WASHINGTON – An experimental acid suppressant was effective for prevention of peptic ulcer recurrence during NSAID therapy, with a safety profile similar to that of a currently marketed proton pump inhibitor, investigators reported.

At 2 years of follow-up, rates of recurrent peptic ulcers or hemorrhagic lesions in the stomach or duodenum among patients who took vonoprazan (marketed in Japan as Takecab) at a 10-mg or 20-mg daily oral dose were numerically but not statistically significantly lower than those for patients who took a 15-mg once daily dose of lansoprazole (Prevacid), said Dr. Yuji Mizokami of University of Tsukuba Hospital in Ibaraki, Japan.

“The long-term safety profile of vonoprazan was similar to lansoprazole, and no safety issues were identified,” he said at the annual Digestive Disease Week.

Proton pump inhibitors (PPIs) such as lansoprazole are frequently prescribed as concomitant gastroprotective agents in patients on long-term therapy with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen.

PIs have relatively short half-lives, however, which may limit their effectiveness as gastroprotectives. In addition, polymorphisms in the gene encoding for cytochrome P2C19 (CYP2C19) can affect PPI metabolism, Dr. Mizokami said.

Vonoprazan belongs to a new class of acid-suppressing drugs called potassium-competitive acid blockers (PCABs), which, unlike PPIs, do not need to be activated by acid to become effective and are not affected by genetic variations. Vonoprazan migrates from blood into the secretory canaliculus of acid-secreting parietal cells, and because of its longer elimination half-life and stability in acidic environments, provides a strong acid-inhibiting effect from the first dose, and remains effective for 24 hours, Dr. Mizokami explained.

He presented data from a 2-year extension of a phase III, 24-week noninferiority study comparing vonoprazan with lansoprazole for prevention of peptic ulcer recurrence. In that study, 5.5% of patients on lansoprazole had recurrent gastric or duodenal ulcers by week 24, compared with 3.3% of patients on 10 mg vonoprazan, and 3.4% of those on 20 mg vonoprazan.

A total of 357 patients completed the extension study: 108 initially assigned to lansoprazole, 131 to vonoprazan 10 mg, and 118 to vonoprazan 20 mg.

At 1 year, the rates of recurrent ulcers were 7% for patients on lansoprazole, 3.6% for those on vonoprazan 10 mg, and 5.4% for those on vonoprazan 20 mg. The respective rates at 2 years were 7.5%. 3.8%, and 5.9%. In a safety analysis (intention-to-treat), treatment-emergent adverse events were mild, did not appear to be dose dependent with vonoprazan, and did not increase over time.

Serious treatment-emergent events occurred in 8.6% among the patients on lansoprazole, 8.3% among patients on 10 mg vonoprazan, and 14.2% among those on 20 mg. Events leading to drug discontinuation occurred in 7.6%, 4.1%, and 12.2% of patients, respectively.

In all three study arms, but especially in the vonoprazan arms, there was an increase in serum gastrin seen at week 4, which increased moderately until week 52. After that, it began to decline among patients on vonoprazan, while plateauing among patients on lansoprazole.

There were also increases in pepsinogen I and II at week 4 in all three treatment groups; the levels remained stable thereafter, as did the ratio of pepsinogen I to pepsinogen II.

Vonoprazan is currently approved only in Japan. The manufacturer, Takeda, has not said if or when it intends to file for a New Drug Application in the United States. The study was supported by Takeda Pharmaceuticals. Dr. Mizokami disclosed serving as a consultant on the study. Four of the coauthors are company employees.

WASHINGTON – An experimental acid suppressant was effective for prevention of peptic ulcer recurrence during NSAID therapy, with a safety profile similar to that of a currently marketed proton pump inhibitor, investigators reported.

At 2 years of follow-up, rates of recurrent peptic ulcers or hemorrhagic lesions in the stomach or duodenum among patients who took vonoprazan (marketed in Japan as Takecab) at a 10-mg or 20-mg daily oral dose were numerically but not statistically significantly lower than those for patients who took a 15-mg once daily dose of lansoprazole (Prevacid), said Dr. Yuji Mizokami of University of Tsukuba Hospital in Ibaraki, Japan.

“The long-term safety profile of vonoprazan was similar to lansoprazole, and no safety issues were identified,” he said at the annual Digestive Disease Week.

Proton pump inhibitors (PPIs) such as lansoprazole are frequently prescribed as concomitant gastroprotective agents in patients on long-term therapy with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen.

PIs have relatively short half-lives, however, which may limit their effectiveness as gastroprotectives. In addition, polymorphisms in the gene encoding for cytochrome P2C19 (CYP2C19) can affect PPI metabolism, Dr. Mizokami said.

Vonoprazan belongs to a new class of acid-suppressing drugs called potassium-competitive acid blockers (PCABs), which, unlike PPIs, do not need to be activated by acid to become effective and are not affected by genetic variations. Vonoprazan migrates from blood into the secretory canaliculus of acid-secreting parietal cells, and because of its longer elimination half-life and stability in acidic environments, provides a strong acid-inhibiting effect from the first dose, and remains effective for 24 hours, Dr. Mizokami explained.

He presented data from a 2-year extension of a phase III, 24-week noninferiority study comparing vonoprazan with lansoprazole for prevention of peptic ulcer recurrence. In that study, 5.5% of patients on lansoprazole had recurrent gastric or duodenal ulcers by week 24, compared with 3.3% of patients on 10 mg vonoprazan, and 3.4% of those on 20 mg vonoprazan.

A total of 357 patients completed the extension study: 108 initially assigned to lansoprazole, 131 to vonoprazan 10 mg, and 118 to vonoprazan 20 mg.

At 1 year, the rates of recurrent ulcers were 7% for patients on lansoprazole, 3.6% for those on vonoprazan 10 mg, and 5.4% for those on vonoprazan 20 mg. The respective rates at 2 years were 7.5%. 3.8%, and 5.9%. In a safety analysis (intention-to-treat), treatment-emergent adverse events were mild, did not appear to be dose dependent with vonoprazan, and did not increase over time.

Serious treatment-emergent events occurred in 8.6% among the patients on lansoprazole, 8.3% among patients on 10 mg vonoprazan, and 14.2% among those on 20 mg. Events leading to drug discontinuation occurred in 7.6%, 4.1%, and 12.2% of patients, respectively.

In all three study arms, but especially in the vonoprazan arms, there was an increase in serum gastrin seen at week 4, which increased moderately until week 52. After that, it began to decline among patients on vonoprazan, while plateauing among patients on lansoprazole.

There were also increases in pepsinogen I and II at week 4 in all three treatment groups; the levels remained stable thereafter, as did the ratio of pepsinogen I to pepsinogen II.

Vonoprazan is currently approved only in Japan. The manufacturer, Takeda, has not said if or when it intends to file for a New Drug Application in the United States. The study was supported by Takeda Pharmaceuticals. Dr. Mizokami disclosed serving as a consultant on the study. Four of the coauthors are company employees.

WASHINGTON – An experimental acid suppressant was effective for prevention of peptic ulcer recurrence during NSAID therapy, with a safety profile similar to that of a currently marketed proton pump inhibitor, investigators reported.

At 2 years of follow-up, rates of recurrent peptic ulcers or hemorrhagic lesions in the stomach or duodenum among patients who took vonoprazan (marketed in Japan as Takecab) at a 10-mg or 20-mg daily oral dose were numerically but not statistically significantly lower than those for patients who took a 15-mg once daily dose of lansoprazole (Prevacid), said Dr. Yuji Mizokami of University of Tsukuba Hospital in Ibaraki, Japan.

“The long-term safety profile of vonoprazan was similar to lansoprazole, and no safety issues were identified,” he said at the annual Digestive Disease Week.

Proton pump inhibitors (PPIs) such as lansoprazole are frequently prescribed as concomitant gastroprotective agents in patients on long-term therapy with a nonsteroidal anti-inflammatory drug (NSAID) such as aspirin or ibuprofen.

PIs have relatively short half-lives, however, which may limit their effectiveness as gastroprotectives. In addition, polymorphisms in the gene encoding for cytochrome P2C19 (CYP2C19) can affect PPI metabolism, Dr. Mizokami said.

Vonoprazan belongs to a new class of acid-suppressing drugs called potassium-competitive acid blockers (PCABs), which, unlike PPIs, do not need to be activated by acid to become effective and are not affected by genetic variations. Vonoprazan migrates from blood into the secretory canaliculus of acid-secreting parietal cells, and because of its longer elimination half-life and stability in acidic environments, provides a strong acid-inhibiting effect from the first dose, and remains effective for 24 hours, Dr. Mizokami explained.

He presented data from a 2-year extension of a phase III, 24-week noninferiority study comparing vonoprazan with lansoprazole for prevention of peptic ulcer recurrence. In that study, 5.5% of patients on lansoprazole had recurrent gastric or duodenal ulcers by week 24, compared with 3.3% of patients on 10 mg vonoprazan, and 3.4% of those on 20 mg vonoprazan.

A total of 357 patients completed the extension study: 108 initially assigned to lansoprazole, 131 to vonoprazan 10 mg, and 118 to vonoprazan 20 mg.

At 1 year, the rates of recurrent ulcers were 7% for patients on lansoprazole, 3.6% for those on vonoprazan 10 mg, and 5.4% for those on vonoprazan 20 mg. The respective rates at 2 years were 7.5%. 3.8%, and 5.9%. In a safety analysis (intention-to-treat), treatment-emergent adverse events were mild, did not appear to be dose dependent with vonoprazan, and did not increase over time.

Serious treatment-emergent events occurred in 8.6% among the patients on lansoprazole, 8.3% among patients on 10 mg vonoprazan, and 14.2% among those on 20 mg. Events leading to drug discontinuation occurred in 7.6%, 4.1%, and 12.2% of patients, respectively.

In all three study arms, but especially in the vonoprazan arms, there was an increase in serum gastrin seen at week 4, which increased moderately until week 52. After that, it began to decline among patients on vonoprazan, while plateauing among patients on lansoprazole.

There were also increases in pepsinogen I and II at week 4 in all three treatment groups; the levels remained stable thereafter, as did the ratio of pepsinogen I to pepsinogen II.

Vonoprazan is currently approved only in Japan. The manufacturer, Takeda, has not said if or when it intends to file for a New Drug Application in the United States. The study was supported by Takeda Pharmaceuticals. Dr. Mizokami disclosed serving as a consultant on the study. Four of the coauthors are company employees.

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza (Spain).

Patrice Wendling/Frontline Medical News

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

[email protected]

On Twitter @pwendl

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza (Spain).

Patrice Wendling/Frontline Medical News

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

[email protected]

On Twitter @pwendl

WASHINGTON – Early resumption of antiplatelet agents or anticoagulants after a major gastrointestinal bleeding event is clearly associated with an increased risk of rebleeding, but a decreased risk of death, results from an observational study show.

Furthermore, anticoagulant treatment “is associated with a higher risk of rebleeding and death compared with antiplatelet treatment after a previous GI event,” Dr. Angel Lanas said to an overflow crowd at the annual Digestive Disease Week.

Patrice Wendling/Frontline Medical News

In a separate case-control study, Dr. Lanas and his associates recently reported that the risk of GI bleeding was twofold higher for anticoagulants than for low-dose aspirin in patients hospitalized for GI bleeding (Clin. Gastroenterol. Hepatol. 2015 May;13:906-12.e2. [doi:10.1016/j.cgh.2014.11.007])

The current study examined adverse events in a cohort of 160 patients who developed a major gastrointestinal bleed (GIB) while using anticoagulants and/or antiplatelet therapy between March 2008 and July 2013. Long-term interruption or short-term resumption of these treatments has important clinical implications and differences in the intrinsic risks between antiplatelet or anticoagulant users after drug resumption are not well established, said Dr. Lanas of the University of Zaragoza (Spain).

Patrice Wendling/Frontline Medical News

Drug use information was prospectively collected during the GIB event, with data during the follow-up period obtained from two different Spanish databases.

Treatment during the index bleeding event was continued without interruption in 11 patients and interrupted in 149 patients (93%). Among those whose therapy was interrupted, 21 (14%) never resumed therapy and 128 (86%) resumed therapy (118 patients within 15 days and 10 patients after 15 days). The 86% treatment resumption rate is much higher than the 40%-66% rates reported in previous studies, indicating that Spanish physicians restarted treatment quite early, Dr. Lanas observed.

The mean age at baseline was 76.6 years, 61.3% of patients were men, and half had a Charlson index score > 4. Median follow-up was 21.5 months (range 1-63 months).

Ischemic events did not differ between patients who did or did not restart anticoagulants or antiplatelets (16.4% vs. 14.3%; P value = .806). However, rebleeding occurred in 32% of patients who resumed therapy versus none who did not (P = .002), but deaths were higher in those who did not restart therapy (38.1% vs. 12.5%; P = .003), Dr. Lanas said.

These differences remain significant in Kaplan-Meier survival curves for death (P = .021) and rebleeding (P = .004).

A comparison of early therapy resumption (≤ 15 days) vs. delayed (mean delay 62 days) or no resumption revealed similar results. Early resumption was associated with a higher rate of rebleeding (32.2% vs. 9.7%; P = .012), but a lower rate of death (11% vs. 35.5%; P = .001), with no difference in ischemic events (17% vs. 13%; P = .586), Dr. Lanas said.

Again, the differences remain significant in Kaplan-Meier survival curves for death (P = .011) and rebleeding (P = .013).

When the investigators looked at rebleeding according to drug use, patients receiving anticoagulants vs. antiplatelets had significantly higher rates of rebleeding (34.7% vs. 20.5%; P = .043), death (22.2% vs. 10.2%; P = .038), and any event (68.1% vs. 52.3%; P = .043).

After adjustment for gender, age, Charlson index, diabetes, and arterial hypertension, the risk of rebleeding was more than threefold higher for dual antiplatelet and anticoagulant users than for antiplatelet-alone users (odds ratio, 3.45; P = .025) and was twofold higher for anticoagulant vs. antiplatelet users (OR, 2.07; P = .045), Dr. Lanas said.

Finally, an analysis of the cause of bleeding suggests the cause of rebleeding may be different from the original event and that there is a shift toward the lower GI tract, he added.

The index bleeding event was caused largely by an upper GI peptic ulcer in 48% of all 160 patients, with 43.7% of events due to lower GI diverticulosis, vascular lesions, ischemic, or other lesions. In contrast, peptic ulcers accounted for only 7% of rebleeding events, while lower GI events accounted for 72%. Proton pump inhibition use was evenly distributed in upper and lower GI bleeding, although effective endoscopic treatment may have influenced upper GI bleeds, Dr. Lanas said.

“The importance of this is that we may have very good therapy tools for the upper GI, but still we have problems controlling the bleeding from the lower GI,” he added.

During a discussion of the study, an audience member asked how many days clinicians should wait to restart anticoagulants or antiplatelets.

“In those patients with peptic ulcer bleeding, it’s better to just give the antiplatelet therapy soon after the bleeding event or just to not interrupt the aspirin because the morality at 30 days was higher in those who were interrupted,” Dr. Lanas advised. “...I think for the cutoff point to show differences for patients with a worse outcome versus those with a better outcome, you shouldn’t restart anticoagulant therapy before day 15 after the bleeding event.”

Dr. Lanas received consulting fees, speaking and teaching fees, other financial support, and grant and research support from Bayer.

[email protected]

On Twitter @pwendl

WASHINGTON – Performed when recommended, cholecystecomy significantly decreases the risk of near-term rehospitalization for acute biliary pancreatitis, results of a retrospective study indicate.

Among more than 23,000 patients with mild to moderate acute biliary pancreatitis, less than 2% of those who underwent cholecystectomy within 30 days, as recommended under American Gastroenterological Association (AGA) guidelines, were rehospitalized for pancreatitis within 6 months.

In contrast, nearly 17% of patients who had cholecystectomy after 1 month or never had it were back in the hospital within half a year, said Dr. Ayesha Kamal, a postdoctoral research fellow at the Johns Hopkins Hospital in Baltimore.

“Cholecystectomy prevents future hospitalization for biliary pancreatitis,” she said at the annual Digestive Disease Week.

The study, based on claims data, also showed that adherence to AGA guidelines is fairly high, on the order of 75%, she said.

Acute pancreatitis is one of the most common gastrointestinal diseases in the United States, accounting for about 300,000 hospitalizations in 2009, at a total cost of about $2.6 billion.

Gallstone disease is the most common cause of acute pancreatitis, responsible for an estimated 40% of all cases, she said.

Guidelines from the AGA and other organizations recommend cholecystectomy either during the same hospitalization for acute biliary pancreatitis, or within 4 weeks.

To see whether clinicians were adhering to the AGA guidelines and whether the guideline-recommended timing of cholecystectomy made a difference, Dr. Kamal and colleagues analyzed data from the MarketScan Commercial Claims & Encounters database, which includes individual-level clinical utilization data for both inpatient and outpatient visits paid for by employer-sponsored health plans.

They looked at data both on patients who were treated in accordance with guidelines (first hospitalization for mild to moderate acute biliary pancreatitis, with cholecystectomy performed either on the day of hospitalization or within 30 days), and outside of the guidelines (no cholecystectomy, or cholecystectomy performed later than 30 days after the index hospitalization).

They assessed recurrences within 30 days of follow-up by International Classification of Diseases, 9th Revision (ICD-9) codes for acute pancreatitis and gallstone disease.

Combing through 8.8 million adult inpatient encounters for acute biliary pancreatitis, they excluded those patients with a diagnosis of severe or chronic pancreatitis, alcohol abuse, less than 30 days of follow-up, deaths during hospitalization, discharge to hospice, and those with a length of stay longer than 30 days.

This left them with a final cohort of 23,515 patients with mild to moderate acute biliary pancreatitis.

They found that 61% of patients had cholecystectomy during their initial hospitalizations, and an additional 14% had the surgery during a subsequent hospitalization within 30 days. Of the remaining patients, 7% had cholecystectomies after 30 days, and 18% never had one.

Among patients treated under the guidelines, 1.3% who had their gallbladders removed during the initial hospitalization had a pancreatitis recurrence within 6 months, and 0.2% had a recurrence more than 6 months later.

In contrast, 36.7% of patients who had a cholecystectomy more than a month after their first hospitalization for pancreatitis had a recurrence within 6 months, and 4.5% had a recurrence after 6 months.

Among patients who never underwent cholecystectomy, the respective recurrence rates were 5.4% and 1.1%.

“One in six patients who did not receive a cholecystectomy within 30 days will be hospitalized again within 6 months,” Dr. Kamal said.

She acknowledged that the study was limited by the authors’ inability to confirm acute biliary pancreatitis with chart review, and by the limitations of the database, which is confined to adults younger than 65 with employer-sponsored medical plans.

In the question and answer portion of the presentation, Dr. Nirav Thosani, a gastroenterologist at Memorial Hermann Hospital in Houston, noted that ICD-9 codes do not distinguish between different types of pancreatitis.

“It might be possible that those patients who never had cholecystectomy never had acute biliary pancreatitis, or some other reason for acute pancreatitis, and that’s the reason for the rehospitalization,” he said.

Dr. Kamal replied that they tried to control for other causes of pancreatitis by including ICD-9 codes for gallstone disease and by excluding patients with diagnoses of alcohol abuse.

WASHINGTON – Performed when recommended, cholecystecomy significantly decreases the risk of near-term rehospitalization for acute biliary pancreatitis, results of a retrospective study indicate.

Among more than 23,000 patients with mild to moderate acute biliary pancreatitis, less than 2% of those who underwent cholecystectomy within 30 days, as recommended under American Gastroenterological Association (AGA) guidelines, were rehospitalized for pancreatitis within 6 months.

In contrast, nearly 17% of patients who had cholecystectomy after 1 month or never had it were back in the hospital within half a year, said Dr. Ayesha Kamal, a postdoctoral research fellow at the Johns Hopkins Hospital in Baltimore.

“Cholecystectomy prevents future hospitalization for biliary pancreatitis,” she said at the annual Digestive Disease Week.

The study, based on claims data, also showed that adherence to AGA guidelines is fairly high, on the order of 75%, she said.

Acute pancreatitis is one of the most common gastrointestinal diseases in the United States, accounting for about 300,000 hospitalizations in 2009, at a total cost of about $2.6 billion.

Gallstone disease is the most common cause of acute pancreatitis, responsible for an estimated 40% of all cases, she said.

Guidelines from the AGA and other organizations recommend cholecystectomy either during the same hospitalization for acute biliary pancreatitis, or within 4 weeks.

To see whether clinicians were adhering to the AGA guidelines and whether the guideline-recommended timing of cholecystectomy made a difference, Dr. Kamal and colleagues analyzed data from the MarketScan Commercial Claims & Encounters database, which includes individual-level clinical utilization data for both inpatient and outpatient visits paid for by employer-sponsored health plans.

They looked at data both on patients who were treated in accordance with guidelines (first hospitalization for mild to moderate acute biliary pancreatitis, with cholecystectomy performed either on the day of hospitalization or within 30 days), and outside of the guidelines (no cholecystectomy, or cholecystectomy performed later than 30 days after the index hospitalization).

They assessed recurrences within 30 days of follow-up by International Classification of Diseases, 9th Revision (ICD-9) codes for acute pancreatitis and gallstone disease.

Combing through 8.8 million adult inpatient encounters for acute biliary pancreatitis, they excluded those patients with a diagnosis of severe or chronic pancreatitis, alcohol abuse, less than 30 days of follow-up, deaths during hospitalization, discharge to hospice, and those with a length of stay longer than 30 days.

This left them with a final cohort of 23,515 patients with mild to moderate acute biliary pancreatitis.

They found that 61% of patients had cholecystectomy during their initial hospitalizations, and an additional 14% had the surgery during a subsequent hospitalization within 30 days. Of the remaining patients, 7% had cholecystectomies after 30 days, and 18% never had one.

Among patients treated under the guidelines, 1.3% who had their gallbladders removed during the initial hospitalization had a pancreatitis recurrence within 6 months, and 0.2% had a recurrence more than 6 months later.

In contrast, 36.7% of patients who had a cholecystectomy more than a month after their first hospitalization for pancreatitis had a recurrence within 6 months, and 4.5% had a recurrence after 6 months.

Among patients who never underwent cholecystectomy, the respective recurrence rates were 5.4% and 1.1%.

“One in six patients who did not receive a cholecystectomy within 30 days will be hospitalized again within 6 months,” Dr. Kamal said.

She acknowledged that the study was limited by the authors’ inability to confirm acute biliary pancreatitis with chart review, and by the limitations of the database, which is confined to adults younger than 65 with employer-sponsored medical plans.

In the question and answer portion of the presentation, Dr. Nirav Thosani, a gastroenterologist at Memorial Hermann Hospital in Houston, noted that ICD-9 codes do not distinguish between different types of pancreatitis.

“It might be possible that those patients who never had cholecystectomy never had acute biliary pancreatitis, or some other reason for acute pancreatitis, and that’s the reason for the rehospitalization,” he said.

Dr. Kamal replied that they tried to control for other causes of pancreatitis by including ICD-9 codes for gallstone disease and by excluding patients with diagnoses of alcohol abuse.

WASHINGTON – Performed when recommended, cholecystecomy significantly decreases the risk of near-term rehospitalization for acute biliary pancreatitis, results of a retrospective study indicate.

Among more than 23,000 patients with mild to moderate acute biliary pancreatitis, less than 2% of those who underwent cholecystectomy within 30 days, as recommended under American Gastroenterological Association (AGA) guidelines, were rehospitalized for pancreatitis within 6 months.

In contrast, nearly 17% of patients who had cholecystectomy after 1 month or never had it were back in the hospital within half a year, said Dr. Ayesha Kamal, a postdoctoral research fellow at the Johns Hopkins Hospital in Baltimore.

“Cholecystectomy prevents future hospitalization for biliary pancreatitis,” she said at the annual Digestive Disease Week.

The study, based on claims data, also showed that adherence to AGA guidelines is fairly high, on the order of 75%, she said.

Acute pancreatitis is one of the most common gastrointestinal diseases in the United States, accounting for about 300,000 hospitalizations in 2009, at a total cost of about $2.6 billion.

Gallstone disease is the most common cause of acute pancreatitis, responsible for an estimated 40% of all cases, she said.

Guidelines from the AGA and other organizations recommend cholecystectomy either during the same hospitalization for acute biliary pancreatitis, or within 4 weeks.

To see whether clinicians were adhering to the AGA guidelines and whether the guideline-recommended timing of cholecystectomy made a difference, Dr. Kamal and colleagues analyzed data from the MarketScan Commercial Claims & Encounters database, which includes individual-level clinical utilization data for both inpatient and outpatient visits paid for by employer-sponsored health plans.

They looked at data both on patients who were treated in accordance with guidelines (first hospitalization for mild to moderate acute biliary pancreatitis, with cholecystectomy performed either on the day of hospitalization or within 30 days), and outside of the guidelines (no cholecystectomy, or cholecystectomy performed later than 30 days after the index hospitalization).

They assessed recurrences within 30 days of follow-up by International Classification of Diseases, 9th Revision (ICD-9) codes for acute pancreatitis and gallstone disease.

Combing through 8.8 million adult inpatient encounters for acute biliary pancreatitis, they excluded those patients with a diagnosis of severe or chronic pancreatitis, alcohol abuse, less than 30 days of follow-up, deaths during hospitalization, discharge to hospice, and those with a length of stay longer than 30 days.

This left them with a final cohort of 23,515 patients with mild to moderate acute biliary pancreatitis.

They found that 61% of patients had cholecystectomy during their initial hospitalizations, and an additional 14% had the surgery during a subsequent hospitalization within 30 days. Of the remaining patients, 7% had cholecystectomies after 30 days, and 18% never had one.

Among patients treated under the guidelines, 1.3% who had their gallbladders removed during the initial hospitalization had a pancreatitis recurrence within 6 months, and 0.2% had a recurrence more than 6 months later.

In contrast, 36.7% of patients who had a cholecystectomy more than a month after their first hospitalization for pancreatitis had a recurrence within 6 months, and 4.5% had a recurrence after 6 months.

Among patients who never underwent cholecystectomy, the respective recurrence rates were 5.4% and 1.1%.

“One in six patients who did not receive a cholecystectomy within 30 days will be hospitalized again within 6 months,” Dr. Kamal said.

She acknowledged that the study was limited by the authors’ inability to confirm acute biliary pancreatitis with chart review, and by the limitations of the database, which is confined to adults younger than 65 with employer-sponsored medical plans.

In the question and answer portion of the presentation, Dr. Nirav Thosani, a gastroenterologist at Memorial Hermann Hospital in Houston, noted that ICD-9 codes do not distinguish between different types of pancreatitis.

“It might be possible that those patients who never had cholecystectomy never had acute biliary pancreatitis, or some other reason for acute pancreatitis, and that’s the reason for the rehospitalization,” he said.

Dr. Kamal replied that they tried to control for other causes of pancreatitis by including ICD-9 codes for gallstone disease and by excluding patients with diagnoses of alcohol abuse.

Transgender youth and young adults suffer a significantly greater burden of mental health conditions and poor mental health outcomes than do nontransgender individuals, known as cisgender individuals, according to a recent study.

“Findings point to the need for gender-affirming mental health services and interventions to support transgender youth,” reported Sari L. Reisner, Sc.D., of Harvard T.H. Chan School of Public Health, Boston (J. Adolesc. Health 2015;56:274-9). “Community-based clinics should be prepared to provide mental health services or referrals for transgender patients.”

Dr. Reisner and his colleagues retrospectively analyzed medical records to compare the mental health outcomes of 106 female-to-male and 74 male-to-female transgender patients, aged 12-29 years, to 180 cisgender controls matched by gender identity, age, race/ethnicity, and visit date at a community health center in Boston between 2002 and 2011.

Cisgender refers to an individual whose self-identified gender identity matches his or her biological sex assigned at birth.

The transgender patients had four times the risk for depression, compared with the matched control patients (50.6% vs. 20.6%; relative risk = 3.95) and more than three times the risk for anxiety (26.7% vs. 10.0%; RR = 3.27), suicide ideation (31.1% vs. 11.1%; RR = 3.61) and suicide attempts (17.2% vs. 6.1%; RR = 3.20). Transgender individuals were more than four times more likely than were cisgender patients to self-harm without suicidal intent (16.7% vs. 4.4%; RR = 4.30).

Overall, 22.8% of transgender patients, compared with 11.1% of cisgender patients, used inpatient mental health care services (RR = 2.36), and 45.6% of transgender patients, compared with 16.1% of cisgender ones, accessed outpatient mental health services (RR = 4.36).

“The elevated mental health burden among transgender youth is hypothesized to result from experiences of social stress such as family rejection, bullying, violence, victimization, and discrimination, which occur due to disadvantaged social status,” all confounders not accounted for if present for these patients, the authors noted. On the other hand, the study’s lack of reliance on a gender identity disorder diagnosis “offers unique comparative data that directly compare the health and well-being of transgender and cisgender youth using a nonpathological perspective of gender variation,” they added.

Other potential limitations of the study were that transgender patients’ greater use of mental health services could have inflated prevalence estimates and that the findings, for an urban population, may not generalize to other geographic or clinical settings.

“Future research is needed to contextualize the mental health concerns of transgender adolescent and emerging adult patients in community-based clinic settings, including prospective assessment of social stressors and mental health symptoms and diagnoses over time,” the authors wrote.

The research was supported by the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors reported no relevant financial disclosures.

Transgender youth and young adults suffer a significantly greater burden of mental health conditions and poor mental health outcomes than do nontransgender individuals, known as cisgender individuals, according to a recent study.

“Findings point to the need for gender-affirming mental health services and interventions to support transgender youth,” reported Sari L. Reisner, Sc.D., of Harvard T.H. Chan School of Public Health, Boston (J. Adolesc. Health 2015;56:274-9). “Community-based clinics should be prepared to provide mental health services or referrals for transgender patients.”

Dr. Reisner and his colleagues retrospectively analyzed medical records to compare the mental health outcomes of 106 female-to-male and 74 male-to-female transgender patients, aged 12-29 years, to 180 cisgender controls matched by gender identity, age, race/ethnicity, and visit date at a community health center in Boston between 2002 and 2011.

Cisgender refers to an individual whose self-identified gender identity matches his or her biological sex assigned at birth.

The transgender patients had four times the risk for depression, compared with the matched control patients (50.6% vs. 20.6%; relative risk = 3.95) and more than three times the risk for anxiety (26.7% vs. 10.0%; RR = 3.27), suicide ideation (31.1% vs. 11.1%; RR = 3.61) and suicide attempts (17.2% vs. 6.1%; RR = 3.20). Transgender individuals were more than four times more likely than were cisgender patients to self-harm without suicidal intent (16.7% vs. 4.4%; RR = 4.30).

Overall, 22.8% of transgender patients, compared with 11.1% of cisgender patients, used inpatient mental health care services (RR = 2.36), and 45.6% of transgender patients, compared with 16.1% of cisgender ones, accessed outpatient mental health services (RR = 4.36).

“The elevated mental health burden among transgender youth is hypothesized to result from experiences of social stress such as family rejection, bullying, violence, victimization, and discrimination, which occur due to disadvantaged social status,” all confounders not accounted for if present for these patients, the authors noted. On the other hand, the study’s lack of reliance on a gender identity disorder diagnosis “offers unique comparative data that directly compare the health and well-being of transgender and cisgender youth using a nonpathological perspective of gender variation,” they added.

Other potential limitations of the study were that transgender patients’ greater use of mental health services could have inflated prevalence estimates and that the findings, for an urban population, may not generalize to other geographic or clinical settings.

“Future research is needed to contextualize the mental health concerns of transgender adolescent and emerging adult patients in community-based clinic settings, including prospective assessment of social stressors and mental health symptoms and diagnoses over time,” the authors wrote.

The research was supported by the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors reported no relevant financial disclosures.

Transgender youth and young adults suffer a significantly greater burden of mental health conditions and poor mental health outcomes than do nontransgender individuals, known as cisgender individuals, according to a recent study.

“Findings point to the need for gender-affirming mental health services and interventions to support transgender youth,” reported Sari L. Reisner, Sc.D., of Harvard T.H. Chan School of Public Health, Boston (J. Adolesc. Health 2015;56:274-9). “Community-based clinics should be prepared to provide mental health services or referrals for transgender patients.”

Dr. Reisner and his colleagues retrospectively analyzed medical records to compare the mental health outcomes of 106 female-to-male and 74 male-to-female transgender patients, aged 12-29 years, to 180 cisgender controls matched by gender identity, age, race/ethnicity, and visit date at a community health center in Boston between 2002 and 2011.

Cisgender refers to an individual whose self-identified gender identity matches his or her biological sex assigned at birth.

The transgender patients had four times the risk for depression, compared with the matched control patients (50.6% vs. 20.6%; relative risk = 3.95) and more than three times the risk for anxiety (26.7% vs. 10.0%; RR = 3.27), suicide ideation (31.1% vs. 11.1%; RR = 3.61) and suicide attempts (17.2% vs. 6.1%; RR = 3.20). Transgender individuals were more than four times more likely than were cisgender patients to self-harm without suicidal intent (16.7% vs. 4.4%; RR = 4.30).

Overall, 22.8% of transgender patients, compared with 11.1% of cisgender patients, used inpatient mental health care services (RR = 2.36), and 45.6% of transgender patients, compared with 16.1% of cisgender ones, accessed outpatient mental health services (RR = 4.36).

“The elevated mental health burden among transgender youth is hypothesized to result from experiences of social stress such as family rejection, bullying, violence, victimization, and discrimination, which occur due to disadvantaged social status,” all confounders not accounted for if present for these patients, the authors noted. On the other hand, the study’s lack of reliance on a gender identity disorder diagnosis “offers unique comparative data that directly compare the health and well-being of transgender and cisgender youth using a nonpathological perspective of gender variation,” they added.

Other potential limitations of the study were that transgender patients’ greater use of mental health services could have inflated prevalence estimates and that the findings, for an urban population, may not generalize to other geographic or clinical settings.

“Future research is needed to contextualize the mental health concerns of transgender adolescent and emerging adult patients in community-based clinic settings, including prospective assessment of social stressors and mental health symptoms and diagnoses over time,” the authors wrote.

The research was supported by the National Institute of Mental Health and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors reported no relevant financial disclosures.

Lower eyelid malposition is both a cosmetic and functional issue for many patients. It often arises from normal aging; however, it also can be due to thyroid disease, trauma, and surgery (iatrogenic). Correction of lower eyelid malposition requires a variety of surgical approaches to elevate the lower eyelid position. These procedures are not without risk. There have been reports of hyaluronic acid injections being used to help stretch the skin and give support to the sagging eyelid.

Le et al published a study (Ophthal Plast Reconstr Surg. 2014;30:504-507) on the effect of autologous fat injection on lower eyelid position. They performed a retrospective pilot study of autologous fat injections to support the lower eyelid in patients presenting for cosmetic reasons. A retrospective chart review was performed identifying 70 patients that had undergone lower eyelid and malar autologous fat injections for cosmetic improvement performed by a single surgeon. Patients were excluded if they had prior eyelid surgery. Photographs were taken in a standardized fashion and evaluated by 2 blinded evaluators. The measurements evaluated were the lower eyelid position (marginal reflex distance 2 [MRD2]) and inferior scleral show (SS).

The fat was harvested from the inner thigh and knee under tumescent anesthesia, strained, and injected with a 1.2-mm blunt cannula into various planes of the facial soft tissues. Approximately 0 to 2 mL was injected into the tear trough areas and 3 to 7 mL into the malar region, both per side. Photographs were repeated at an average of 117, 125, and 316 days.

Results showed that the MRD2 distance improved 0.5 mm bilaterally and was maintained at 316 days. Similarly, the SS measurement improved by 0.5 mm and was maintained at 125 days. Results improved slightly more in patients who had simultaneous face-lifts, but the difference was not statistically significant.

What’s the issue?

Lower eyelid malposition can make patients appear aged or tired while functionally causing dry eye or excessive tearing. Finding a way to improve this condition without surgery is key because the surgeries are fraught with risk. This study suggests that we should look more critically at lower eyelid positions in our patients who are receiving synthetic fillers or autologous fat to see if we are improving the MRD2 and SS measurements. Have you been seeing an increase in patients seeking improvement for “tired-looking eyes,” or do patients know they look tired but cannot pinpoint why?

We want to know your views! Tell us what you think.

Lower eyelid malposition is both a cosmetic and functional issue for many patients. It often arises from normal aging; however, it also can be due to thyroid disease, trauma, and surgery (iatrogenic). Correction of lower eyelid malposition requires a variety of surgical approaches to elevate the lower eyelid position. These procedures are not without risk. There have been reports of hyaluronic acid injections being used to help stretch the skin and give support to the sagging eyelid.

Le et al published a study (Ophthal Plast Reconstr Surg. 2014;30:504-507) on the effect of autologous fat injection on lower eyelid position. They performed a retrospective pilot study of autologous fat injections to support the lower eyelid in patients presenting for cosmetic reasons. A retrospective chart review was performed identifying 70 patients that had undergone lower eyelid and malar autologous fat injections for cosmetic improvement performed by a single surgeon. Patients were excluded if they had prior eyelid surgery. Photographs were taken in a standardized fashion and evaluated by 2 blinded evaluators. The measurements evaluated were the lower eyelid position (marginal reflex distance 2 [MRD2]) and inferior scleral show (SS).

The fat was harvested from the inner thigh and knee under tumescent anesthesia, strained, and injected with a 1.2-mm blunt cannula into various planes of the facial soft tissues. Approximately 0 to 2 mL was injected into the tear trough areas and 3 to 7 mL into the malar region, both per side. Photographs were repeated at an average of 117, 125, and 316 days.

Results showed that the MRD2 distance improved 0.5 mm bilaterally and was maintained at 316 days. Similarly, the SS measurement improved by 0.5 mm and was maintained at 125 days. Results improved slightly more in patients who had simultaneous face-lifts, but the difference was not statistically significant.

What’s the issue?

Lower eyelid malposition can make patients appear aged or tired while functionally causing dry eye or excessive tearing. Finding a way to improve this condition without surgery is key because the surgeries are fraught with risk. This study suggests that we should look more critically at lower eyelid positions in our patients who are receiving synthetic fillers or autologous fat to see if we are improving the MRD2 and SS measurements. Have you been seeing an increase in patients seeking improvement for “tired-looking eyes,” or do patients know they look tired but cannot pinpoint why?

We want to know your views! Tell us what you think.

Lower eyelid malposition is both a cosmetic and functional issue for many patients. It often arises from normal aging; however, it also can be due to thyroid disease, trauma, and surgery (iatrogenic). Correction of lower eyelid malposition requires a variety of surgical approaches to elevate the lower eyelid position. These procedures are not without risk. There have been reports of hyaluronic acid injections being used to help stretch the skin and give support to the sagging eyelid.

Le et al published a study (Ophthal Plast Reconstr Surg. 2014;30:504-507) on the effect of autologous fat injection on lower eyelid position. They performed a retrospective pilot study of autologous fat injections to support the lower eyelid in patients presenting for cosmetic reasons. A retrospective chart review was performed identifying 70 patients that had undergone lower eyelid and malar autologous fat injections for cosmetic improvement performed by a single surgeon. Patients were excluded if they had prior eyelid surgery. Photographs were taken in a standardized fashion and evaluated by 2 blinded evaluators. The measurements evaluated were the lower eyelid position (marginal reflex distance 2 [MRD2]) and inferior scleral show (SS).

The fat was harvested from the inner thigh and knee under tumescent anesthesia, strained, and injected with a 1.2-mm blunt cannula into various planes of the facial soft tissues. Approximately 0 to 2 mL was injected into the tear trough areas and 3 to 7 mL into the malar region, both per side. Photographs were repeated at an average of 117, 125, and 316 days.

Results showed that the MRD2 distance improved 0.5 mm bilaterally and was maintained at 316 days. Similarly, the SS measurement improved by 0.5 mm and was maintained at 125 days. Results improved slightly more in patients who had simultaneous face-lifts, but the difference was not statistically significant.

What’s the issue?

Lower eyelid malposition can make patients appear aged or tired while functionally causing dry eye or excessive tearing. Finding a way to improve this condition without surgery is key because the surgeries are fraught with risk. This study suggests that we should look more critically at lower eyelid positions in our patients who are receiving synthetic fillers or autologous fat to see if we are improving the MRD2 and SS measurements. Have you been seeing an increase in patients seeking improvement for “tired-looking eyes,” or do patients know they look tired but cannot pinpoint why?

We want to know your views! Tell us what you think.

“Decrease readmissions, and decrease them stat!” This mantra, or some, perhaps more subtle version thereof, is echoed over and over at hospitals across the country, and for good reason. Not only do readmissions have the potential to cost hospital systems millions of dollars through Medicare payment reductions, they also signal a more important, though less vocalized concern. If our patients keep returning to the hospital, are we really providing them with 100% of the resources they need?

On the surface, it may seem like there is little we can do for that two-pack-per-day smoker with end-stage chronic obstructive pulmonary disease who keeps getting readmitted with an exacerbation. And, while in reality, we may never get him to stop smoking and start taking his mediations as prescribed, perhaps we can help decrease the frequency of readmissions from three to four per year to two to three. While seemingly small, this decrease is actually quite dramatic, correlating to a 25%-50% reduction in the use of hospital services, not to mention the profound impact that fewer days spent in the hospital will have on his quality of life.

It is remarkable how much change occurs in the health care system over time. One year a drug may be touted as a huge breakthrough in treatment, and the next it may be taken off the market because of previously unrecognized, potentially fatal side effects. And just as the field of medicine is ever changing, so are all the fields that support it.

For example, the Agency for Healthcare Research and Qualify (AHRQ) has developed the Re-Engineered Discharge (RED) tool kit, which has been highly successful in reducing hospital readmissions. Originally developed by a group of AHRQ-funded researchers in Boston, RED provides evidence-based tools that help hospitals re-engineer their discharge process. One success story – within 3 months of implementing RED, the Valley Baptist Medical Center in Harlingen, Tex., decreased readmissions from 26% to 15%.

The RED model focuses on comprehensive discharge planning, educating patients about their discharge, and postdischarge follow-up care. It uses dedicated discharge advocates to help patients reconcile their medications and schedule much-needed follow-up appointments.

Other models exist as well. For instance, some hospitals have a palliative care team that focuses not only on keeping patients comfortable while in the hospital, but also on helping them access community services after discharge and make necessary appointments, geared at optimizing their health and ultimately decreasing the need for excessive hospitalizations.

As every health care dollar spent will be scrutinized more and more over time, innovative programs to help us rethink our long-established routines will likely play a major role in catapulting us from where we are to where we want to be.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

“Decrease readmissions, and decrease them stat!” This mantra, or some, perhaps more subtle version thereof, is echoed over and over at hospitals across the country, and for good reason. Not only do readmissions have the potential to cost hospital systems millions of dollars through Medicare payment reductions, they also signal a more important, though less vocalized concern. If our patients keep returning to the hospital, are we really providing them with 100% of the resources they need?

On the surface, it may seem like there is little we can do for that two-pack-per-day smoker with end-stage chronic obstructive pulmonary disease who keeps getting readmitted with an exacerbation. And, while in reality, we may never get him to stop smoking and start taking his mediations as prescribed, perhaps we can help decrease the frequency of readmissions from three to four per year to two to three. While seemingly small, this decrease is actually quite dramatic, correlating to a 25%-50% reduction in the use of hospital services, not to mention the profound impact that fewer days spent in the hospital will have on his quality of life.

It is remarkable how much change occurs in the health care system over time. One year a drug may be touted as a huge breakthrough in treatment, and the next it may be taken off the market because of previously unrecognized, potentially fatal side effects. And just as the field of medicine is ever changing, so are all the fields that support it.

For example, the Agency for Healthcare Research and Qualify (AHRQ) has developed the Re-Engineered Discharge (RED) tool kit, which has been highly successful in reducing hospital readmissions. Originally developed by a group of AHRQ-funded researchers in Boston, RED provides evidence-based tools that help hospitals re-engineer their discharge process. One success story – within 3 months of implementing RED, the Valley Baptist Medical Center in Harlingen, Tex., decreased readmissions from 26% to 15%.

The RED model focuses on comprehensive discharge planning, educating patients about their discharge, and postdischarge follow-up care. It uses dedicated discharge advocates to help patients reconcile their medications and schedule much-needed follow-up appointments.

Other models exist as well. For instance, some hospitals have a palliative care team that focuses not only on keeping patients comfortable while in the hospital, but also on helping them access community services after discharge and make necessary appointments, geared at optimizing their health and ultimately decreasing the need for excessive hospitalizations.

As every health care dollar spent will be scrutinized more and more over time, innovative programs to help us rethink our long-established routines will likely play a major role in catapulting us from where we are to where we want to be.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

“Decrease readmissions, and decrease them stat!” This mantra, or some, perhaps more subtle version thereof, is echoed over and over at hospitals across the country, and for good reason. Not only do readmissions have the potential to cost hospital systems millions of dollars through Medicare payment reductions, they also signal a more important, though less vocalized concern. If our patients keep returning to the hospital, are we really providing them with 100% of the resources they need?

On the surface, it may seem like there is little we can do for that two-pack-per-day smoker with end-stage chronic obstructive pulmonary disease who keeps getting readmitted with an exacerbation. And, while in reality, we may never get him to stop smoking and start taking his mediations as prescribed, perhaps we can help decrease the frequency of readmissions from three to four per year to two to three. While seemingly small, this decrease is actually quite dramatic, correlating to a 25%-50% reduction in the use of hospital services, not to mention the profound impact that fewer days spent in the hospital will have on his quality of life.

It is remarkable how much change occurs in the health care system over time. One year a drug may be touted as a huge breakthrough in treatment, and the next it may be taken off the market because of previously unrecognized, potentially fatal side effects. And just as the field of medicine is ever changing, so are all the fields that support it.

For example, the Agency for Healthcare Research and Qualify (AHRQ) has developed the Re-Engineered Discharge (RED) tool kit, which has been highly successful in reducing hospital readmissions. Originally developed by a group of AHRQ-funded researchers in Boston, RED provides evidence-based tools that help hospitals re-engineer their discharge process. One success story – within 3 months of implementing RED, the Valley Baptist Medical Center in Harlingen, Tex., decreased readmissions from 26% to 15%.

The RED model focuses on comprehensive discharge planning, educating patients about their discharge, and postdischarge follow-up care. It uses dedicated discharge advocates to help patients reconcile their medications and schedule much-needed follow-up appointments.

Other models exist as well. For instance, some hospitals have a palliative care team that focuses not only on keeping patients comfortable while in the hospital, but also on helping them access community services after discharge and make necessary appointments, geared at optimizing their health and ultimately decreasing the need for excessive hospitalizations.

As every health care dollar spent will be scrutinized more and more over time, innovative programs to help us rethink our long-established routines will likely play a major role in catapulting us from where we are to where we want to be.

Dr. Hester is a hospitalist at Baltimore-Washington Medical Center in Glen Burnie, Md. She is the creator of the Patient Whiz, a patient-engagement app for iOS. Reach her at [email protected].

VIENNA – Sonothrombolysis proved to be an effective alternative to endovascular treatment in patients with large intracranial occlusions, but clot removal via a retrievable stent appeared to have the edge when it came to achieving a good functional outcome, according to data presented at the annual European Stroke Conference.

In the first head-to-head comparison of the two strategies, there was no difference in the primary end point of the final modified Rankin Scale (mRS) score at the end of neurorehabilitation or death within 90 days. The mean final mRS was 3.78 with endovascular treatment and 3.95 with sonothrombolysis, with a nonsignificant (P = .12) odds ratio of 1.70 favoring the noninvasive procedure.

However, patients who underwent endovascular therapy were 3.89 times more likely than were those who had sonothrombolysis to achieve the secondary end point of a good functional outcome defined as a final mRS of 0-2 (24.7% vs. 13.6%; P = .02). Early recanalization was also possible in more patients with endovascular therapy than with sonothrombolysis (82.2% vs. 32.2%; OR, 15.77; P < .001).

“At the moment, everything veers toward using stent retrieval with thrombectomy, which requires very high costs at present and cannot be performed in every center,” noted study investigator Matthias Reinhard of the University Medical Center Freiburg (Germany) in an interview. On the other hand, Dr. Reinhard said, “sonothrombolysis is much less invasive and does not need specific interventionists, and it can be done with normal ultrasound devices, which are already available in every stroke unit.”

Sonothrombolysis enhances the thrombolytic activity of recombinant tissue plasminogen activator (rTPA) near to the clot, he explained, and has been shown in a Cochrane review to double the odds for functional independence, as well as upping the chances for recanalization around threefold (Cochrane Database Syst. Rev. 2012;10:CD008348). This is on a par with the results obtained with endovascular treatment in recent trials.

Since the two methods for enhancing thrombolysis with rTPA had not been directly compared before, Dr. Reinhard and his associates decided to look back at the medical records of patients with acute anterior circulation stroke with M1 or carotid T occlusion who were treated at two adjacent medical centers that used one or other of the methods as a standard treatment. After thrombolysis with rTPA, patients at one center underwent endovascular treatment with stent retrieval while patients at the other center had sonothrombolysis.

A total of 132 patients were assessed: 73 underwent endovascular treatment and 59 had sonothrombolysis. The median age in each group was 71 and 75 years, respectively, with around half the participants in each group being male. The groups had similar mean National Institutes of Health Stroke Scale scores (15 and 13). The majority of patients in each group had M1 vessel occlusions (60% and 69%) with the remainder (40% and 31%) having carotid T vessel occlusions. The mean onset to rTPA was 117 minutes and 105 minutes, respectively.

Subgroup analysis showed a significant benefit for endovascular treatment over sonothrombolysis in patients with carotid T occlusions, with an adjusted OR of 5.61 (P = .008). However, the two methods were comparable (OR, 1.07; P = .880) in patients with M1 occlusions.

“The main finding was that sonothrombolysis might perhaps be as equally effective as endovascular treatment in moderate-size occlusions such as middle cerebral artery occlusions but not in the very proximal occlusions of the carotid T,” Dr. Reinhard said. “So, one strategy might be to first apply sonothrombolysis and if this does not work, then to move the patient to the endovascular treatment,” he suggested, noting that this might be a better strategy to test in a future clinical trial than directly comparing the methods in a larger number of patients.

In terms of safety, there was no significant advantage of using one procedure over the other, despite three (4.1%) patients in the endovascular group and none in the sonothrombolysis group experiencing symptomatic intracranial hemorrhage (P = .25). Type 1 parenchymal hematomas were more common in patients who had sonothrombolysis than in those who had endovascular therapy (15.3% vs. 5.5%, P = .09). Mortality at 90 days was around 20% in both groups.

Dr. Reinhard had no disclosures.

VIENNA – Sonothrombolysis proved to be an effective alternative to endovascular treatment in patients with large intracranial occlusions, but clot removal via a retrievable stent appeared to have the edge when it came to achieving a good functional outcome, according to data presented at the annual European Stroke Conference.

In the first head-to-head comparison of the two strategies, there was no difference in the primary end point of the final modified Rankin Scale (mRS) score at the end of neurorehabilitation or death within 90 days. The mean final mRS was 3.78 with endovascular treatment and 3.95 with sonothrombolysis, with a nonsignificant (P = .12) odds ratio of 1.70 favoring the noninvasive procedure.

However, patients who underwent endovascular therapy were 3.89 times more likely than were those who had sonothrombolysis to achieve the secondary end point of a good functional outcome defined as a final mRS of 0-2 (24.7% vs. 13.6%; P = .02). Early recanalization was also possible in more patients with endovascular therapy than with sonothrombolysis (82.2% vs. 32.2%; OR, 15.77; P < .001).

“At the moment, everything veers toward using stent retrieval with thrombectomy, which requires very high costs at present and cannot be performed in every center,” noted study investigator Matthias Reinhard of the University Medical Center Freiburg (Germany) in an interview. On the other hand, Dr. Reinhard said, “sonothrombolysis is much less invasive and does not need specific interventionists, and it can be done with normal ultrasound devices, which are already available in every stroke unit.”

Sonothrombolysis enhances the thrombolytic activity of recombinant tissue plasminogen activator (rTPA) near to the clot, he explained, and has been shown in a Cochrane review to double the odds for functional independence, as well as upping the chances for recanalization around threefold (Cochrane Database Syst. Rev. 2012;10:CD008348). This is on a par with the results obtained with endovascular treatment in recent trials.

Since the two methods for enhancing thrombolysis with rTPA had not been directly compared before, Dr. Reinhard and his associates decided to look back at the medical records of patients with acute anterior circulation stroke with M1 or carotid T occlusion who were treated at two adjacent medical centers that used one or other of the methods as a standard treatment. After thrombolysis with rTPA, patients at one center underwent endovascular treatment with stent retrieval while patients at the other center had sonothrombolysis.

A total of 132 patients were assessed: 73 underwent endovascular treatment and 59 had sonothrombolysis. The median age in each group was 71 and 75 years, respectively, with around half the participants in each group being male. The groups had similar mean National Institutes of Health Stroke Scale scores (15 and 13). The majority of patients in each group had M1 vessel occlusions (60% and 69%) with the remainder (40% and 31%) having carotid T vessel occlusions. The mean onset to rTPA was 117 minutes and 105 minutes, respectively.

Subgroup analysis showed a significant benefit for endovascular treatment over sonothrombolysis in patients with carotid T occlusions, with an adjusted OR of 5.61 (P = .008). However, the two methods were comparable (OR, 1.07; P = .880) in patients with M1 occlusions.

“The main finding was that sonothrombolysis might perhaps be as equally effective as endovascular treatment in moderate-size occlusions such as middle cerebral artery occlusions but not in the very proximal occlusions of the carotid T,” Dr. Reinhard said. “So, one strategy might be to first apply sonothrombolysis and if this does not work, then to move the patient to the endovascular treatment,” he suggested, noting that this might be a better strategy to test in a future clinical trial than directly comparing the methods in a larger number of patients.

In terms of safety, there was no significant advantage of using one procedure over the other, despite three (4.1%) patients in the endovascular group and none in the sonothrombolysis group experiencing symptomatic intracranial hemorrhage (P = .25). Type 1 parenchymal hematomas were more common in patients who had sonothrombolysis than in those who had endovascular therapy (15.3% vs. 5.5%, P = .09). Mortality at 90 days was around 20% in both groups.

Dr. Reinhard had no disclosures.

VIENNA – Sonothrombolysis proved to be an effective alternative to endovascular treatment in patients with large intracranial occlusions, but clot removal via a retrievable stent appeared to have the edge when it came to achieving a good functional outcome, according to data presented at the annual European Stroke Conference.

In the first head-to-head comparison of the two strategies, there was no difference in the primary end point of the final modified Rankin Scale (mRS) score at the end of neurorehabilitation or death within 90 days. The mean final mRS was 3.78 with endovascular treatment and 3.95 with sonothrombolysis, with a nonsignificant (P = .12) odds ratio of 1.70 favoring the noninvasive procedure.

However, patients who underwent endovascular therapy were 3.89 times more likely than were those who had sonothrombolysis to achieve the secondary end point of a good functional outcome defined as a final mRS of 0-2 (24.7% vs. 13.6%; P = .02). Early recanalization was also possible in more patients with endovascular therapy than with sonothrombolysis (82.2% vs. 32.2%; OR, 15.77; P < .001).

“At the moment, everything veers toward using stent retrieval with thrombectomy, which requires very high costs at present and cannot be performed in every center,” noted study investigator Matthias Reinhard of the University Medical Center Freiburg (Germany) in an interview. On the other hand, Dr. Reinhard said, “sonothrombolysis is much less invasive and does not need specific interventionists, and it can be done with normal ultrasound devices, which are already available in every stroke unit.”

Sonothrombolysis enhances the thrombolytic activity of recombinant tissue plasminogen activator (rTPA) near to the clot, he explained, and has been shown in a Cochrane review to double the odds for functional independence, as well as upping the chances for recanalization around threefold (Cochrane Database Syst. Rev. 2012;10:CD008348). This is on a par with the results obtained with endovascular treatment in recent trials.

Since the two methods for enhancing thrombolysis with rTPA had not been directly compared before, Dr. Reinhard and his associates decided to look back at the medical records of patients with acute anterior circulation stroke with M1 or carotid T occlusion who were treated at two adjacent medical centers that used one or other of the methods as a standard treatment. After thrombolysis with rTPA, patients at one center underwent endovascular treatment with stent retrieval while patients at the other center had sonothrombolysis.

A total of 132 patients were assessed: 73 underwent endovascular treatment and 59 had sonothrombolysis. The median age in each group was 71 and 75 years, respectively, with around half the participants in each group being male. The groups had similar mean National Institutes of Health Stroke Scale scores (15 and 13). The majority of patients in each group had M1 vessel occlusions (60% and 69%) with the remainder (40% and 31%) having carotid T vessel occlusions. The mean onset to rTPA was 117 minutes and 105 minutes, respectively.

Subgroup analysis showed a significant benefit for endovascular treatment over sonothrombolysis in patients with carotid T occlusions, with an adjusted OR of 5.61 (P = .008). However, the two methods were comparable (OR, 1.07; P = .880) in patients with M1 occlusions.

“The main finding was that sonothrombolysis might perhaps be as equally effective as endovascular treatment in moderate-size occlusions such as middle cerebral artery occlusions but not in the very proximal occlusions of the carotid T,” Dr. Reinhard said. “So, one strategy might be to first apply sonothrombolysis and if this does not work, then to move the patient to the endovascular treatment,” he suggested, noting that this might be a better strategy to test in a future clinical trial than directly comparing the methods in a larger number of patients.

In terms of safety, there was no significant advantage of using one procedure over the other, despite three (4.1%) patients in the endovascular group and none in the sonothrombolysis group experiencing symptomatic intracranial hemorrhage (P = .25). Type 1 parenchymal hematomas were more common in patients who had sonothrombolysis than in those who had endovascular therapy (15.3% vs. 5.5%, P = .09). Mortality at 90 days was around 20% in both groups.

Dr. Reinhard had no disclosures.

Brief cognitive screening is essential for assessing neurocognitive disor­ders. Such screening can give clini­cians a snapshot of patients’ cognitive abilities across a range of disorders and help tailor interventions to yield better outcomes. Appropriate administration of a brief cognitive screening using telehealth technology can improve access to care and treatment planning.

Neurocognitive decline can be a barrier to treatment
Persons with neurocognitive impairment, regardless of the cause, often face barriers when they seek treatment. Memory and attention difficulties often interfere with attending appointments; driving restric­tions, smaller social networks, caregiver burden, and medical conditions limit access to care. For such patients, tele­health assessment is a tool that physicians can use to help patients overcome these barriers.

Cognitive screening tools
Brief cognitive assessments need to dem­onstrate (1) consistent and accurate scores over time (reliability) and (2) that they are measuring the intended cognitive domain (validity). The Mini-Mental State Examination is used often; the Montreal Cognitive Assessment and the Short Blessed Test are additional cognitive screeners that have support in the literature for use with telehealth technology.¹

Telehealth assessment modalities
Modalities for telehealth assessment² include:
   • Audio-based systems. Pro: Telephone-based telehealth screening usually does not require extra equipment or advanced planning. Con: Visual information is absent and there is overreliance on verbal tasks.
   • Video-based systems. Pro: Using video­phones or video conferencing systems allow physicians to observe patients’ behaviors and their ability to complete tasks on paper. Con: A video system often requires more planning and effort to set up than other types of systems.
   • Web-based systems. Pro: Web sites on which patient and provider can interact in real time—through a combination of audio, video, and programmed applications—offer immediate access to a patient’s responses and test results, thus providing a wealth of clinical information such as exact timing and calculation of patients’ responses, abil­ity to record and review patients’ approach to construction tasks, and the capability to adapt test batteries in real-time based on patients’ ongoing performance. Con: Such systems require specialized software and infrastructure.

Support for telehealth screening
Our patients report feeling comfortable with telehealth screening; they overwhelmingly report that they prefer telehealth services to in-person services that require travel. Studies on the reliability and validity of using cog­nitive screeners have shown that telehealth screening is a feasible and acceptable prac­tice.³ Although the telehealth approaches mentioned here can all be used effectively, we have found that video-based cognitive screening might offer the best balance of flexibility, accessibility, and ease of use at this time.

Our recommendations
Consider your resources, patient popula­tion, and the scope of available telehealth services to guide your approach. Use vali­dated measures that fit the limitations of the modality you have chosen:
   • Telephone-based screenings should use verbally based measures (eg, the Short Blessed Test and the Telephone Interview for Cognitive Status).
   • Video-based screenings can include visual elements, but you need to decide how to best administer, record, and score the patient’s written responses. You might need to mail portions of tests along with a writing utensil and paper to their home. Patients can hold up their responses to the camera or send back the completed tests for scoring.
   • Adapt testing to the constraints of a particular situation, but modifications to tests should be limited as much as possible to minimize decreases in reliability and validity.
   • Have a clear policy for dealing with unexpected events, such as technological malfunctions, patient privacy concerns, and mental health emergencies.

Acknowledgement
This article was supported by the facilities and resources of the Salem VA Medical Center. The views expressed in this article are those of the authors and not necessarily those of the Department of Veterans Affairs.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or wiith manufacturers of competing products.

Brief cognitive screening is essential for assessing neurocognitive disor­ders. Such screening can give clini­cians a snapshot of patients’ cognitive abilities across a range of disorders and help tailor interventions to yield better outcomes. Appropriate administration of a brief cognitive screening using telehealth technology can improve access to care and treatment planning.

Neurocognitive decline can be a barrier to treatment
Persons with neurocognitive impairment, regardless of the cause, often face barriers when they seek treatment. Memory and attention difficulties often interfere with attending appointments; driving restric­tions, smaller social networks, caregiver burden, and medical conditions limit access to care. For such patients, tele­health assessment is a tool that physicians can use to help patients overcome these barriers.

Cognitive screening tools
Brief cognitive assessments need to dem­onstrate (1) consistent and accurate scores over time (reliability) and (2) that they are measuring the intended cognitive domain (validity). The Mini-Mental State Examination is used often; the Montreal Cognitive Assessment and the Short Blessed Test are additional cognitive screeners that have support in the literature for use with telehealth technology.¹

Telehealth assessment modalities
Modalities for telehealth assessment² include:
   • Audio-based systems. Pro: Telephone-based telehealth screening usually does not require extra equipment or advanced planning. Con: Visual information is absent and there is overreliance on verbal tasks.
   • Video-based systems. Pro: Using video­phones or video conferencing systems allow physicians to observe patients’ behaviors and their ability to complete tasks on paper. Con: A video system often requires more planning and effort to set up than other types of systems.
   • Web-based systems. Pro: Web sites on which patient and provider can interact in real time—through a combination of audio, video, and programmed applications—offer immediate access to a patient’s responses and test results, thus providing a wealth of clinical information such as exact timing and calculation of patients’ responses, abil­ity to record and review patients’ approach to construction tasks, and the capability to adapt test batteries in real-time based on patients’ ongoing performance. Con: Such systems require specialized software and infrastructure.

Support for telehealth screening
Our patients report feeling comfortable with telehealth screening; they overwhelmingly report that they prefer telehealth services to in-person services that require travel. Studies on the reliability and validity of using cog­nitive screeners have shown that telehealth screening is a feasible and acceptable prac­tice.³ Although the telehealth approaches mentioned here can all be used effectively, we have found that video-based cognitive screening might offer the best balance of flexibility, accessibility, and ease of use at this time.

Our recommendations
Consider your resources, patient popula­tion, and the scope of available telehealth services to guide your approach. Use vali­dated measures that fit the limitations of the modality you have chosen:
   • Telephone-based screenings should use verbally based measures (eg, the Short Blessed Test and the Telephone Interview for Cognitive Status).
   • Video-based screenings can include visual elements, but you need to decide how to best administer, record, and score the patient’s written responses. You might need to mail portions of tests along with a writing utensil and paper to their home. Patients can hold up their responses to the camera or send back the completed tests for scoring.
   • Adapt testing to the constraints of a particular situation, but modifications to tests should be limited as much as possible to minimize decreases in reliability and validity.
   • Have a clear policy for dealing with unexpected events, such as technological malfunctions, patient privacy concerns, and mental health emergencies.

Acknowledgement
This article was supported by the facilities and resources of the Salem VA Medical Center. The views expressed in this article are those of the authors and not necessarily those of the Department of Veterans Affairs.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or wiith manufacturers of competing products.

Brief cognitive screening is essential for assessing neurocognitive disor­ders. Such screening can give clini­cians a snapshot of patients’ cognitive abilities across a range of disorders and help tailor interventions to yield better outcomes. Appropriate administration of a brief cognitive screening using telehealth technology can improve access to care and treatment planning.

Neurocognitive decline can be a barrier to treatment
Persons with neurocognitive impairment, regardless of the cause, often face barriers when they seek treatment. Memory and attention difficulties often interfere with attending appointments; driving restric­tions, smaller social networks, caregiver burden, and medical conditions limit access to care. For such patients, tele­health assessment is a tool that physicians can use to help patients overcome these barriers.

Cognitive screening tools
Brief cognitive assessments need to dem­onstrate (1) consistent and accurate scores over time (reliability) and (2) that they are measuring the intended cognitive domain (validity). The Mini-Mental State Examination is used often; the Montreal Cognitive Assessment and the Short Blessed Test are additional cognitive screeners that have support in the literature for use with telehealth technology.¹

Telehealth assessment modalities
Modalities for telehealth assessment² include:
   • Audio-based systems. Pro: Telephone-based telehealth screening usually does not require extra equipment or advanced planning. Con: Visual information is absent and there is overreliance on verbal tasks.
   • Video-based systems. Pro: Using video­phones or video conferencing systems allow physicians to observe patients’ behaviors and their ability to complete tasks on paper. Con: A video system often requires more planning and effort to set up than other types of systems.
   • Web-based systems. Pro: Web sites on which patient and provider can interact in real time—through a combination of audio, video, and programmed applications—offer immediate access to a patient’s responses and test results, thus providing a wealth of clinical information such as exact timing and calculation of patients’ responses, abil­ity to record and review patients’ approach to construction tasks, and the capability to adapt test batteries in real-time based on patients’ ongoing performance. Con: Such systems require specialized software and infrastructure.

Support for telehealth screening
Our patients report feeling comfortable with telehealth screening; they overwhelmingly report that they prefer telehealth services to in-person services that require travel. Studies on the reliability and validity of using cog­nitive screeners have shown that telehealth screening is a feasible and acceptable prac­tice.³ Although the telehealth approaches mentioned here can all be used effectively, we have found that video-based cognitive screening might offer the best balance of flexibility, accessibility, and ease of use at this time.

Our recommendations
Consider your resources, patient popula­tion, and the scope of available telehealth services to guide your approach. Use vali­dated measures that fit the limitations of the modality you have chosen:
   • Telephone-based screenings should use verbally based measures (eg, the Short Blessed Test and the Telephone Interview for Cognitive Status).
   • Video-based screenings can include visual elements, but you need to decide how to best administer, record, and score the patient’s written responses. You might need to mail portions of tests along with a writing utensil and paper to their home. Patients can hold up their responses to the camera or send back the completed tests for scoring.
   • Adapt testing to the constraints of a particular situation, but modifications to tests should be limited as much as possible to minimize decreases in reliability and validity.
   • Have a clear policy for dealing with unexpected events, such as technological malfunctions, patient privacy concerns, and mental health emergencies.

Acknowledgement
This article was supported by the facilities and resources of the Salem VA Medical Center. The views expressed in this article are those of the authors and not necessarily those of the Department of Veterans Affairs.

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or wiith manufacturers of competing products.

Psychiatric providers often encounter older adult patients who report dif­ficulty with memory and express the fear they are “developing dementia.” Often, after a thorough evaluation of the reported deficits and history, we find that a serious or progressive neurocognitive disorder is unlikely. However, such occasions are an opportunity to discuss lifestyle changes that may help prevent, or at least slow, development of later-life cognitive decline.

Although I inform my patients that the body of evidence supporting many of these preventive measures still is evolving, I suggest the following approach that may provide a DEFENSE against future cogni­tive disability.

Diet options that are “heart healthy” seem to be “brain healthy” as well. This may be due, in part, to the antioxidant and anti-inflammatory effects of particular foods.¹ Therefore, I suggest patients try to implement a Mediterranean-type diet that emphasizes fish (especially those rich in omega-3 fats, such as salmon and tuna), poultry, fresh fruit, and vegetables, as well as legumes.

ETOH has been shown, in a moderate amount (eg, 1 drink a day for women and 1 to 2 drinks for men), to be brain protec­tive because of the antioxidants found in the alcohol or the direct relaxation effects that are produced—or both. Although red wine often is recommended, recent stud­ies have shown that those who enjoyed an active life into their 70s and 80s had consumed a moderate amount of alcohol over their lifetime regardless of the type of spirit (eg, 12 oz of beer, 4 oz of wine, 1 oz of hard liquor).²

Friends contribute to an active, stimulating, and emotionally supported life. Having a strong social network, an antidote to lone­liness and depression, has been shown to reduce the risk of “turning on” specific genes that stimulate an inflammatory process that can lead to brain cell death and neural damage.³

Exercise might be the most important ingre­dient for a longer, healthier, and more cogni­tively intact life. Moderate exercise, several times a week, increases blood flow to the brain and, subsequently, stimulates neuronal synapses and the hippocampus.⁴ The forms of exercise include walking, biking, swimming, resistance training, and even gardening.

No tobacco! It is known that smoking leads to accelerated aging for the heart and brain, so it is our responsibility to remain vigilant in promoting smoking cessation strategies.

Sleep has received increased attention, with recent studies providing evidence that the brain uses that time to “flush out” neurotoxic by-products of cognitive activity that have accumulated throughout the day.⁵ As evi­dence continues to be examined on this pro­cess, it is reasonable to recommend adequate sleep and a consistent sleep pattern as pos­sible defenses against brain cell insult.

Engagement in tasks that are cognitively stimulating has been promoted as potential “brain exercises” to stave off future memory loss. For example, computer games that are mentally challenging; lively and frequent conversations; and learning a language all appear to increase neural activation and communication throughout the brain.⁶

As brain research continues to expand, providers will become more knowledgeable and aware of the steps our patients can take when they discuss concerns about their risk of progressive cognitive disability and mem­ory loss. For now, however, it is important to describe what we do know based on cur­rent research and help our patients develop the best defense they can against age-related cognitive decline.

Disclosure
The author reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Psychiatric providers often encounter older adult patients who report dif­ficulty with memory and express the fear they are “developing dementia.” Often, after a thorough evaluation of the reported deficits and history, we find that a serious or progressive neurocognitive disorder is unlikely. However, such occasions are an opportunity to discuss lifestyle changes that may help prevent, or at least slow, development of later-life cognitive decline.

Although I inform my patients that the body of evidence supporting many of these preventive measures still is evolving, I suggest the following approach that may provide a DEFENSE against future cogni­tive disability.

Diet options that are “heart healthy” seem to be “brain healthy” as well. This may be due, in part, to the antioxidant and anti-inflammatory effects of particular foods.¹ Therefore, I suggest patients try to implement a Mediterranean-type diet that emphasizes fish (especially those rich in omega-3 fats, such as salmon and tuna), poultry, fresh fruit, and vegetables, as well as legumes.

ETOH has been shown, in a moderate amount (eg, 1 drink a day for women and 1 to 2 drinks for men), to be brain protec­tive because of the antioxidants found in the alcohol or the direct relaxation effects that are produced—or both. Although red wine often is recommended, recent stud­ies have shown that those who enjoyed an active life into their 70s and 80s had consumed a moderate amount of alcohol over their lifetime regardless of the type of spirit (eg, 12 oz of beer, 4 oz of wine, 1 oz of hard liquor).²

Friends contribute to an active, stimulating, and emotionally supported life. Having a strong social network, an antidote to lone­liness and depression, has been shown to reduce the risk of “turning on” specific genes that stimulate an inflammatory process that can lead to brain cell death and neural damage.³

Exercise might be the most important ingre­dient for a longer, healthier, and more cogni­tively intact life. Moderate exercise, several times a week, increases blood flow to the brain and, subsequently, stimulates neuronal synapses and the hippocampus.⁴ The forms of exercise include walking, biking, swimming, resistance training, and even gardening.

No tobacco! It is known that smoking leads to accelerated aging for the heart and brain, so it is our responsibility to remain vigilant in promoting smoking cessation strategies.

Sleep has received increased attention, with recent studies providing evidence that the brain uses that time to “flush out” neurotoxic by-products of cognitive activity that have accumulated throughout the day.⁵ As evi­dence continues to be examined on this pro­cess, it is reasonable to recommend adequate sleep and a consistent sleep pattern as pos­sible defenses against brain cell insult.

Engagement in tasks that are cognitively stimulating has been promoted as potential “brain exercises” to stave off future memory loss. For example, computer games that are mentally challenging; lively and frequent conversations; and learning a language all appear to increase neural activation and communication throughout the brain.⁶

As brain research continues to expand, providers will become more knowledgeable and aware of the steps our patients can take when they discuss concerns about their risk of progressive cognitive disability and mem­ory loss. For now, however, it is important to describe what we do know based on cur­rent research and help our patients develop the best defense they can against age-related cognitive decline.

Disclosure
The author reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

Psychiatric providers often encounter older adult patients who report dif­ficulty with memory and express the fear they are “developing dementia.” Often, after a thorough evaluation of the reported deficits and history, we find that a serious or progressive neurocognitive disorder is unlikely. However, such occasions are an opportunity to discuss lifestyle changes that may help prevent, or at least slow, development of later-life cognitive decline.

Although I inform my patients that the body of evidence supporting many of these preventive measures still is evolving, I suggest the following approach that may provide a DEFENSE against future cogni­tive disability.

Diet options that are “heart healthy” seem to be “brain healthy” as well. This may be due, in part, to the antioxidant and anti-inflammatory effects of particular foods.¹ Therefore, I suggest patients try to implement a Mediterranean-type diet that emphasizes fish (especially those rich in omega-3 fats, such as salmon and tuna), poultry, fresh fruit, and vegetables, as well as legumes.

ETOH has been shown, in a moderate amount (eg, 1 drink a day for women and 1 to 2 drinks for men), to be brain protec­tive because of the antioxidants found in the alcohol or the direct relaxation effects that are produced—or both. Although red wine often is recommended, recent stud­ies have shown that those who enjoyed an active life into their 70s and 80s had consumed a moderate amount of alcohol over their lifetime regardless of the type of spirit (eg, 12 oz of beer, 4 oz of wine, 1 oz of hard liquor).²

Friends contribute to an active, stimulating, and emotionally supported life. Having a strong social network, an antidote to lone­liness and depression, has been shown to reduce the risk of “turning on” specific genes that stimulate an inflammatory process that can lead to brain cell death and neural damage.³

Exercise might be the most important ingre­dient for a longer, healthier, and more cogni­tively intact life. Moderate exercise, several times a week, increases blood flow to the brain and, subsequently, stimulates neuronal synapses and the hippocampus.⁴ The forms of exercise include walking, biking, swimming, resistance training, and even gardening.

No tobacco! It is known that smoking leads to accelerated aging for the heart and brain, so it is our responsibility to remain vigilant in promoting smoking cessation strategies.

Sleep has received increased attention, with recent studies providing evidence that the brain uses that time to “flush out” neurotoxic by-products of cognitive activity that have accumulated throughout the day.⁵ As evi­dence continues to be examined on this pro­cess, it is reasonable to recommend adequate sleep and a consistent sleep pattern as pos­sible defenses against brain cell insult.

Engagement in tasks that are cognitively stimulating has been promoted as potential “brain exercises” to stave off future memory loss. For example, computer games that are mentally challenging; lively and frequent conversations; and learning a language all appear to increase neural activation and communication throughout the brain.⁶

As brain research continues to expand, providers will become more knowledgeable and aware of the steps our patients can take when they discuss concerns about their risk of progressive cognitive disability and mem­ory loss. For now, however, it is important to describe what we do know based on cur­rent research and help our patients develop the best defense they can against age-related cognitive decline.

Disclosure
The author reports no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE Light-headed
Mr. M, age 73, is a retired project manager who feels light-headed while walking his dog, causing him to go to the emergency depart­ment. His history is significant for hyperten­sion, coronary artery disease (CAD), 3-vessel coronary artery bypass graft surgery (CABG), hyperlipidemia, erectile dysfunction, open-angle glaucoma, hemiretinal vein occlusion, symptoms suggesting rapid eye-movement behavior disorder (RBD), and major depressive disorder (MDD).

The psychiatry consultation-liaison service is asked to help manage Mr. M’s psychiat­ric medications in the context of orthostatic hypotension and cognitive deficits.

What could be causing Mr. M’s symptoms?
   a) drug adverse effect
   b) progressive cardiovascular disease
   c) MDD
   d) all of the above

HISTORY Depression, heart disease
15 years ago. Mr. M experienced his first major depressive episode. His primary care physician (PCP) commented on a history of falling asleep while driving and 1 episode of sleepwalking. His depression was treated to remission with fluoxetine and methylphenidate (dosages were not recorded), the latter also addressed his falling asleep while driving.

5 years ago. Mr. M had another depres­sive episode characterized by anxiety, difficulty sleeping, and irritability. He also described chest pain; a cardiac work-up revealed extensive CAD, which led to 3-vessel CABG later that year. He also reported dizziness upon standing, which was treated with compression stockings and an increase in sodium intake.

Mr. M continued to express feelings of depression. His cardiologist started him on par­oxetine, 10 mg/d, which he took for 2 months and decided to stop because he felt better. He declined psychiatric referral.

4 years ago. Mr. M’s PCP referred him to a psychiatrist for depressed mood, anhedonia, decreased appetite, decreased energy, and dif­ficulty concentrating. Immediate and delayed recall were found to be intact. The psychiatrist diagnosed MDD and Mr. M started escitalopram, 5 mg/d, titrated to 15 mg/d, and trazodone, 50 mg/d.

After starting treatment, Mr. M reported decreased libido. Sustained-release bupropion, 150 mg/d, was added to boost the effects of escitalopram and counteract sexual side effects.

At follow-up, Mr. M reported that his depres­sive symptoms and libido had improved, but that he had been experiencing unsteady gait when getting out of his car, which he had been noticing “for a while”—before he began trazo­done. Mr. M was referred to his PCP, who attrib­uted his symptoms to orthostasis. No treatment was indicated at the time because Mr. M’s light­headedness had resolved.

3 years ago. Mr. M reported a syncopal attack and continued “dizziness.” His PCP pre­scribed fludrocortisone, 0.1 mg/d, later to be dosed 0.2 mg/d, and symptoms improved.

Although Mr. M had a history of orthostatic hypotension, he was later noted to have supine hypertension. Mr. M’s PCP was concerned that fludrocortisone could be causing the supine hypertension but that decreasing the dosage would cause his orthostatic hypotension to return.

The PCP also was concerned that the psy­chiatric medications (escitalopram, trazodone, and bupropion) could be causing orthostasis. There was discussion among Mr. M, his PCP, and his psychiatrist of stopping the psycho­tropics to see if the symptoms would remit; however, because of concerns about Mr. M’s depression, the medications were continued. Mr. M monitored his blood pressure at home and was referred to a neurologist for work-up of potential autonomic dysfunction.

Shortly afterward, Mr. M reported intermit­tent difficulty keeping track of his thoughts and finishing sentences. His psychiatrist ordered an MRI, which showed chronic small vessel ischemic changes, and started him on donepezil, 5 mg/d.

Neuropsychological testing revealed decreased processing speed and poor rec­ognition memory; otherwise, results showed above-average intellectual ability and average or above-average performance in measures of language, attention, visuospatial/construc­tional functions, and executive functions—a pattern typically attributable to psychogenic factors, such as depression.

Mr. M reported to his neurologist that he for­gets directions while driving but can focus bet­ter if he makes a conscious effort. Physical exam was significant hypotension; flat affect; deficits in concentration and short-term recall; mild impairment of Luria motor sequence (com­posed of a go/no-go and a reciprocal motor task); and vertical and horizontal saccades.¹

Mr. M consulted with an ophthalmologist for anterior iridocyclitis and ocular hypertension, which was controlled with travoprost. He con­tinued to experience trouble with his vision and was given a diagnosis of right inferior hemireti­nal vein occlusion, macular edema, and sus­pected glaucoma. Subsequent notes recorded a history of Posner-Schlossman syndrome (a disease characterized by recurrent attacks of increased intraocular pressure in 1 eye with concomitant anterior chamber inflammation). His vision deteriorated until he was diagnosed with ocular hypertension, open-angle glau­coma, and dermatochalasis.

The authors’ observations
Involvement of multiple specialties in a patient’s care brings to question one’s philosophy on medical diagnosis. Interdisciplinary communication would seem to promote the principle of diagnostic parsimony, or Occam’s razor, which sug­gests a unifying diagnosis to explain all of the patient’s symptoms. Lack of communi­cation might favor Hickam’s dictum, which states that “patients can have as many dis­eases as they damn well please.”

HISTORY Low energy, forgetfulness
2 years ago. Mr. M noticed low energy and motivation. He continued to work full-time but thought that it was taking him longer to get work done. He was tapered off escitalo­pram and started on desvenlafaxine, 50 mg/d; donepezil was increased to 10 mg/d.

The syncopal episodes resolved but blood pressure measured at home averaged 150/70 mm Hg. Mr. M was advised to decrease fludrocortisone from 0.2 mg/d to 0.1 mg/d. He tolerated the change and blood pressure measured at home dropped on average to 120 to 130/70 mm Hg.

1 year ago. Mr. M reported that his mem­ory loss had become worse. He perceived hav­ing more stress because of forgetfulness and visual difficulties, which had led him to stop driving at night.

At a follow-up appointment with his psy­chiatrist, Mr. M reported that, first, he had not tapered escitalopram as discussed and, second, he forgot to increase the dosage of desvenlafaxine. A home blood pressure log revealed consistent hypotension; the psychia­trist was concerned that hypotension could be the cause of concentration difficulties and malaise. The psychiatrist advised Mr. M to fol­low-up with his PCP and neurologist.

Current admission. Shortly after the visit to the psychiatrist, Mr. M presented to the emergency department for increased synco­pal events. Work-up was negative for a car­diac cause. A cosyntropin stimulation test was negative, showing that adrenal insufficiency did not cause his orthostatic hypotension. Chart review showed he had been having blood pressure problems for many years, inde­pendent of antidepressants. Physical exam revealed lower extremity ataxia and a bilateral extensor plantar reflex.

What diagnosis explains Mr. M’s symptoms?
   a) Parkinson’s disease
   b) multiple system atrophy (MSA)
   c) depression due to a general medical condition
  d) dementia

The authors’ observations
MSA, previously referred to as Shy-Drager syndrome, is a rare, rapidly progressive neurodegenerative disorder with an esti­mated prevalence of 3.7 cases for every 100,000 people worldwide.² MSA primarily affects middle-aged patients; because it has no cure, most patients die in 7 to 10 years.³

MSA has 2 clinical variants^4,5:
   • parkinsonian type (MSA-P), charac­terized by striatonigral degeneration and increased spasticity
   • cerebellar type (MSA-C), character­ized by more autonomic dysfunction.

MSA has a range of symptoms, mak­ing it a challenging diagnosis (Table).⁶ Although psychiatric symptoms are not part of the diagnostic criteria, they can aid in its diagnosis. In Mr. M’s case, depres­sion, anxiety, orthostatic hypotension, and ataxia support a diagnosis of MSA.

Gilman et al⁶ delineated 3 diagnostic categories for MSA: definite MSA, prob­able MSA, and possible MSA. Clinical cri­teria shared by the 3 diagnostic categories are sporadic and progressive onset after age 30.

Definite MSA requires “neuropathological findings of widespread and abundant CNS alpha-synuclein-positive glial cytoplasmic inclusions,” along with “neurodegenera­tive changes in striatonigral or olivoponto­cerebellar structures” at autopsy.⁶

Probable MSA. Without autopsy findings required for definite MSA, the next most specific diagnostic category is probable MSA. Probable MSA also specifies that the patient show either autonomic fail­ure involving urinary incontinence—this includes erectile dysfunction in men—or, if autonomic failure is absent, orthostatic hypotension within 3 minutes of standing by at least 30 mm Hg systolic pressure or 15 mm Hg diastolic pressure.

Possible MSA has less stringent crite­ria for orthostatic hypotension. The cat­egory includes patients who have only 1 symptom that suggests autonomic failure. Criteria for possible MSA include parkin­sonism or a cerebellar syndrome in addition to symptoms of MSA listed in the Table, whereas probable MSA has specific crite­ria of either a poorly levodopa-responsive parkinsonism (MSA-P) or a cerebellar syn­drome (MSA-C). In addition to having par­kinsonism or a cerebellar syndrome, and 1 sign of autonomic failure or orthostatic hypotension, patients also must have ≥1 additional feature to be assigned a diagno­sis of possible MSA, including:
   • rapidly progressive parkinsonism
   • poor response to levodopa
   • postural instability within 3 years of motor onset
   • gait ataxia, cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction
   • dysphagia within 5 years of motor onset
   • atrophy on MRI of putamen, mid­dle cerebellar peduncle, pons, or cerebellum
   • hypometabolism on fluorodeoxyglucose- PET in putamen, brainstem, or cerebellum.⁶

Diagnosing MSA can be challenging because its features are similar to those of many other disorders. Nonetheless, Gilman et al6 lists specific criteria for prob­able MSA, including autonomic dysfunc­tion, orthostatic hypotension, and either parkinsonism or cerebellar syndrome symptoms. Although a definite MSA diag­nosis only can be made by postmortem brain specimen analysis, Osaki et al⁷ found that a probable MSA diagnosis has a posi­tive predictive value of 92% with a sensi­tivity of 22% for definite MSA.

Mr. M’s symptoms were consistent with a diagnosis of probable MSA, cerebellar type (Figure).

Psychiatric manifestations of MSA
There are a few case reports of depression identified early in patients who were later given a diagnosis of MSA.⁸

Depression. In a study by Benrud-Larson et al⁹ (N = 99), 49% of patients who had MSA reported moderate or severe depres­sion, as indicated by a score of ≥17 on the Beck Depression Inventory (BDI); 80% reported at least mild depression (BDI ≥10, mean 17.0, standard deviation, 8.7).

In a similar study, by Balas et al,¹⁰ depres­sion was reported as a common symptom and was statistically significant in MSA-P patients compared with controls (P = .013).

Anxiety, another symptom that was reported by Mr. M, is another psychiat­ric manifestation described by Balas et al¹⁰ and Chang et al.¹¹ Balas et al¹⁰ noted that MSA-C and MSA-P patients had sig­nificantly more state anxiety (P = .009 and P = .022, respectively) compared with con­trols, although Chang et al¹¹ noted higher anxiety scores in MSA-C patients com­pared with controls and MSA-P patients (P < .01).

Balas et al¹⁰ hypothesized that anxiety and depression contribute to cognitive decline; their study showed that MSA-C patients had difficulty learning new ver­bal information (P < .022) and controlling attention (P < .023). Mr. M exhibited some of these cognitive difficulties in his reports of losing track of conversations, forgetting the topic of a conversation when speaking, trouble focusing, and difficulty concentrat­ing when driving.

Mr. M had depression and anxiety well before onset of autonomic dysfunction (orthostatic hypotension and erectile dys­function), which eventually led to an MSA diagnosis. Psychiatrists should under­stand additional manifestations of MSA so that they can use psychiatric symptoms to identify these conditions in their patients. One of the most well-known and early manifestations of MSA is autonomic dys­function; among men, another early sign is erectile dysfunction.⁶ Our patient also exhibited other less well-known symptoms linked to MSA and autonomic dysregula­tion, including RBD and ocular symptoms (iridocyclitis, glaucoma, decreased visual acuity).

Rapid eye-movement behavior disorder. Psychiatrists should consider screen­ing for RBD during assessment of sleep problems. Identifying RBD is important because early studies have shown a strong association between RBD and develop­ment of a neurodegenerative disorder. Mr. M’s clinicians did not consider RBD, although his symptoms of sleepwalking and falling asleep while driving suggest a possible diagnosis. Also, considering this diagnosis would aid in diagnosing a synu­cleinopathy disorder because a higher incidence of RBD was noted in patients who developed synucleinopathy disor­ders (eg, Parkinson’s disease [PD] and dementia with Lewy bodies [DLB]) com­pared with patients who developed non-synucleinopathies (eg, frontotemporal dementia, corticobasal degeneration, pro­gressive supranuclear palsy, mild cogni­tive impairment, primary progressive aphasia, and posterior cortical atrophy) or tauopathies (eg, Alzheimer’s disease).¹²

Zanigni et al¹³ reported similar findings in a later study that classified patients with RBD as having idiopathic RBD (IRBD) or RBD sec­ondary to an underlying neurodegenerative disorder, particularly an α-synucleinopathy: PD, MSA, and DLB. Most IRBD patients developed 1 of the above mentioned neuro­degenerative disorders as long as 10 years after a diagnosis of RBD.

In a study by Iranzo et al,¹⁴ patients with MSA were noted to have more severe RBD compared with PD patients. Severity is illus­trated by greater periodic leg movements during sleep (P = .001), less total sleep time (P = .023), longer sleep onset latency (P = .023), and a higher percentage of REM sleep without atonia (RSWA, P = .001). McCarter et al¹⁵ also noted a higher inci­dence of RSWA in patients with MSA.

Patients with MSA might therefore be more likely to exhibit difficulty initiating and maintaining sleep and as having RSWA years before the MSA diagnosis.

Several psychotropics (eg, first-generation antipsychotics, tricyclic anti­depressants, lithium, benzodiazepines, carbamazepine, topiramate, and selective serotonin reuptake inhibitors) can cause adverse ocular effects, such as closed-angle glaucoma in predisposed persons and retinopathy.¹⁶ Therefore, it is important for psychiatrists to ask about ocular symptoms because they might be an early sign of auto­nomic dysfunction.

Posner and Schlossman¹⁷ theorized a causal relationship between autonomic dys­function and ocular diseases after studying a group of patients who had intermittent unilateral attacks of iridocyclitis and glau­coma (now known as Posner-Schlossman syndrome). They hypothesized that a cen­tral cause in the hypothalamus, combined with underlying autonomic dysregulation, could cause the intermittent attacks.

Gherghel et al¹⁸ noted a significant differ­ence in ocular blood flow and blood pres­sure in patients with primary open-angle glaucoma (POAG) compared with con­trols. Patients with POAG did not show an increase in blood pressure or ocular blood flow when challenged by cold water, which should have increased their sympathetic activity. Gherghel et al¹⁸ concluded that this indicated possible systemic autonomic dys­function in patients with POAG. In a study by Fischer et al,¹⁹ MSA patients also were noted to have significant loss of nasal reti­nal nerve fiber layer thickness vs controls (P < .05), leading to decreased peripheral vision sensitivity.

Bottom Line
Although psychiatric symptoms are not part of the diagnostic criteria for multiple system atrophy (MSA), they may serve as a clue to consider when they occur with other MSA symptoms. Evaluate the importance of psychiatric symptoms in terms of the whole picture of the patient. Although the diagnosis might not alter the patient’s course, it can allow family members to understand the patient’s condition and prepare for complications that will arise.

Related Resources
• The MSA Coalition. www.multiplesystematrophy.org.
• National Institute of Neurological Disorders and Stroke. Multiple system atrophy fact sheet. www.ninds.nih.gov/disorders/msa/detailmsa.htm.
• Wenning GK, Fanciulli A, eds. Multiple system atrophy. Vienna, Austria: Springer-Verlag Wien; 2014.

Drug Brand Names
Bupropion • Wellbutrin                Lithium • Eskalith, Lithobid
Carbamazepine • Tegretol           Methylphenidate • Ritalin
Desvenlafaxine • Pristiq              Paroxetine • Paxil
Donepezil • Aricept                     Travoprost • Travatan
Escitalopram • Lexapro               Trazodone • Desyrel, Oleptro
Fludrocortisone • Florinef            Topiramate • Topamax
Fluoxetine • Prozac

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE Light-headed
Mr. M, age 73, is a retired project manager who feels light-headed while walking his dog, causing him to go to the emergency depart­ment. His history is significant for hyperten­sion, coronary artery disease (CAD), 3-vessel coronary artery bypass graft surgery (CABG), hyperlipidemia, erectile dysfunction, open-angle glaucoma, hemiretinal vein occlusion, symptoms suggesting rapid eye-movement behavior disorder (RBD), and major depressive disorder (MDD).

The psychiatry consultation-liaison service is asked to help manage Mr. M’s psychiat­ric medications in the context of orthostatic hypotension and cognitive deficits.

What could be causing Mr. M’s symptoms?
   a) drug adverse effect
   b) progressive cardiovascular disease
   c) MDD
   d) all of the above

HISTORY Depression, heart disease
15 years ago. Mr. M experienced his first major depressive episode. His primary care physician (PCP) commented on a history of falling asleep while driving and 1 episode of sleepwalking. His depression was treated to remission with fluoxetine and methylphenidate (dosages were not recorded), the latter also addressed his falling asleep while driving.

5 years ago. Mr. M had another depres­sive episode characterized by anxiety, difficulty sleeping, and irritability. He also described chest pain; a cardiac work-up revealed extensive CAD, which led to 3-vessel CABG later that year. He also reported dizziness upon standing, which was treated with compression stockings and an increase in sodium intake.

Mr. M continued to express feelings of depression. His cardiologist started him on par­oxetine, 10 mg/d, which he took for 2 months and decided to stop because he felt better. He declined psychiatric referral.

4 years ago. Mr. M’s PCP referred him to a psychiatrist for depressed mood, anhedonia, decreased appetite, decreased energy, and dif­ficulty concentrating. Immediate and delayed recall were found to be intact. The psychiatrist diagnosed MDD and Mr. M started escitalopram, 5 mg/d, titrated to 15 mg/d, and trazodone, 50 mg/d.

After starting treatment, Mr. M reported decreased libido. Sustained-release bupropion, 150 mg/d, was added to boost the effects of escitalopram and counteract sexual side effects.

At follow-up, Mr. M reported that his depres­sive symptoms and libido had improved, but that he had been experiencing unsteady gait when getting out of his car, which he had been noticing “for a while”—before he began trazo­done. Mr. M was referred to his PCP, who attrib­uted his symptoms to orthostasis. No treatment was indicated at the time because Mr. M’s light­headedness had resolved.

3 years ago. Mr. M reported a syncopal attack and continued “dizziness.” His PCP pre­scribed fludrocortisone, 0.1 mg/d, later to be dosed 0.2 mg/d, and symptoms improved.

Although Mr. M had a history of orthostatic hypotension, he was later noted to have supine hypertension. Mr. M’s PCP was concerned that fludrocortisone could be causing the supine hypertension but that decreasing the dosage would cause his orthostatic hypotension to return.

The PCP also was concerned that the psy­chiatric medications (escitalopram, trazodone, and bupropion) could be causing orthostasis. There was discussion among Mr. M, his PCP, and his psychiatrist of stopping the psycho­tropics to see if the symptoms would remit; however, because of concerns about Mr. M’s depression, the medications were continued. Mr. M monitored his blood pressure at home and was referred to a neurologist for work-up of potential autonomic dysfunction.

Shortly afterward, Mr. M reported intermit­tent difficulty keeping track of his thoughts and finishing sentences. His psychiatrist ordered an MRI, which showed chronic small vessel ischemic changes, and started him on donepezil, 5 mg/d.

Neuropsychological testing revealed decreased processing speed and poor rec­ognition memory; otherwise, results showed above-average intellectual ability and average or above-average performance in measures of language, attention, visuospatial/construc­tional functions, and executive functions—a pattern typically attributable to psychogenic factors, such as depression.

Mr. M reported to his neurologist that he for­gets directions while driving but can focus bet­ter if he makes a conscious effort. Physical exam was significant hypotension; flat affect; deficits in concentration and short-term recall; mild impairment of Luria motor sequence (com­posed of a go/no-go and a reciprocal motor task); and vertical and horizontal saccades.¹

Mr. M consulted with an ophthalmologist for anterior iridocyclitis and ocular hypertension, which was controlled with travoprost. He con­tinued to experience trouble with his vision and was given a diagnosis of right inferior hemireti­nal vein occlusion, macular edema, and sus­pected glaucoma. Subsequent notes recorded a history of Posner-Schlossman syndrome (a disease characterized by recurrent attacks of increased intraocular pressure in 1 eye with concomitant anterior chamber inflammation). His vision deteriorated until he was diagnosed with ocular hypertension, open-angle glau­coma, and dermatochalasis.

The authors’ observations
Involvement of multiple specialties in a patient’s care brings to question one’s philosophy on medical diagnosis. Interdisciplinary communication would seem to promote the principle of diagnostic parsimony, or Occam’s razor, which sug­gests a unifying diagnosis to explain all of the patient’s symptoms. Lack of communi­cation might favor Hickam’s dictum, which states that “patients can have as many dis­eases as they damn well please.”

HISTORY Low energy, forgetfulness
2 years ago. Mr. M noticed low energy and motivation. He continued to work full-time but thought that it was taking him longer to get work done. He was tapered off escitalo­pram and started on desvenlafaxine, 50 mg/d; donepezil was increased to 10 mg/d.

The syncopal episodes resolved but blood pressure measured at home averaged 150/70 mm Hg. Mr. M was advised to decrease fludrocortisone from 0.2 mg/d to 0.1 mg/d. He tolerated the change and blood pressure measured at home dropped on average to 120 to 130/70 mm Hg.

1 year ago. Mr. M reported that his mem­ory loss had become worse. He perceived hav­ing more stress because of forgetfulness and visual difficulties, which had led him to stop driving at night.

At a follow-up appointment with his psy­chiatrist, Mr. M reported that, first, he had not tapered escitalopram as discussed and, second, he forgot to increase the dosage of desvenlafaxine. A home blood pressure log revealed consistent hypotension; the psychia­trist was concerned that hypotension could be the cause of concentration difficulties and malaise. The psychiatrist advised Mr. M to fol­low-up with his PCP and neurologist.

Current admission. Shortly after the visit to the psychiatrist, Mr. M presented to the emergency department for increased synco­pal events. Work-up was negative for a car­diac cause. A cosyntropin stimulation test was negative, showing that adrenal insufficiency did not cause his orthostatic hypotension. Chart review showed he had been having blood pressure problems for many years, inde­pendent of antidepressants. Physical exam revealed lower extremity ataxia and a bilateral extensor plantar reflex.

What diagnosis explains Mr. M’s symptoms?
   a) Parkinson’s disease
   b) multiple system atrophy (MSA)
   c) depression due to a general medical condition
  d) dementia

The authors’ observations
MSA, previously referred to as Shy-Drager syndrome, is a rare, rapidly progressive neurodegenerative disorder with an esti­mated prevalence of 3.7 cases for every 100,000 people worldwide.² MSA primarily affects middle-aged patients; because it has no cure, most patients die in 7 to 10 years.³

MSA has 2 clinical variants^4,5:
   • parkinsonian type (MSA-P), charac­terized by striatonigral degeneration and increased spasticity
   • cerebellar type (MSA-C), character­ized by more autonomic dysfunction.

MSA has a range of symptoms, mak­ing it a challenging diagnosis (Table).⁶ Although psychiatric symptoms are not part of the diagnostic criteria, they can aid in its diagnosis. In Mr. M’s case, depres­sion, anxiety, orthostatic hypotension, and ataxia support a diagnosis of MSA.

Gilman et al⁶ delineated 3 diagnostic categories for MSA: definite MSA, prob­able MSA, and possible MSA. Clinical cri­teria shared by the 3 diagnostic categories are sporadic and progressive onset after age 30.

Definite MSA requires “neuropathological findings of widespread and abundant CNS alpha-synuclein-positive glial cytoplasmic inclusions,” along with “neurodegenera­tive changes in striatonigral or olivoponto­cerebellar structures” at autopsy.⁶

Probable MSA. Without autopsy findings required for definite MSA, the next most specific diagnostic category is probable MSA. Probable MSA also specifies that the patient show either autonomic fail­ure involving urinary incontinence—this includes erectile dysfunction in men—or, if autonomic failure is absent, orthostatic hypotension within 3 minutes of standing by at least 30 mm Hg systolic pressure or 15 mm Hg diastolic pressure.

Possible MSA has less stringent crite­ria for orthostatic hypotension. The cat­egory includes patients who have only 1 symptom that suggests autonomic failure. Criteria for possible MSA include parkin­sonism or a cerebellar syndrome in addition to symptoms of MSA listed in the Table, whereas probable MSA has specific crite­ria of either a poorly levodopa-responsive parkinsonism (MSA-P) or a cerebellar syn­drome (MSA-C). In addition to having par­kinsonism or a cerebellar syndrome, and 1 sign of autonomic failure or orthostatic hypotension, patients also must have ≥1 additional feature to be assigned a diagno­sis of possible MSA, including:
   • rapidly progressive parkinsonism
   • poor response to levodopa
   • postural instability within 3 years of motor onset
   • gait ataxia, cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction
   • dysphagia within 5 years of motor onset
   • atrophy on MRI of putamen, mid­dle cerebellar peduncle, pons, or cerebellum
   • hypometabolism on fluorodeoxyglucose- PET in putamen, brainstem, or cerebellum.⁶

Diagnosing MSA can be challenging because its features are similar to those of many other disorders. Nonetheless, Gilman et al6 lists specific criteria for prob­able MSA, including autonomic dysfunc­tion, orthostatic hypotension, and either parkinsonism or cerebellar syndrome symptoms. Although a definite MSA diag­nosis only can be made by postmortem brain specimen analysis, Osaki et al⁷ found that a probable MSA diagnosis has a posi­tive predictive value of 92% with a sensi­tivity of 22% for definite MSA.

Mr. M’s symptoms were consistent with a diagnosis of probable MSA, cerebellar type (Figure).

Psychiatric manifestations of MSA
There are a few case reports of depression identified early in patients who were later given a diagnosis of MSA.⁸

Depression. In a study by Benrud-Larson et al⁹ (N = 99), 49% of patients who had MSA reported moderate or severe depres­sion, as indicated by a score of ≥17 on the Beck Depression Inventory (BDI); 80% reported at least mild depression (BDI ≥10, mean 17.0, standard deviation, 8.7).

In a similar study, by Balas et al,¹⁰ depres­sion was reported as a common symptom and was statistically significant in MSA-P patients compared with controls (P = .013).

Anxiety, another symptom that was reported by Mr. M, is another psychiat­ric manifestation described by Balas et al¹⁰ and Chang et al.¹¹ Balas et al¹⁰ noted that MSA-C and MSA-P patients had sig­nificantly more state anxiety (P = .009 and P = .022, respectively) compared with con­trols, although Chang et al¹¹ noted higher anxiety scores in MSA-C patients com­pared with controls and MSA-P patients (P < .01).

Balas et al¹⁰ hypothesized that anxiety and depression contribute to cognitive decline; their study showed that MSA-C patients had difficulty learning new ver­bal information (P < .022) and controlling attention (P < .023). Mr. M exhibited some of these cognitive difficulties in his reports of losing track of conversations, forgetting the topic of a conversation when speaking, trouble focusing, and difficulty concentrat­ing when driving.

Mr. M had depression and anxiety well before onset of autonomic dysfunction (orthostatic hypotension and erectile dys­function), which eventually led to an MSA diagnosis. Psychiatrists should under­stand additional manifestations of MSA so that they can use psychiatric symptoms to identify these conditions in their patients. One of the most well-known and early manifestations of MSA is autonomic dys­function; among men, another early sign is erectile dysfunction.⁶ Our patient also exhibited other less well-known symptoms linked to MSA and autonomic dysregula­tion, including RBD and ocular symptoms (iridocyclitis, glaucoma, decreased visual acuity).

Rapid eye-movement behavior disorder. Psychiatrists should consider screen­ing for RBD during assessment of sleep problems. Identifying RBD is important because early studies have shown a strong association between RBD and develop­ment of a neurodegenerative disorder. Mr. M’s clinicians did not consider RBD, although his symptoms of sleepwalking and falling asleep while driving suggest a possible diagnosis. Also, considering this diagnosis would aid in diagnosing a synu­cleinopathy disorder because a higher incidence of RBD was noted in patients who developed synucleinopathy disor­ders (eg, Parkinson’s disease [PD] and dementia with Lewy bodies [DLB]) com­pared with patients who developed non-synucleinopathies (eg, frontotemporal dementia, corticobasal degeneration, pro­gressive supranuclear palsy, mild cogni­tive impairment, primary progressive aphasia, and posterior cortical atrophy) or tauopathies (eg, Alzheimer’s disease).¹²

Zanigni et al¹³ reported similar findings in a later study that classified patients with RBD as having idiopathic RBD (IRBD) or RBD sec­ondary to an underlying neurodegenerative disorder, particularly an α-synucleinopathy: PD, MSA, and DLB. Most IRBD patients developed 1 of the above mentioned neuro­degenerative disorders as long as 10 years after a diagnosis of RBD.

In a study by Iranzo et al,¹⁴ patients with MSA were noted to have more severe RBD compared with PD patients. Severity is illus­trated by greater periodic leg movements during sleep (P = .001), less total sleep time (P = .023), longer sleep onset latency (P = .023), and a higher percentage of REM sleep without atonia (RSWA, P = .001). McCarter et al¹⁵ also noted a higher inci­dence of RSWA in patients with MSA.

Patients with MSA might therefore be more likely to exhibit difficulty initiating and maintaining sleep and as having RSWA years before the MSA diagnosis.

Several psychotropics (eg, first-generation antipsychotics, tricyclic anti­depressants, lithium, benzodiazepines, carbamazepine, topiramate, and selective serotonin reuptake inhibitors) can cause adverse ocular effects, such as closed-angle glaucoma in predisposed persons and retinopathy.¹⁶ Therefore, it is important for psychiatrists to ask about ocular symptoms because they might be an early sign of auto­nomic dysfunction.

Posner and Schlossman¹⁷ theorized a causal relationship between autonomic dys­function and ocular diseases after studying a group of patients who had intermittent unilateral attacks of iridocyclitis and glau­coma (now known as Posner-Schlossman syndrome). They hypothesized that a cen­tral cause in the hypothalamus, combined with underlying autonomic dysregulation, could cause the intermittent attacks.

Gherghel et al¹⁸ noted a significant differ­ence in ocular blood flow and blood pres­sure in patients with primary open-angle glaucoma (POAG) compared with con­trols. Patients with POAG did not show an increase in blood pressure or ocular blood flow when challenged by cold water, which should have increased their sympathetic activity. Gherghel et al¹⁸ concluded that this indicated possible systemic autonomic dys­function in patients with POAG. In a study by Fischer et al,¹⁹ MSA patients also were noted to have significant loss of nasal reti­nal nerve fiber layer thickness vs controls (P < .05), leading to decreased peripheral vision sensitivity.

Bottom Line
Although psychiatric symptoms are not part of the diagnostic criteria for multiple system atrophy (MSA), they may serve as a clue to consider when they occur with other MSA symptoms. Evaluate the importance of psychiatric symptoms in terms of the whole picture of the patient. Although the diagnosis might not alter the patient’s course, it can allow family members to understand the patient’s condition and prepare for complications that will arise.

Related Resources
• The MSA Coalition. www.multiplesystematrophy.org.
• National Institute of Neurological Disorders and Stroke. Multiple system atrophy fact sheet. www.ninds.nih.gov/disorders/msa/detailmsa.htm.
• Wenning GK, Fanciulli A, eds. Multiple system atrophy. Vienna, Austria: Springer-Verlag Wien; 2014.

Drug Brand Names
Bupropion • Wellbutrin                Lithium • Eskalith, Lithobid
Carbamazepine • Tegretol           Methylphenidate • Ritalin
Desvenlafaxine • Pristiq              Paroxetine • Paxil
Donepezil • Aricept                     Travoprost • Travatan
Escitalopram • Lexapro               Trazodone • Desyrel, Oleptro
Fludrocortisone • Florinef            Topiramate • Topamax
Fluoxetine • Prozac

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.

CASE Light-headed
Mr. M, age 73, is a retired project manager who feels light-headed while walking his dog, causing him to go to the emergency depart­ment. His history is significant for hyperten­sion, coronary artery disease (CAD), 3-vessel coronary artery bypass graft surgery (CABG), hyperlipidemia, erectile dysfunction, open-angle glaucoma, hemiretinal vein occlusion, symptoms suggesting rapid eye-movement behavior disorder (RBD), and major depressive disorder (MDD).

The psychiatry consultation-liaison service is asked to help manage Mr. M’s psychiat­ric medications in the context of orthostatic hypotension and cognitive deficits.

What could be causing Mr. M’s symptoms?
   a) drug adverse effect
   b) progressive cardiovascular disease
   c) MDD
   d) all of the above

HISTORY Depression, heart disease
15 years ago. Mr. M experienced his first major depressive episode. His primary care physician (PCP) commented on a history of falling asleep while driving and 1 episode of sleepwalking. His depression was treated to remission with fluoxetine and methylphenidate (dosages were not recorded), the latter also addressed his falling asleep while driving.

5 years ago. Mr. M had another depres­sive episode characterized by anxiety, difficulty sleeping, and irritability. He also described chest pain; a cardiac work-up revealed extensive CAD, which led to 3-vessel CABG later that year. He also reported dizziness upon standing, which was treated with compression stockings and an increase in sodium intake.

Mr. M continued to express feelings of depression. His cardiologist started him on par­oxetine, 10 mg/d, which he took for 2 months and decided to stop because he felt better. He declined psychiatric referral.

4 years ago. Mr. M’s PCP referred him to a psychiatrist for depressed mood, anhedonia, decreased appetite, decreased energy, and dif­ficulty concentrating. Immediate and delayed recall were found to be intact. The psychiatrist diagnosed MDD and Mr. M started escitalopram, 5 mg/d, titrated to 15 mg/d, and trazodone, 50 mg/d.

After starting treatment, Mr. M reported decreased libido. Sustained-release bupropion, 150 mg/d, was added to boost the effects of escitalopram and counteract sexual side effects.

At follow-up, Mr. M reported that his depres­sive symptoms and libido had improved, but that he had been experiencing unsteady gait when getting out of his car, which he had been noticing “for a while”—before he began trazo­done. Mr. M was referred to his PCP, who attrib­uted his symptoms to orthostasis. No treatment was indicated at the time because Mr. M’s light­headedness had resolved.

3 years ago. Mr. M reported a syncopal attack and continued “dizziness.” His PCP pre­scribed fludrocortisone, 0.1 mg/d, later to be dosed 0.2 mg/d, and symptoms improved.

Although Mr. M had a history of orthostatic hypotension, he was later noted to have supine hypertension. Mr. M’s PCP was concerned that fludrocortisone could be causing the supine hypertension but that decreasing the dosage would cause his orthostatic hypotension to return.

The PCP also was concerned that the psy­chiatric medications (escitalopram, trazodone, and bupropion) could be causing orthostasis. There was discussion among Mr. M, his PCP, and his psychiatrist of stopping the psycho­tropics to see if the symptoms would remit; however, because of concerns about Mr. M’s depression, the medications were continued. Mr. M monitored his blood pressure at home and was referred to a neurologist for work-up of potential autonomic dysfunction.

Shortly afterward, Mr. M reported intermit­tent difficulty keeping track of his thoughts and finishing sentences. His psychiatrist ordered an MRI, which showed chronic small vessel ischemic changes, and started him on donepezil, 5 mg/d.

Neuropsychological testing revealed decreased processing speed and poor rec­ognition memory; otherwise, results showed above-average intellectual ability and average or above-average performance in measures of language, attention, visuospatial/construc­tional functions, and executive functions—a pattern typically attributable to psychogenic factors, such as depression.

Mr. M reported to his neurologist that he for­gets directions while driving but can focus bet­ter if he makes a conscious effort. Physical exam was significant hypotension; flat affect; deficits in concentration and short-term recall; mild impairment of Luria motor sequence (com­posed of a go/no-go and a reciprocal motor task); and vertical and horizontal saccades.¹

Mr. M consulted with an ophthalmologist for anterior iridocyclitis and ocular hypertension, which was controlled with travoprost. He con­tinued to experience trouble with his vision and was given a diagnosis of right inferior hemireti­nal vein occlusion, macular edema, and sus­pected glaucoma. Subsequent notes recorded a history of Posner-Schlossman syndrome (a disease characterized by recurrent attacks of increased intraocular pressure in 1 eye with concomitant anterior chamber inflammation). His vision deteriorated until he was diagnosed with ocular hypertension, open-angle glau­coma, and dermatochalasis.

The authors’ observations
Involvement of multiple specialties in a patient’s care brings to question one’s philosophy on medical diagnosis. Interdisciplinary communication would seem to promote the principle of diagnostic parsimony, or Occam’s razor, which sug­gests a unifying diagnosis to explain all of the patient’s symptoms. Lack of communi­cation might favor Hickam’s dictum, which states that “patients can have as many dis­eases as they damn well please.”

HISTORY Low energy, forgetfulness
2 years ago. Mr. M noticed low energy and motivation. He continued to work full-time but thought that it was taking him longer to get work done. He was tapered off escitalo­pram and started on desvenlafaxine, 50 mg/d; donepezil was increased to 10 mg/d.

The syncopal episodes resolved but blood pressure measured at home averaged 150/70 mm Hg. Mr. M was advised to decrease fludrocortisone from 0.2 mg/d to 0.1 mg/d. He tolerated the change and blood pressure measured at home dropped on average to 120 to 130/70 mm Hg.

1 year ago. Mr. M reported that his mem­ory loss had become worse. He perceived hav­ing more stress because of forgetfulness and visual difficulties, which had led him to stop driving at night.

At a follow-up appointment with his psy­chiatrist, Mr. M reported that, first, he had not tapered escitalopram as discussed and, second, he forgot to increase the dosage of desvenlafaxine. A home blood pressure log revealed consistent hypotension; the psychia­trist was concerned that hypotension could be the cause of concentration difficulties and malaise. The psychiatrist advised Mr. M to fol­low-up with his PCP and neurologist.

Current admission. Shortly after the visit to the psychiatrist, Mr. M presented to the emergency department for increased synco­pal events. Work-up was negative for a car­diac cause. A cosyntropin stimulation test was negative, showing that adrenal insufficiency did not cause his orthostatic hypotension. Chart review showed he had been having blood pressure problems for many years, inde­pendent of antidepressants. Physical exam revealed lower extremity ataxia and a bilateral extensor plantar reflex.

What diagnosis explains Mr. M’s symptoms?
   a) Parkinson’s disease
   b) multiple system atrophy (MSA)
   c) depression due to a general medical condition
  d) dementia

The authors’ observations
MSA, previously referred to as Shy-Drager syndrome, is a rare, rapidly progressive neurodegenerative disorder with an esti­mated prevalence of 3.7 cases for every 100,000 people worldwide.² MSA primarily affects middle-aged patients; because it has no cure, most patients die in 7 to 10 years.³

MSA has 2 clinical variants^4,5:
   • parkinsonian type (MSA-P), charac­terized by striatonigral degeneration and increased spasticity
   • cerebellar type (MSA-C), character­ized by more autonomic dysfunction.

MSA has a range of symptoms, mak­ing it a challenging diagnosis (Table).⁶ Although psychiatric symptoms are not part of the diagnostic criteria, they can aid in its diagnosis. In Mr. M’s case, depres­sion, anxiety, orthostatic hypotension, and ataxia support a diagnosis of MSA.

Gilman et al⁶ delineated 3 diagnostic categories for MSA: definite MSA, prob­able MSA, and possible MSA. Clinical cri­teria shared by the 3 diagnostic categories are sporadic and progressive onset after age 30.

Definite MSA requires “neuropathological findings of widespread and abundant CNS alpha-synuclein-positive glial cytoplasmic inclusions,” along with “neurodegenera­tive changes in striatonigral or olivoponto­cerebellar structures” at autopsy.⁶

Probable MSA. Without autopsy findings required for definite MSA, the next most specific diagnostic category is probable MSA. Probable MSA also specifies that the patient show either autonomic fail­ure involving urinary incontinence—this includes erectile dysfunction in men—or, if autonomic failure is absent, orthostatic hypotension within 3 minutes of standing by at least 30 mm Hg systolic pressure or 15 mm Hg diastolic pressure.

Possible MSA has less stringent crite­ria for orthostatic hypotension. The cat­egory includes patients who have only 1 symptom that suggests autonomic failure. Criteria for possible MSA include parkin­sonism or a cerebellar syndrome in addition to symptoms of MSA listed in the Table, whereas probable MSA has specific crite­ria of either a poorly levodopa-responsive parkinsonism (MSA-P) or a cerebellar syn­drome (MSA-C). In addition to having par­kinsonism or a cerebellar syndrome, and 1 sign of autonomic failure or orthostatic hypotension, patients also must have ≥1 additional feature to be assigned a diagno­sis of possible MSA, including:
   • rapidly progressive parkinsonism
   • poor response to levodopa
   • postural instability within 3 years of motor onset
   • gait ataxia, cerebellar dysarthria, limb ataxia, or cerebellar oculomotor dysfunction
   • dysphagia within 5 years of motor onset
   • atrophy on MRI of putamen, mid­dle cerebellar peduncle, pons, or cerebellum
   • hypometabolism on fluorodeoxyglucose- PET in putamen, brainstem, or cerebellum.⁶

Diagnosing MSA can be challenging because its features are similar to those of many other disorders. Nonetheless, Gilman et al6 lists specific criteria for prob­able MSA, including autonomic dysfunc­tion, orthostatic hypotension, and either parkinsonism or cerebellar syndrome symptoms. Although a definite MSA diag­nosis only can be made by postmortem brain specimen analysis, Osaki et al⁷ found that a probable MSA diagnosis has a posi­tive predictive value of 92% with a sensi­tivity of 22% for definite MSA.

Mr. M’s symptoms were consistent with a diagnosis of probable MSA, cerebellar type (Figure).

Psychiatric manifestations of MSA
There are a few case reports of depression identified early in patients who were later given a diagnosis of MSA.⁸

Depression. In a study by Benrud-Larson et al⁹ (N = 99), 49% of patients who had MSA reported moderate or severe depres­sion, as indicated by a score of ≥17 on the Beck Depression Inventory (BDI); 80% reported at least mild depression (BDI ≥10, mean 17.0, standard deviation, 8.7).

In a similar study, by Balas et al,¹⁰ depres­sion was reported as a common symptom and was statistically significant in MSA-P patients compared with controls (P = .013).

Anxiety, another symptom that was reported by Mr. M, is another psychiat­ric manifestation described by Balas et al¹⁰ and Chang et al.¹¹ Balas et al¹⁰ noted that MSA-C and MSA-P patients had sig­nificantly more state anxiety (P = .009 and P = .022, respectively) compared with con­trols, although Chang et al¹¹ noted higher anxiety scores in MSA-C patients com­pared with controls and MSA-P patients (P < .01).

Balas et al¹⁰ hypothesized that anxiety and depression contribute to cognitive decline; their study showed that MSA-C patients had difficulty learning new ver­bal information (P < .022) and controlling attention (P < .023). Mr. M exhibited some of these cognitive difficulties in his reports of losing track of conversations, forgetting the topic of a conversation when speaking, trouble focusing, and difficulty concentrat­ing when driving.

Mr. M had depression and anxiety well before onset of autonomic dysfunction (orthostatic hypotension and erectile dys­function), which eventually led to an MSA diagnosis. Psychiatrists should under­stand additional manifestations of MSA so that they can use psychiatric symptoms to identify these conditions in their patients. One of the most well-known and early manifestations of MSA is autonomic dys­function; among men, another early sign is erectile dysfunction.⁶ Our patient also exhibited other less well-known symptoms linked to MSA and autonomic dysregula­tion, including RBD and ocular symptoms (iridocyclitis, glaucoma, decreased visual acuity).

Rapid eye-movement behavior disorder. Psychiatrists should consider screen­ing for RBD during assessment of sleep problems. Identifying RBD is important because early studies have shown a strong association between RBD and develop­ment of a neurodegenerative disorder. Mr. M’s clinicians did not consider RBD, although his symptoms of sleepwalking and falling asleep while driving suggest a possible diagnosis. Also, considering this diagnosis would aid in diagnosing a synu­cleinopathy disorder because a higher incidence of RBD was noted in patients who developed synucleinopathy disor­ders (eg, Parkinson’s disease [PD] and dementia with Lewy bodies [DLB]) com­pared with patients who developed non-synucleinopathies (eg, frontotemporal dementia, corticobasal degeneration, pro­gressive supranuclear palsy, mild cogni­tive impairment, primary progressive aphasia, and posterior cortical atrophy) or tauopathies (eg, Alzheimer’s disease).¹²

Zanigni et al¹³ reported similar findings in a later study that classified patients with RBD as having idiopathic RBD (IRBD) or RBD sec­ondary to an underlying neurodegenerative disorder, particularly an α-synucleinopathy: PD, MSA, and DLB. Most IRBD patients developed 1 of the above mentioned neuro­degenerative disorders as long as 10 years after a diagnosis of RBD.

In a study by Iranzo et al,¹⁴ patients with MSA were noted to have more severe RBD compared with PD patients. Severity is illus­trated by greater periodic leg movements during sleep (P = .001), less total sleep time (P = .023), longer sleep onset latency (P = .023), and a higher percentage of REM sleep without atonia (RSWA, P = .001). McCarter et al¹⁵ also noted a higher inci­dence of RSWA in patients with MSA.

Patients with MSA might therefore be more likely to exhibit difficulty initiating and maintaining sleep and as having RSWA years before the MSA diagnosis.

Several psychotropics (eg, first-generation antipsychotics, tricyclic anti­depressants, lithium, benzodiazepines, carbamazepine, topiramate, and selective serotonin reuptake inhibitors) can cause adverse ocular effects, such as closed-angle glaucoma in predisposed persons and retinopathy.¹⁶ Therefore, it is important for psychiatrists to ask about ocular symptoms because they might be an early sign of auto­nomic dysfunction.

Posner and Schlossman¹⁷ theorized a causal relationship between autonomic dys­function and ocular diseases after studying a group of patients who had intermittent unilateral attacks of iridocyclitis and glau­coma (now known as Posner-Schlossman syndrome). They hypothesized that a cen­tral cause in the hypothalamus, combined with underlying autonomic dysregulation, could cause the intermittent attacks.

Gherghel et al¹⁸ noted a significant differ­ence in ocular blood flow and blood pres­sure in patients with primary open-angle glaucoma (POAG) compared with con­trols. Patients with POAG did not show an increase in blood pressure or ocular blood flow when challenged by cold water, which should have increased their sympathetic activity. Gherghel et al¹⁸ concluded that this indicated possible systemic autonomic dys­function in patients with POAG. In a study by Fischer et al,¹⁹ MSA patients also were noted to have significant loss of nasal reti­nal nerve fiber layer thickness vs controls (P < .05), leading to decreased peripheral vision sensitivity.

Bottom Line
Although psychiatric symptoms are not part of the diagnostic criteria for multiple system atrophy (MSA), they may serve as a clue to consider when they occur with other MSA symptoms. Evaluate the importance of psychiatric symptoms in terms of the whole picture of the patient. Although the diagnosis might not alter the patient’s course, it can allow family members to understand the patient’s condition and prepare for complications that will arise.

Related Resources
• The MSA Coalition. www.multiplesystematrophy.org.
• National Institute of Neurological Disorders and Stroke. Multiple system atrophy fact sheet. www.ninds.nih.gov/disorders/msa/detailmsa.htm.
• Wenning GK, Fanciulli A, eds. Multiple system atrophy. Vienna, Austria: Springer-Verlag Wien; 2014.

Drug Brand Names
Bupropion • Wellbutrin                Lithium • Eskalith, Lithobid
Carbamazepine • Tegretol           Methylphenidate • Ritalin
Desvenlafaxine • Pristiq              Paroxetine • Paxil
Donepezil • Aricept                     Travoprost • Travatan
Escitalopram • Lexapro               Trazodone • Desyrel, Oleptro
Fludrocortisone • Florinef            Topiramate • Topamax
Fluoxetine • Prozac

Disclosures
The authors report no financial relationships with any company whose products are mentioned in this article or with manufacturers of competing products.