring program.

CDC/Athalia Christie

The Surveillance Active en Ceinture obtained data on 1,130 (89%) of survivors of Ebola virus disease who were discharged from Ebola treatment units in Guinea. Compared with the general Guinean population, survivors of Ebola virus showed a five times increased risk of mortality within a year of follow-up after discharge, according to a survey of patients’ medical records and patients’ relatives, reported researchers Mory Keita, MD, and colleagues.

After 1 year, the difference in mortality between Ebola survivors and the general population had disappeared, according to the study published online in the Lancet Infectious Diseases.

A total of 59 deaths were reported among the discharged survivors available for follow-up. Renal failure was the assumed cause in 37 (63%) of these patients based on a description of reported anuria. The exact date of death was unknown for 43 of the 59 deaths. Of the 16 initial survivors for whom an exact date of death was available, 5 died within a month of discharge from Ebola treatment units, an additional 3 died within 3 months of discharge, 4 died 3-12 months after discharge, and 4 died more than a year after discharge (up to 21 months).

Age and area of residence (urban vs. nonurban area) were independently and significantly associated with mortality, with patients of older age (55 years or greater) and those from nonurban areas being at greater risk. Patient sex was not associated with survival.

Those survivors who were hospitalized for 12 days or more had more than double the risk of death than did those hospitalized less than 12 days, which was a statistically significant association.

“Survivors’ monitoring programs should be strengthened and should not focus exclusively on testing of bodily fluids,” the authors advised. “Furthermore, our study provides preliminary evidence that survivors hospitalized for longer than 12 days with Ebola virus disease could be at particularly high risk of mortality and should be specifically targeted, and perhaps also evidence that renal function should be monitored,” Dr. Keita and colleagues concluded.

The study was funded by the World Health Organization, International Medical Corps, and the Guinean Red Cross. The authors reported that they had no conflicts

[email protected]

SOURCE: Keita M et al. Lancet Infect Dis 2019 Sept 4. doi: 10.1016/S1473-3099(19)30313-5.

Survivors of the 2013-2016 Ebola epidemic in West Africa had lingering health effects of the disease. These patients had a much greater mortality in the first year after discharge, compared with the general population. Among those survivors who died, the majority appear to have expired because of renal failure, according to the results of an assessment the by the Guinean national survivors’ monitoring program.

CDC/Athalia Christie

The Surveillance Active en Ceinture obtained data on 1,130 (89%) of survivors of Ebola virus disease who were discharged from Ebola treatment units in Guinea. Compared with the general Guinean population, survivors of Ebola virus showed a five times increased risk of mortality within a year of follow-up after discharge, according to a survey of patients’ medical records and patients’ relatives, reported researchers Mory Keita, MD, and colleagues.

After 1 year, the difference in mortality between Ebola survivors and the general population had disappeared, according to the study published online in the Lancet Infectious Diseases.

A total of 59 deaths were reported among the discharged survivors available for follow-up. Renal failure was the assumed cause in 37 (63%) of these patients based on a description of reported anuria. The exact date of death was unknown for 43 of the 59 deaths. Of the 16 initial survivors for whom an exact date of death was available, 5 died within a month of discharge from Ebola treatment units, an additional 3 died within 3 months of discharge, 4 died 3-12 months after discharge, and 4 died more than a year after discharge (up to 21 months).

Age and area of residence (urban vs. nonurban area) were independently and significantly associated with mortality, with patients of older age (55 years or greater) and those from nonurban areas being at greater risk. Patient sex was not associated with survival.

Those survivors who were hospitalized for 12 days or more had more than double the risk of death than did those hospitalized less than 12 days, which was a statistically significant association.

“Survivors’ monitoring programs should be strengthened and should not focus exclusively on testing of bodily fluids,” the authors advised. “Furthermore, our study provides preliminary evidence that survivors hospitalized for longer than 12 days with Ebola virus disease could be at particularly high risk of mortality and should be specifically targeted, and perhaps also evidence that renal function should be monitored,” Dr. Keita and colleagues concluded.

The study was funded by the World Health Organization, International Medical Corps, and the Guinean Red Cross. The authors reported that they had no conflicts

[email protected]

SOURCE: Keita M et al. Lancet Infect Dis 2019 Sept 4. doi: 10.1016/S1473-3099(19)30313-5.

Survivors of the 2013-2016 Ebola epidemic in West Africa had lingering health effects of the disease. These patients had a much greater mortality in the first year after discharge, compared with the general population. Among those survivors who died, the majority appear to have expired because of renal failure, according to the results of an assessment the by the Guinean national survivors’ monitoring program.

CDC/Athalia Christie

The Surveillance Active en Ceinture obtained data on 1,130 (89%) of survivors of Ebola virus disease who were discharged from Ebola treatment units in Guinea. Compared with the general Guinean population, survivors of Ebola virus showed a five times increased risk of mortality within a year of follow-up after discharge, according to a survey of patients’ medical records and patients’ relatives, reported researchers Mory Keita, MD, and colleagues.

After 1 year, the difference in mortality between Ebola survivors and the general population had disappeared, according to the study published online in the Lancet Infectious Diseases.

A total of 59 deaths were reported among the discharged survivors available for follow-up. Renal failure was the assumed cause in 37 (63%) of these patients based on a description of reported anuria. The exact date of death was unknown for 43 of the 59 deaths. Of the 16 initial survivors for whom an exact date of death was available, 5 died within a month of discharge from Ebola treatment units, an additional 3 died within 3 months of discharge, 4 died 3-12 months after discharge, and 4 died more than a year after discharge (up to 21 months).

Age and area of residence (urban vs. nonurban area) were independently and significantly associated with mortality, with patients of older age (55 years or greater) and those from nonurban areas being at greater risk. Patient sex was not associated with survival.

Those survivors who were hospitalized for 12 days or more had more than double the risk of death than did those hospitalized less than 12 days, which was a statistically significant association.

“Survivors’ monitoring programs should be strengthened and should not focus exclusively on testing of bodily fluids,” the authors advised. “Furthermore, our study provides preliminary evidence that survivors hospitalized for longer than 12 days with Ebola virus disease could be at particularly high risk of mortality and should be specifically targeted, and perhaps also evidence that renal function should be monitored,” Dr. Keita and colleagues concluded.

The study was funded by the World Health Organization, International Medical Corps, and the Guinean Red Cross. The authors reported that they had no conflicts

[email protected]

SOURCE: Keita M et al. Lancet Infect Dis 2019 Sept 4. doi: 10.1016/S1473-3099(19)30313-5.

Care providers encountered significant challenges when addressing the mental health needs of unaccompanied immigrant children in federal custody, including overwhelming caseloads and the deteriorating mental health of some patients, according to a new report by the Office of Inspector General (OIG).

In the report, released Sept. 3, the OIG outlined findings from its analysis of 45 Office of Refugee Resettlement (ORR) facilities between August and September 2018. The U.S. Department of Health & Human Services ORR is the legal custodian of unaccompanied immigrant children in its care who have no parent or legal guardian available. This includes children who arrive in the United States unaccompanied and children who are separated from their parents or guardians by immigration authorities after arriving in the country.

For the analysis, OIG investigators collected data from interviews with mental health clinicians, medical coordinators, facility leadership, and ORR federal field specialists at the 45 selected facilities.

Investigators recorded numerous serious challenges experienced by providers when attempting to provide mental health care to the children. Namely, they cited overwhelming patient caseloads, and difficulty accessing external mental health clinicians and referring children to providers within ORR’s network, according to the OIG’s report.

Mental health clinicians reported that the high caseloads hurt their ability to build rapport with young patients – and allowed less time for counseling and less frequent sessions for children with greater needs. The heavy caseloads were generated by heightened immigration enforcement beginning in 2017, and the separation of many more families at the border and more children being placed in federal custody, according to the report.

In addition, providers reported challenges when addressing the mental health needs of children who had experienced significant trauma before coming into federal custody. Intense trauma was common among children who entered care provider facilities, the report found. This included trauma that occurred while the children lived in the countries of origin, trauma during their journey to the United States, and trauma upon their arrival in the United States.

Separation from parents and a chaotic reunification process added to the trauma that children had already experienced, providers reported, and put extreme pressure on facility staff. Separated children exhibited “more fear, feelings of abandonment, and posttraumatic stress than did children who were not separated,” according to the findings. Separated children also experienced elevated feelings of anxiety and loss as a consequence of unexpected separation from loved ones.

Also, facilities reported that longer lengths of stay resulted in deteriorating mental health for some children and increased demands on staff. Facilities reported that children who stayed in federal custody for longer periods experienced more stress, anxiety, and behavioral issues. According to the facilities, the longer stays resulted in higher levels of defiance, hopelessness, and frustration among children – in addition to more instances of self-harm and suicidal ideation.

As long as the United States continues to detain children, the psychological harm created by such detainments is likely to continue, said Kim A. Baranowski, PhD, a psychologist and lecturer at Columbia University in New York. At a minimum, unaccompanied minors should have access to highly trained licensed clinicians who can respond to their immediate mental health needs within the initial hours and days following their arrival in the United States, and such children should be released rapidly from government custody and reunited with their families, said Dr. Baranowski, a coauthor of the Social Science & Medicine study.

“We need to effectively support their integration into the community, and connect children and their families with linguistically, culturally, and developmentally appropriate trauma-informed pro bono treatment services that respond to their experiences” of premigration, migration, and postmigration stressors, “as well as potential exposure to trauma,” she said in an interview.

The OIG issued several recommendations for practical steps that ORR can take to assist facilities and better provide mental health care to immigrant children in federal custody. The agency advised that the ORR should provide facilities with evidence-based guidance on addressing trauma in short-term therapy and that the ORR also should develop strategies for overcoming challenges to hiring and retaining qualified mental health clinicians.

The Office of Inspector General also suggested that facilities consider maximum caseloads for individual clinicians. Finally, the OIG recommends that ORR address gaps in options for children who require more specialized treatment and that the office take reasonable steps to minimize the length of time that children remain in custody.

[email protected]

*This article was updated 9/5/2019.

Care providers encountered significant challenges when addressing the mental health needs of unaccompanied immigrant children in federal custody, including overwhelming caseloads and the deteriorating mental health of some patients, according to a new report by the Office of Inspector General (OIG).

In the report, released Sept. 3, the OIG outlined findings from its analysis of 45 Office of Refugee Resettlement (ORR) facilities between August and September 2018. The U.S. Department of Health & Human Services ORR is the legal custodian of unaccompanied immigrant children in its care who have no parent or legal guardian available. This includes children who arrive in the United States unaccompanied and children who are separated from their parents or guardians by immigration authorities after arriving in the country.

For the analysis, OIG investigators collected data from interviews with mental health clinicians, medical coordinators, facility leadership, and ORR federal field specialists at the 45 selected facilities.

Investigators recorded numerous serious challenges experienced by providers when attempting to provide mental health care to the children. Namely, they cited overwhelming patient caseloads, and difficulty accessing external mental health clinicians and referring children to providers within ORR’s network, according to the OIG’s report.

Mental health clinicians reported that the high caseloads hurt their ability to build rapport with young patients – and allowed less time for counseling and less frequent sessions for children with greater needs. The heavy caseloads were generated by heightened immigration enforcement beginning in 2017, and the separation of many more families at the border and more children being placed in federal custody, according to the report.

In addition, providers reported challenges when addressing the mental health needs of children who had experienced significant trauma before coming into federal custody. Intense trauma was common among children who entered care provider facilities, the report found. This included trauma that occurred while the children lived in the countries of origin, trauma during their journey to the United States, and trauma upon their arrival in the United States.

Separation from parents and a chaotic reunification process added to the trauma that children had already experienced, providers reported, and put extreme pressure on facility staff. Separated children exhibited “more fear, feelings of abandonment, and posttraumatic stress than did children who were not separated,” according to the findings. Separated children also experienced elevated feelings of anxiety and loss as a consequence of unexpected separation from loved ones.

Also, facilities reported that longer lengths of stay resulted in deteriorating mental health for some children and increased demands on staff. Facilities reported that children who stayed in federal custody for longer periods experienced more stress, anxiety, and behavioral issues. According to the facilities, the longer stays resulted in higher levels of defiance, hopelessness, and frustration among children – in addition to more instances of self-harm and suicidal ideation.

As long as the United States continues to detain children, the psychological harm created by such detainments is likely to continue, said Kim A. Baranowski, PhD, a psychologist and lecturer at Columbia University in New York. At a minimum, unaccompanied minors should have access to highly trained licensed clinicians who can respond to their immediate mental health needs within the initial hours and days following their arrival in the United States, and such children should be released rapidly from government custody and reunited with their families, said Dr. Baranowski, a coauthor of the Social Science & Medicine study.

“We need to effectively support their integration into the community, and connect children and their families with linguistically, culturally, and developmentally appropriate trauma-informed pro bono treatment services that respond to their experiences” of premigration, migration, and postmigration stressors, “as well as potential exposure to trauma,” she said in an interview.

The OIG issued several recommendations for practical steps that ORR can take to assist facilities and better provide mental health care to immigrant children in federal custody. The agency advised that the ORR should provide facilities with evidence-based guidance on addressing trauma in short-term therapy and that the ORR also should develop strategies for overcoming challenges to hiring and retaining qualified mental health clinicians.

The Office of Inspector General also suggested that facilities consider maximum caseloads for individual clinicians. Finally, the OIG recommends that ORR address gaps in options for children who require more specialized treatment and that the office take reasonable steps to minimize the length of time that children remain in custody.

[email protected]

*This article was updated 9/5/2019.

Care providers encountered significant challenges when addressing the mental health needs of unaccompanied immigrant children in federal custody, including overwhelming caseloads and the deteriorating mental health of some patients, according to a new report by the Office of Inspector General (OIG).

In the report, released Sept. 3, the OIG outlined findings from its analysis of 45 Office of Refugee Resettlement (ORR) facilities between August and September 2018. The U.S. Department of Health & Human Services ORR is the legal custodian of unaccompanied immigrant children in its care who have no parent or legal guardian available. This includes children who arrive in the United States unaccompanied and children who are separated from their parents or guardians by immigration authorities after arriving in the country.

For the analysis, OIG investigators collected data from interviews with mental health clinicians, medical coordinators, facility leadership, and ORR federal field specialists at the 45 selected facilities.

Investigators recorded numerous serious challenges experienced by providers when attempting to provide mental health care to the children. Namely, they cited overwhelming patient caseloads, and difficulty accessing external mental health clinicians and referring children to providers within ORR’s network, according to the OIG’s report.

Mental health clinicians reported that the high caseloads hurt their ability to build rapport with young patients – and allowed less time for counseling and less frequent sessions for children with greater needs. The heavy caseloads were generated by heightened immigration enforcement beginning in 2017, and the separation of many more families at the border and more children being placed in federal custody, according to the report.

In addition, providers reported challenges when addressing the mental health needs of children who had experienced significant trauma before coming into federal custody. Intense trauma was common among children who entered care provider facilities, the report found. This included trauma that occurred while the children lived in the countries of origin, trauma during their journey to the United States, and trauma upon their arrival in the United States.

Separation from parents and a chaotic reunification process added to the trauma that children had already experienced, providers reported, and put extreme pressure on facility staff. Separated children exhibited “more fear, feelings of abandonment, and posttraumatic stress than did children who were not separated,” according to the findings. Separated children also experienced elevated feelings of anxiety and loss as a consequence of unexpected separation from loved ones.

Also, facilities reported that longer lengths of stay resulted in deteriorating mental health for some children and increased demands on staff. Facilities reported that children who stayed in federal custody for longer periods experienced more stress, anxiety, and behavioral issues. According to the facilities, the longer stays resulted in higher levels of defiance, hopelessness, and frustration among children – in addition to more instances of self-harm and suicidal ideation.

As long as the United States continues to detain children, the psychological harm created by such detainments is likely to continue, said Kim A. Baranowski, PhD, a psychologist and lecturer at Columbia University in New York. At a minimum, unaccompanied minors should have access to highly trained licensed clinicians who can respond to their immediate mental health needs within the initial hours and days following their arrival in the United States, and such children should be released rapidly from government custody and reunited with their families, said Dr. Baranowski, a coauthor of the Social Science & Medicine study.

“We need to effectively support their integration into the community, and connect children and their families with linguistically, culturally, and developmentally appropriate trauma-informed pro bono treatment services that respond to their experiences” of premigration, migration, and postmigration stressors, “as well as potential exposure to trauma,” she said in an interview.

The OIG issued several recommendations for practical steps that ORR can take to assist facilities and better provide mental health care to immigrant children in federal custody. The agency advised that the ORR should provide facilities with evidence-based guidance on addressing trauma in short-term therapy and that the ORR also should develop strategies for overcoming challenges to hiring and retaining qualified mental health clinicians.

The Office of Inspector General also suggested that facilities consider maximum caseloads for individual clinicians. Finally, the OIG recommends that ORR address gaps in options for children who require more specialized treatment and that the office take reasonable steps to minimize the length of time that children remain in custody.

[email protected]

*This article was updated 9/5/2019.

More financial reinforcements are arriving in the battle against the opioid crisis, with the Trump administration promising more than $1.8 billion in new funds to help states address the crisis.

Speaking at a Sept. 4 press conference announcing the funding, President Donald Trump said the money will be used “to increase access to medication and medication-assisted treatment and mental health resources, which are critical for ending homelessness and getting people the help they deserve.” The president added that the grants also will help state and local governments obtain high-quality, comprehensive data.

The Centers for Disease Control and Prevention will provide more than $900 million in new funding over the next 3 years to “advance the understanding of the opioid overdose epidemic and to scale-up prevention and response activities,” the Department of Health & Human Services said in a statement announcing the funding.

“This money will help states and local communities track overdose data and develop strategies that save lives,” HHS Secretary Alex Azar said during the press conference.

He noted that, when the Trump administration began, overdose data were published with a 12-month lag. That lag has since shortened to 6 months. One of the goals with the new funding is to bring data publishing as close to real time as possible.

Separately, the Substance Abuse and Mental Health Services Administration awarded $932 million to all 50 states as part of its State Opioid Response grants, which “provide flexible funding to state governments to support prevention, treatment, and recovery services in the ways that meet the needs of their state,” according to the HHS statement.

That flexibility “can mean everything from expanding the use of medication-assisted treatment in criminal justice settings or in rural areas via telemedicine, to youth-focused community-based prevention efforts,” Secretary Azar explained. The funds can also support employment coaching and naloxone distribution, he added.

[email protected]

More financial reinforcements are arriving in the battle against the opioid crisis, with the Trump administration promising more than $1.8 billion in new funds to help states address the crisis.

Speaking at a Sept. 4 press conference announcing the funding, President Donald Trump said the money will be used “to increase access to medication and medication-assisted treatment and mental health resources, which are critical for ending homelessness and getting people the help they deserve.” The president added that the grants also will help state and local governments obtain high-quality, comprehensive data.

The Centers for Disease Control and Prevention will provide more than $900 million in new funding over the next 3 years to “advance the understanding of the opioid overdose epidemic and to scale-up prevention and response activities,” the Department of Health & Human Services said in a statement announcing the funding.

“This money will help states and local communities track overdose data and develop strategies that save lives,” HHS Secretary Alex Azar said during the press conference.

He noted that, when the Trump administration began, overdose data were published with a 12-month lag. That lag has since shortened to 6 months. One of the goals with the new funding is to bring data publishing as close to real time as possible.

Separately, the Substance Abuse and Mental Health Services Administration awarded $932 million to all 50 states as part of its State Opioid Response grants, which “provide flexible funding to state governments to support prevention, treatment, and recovery services in the ways that meet the needs of their state,” according to the HHS statement.

That flexibility “can mean everything from expanding the use of medication-assisted treatment in criminal justice settings or in rural areas via telemedicine, to youth-focused community-based prevention efforts,” Secretary Azar explained. The funds can also support employment coaching and naloxone distribution, he added.

[email protected]

More financial reinforcements are arriving in the battle against the opioid crisis, with the Trump administration promising more than $1.8 billion in new funds to help states address the crisis.

Speaking at a Sept. 4 press conference announcing the funding, President Donald Trump said the money will be used “to increase access to medication and medication-assisted treatment and mental health resources, which are critical for ending homelessness and getting people the help they deserve.” The president added that the grants also will help state and local governments obtain high-quality, comprehensive data.

The Centers for Disease Control and Prevention will provide more than $900 million in new funding over the next 3 years to “advance the understanding of the opioid overdose epidemic and to scale-up prevention and response activities,” the Department of Health & Human Services said in a statement announcing the funding.

“This money will help states and local communities track overdose data and develop strategies that save lives,” HHS Secretary Alex Azar said during the press conference.

He noted that, when the Trump administration began, overdose data were published with a 12-month lag. That lag has since shortened to 6 months. One of the goals with the new funding is to bring data publishing as close to real time as possible.

Separately, the Substance Abuse and Mental Health Services Administration awarded $932 million to all 50 states as part of its State Opioid Response grants, which “provide flexible funding to state governments to support prevention, treatment, and recovery services in the ways that meet the needs of their state,” according to the HHS statement.

That flexibility “can mean everything from expanding the use of medication-assisted treatment in criminal justice settings or in rural areas via telemedicine, to youth-focused community-based prevention efforts,” Secretary Azar explained. The funds can also support employment coaching and naloxone distribution, he added.

[email protected]

A new oral antidepressant that targets the gamma-aminobutyric acid type A (GABA_A) receptors in the brain has been found to achieve a reduction in symptoms in adult patients with moderate to severe major depressive disorder, with no serious safety signals, results of a double-blind, phase 2 trial show.

The study involved 89 participants with major depression, excluding those with a history of treatment-resistant depression, who were randomized either to a once-daily dose of 30 mg of SAGE-217, a synthetic neurosteroid that acts as a positive allosteric modulator of GABA_A receptors, or placebo for 14 days. Thirty-six of the 45 patients in the SAGE-217 group were black, as were 28 of the 44 patients in the placebo group, reported Handan Gunduz-Bruce, MD, of Sage Therapeutics and coauthors. Their study was published in the New England Journal of Medicine.

“One hypothesis for the mechanism of depression implicates deficits in gamma-aminobutyric acid and downstream alterations in monoaminergic neurotransmission,” wrote Dr. Gunduz-Bruce and coauthors. “Preclinical studies have shown that the naturally occurring neurosteroid allopregnanolone is a positive allosteric modulator of synaptic and extrasynaptic GABA_A receptors that affects both phasic and tonic inhibition of neurons.”

At day 15 of the study, there was a significantly greater mean change from baseline in Hamilton Depression Rating Scale scores in the treatment group, compared with the placebo group (–17.4 vs. –10.3, P less than .001), and 79% of participants in the treatment arm showed a greater than 50% reduction in depression scores, compared with 41% of the placebo group.

At day 28, 62% of the treatment group and 46% of the placebo group had a reduction of more than 50% from baseline depression scores.

No serious or severe adverse events were seen in either group, and the most common adverse events in the SAGE-217 group included headache (18%), dizziness (11%), and nausea (11%). One patient in the treatment arm also reported euphoria.

The authors commented that somnolence and sedation were expected adverse events, based on the pharmacological properties of SAGE-217.

Six patients in the treatment arm also had dose reductions as a result of adverse events. Two patients in the SAGE-217 arm stopped treatment because they met prespecified criteria for discontinuation; the investigators reported nausea, dizziness, and headache in one patient, and increased levels of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in the other. However, the second patient had shown mildly elevated values of these at baseline, was asymptomatic throughout the trial, and the patient’s values returned to baseline or near-baseline after stopping treatment.

About one-quarter of both the SAGE-217 and placebo groups were receiving antidepressant treatment at baseline (27% and 23% respectively), with the duration of prior treatment ranging from 2 to 48 months. Investigators also gave three patients in the treatment arm and 11 in the placebo arm concomitant antidepressants during the follow-up period.

The small sample size and limited racial diversity among the participants were cited as limitations.

The study was supported by SAGE-217 manufacturer Sage Therapeutics. Ten authors were employees or directors of Sage Therapeutics, with stock options and patent interests. Three authors declared grants, personal fees, or advisory board positions with the pharmaceutical sector, including from Sage, and one also declared interest in a range of patents outside the study. One author had no disclosures.

SOURCE: Gunduz-Bruce H et al. N Engl J Med. 2019 Sep 5;381:903-11. doi: 10.1056/NEJMoa1815981.

A new oral antidepressant that targets the gamma-aminobutyric acid type A (GABA_A) receptors in the brain has been found to achieve a reduction in symptoms in adult patients with moderate to severe major depressive disorder, with no serious safety signals, results of a double-blind, phase 2 trial show.

The study involved 89 participants with major depression, excluding those with a history of treatment-resistant depression, who were randomized either to a once-daily dose of 30 mg of SAGE-217, a synthetic neurosteroid that acts as a positive allosteric modulator of GABA_A receptors, or placebo for 14 days. Thirty-six of the 45 patients in the SAGE-217 group were black, as were 28 of the 44 patients in the placebo group, reported Handan Gunduz-Bruce, MD, of Sage Therapeutics and coauthors. Their study was published in the New England Journal of Medicine.

“One hypothesis for the mechanism of depression implicates deficits in gamma-aminobutyric acid and downstream alterations in monoaminergic neurotransmission,” wrote Dr. Gunduz-Bruce and coauthors. “Preclinical studies have shown that the naturally occurring neurosteroid allopregnanolone is a positive allosteric modulator of synaptic and extrasynaptic GABA_A receptors that affects both phasic and tonic inhibition of neurons.”

At day 15 of the study, there was a significantly greater mean change from baseline in Hamilton Depression Rating Scale scores in the treatment group, compared with the placebo group (–17.4 vs. –10.3, P less than .001), and 79% of participants in the treatment arm showed a greater than 50% reduction in depression scores, compared with 41% of the placebo group.

At day 28, 62% of the treatment group and 46% of the placebo group had a reduction of more than 50% from baseline depression scores.

No serious or severe adverse events were seen in either group, and the most common adverse events in the SAGE-217 group included headache (18%), dizziness (11%), and nausea (11%). One patient in the treatment arm also reported euphoria.

The authors commented that somnolence and sedation were expected adverse events, based on the pharmacological properties of SAGE-217.

Six patients in the treatment arm also had dose reductions as a result of adverse events. Two patients in the SAGE-217 arm stopped treatment because they met prespecified criteria for discontinuation; the investigators reported nausea, dizziness, and headache in one patient, and increased levels of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in the other. However, the second patient had shown mildly elevated values of these at baseline, was asymptomatic throughout the trial, and the patient’s values returned to baseline or near-baseline after stopping treatment.

About one-quarter of both the SAGE-217 and placebo groups were receiving antidepressant treatment at baseline (27% and 23% respectively), with the duration of prior treatment ranging from 2 to 48 months. Investigators also gave three patients in the treatment arm and 11 in the placebo arm concomitant antidepressants during the follow-up period.

The small sample size and limited racial diversity among the participants were cited as limitations.

The study was supported by SAGE-217 manufacturer Sage Therapeutics. Ten authors were employees or directors of Sage Therapeutics, with stock options and patent interests. Three authors declared grants, personal fees, or advisory board positions with the pharmaceutical sector, including from Sage, and one also declared interest in a range of patents outside the study. One author had no disclosures.

SOURCE: Gunduz-Bruce H et al. N Engl J Med. 2019 Sep 5;381:903-11. doi: 10.1056/NEJMoa1815981.

A new oral antidepressant that targets the gamma-aminobutyric acid type A (GABA_A) receptors in the brain has been found to achieve a reduction in symptoms in adult patients with moderate to severe major depressive disorder, with no serious safety signals, results of a double-blind, phase 2 trial show.

The study involved 89 participants with major depression, excluding those with a history of treatment-resistant depression, who were randomized either to a once-daily dose of 30 mg of SAGE-217, a synthetic neurosteroid that acts as a positive allosteric modulator of GABA_A receptors, or placebo for 14 days. Thirty-six of the 45 patients in the SAGE-217 group were black, as were 28 of the 44 patients in the placebo group, reported Handan Gunduz-Bruce, MD, of Sage Therapeutics and coauthors. Their study was published in the New England Journal of Medicine.

“One hypothesis for the mechanism of depression implicates deficits in gamma-aminobutyric acid and downstream alterations in monoaminergic neurotransmission,” wrote Dr. Gunduz-Bruce and coauthors. “Preclinical studies have shown that the naturally occurring neurosteroid allopregnanolone is a positive allosteric modulator of synaptic and extrasynaptic GABA_A receptors that affects both phasic and tonic inhibition of neurons.”

At day 15 of the study, there was a significantly greater mean change from baseline in Hamilton Depression Rating Scale scores in the treatment group, compared with the placebo group (–17.4 vs. –10.3, P less than .001), and 79% of participants in the treatment arm showed a greater than 50% reduction in depression scores, compared with 41% of the placebo group.

At day 28, 62% of the treatment group and 46% of the placebo group had a reduction of more than 50% from baseline depression scores.

No serious or severe adverse events were seen in either group, and the most common adverse events in the SAGE-217 group included headache (18%), dizziness (11%), and nausea (11%). One patient in the treatment arm also reported euphoria.

The authors commented that somnolence and sedation were expected adverse events, based on the pharmacological properties of SAGE-217.

Six patients in the treatment arm also had dose reductions as a result of adverse events. Two patients in the SAGE-217 arm stopped treatment because they met prespecified criteria for discontinuation; the investigators reported nausea, dizziness, and headache in one patient, and increased levels of alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in the other. However, the second patient had shown mildly elevated values of these at baseline, was asymptomatic throughout the trial, and the patient’s values returned to baseline or near-baseline after stopping treatment.

About one-quarter of both the SAGE-217 and placebo groups were receiving antidepressant treatment at baseline (27% and 23% respectively), with the duration of prior treatment ranging from 2 to 48 months. Investigators also gave three patients in the treatment arm and 11 in the placebo arm concomitant antidepressants during the follow-up period.

The small sample size and limited racial diversity among the participants were cited as limitations.

The study was supported by SAGE-217 manufacturer Sage Therapeutics. Ten authors were employees or directors of Sage Therapeutics, with stock options and patent interests. Three authors declared grants, personal fees, or advisory board positions with the pharmaceutical sector, including from Sage, and one also declared interest in a range of patents outside the study. One author had no disclosures.

SOURCE: Gunduz-Bruce H et al. N Engl J Med. 2019 Sep 5;381:903-11. doi: 10.1056/NEJMoa1815981.

Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.

After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.

“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.

The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.

The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.

Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.

At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).

Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.

“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.

With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).

“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.

Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
 

SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.

Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.

After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.

“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.

The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.

The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.

Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.

At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).

Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.

“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.

With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).

“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.

Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
 

SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.

Mitapivat showed positive safety and efficacy outcomes in patients with pyruvate kinase deficiency, according to results from a phase 2 trial.

After 24 weeks of treatment, the therapy was associated with a rapid rise in hemoglobin levels in 50% of study participants, while the majority of toxicities reported were transient and low grade.

“The primary objective of this study was to assess the safety and side-effect profile of mitapivat administration in patients with pyruvate kinase deficiency,” wrote Rachael F. Grace, MD, of the Dana-Farber Cancer Institute and Harvard Medical School, Boston, and coinvestigators. The findings were published in the New England Journal of Medicine.

The uncontrolled study included 52 adults with pyruvate kinase deficiency who were not undergoing regular transfusions.

The median age at baseline was 34 years (range, 18-61 years), 62% of patients were male, and the median baseline hemoglobin level was 8.9 g/dL (range, 6.5-12.3 g/dL). In addition, 73% and 83% of patients had previously undergone cholecystectomy and splenectomy, respectively.

Study patients received oral mitapivat at 50 mg or 300 mg twice weekly for a total of 24 weeks. Eligible participants were subsequently enrolled into an extension phase that continued to monitor safety.

At 24 weeks, the team reported that 26 patients – 50% – experienced a greater than 1.0-g/dL rise in hemoglobin levels, with a maximum mean increase of 3.4 g/dL (range, 1.1-5.8 g/dL). The first rise of greater than 1.0 g/dL was observed after a median duration of 10 days (range, 7-187 days).

Of the 26 patients, 20 had an increase from baseline of more than 1.0 g/dL at more than half of the assessment during the core study period. That met the definition for hemoglobin response, according to the researchers.

“The hemoglobin response was maintained in the 19 patients who were continuing to be treated in the extension phase, all of whom had at least 21.6 months of treatment,” they wrote.

With respect to safety, the majority of adverse events were of low severity (grade 1-2) and transient in nature, with most resolving within 7 days. The most frequently reported toxicities in the core period and extension phase were headache (46%), insomnia (42%), and nausea (40%). The most serious reported toxicities were pharyngitis (4%) and hemolytic anemia (4%).

“Patient-reported quality of life was not assessed in this phase 2 safety study, although such outcome measures are being evaluated in the ongoing phase 3 trials,” Dr. Grace and colleagues wrote. “This study establishes proof of concept for a molecular therapy targeting the underlying enzymatic defect of a hereditary enzymopathy,” they concluded.

Agios Pharmaceuticals funded the study. Dr. Grace reported research funding from and consulting for Agios, and several authors reported employment, consulting, or research funding with the company.
 

SOURCE: Grace RF et al. N Engl J Med. 2019;381:933-44.