High-dose cyclophosphamide is safe and effective when given as prophylaxis for chronic graft-versus-host disease (GVHD) to patients who have undergone transplantation of mobilized blood cells, finds a phase 2 trial reported in Blood.

Investigators led by Dr. Marco Mielcarek, medical director of the Adult Blood and Marrow Transplant Program and an oncologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington, enrolled in the trial 43 patients with high-risk hematologic malignancies.

The patients underwent myeloablative conditioning followed by transplantation with growth factor–mobilized blood cells from related or unrelated donors, and were given high-dose cyclophosphamide on two early posttransplantation days.

Main results showed that the cumulative 1-year incidence of chronic GVHD was 16%, less than half of the roughly 35% seen historically with conventional immunosuppression.

Moreover, cyclophosphamide did not appear to compromise engraftment or control of the underlying malignancy. Only a single patient, one with an HLA-mismatched donor, had failure of primary engraftment; after amendment of the protocol to require HLA matching, there were no additional cases. Just 17% of patients experienced a recurrence of their malignancy by 2 years.

Taken together, the findings suggest that high-dose cyclophosphamide—as combined with two myeloablative conditioning options (to accommodate different malignancies) and with posttransplantation cyclosporine (to reduce the risk of acute GVHD)—may eliminate most of the drawbacks to using mobilized blood cells for transplantation, according to the investigators.

“If these findings are confirmed in future studies, HLA-matched mobilized blood cell transplantation may gain even greater acceptance and further replace marrow as a source of stem cells for most indications,” they maintain.

The patients studied had a median age of 43 years, and slightly more than half were in remission without minimal residual disease.

Blood cells were mobilized with granulocyte colony-stimulating factor (G-CSF). Overall, 28% of patients received grafts from related donors, while 72% received grafts from unrelated donors.

For pretransplant conditioning, patients received fludarabine and targeted busulfan, or total body irradiation with use of a minimum dose of 12 Gy.

The patients were given cyclophosphamide at 50 mg/kg per day on days 3 and 4 after transplantation. This was followed by cyclosporine starting on day 5.

The cumulative 1-year incidence of chronic GVHD as defined by National Institutes of Health criteria (i.e., that requiring systemic immunosuppressive therapy)—the trial’s primary endpoint—was 16%, which fell just short of the goal of 15% the investigators were aiming for (Blood. 2016;127:1502-8). Analyses failed to identify any predictors of this outcome.

Although the estimated cumulative incidence of grade 2 acute GVHD was high, at 77%, none of the patients developed grade 3 or 4 acute GVHD, according to the investigators, who disclosed that they had no competing financial interests.

The single patient who experienced failure of primary engraftment had familial myelodysplastic syndrome and had received a graft from an HLA A-antigen–mismatched unrelated donor.

The 2-year cumulative incidence of nonrelapse mortality was 14%, and the 2-year cumulative incidence of recurrent malignancy was 17%. Projected overall survival was 70%.

Among the 42 patients having at least a year of follow-up, 50% were alive and free of relapse without any systemic immunosuppression at 1 year after transplantation.

High-dose cyclophosphamide is safe and effective when given as prophylaxis for chronic graft-versus-host disease (GVHD) to patients who have undergone transplantation of mobilized blood cells, finds a phase 2 trial reported in Blood.

Investigators led by Dr. Marco Mielcarek, medical director of the Adult Blood and Marrow Transplant Program and an oncologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington, enrolled in the trial 43 patients with high-risk hematologic malignancies.

The patients underwent myeloablative conditioning followed by transplantation with growth factor–mobilized blood cells from related or unrelated donors, and were given high-dose cyclophosphamide on two early posttransplantation days.

Main results showed that the cumulative 1-year incidence of chronic GVHD was 16%, less than half of the roughly 35% seen historically with conventional immunosuppression.

Moreover, cyclophosphamide did not appear to compromise engraftment or control of the underlying malignancy. Only a single patient, one with an HLA-mismatched donor, had failure of primary engraftment; after amendment of the protocol to require HLA matching, there were no additional cases. Just 17% of patients experienced a recurrence of their malignancy by 2 years.

Taken together, the findings suggest that high-dose cyclophosphamide—as combined with two myeloablative conditioning options (to accommodate different malignancies) and with posttransplantation cyclosporine (to reduce the risk of acute GVHD)—may eliminate most of the drawbacks to using mobilized blood cells for transplantation, according to the investigators.

“If these findings are confirmed in future studies, HLA-matched mobilized blood cell transplantation may gain even greater acceptance and further replace marrow as a source of stem cells for most indications,” they maintain.

The patients studied had a median age of 43 years, and slightly more than half were in remission without minimal residual disease.

Blood cells were mobilized with granulocyte colony-stimulating factor (G-CSF). Overall, 28% of patients received grafts from related donors, while 72% received grafts from unrelated donors.

For pretransplant conditioning, patients received fludarabine and targeted busulfan, or total body irradiation with use of a minimum dose of 12 Gy.

The patients were given cyclophosphamide at 50 mg/kg per day on days 3 and 4 after transplantation. This was followed by cyclosporine starting on day 5.

The cumulative 1-year incidence of chronic GVHD as defined by National Institutes of Health criteria (i.e., that requiring systemic immunosuppressive therapy)—the trial’s primary endpoint—was 16%, which fell just short of the goal of 15% the investigators were aiming for (Blood. 2016;127:1502-8). Analyses failed to identify any predictors of this outcome.

Although the estimated cumulative incidence of grade 2 acute GVHD was high, at 77%, none of the patients developed grade 3 or 4 acute GVHD, according to the investigators, who disclosed that they had no competing financial interests.

The single patient who experienced failure of primary engraftment had familial myelodysplastic syndrome and had received a graft from an HLA A-antigen–mismatched unrelated donor.

The 2-year cumulative incidence of nonrelapse mortality was 14%, and the 2-year cumulative incidence of recurrent malignancy was 17%. Projected overall survival was 70%.

Among the 42 patients having at least a year of follow-up, 50% were alive and free of relapse without any systemic immunosuppression at 1 year after transplantation.

High-dose cyclophosphamide is safe and effective when given as prophylaxis for chronic graft-versus-host disease (GVHD) to patients who have undergone transplantation of mobilized blood cells, finds a phase 2 trial reported in Blood.

Investigators led by Dr. Marco Mielcarek, medical director of the Adult Blood and Marrow Transplant Program and an oncologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington, enrolled in the trial 43 patients with high-risk hematologic malignancies.

The patients underwent myeloablative conditioning followed by transplantation with growth factor–mobilized blood cells from related or unrelated donors, and were given high-dose cyclophosphamide on two early posttransplantation days.

Main results showed that the cumulative 1-year incidence of chronic GVHD was 16%, less than half of the roughly 35% seen historically with conventional immunosuppression.

Moreover, cyclophosphamide did not appear to compromise engraftment or control of the underlying malignancy. Only a single patient, one with an HLA-mismatched donor, had failure of primary engraftment; after amendment of the protocol to require HLA matching, there were no additional cases. Just 17% of patients experienced a recurrence of their malignancy by 2 years.

Taken together, the findings suggest that high-dose cyclophosphamide—as combined with two myeloablative conditioning options (to accommodate different malignancies) and with posttransplantation cyclosporine (to reduce the risk of acute GVHD)—may eliminate most of the drawbacks to using mobilized blood cells for transplantation, according to the investigators.

“If these findings are confirmed in future studies, HLA-matched mobilized blood cell transplantation may gain even greater acceptance and further replace marrow as a source of stem cells for most indications,” they maintain.

The patients studied had a median age of 43 years, and slightly more than half were in remission without minimal residual disease.

Blood cells were mobilized with granulocyte colony-stimulating factor (G-CSF). Overall, 28% of patients received grafts from related donors, while 72% received grafts from unrelated donors.

For pretransplant conditioning, patients received fludarabine and targeted busulfan, or total body irradiation with use of a minimum dose of 12 Gy.

The patients were given cyclophosphamide at 50 mg/kg per day on days 3 and 4 after transplantation. This was followed by cyclosporine starting on day 5.

The cumulative 1-year incidence of chronic GVHD as defined by National Institutes of Health criteria (i.e., that requiring systemic immunosuppressive therapy)—the trial’s primary endpoint—was 16%, which fell just short of the goal of 15% the investigators were aiming for (Blood. 2016;127:1502-8). Analyses failed to identify any predictors of this outcome.

Although the estimated cumulative incidence of grade 2 acute GVHD was high, at 77%, none of the patients developed grade 3 or 4 acute GVHD, according to the investigators, who disclosed that they had no competing financial interests.

The single patient who experienced failure of primary engraftment had familial myelodysplastic syndrome and had received a graft from an HLA A-antigen–mismatched unrelated donor.

The 2-year cumulative incidence of nonrelapse mortality was 14%, and the 2-year cumulative incidence of recurrent malignancy was 17%. Projected overall survival was 70%.

Among the 42 patients having at least a year of follow-up, 50% were alive and free of relapse without any systemic immunosuppression at 1 year after transplantation.

CHICAGO – The severity of heart failure in the setting of acute myocardial infarction predicts long-term cardiovascular death risk, according to a post hoc analysis of data from the IMPROVE IT Trial.

Among 11,185 individuals with MI and known Killip Classification who were part of that randomized, double-blind trial, those with Killip Class II or greater had more than double the risk of long-term cardiovascular death, compared with those with Killip Class I heart failure, Dr Michael G. Silverman, a cardiovascular medicine fellow at Brigham and Women’s Hospital, Boston and a research fellow at the Thrombolysis in MI (TIMI) Study Group reported in a poster at the annual meeting of the American College of Cardiology.

After adjusting for a number of factors, including age, gender, diabetes, hypertension, left ventricular ejection fraction (LVEF), beta blocker and ACE inhibitor/angiotensin receptor blocker use at randomization, and percutaneous coronary intervention at the index event, the 7-year event rate was 14.5% among those with Killip Class II or higher vs. 5.7% those with Killip Class I heart failure (adjusted hazard ratio, 1.9), Dr. Silverman reported on behalf of the TIMI Study Group.

The event rates from 30 days to 6 months were 4.85% and 1.25% in the groups, respectively (adjusted hazard ratio, 1.96), and from 6 months to 7 years they were 1.52% and 0.61%, in the groups, respectively, (adjusted hazard ratio, 1.85).

Further, the increased risk of cardiovascular death associated with Killip Class II or higher was also apparent among important subgroups, including those with ST Segment Elevation MI, those with non-STEMI, those with LVEF of 50 or greater, those with LVEF less than 50, those with diabetes, those without diabetes, men, and women (adjusted hazard ratios ranging from 1.6 to 2.1), Dr Silverman explained in an interview.

The severity of heart failure according to Killip Class is a strong independent predictor of mortality in the setting of acute MI, and the current findings demonstrate that it also predicts cardiovascular death for at least 7 years, suggesting a need for careful attention to the findings of the physical exam in AMI, as it can serve as an important biomarker of long-term cardiovascular death risk, he said.

“AMI patients with Killip Class II or greater warrant continued close medical follow-up and adherence to guideline -directed medial therapy beyond the acute hospitalization to prevent this potentially modifiable outcome,” he concluded.

Dr. Silverman reported having no disclosures.

[email protected]

CHICAGO – The severity of heart failure in the setting of acute myocardial infarction predicts long-term cardiovascular death risk, according to a post hoc analysis of data from the IMPROVE IT Trial.

Among 11,185 individuals with MI and known Killip Classification who were part of that randomized, double-blind trial, those with Killip Class II or greater had more than double the risk of long-term cardiovascular death, compared with those with Killip Class I heart failure, Dr Michael G. Silverman, a cardiovascular medicine fellow at Brigham and Women’s Hospital, Boston and a research fellow at the Thrombolysis in MI (TIMI) Study Group reported in a poster at the annual meeting of the American College of Cardiology.

After adjusting for a number of factors, including age, gender, diabetes, hypertension, left ventricular ejection fraction (LVEF), beta blocker and ACE inhibitor/angiotensin receptor blocker use at randomization, and percutaneous coronary intervention at the index event, the 7-year event rate was 14.5% among those with Killip Class II or higher vs. 5.7% those with Killip Class I heart failure (adjusted hazard ratio, 1.9), Dr. Silverman reported on behalf of the TIMI Study Group.

The event rates from 30 days to 6 months were 4.85% and 1.25% in the groups, respectively (adjusted hazard ratio, 1.96), and from 6 months to 7 years they were 1.52% and 0.61%, in the groups, respectively, (adjusted hazard ratio, 1.85).

Further, the increased risk of cardiovascular death associated with Killip Class II or higher was also apparent among important subgroups, including those with ST Segment Elevation MI, those with non-STEMI, those with LVEF of 50 or greater, those with LVEF less than 50, those with diabetes, those without diabetes, men, and women (adjusted hazard ratios ranging from 1.6 to 2.1), Dr Silverman explained in an interview.

The severity of heart failure according to Killip Class is a strong independent predictor of mortality in the setting of acute MI, and the current findings demonstrate that it also predicts cardiovascular death for at least 7 years, suggesting a need for careful attention to the findings of the physical exam in AMI, as it can serve as an important biomarker of long-term cardiovascular death risk, he said.

“AMI patients with Killip Class II or greater warrant continued close medical follow-up and adherence to guideline -directed medial therapy beyond the acute hospitalization to prevent this potentially modifiable outcome,” he concluded.

Dr. Silverman reported having no disclosures.

[email protected]

CHICAGO – The severity of heart failure in the setting of acute myocardial infarction predicts long-term cardiovascular death risk, according to a post hoc analysis of data from the IMPROVE IT Trial.

Among 11,185 individuals with MI and known Killip Classification who were part of that randomized, double-blind trial, those with Killip Class II or greater had more than double the risk of long-term cardiovascular death, compared with those with Killip Class I heart failure, Dr Michael G. Silverman, a cardiovascular medicine fellow at Brigham and Women’s Hospital, Boston and a research fellow at the Thrombolysis in MI (TIMI) Study Group reported in a poster at the annual meeting of the American College of Cardiology.

After adjusting for a number of factors, including age, gender, diabetes, hypertension, left ventricular ejection fraction (LVEF), beta blocker and ACE inhibitor/angiotensin receptor blocker use at randomization, and percutaneous coronary intervention at the index event, the 7-year event rate was 14.5% among those with Killip Class II or higher vs. 5.7% those with Killip Class I heart failure (adjusted hazard ratio, 1.9), Dr. Silverman reported on behalf of the TIMI Study Group.

The event rates from 30 days to 6 months were 4.85% and 1.25% in the groups, respectively (adjusted hazard ratio, 1.96), and from 6 months to 7 years they were 1.52% and 0.61%, in the groups, respectively, (adjusted hazard ratio, 1.85).

Further, the increased risk of cardiovascular death associated with Killip Class II or higher was also apparent among important subgroups, including those with ST Segment Elevation MI, those with non-STEMI, those with LVEF of 50 or greater, those with LVEF less than 50, those with diabetes, those without diabetes, men, and women (adjusted hazard ratios ranging from 1.6 to 2.1), Dr Silverman explained in an interview.

The severity of heart failure according to Killip Class is a strong independent predictor of mortality in the setting of acute MI, and the current findings demonstrate that it also predicts cardiovascular death for at least 7 years, suggesting a need for careful attention to the findings of the physical exam in AMI, as it can serve as an important biomarker of long-term cardiovascular death risk, he said.

“AMI patients with Killip Class II or greater warrant continued close medical follow-up and adherence to guideline -directed medial therapy beyond the acute hospitalization to prevent this potentially modifiable outcome,” he concluded.

Dr. Silverman reported having no disclosures.

[email protected]

CHICAGO – The HOPE-3 trial has brought the primary prevention of cardiovascular disease front-and-center as a hot topic of discussion at the annual meeting of the American College of Cardiology.

The large, randomized trial provides new evidence of a significant reduction in cardiovascular events in an intermediate-risk population that hasn’t previously been the focus of risk reduction via pharmacotherapy.

The double-blind study randomized nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease to lipid-lowering with rosuvastatin (Crestor) at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke compared with placebo-treated controls. Impressively, the benefit was similar regardless of baseline LDL-cholesterol level; however, only subjects with hypertension benefited from the dual-antihypertensive therapy.

In this interview, Dr. B. Hadley Wilson of the Sanger Clinic in Charlotte, N.C., explains why he considers HOPE-3 to be a giant step forward in preventive cardiolo

[email protected]

CHICAGO – The HOPE-3 trial has brought the primary prevention of cardiovascular disease front-and-center as a hot topic of discussion at the annual meeting of the American College of Cardiology.

The large, randomized trial provides new evidence of a significant reduction in cardiovascular events in an intermediate-risk population that hasn’t previously been the focus of risk reduction via pharmacotherapy.

The double-blind study randomized nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease to lipid-lowering with rosuvastatin (Crestor) at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke compared with placebo-treated controls. Impressively, the benefit was similar regardless of baseline LDL-cholesterol level; however, only subjects with hypertension benefited from the dual-antihypertensive therapy.

In this interview, Dr. B. Hadley Wilson of the Sanger Clinic in Charlotte, N.C., explains why he considers HOPE-3 to be a giant step forward in preventive cardiolo

[email protected]

CHICAGO – The HOPE-3 trial has brought the primary prevention of cardiovascular disease front-and-center as a hot topic of discussion at the annual meeting of the American College of Cardiology.

The large, randomized trial provides new evidence of a significant reduction in cardiovascular events in an intermediate-risk population that hasn’t previously been the focus of risk reduction via pharmacotherapy.

The double-blind study randomized nearly 13,000 intermediate-risk men and women with no baseline cardiovascular disease to lipid-lowering with rosuvastatin (Crestor) at 10 mg/day or placebo, dual-antihypertensive therapy with candesartan plus chlorothiazide or placebo regardless of baseline blood pressure, or all three drugs or placebo. After a median of 5.6 years, the combined-therapy group had a 29% reduction in the composite of cardiovascular death or nonfatal MI or stroke compared with placebo-treated controls. Impressively, the benefit was similar regardless of baseline LDL-cholesterol level; however, only subjects with hypertension benefited from the dual-antihypertensive therapy.

In this interview, Dr. B. Hadley Wilson of the Sanger Clinic in Charlotte, N.C., explains why he considers HOPE-3 to be a giant step forward in preventive cardiolo

[email protected]

Yesterday, my secretary passed a message that someone from television had called with a question. Not knowing what to expect, but trying to be helpful, I returned the call that afternoon.

The fellow was nice enough, and explained he worked for a marketing company. A vitamin company had hired him to promote an over-the-counter supplement to treat Alzheimer’s disease, and he was looking for a neurologist to endorse it in an infomercial. He said I’d be compensated $5,000-$10,000 for the spot.

That’s a pretty decent chunk of change. I could use it. For a few seconds I hemmed and hawed, trying to think of a way to rationalize it. Then I realized ... I just couldn’t. I politely told him “No,” and got off the phone.

I know they’ll find someone to do it. But I just can’t. I’m sure they have some data to back it up, but crappy research papers are a dime a dozen.

I spend a lot of time explaining studies and data to those affected by this terrible disease. I’m trying to help them work their way through a maze of tests, treatments of limited benefit, and reasonable expectations.

Sadly, as with all tragic and incurable diseases, there’s no shortage of hucksters trying to take advantage of the desperate. Part of my job is to help people understand this. They bring in ads from magazines and newspaper promising miracle cures for a host of awful illnesses. I can’t stop them from buying it, but I want to do my best to warn them it’s a scam.

I can’t do that if I switch sides. Once I start plugging non–FDA-approved, non–clinically meaningful junk on late-night TV, I’ve joined the snake-oil salesmen of yesteryear.

I owe my patients better than that. They trust me to help them and to do what’s right.

Like everyone else, I don’t have a perfect reputation, but outside of my online reviews, I think I’m reasonably well thought of in the local community. A decent reputation takes years to build and one crappy decision to lose. I don’t want to do that either.

And under all that, I still have to believe in myself. That everyday I’m trying to do what’s right for people. Because if I’m not doing that, it’s time to hang up my reflex hammer. The first person I have to face every morning is in the mirror. I want to be able to look at him and still believe he’s doing the best he can for those who need his help.

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

Yesterday, my secretary passed a message that someone from television had called with a question. Not knowing what to expect, but trying to be helpful, I returned the call that afternoon.

The fellow was nice enough, and explained he worked for a marketing company. A vitamin company had hired him to promote an over-the-counter supplement to treat Alzheimer’s disease, and he was looking for a neurologist to endorse it in an infomercial. He said I’d be compensated $5,000-$10,000 for the spot.

That’s a pretty decent chunk of change. I could use it. For a few seconds I hemmed and hawed, trying to think of a way to rationalize it. Then I realized ... I just couldn’t. I politely told him “No,” and got off the phone.

I know they’ll find someone to do it. But I just can’t. I’m sure they have some data to back it up, but crappy research papers are a dime a dozen.

I spend a lot of time explaining studies and data to those affected by this terrible disease. I’m trying to help them work their way through a maze of tests, treatments of limited benefit, and reasonable expectations.

Sadly, as with all tragic and incurable diseases, there’s no shortage of hucksters trying to take advantage of the desperate. Part of my job is to help people understand this. They bring in ads from magazines and newspaper promising miracle cures for a host of awful illnesses. I can’t stop them from buying it, but I want to do my best to warn them it’s a scam.

I can’t do that if I switch sides. Once I start plugging non–FDA-approved, non–clinically meaningful junk on late-night TV, I’ve joined the snake-oil salesmen of yesteryear.

I owe my patients better than that. They trust me to help them and to do what’s right.

Like everyone else, I don’t have a perfect reputation, but outside of my online reviews, I think I’m reasonably well thought of in the local community. A decent reputation takes years to build and one crappy decision to lose. I don’t want to do that either.

And under all that, I still have to believe in myself. That everyday I’m trying to do what’s right for people. Because if I’m not doing that, it’s time to hang up my reflex hammer. The first person I have to face every morning is in the mirror. I want to be able to look at him and still believe he’s doing the best he can for those who need his help.

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

Yesterday, my secretary passed a message that someone from television had called with a question. Not knowing what to expect, but trying to be helpful, I returned the call that afternoon.

The fellow was nice enough, and explained he worked for a marketing company. A vitamin company had hired him to promote an over-the-counter supplement to treat Alzheimer’s disease, and he was looking for a neurologist to endorse it in an infomercial. He said I’d be compensated $5,000-$10,000 for the spot.

That’s a pretty decent chunk of change. I could use it. For a few seconds I hemmed and hawed, trying to think of a way to rationalize it. Then I realized ... I just couldn’t. I politely told him “No,” and got off the phone.

I know they’ll find someone to do it. But I just can’t. I’m sure they have some data to back it up, but crappy research papers are a dime a dozen.

I spend a lot of time explaining studies and data to those affected by this terrible disease. I’m trying to help them work their way through a maze of tests, treatments of limited benefit, and reasonable expectations.

Sadly, as with all tragic and incurable diseases, there’s no shortage of hucksters trying to take advantage of the desperate. Part of my job is to help people understand this. They bring in ads from magazines and newspaper promising miracle cures for a host of awful illnesses. I can’t stop them from buying it, but I want to do my best to warn them it’s a scam.

I can’t do that if I switch sides. Once I start plugging non–FDA-approved, non–clinically meaningful junk on late-night TV, I’ve joined the snake-oil salesmen of yesteryear.

I owe my patients better than that. They trust me to help them and to do what’s right.

Like everyone else, I don’t have a perfect reputation, but outside of my online reviews, I think I’m reasonably well thought of in the local community. A decent reputation takes years to build and one crappy decision to lose. I don’t want to do that either.

And under all that, I still have to believe in myself. That everyday I’m trying to do what’s right for people. Because if I’m not doing that, it’s time to hang up my reflex hammer. The first person I have to face every morning is in the mirror. I want to be able to look at him and still believe he’s doing the best he can for those who need his help.

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

WASHINGTON – Another population-based study has found a link between severe psoriasis and kidney disease – this one discovering almost a fivefold increase in the risk of immunoglobulin A nephropathy (IgAN) and a doubling in the risk of glomerular disease.

The findings suggest yet again that psoriasis is a systemic illness, and not something that affects only the skin, Sungat Grewal said at the annual meeting of the American Academy of Dermatology.

©Waldemarus/Thinkstock

“Numerous case reports have generated a hypothesis that psoriasis may be associated,” with an increased risk of IgAN, said Ms. Grewal, of the department of dermatology at the University of Pennsylvania, Philadelphia. “Our study is the first to test this, and it supports the notion that this is no coincidence. Now we need further research to determine if this association is due to causality or to a shared pathophysiology.”

The link between psoriasis and kidney disease has long been noted, but the first study formally investigating this association was published in 2013 (BMJ. 2013 Oct;347:f5961). The study, also conducted by University of Pennsylvania investigators, used a large patient database in the United Kingdom, matched about 143,000 patients with psoriasis with up to five controls without psoriasis each, and found the risk of chronic kidney disease was nearly doubled for those with severe psoriasis (hazard ratio, 1.93).

A similar finding emerged from Taiwan in 2015. Using the national healthcare database, researchers matched about 4,600 patients with psoriasis with about 923,000 controls. They found that having severe psoriasis was associated with almost a doubling in the risk of chronic kidney disease (HR, 1.90) and almost a tripling in the risk of end stage renal disease (HR, 2.97), after adjusting for age, gender, comorbidities, and use of nonsteroidal anti-inflammatory drugs (J Dermatol Sci. 2015 Jun;78[3]:232-8).

Ms. Grewal and her coinvestigators used data from The Health Improvement Network in the United Kingdom – the same database used in the 2013 study. The study group comprised 206,000 patients with psoriasis and about 1 million controls.

In the overall group of patients, the risk of IgAN was not significantly increased. Nor was there a significant overall association with glomerular disease. And when the group was divided by disease severity, there were no significant associations with either IgAN or glomerular disease in the group with mild psoriasis.

Among those with severe psoriasis, however, the risk of IgAN was almost five times higher (HR, 4.75) and the risk of glomerular disease was doubled (HR, 2.05).

But although the hazard ratios look impressive, the clinical reality shouldn’t spark too much concern, Ms. Grewal said. “To keep things in context, it’s very important to remember that the excess risk of nephropathy attributed to severe psoriasis was still quite small – similar to the chance of a spontaneous pregnancy resulting in triplets.”

Still, she said, the link is intriguing, and something clinicians should keep in mind when managing patients with severe psoriasis.

Ms. Grewal had no financial disclosures. She is a medical student at the Commonwealth Medical College (Scranton, Pa.), and is currently spending a year at the Gelfand Clinical Research Lab at the University of Pennsylvania, Philadelphia.

WASHINGTON – Another population-based study has found a link between severe psoriasis and kidney disease – this one discovering almost a fivefold increase in the risk of immunoglobulin A nephropathy (IgAN) and a doubling in the risk of glomerular disease.

The findings suggest yet again that psoriasis is a systemic illness, and not something that affects only the skin, Sungat Grewal said at the annual meeting of the American Academy of Dermatology.

©Waldemarus/Thinkstock

“Numerous case reports have generated a hypothesis that psoriasis may be associated,” with an increased risk of IgAN, said Ms. Grewal, of the department of dermatology at the University of Pennsylvania, Philadelphia. “Our study is the first to test this, and it supports the notion that this is no coincidence. Now we need further research to determine if this association is due to causality or to a shared pathophysiology.”

The link between psoriasis and kidney disease has long been noted, but the first study formally investigating this association was published in 2013 (BMJ. 2013 Oct;347:f5961). The study, also conducted by University of Pennsylvania investigators, used a large patient database in the United Kingdom, matched about 143,000 patients with psoriasis with up to five controls without psoriasis each, and found the risk of chronic kidney disease was nearly doubled for those with severe psoriasis (hazard ratio, 1.93).

A similar finding emerged from Taiwan in 2015. Using the national healthcare database, researchers matched about 4,600 patients with psoriasis with about 923,000 controls. They found that having severe psoriasis was associated with almost a doubling in the risk of chronic kidney disease (HR, 1.90) and almost a tripling in the risk of end stage renal disease (HR, 2.97), after adjusting for age, gender, comorbidities, and use of nonsteroidal anti-inflammatory drugs (J Dermatol Sci. 2015 Jun;78[3]:232-8).

Ms. Grewal and her coinvestigators used data from The Health Improvement Network in the United Kingdom – the same database used in the 2013 study. The study group comprised 206,000 patients with psoriasis and about 1 million controls.

In the overall group of patients, the risk of IgAN was not significantly increased. Nor was there a significant overall association with glomerular disease. And when the group was divided by disease severity, there were no significant associations with either IgAN or glomerular disease in the group with mild psoriasis.

Among those with severe psoriasis, however, the risk of IgAN was almost five times higher (HR, 4.75) and the risk of glomerular disease was doubled (HR, 2.05).

But although the hazard ratios look impressive, the clinical reality shouldn’t spark too much concern, Ms. Grewal said. “To keep things in context, it’s very important to remember that the excess risk of nephropathy attributed to severe psoriasis was still quite small – similar to the chance of a spontaneous pregnancy resulting in triplets.”

Still, she said, the link is intriguing, and something clinicians should keep in mind when managing patients with severe psoriasis.

Ms. Grewal had no financial disclosures. She is a medical student at the Commonwealth Medical College (Scranton, Pa.), and is currently spending a year at the Gelfand Clinical Research Lab at the University of Pennsylvania, Philadelphia.

WASHINGTON – Another population-based study has found a link between severe psoriasis and kidney disease – this one discovering almost a fivefold increase in the risk of immunoglobulin A nephropathy (IgAN) and a doubling in the risk of glomerular disease.

The findings suggest yet again that psoriasis is a systemic illness, and not something that affects only the skin, Sungat Grewal said at the annual meeting of the American Academy of Dermatology.

©Waldemarus/Thinkstock

“Numerous case reports have generated a hypothesis that psoriasis may be associated,” with an increased risk of IgAN, said Ms. Grewal, of the department of dermatology at the University of Pennsylvania, Philadelphia. “Our study is the first to test this, and it supports the notion that this is no coincidence. Now we need further research to determine if this association is due to causality or to a shared pathophysiology.”

The link between psoriasis and kidney disease has long been noted, but the first study formally investigating this association was published in 2013 (BMJ. 2013 Oct;347:f5961). The study, also conducted by University of Pennsylvania investigators, used a large patient database in the United Kingdom, matched about 143,000 patients with psoriasis with up to five controls without psoriasis each, and found the risk of chronic kidney disease was nearly doubled for those with severe psoriasis (hazard ratio, 1.93).

A similar finding emerged from Taiwan in 2015. Using the national healthcare database, researchers matched about 4,600 patients with psoriasis with about 923,000 controls. They found that having severe psoriasis was associated with almost a doubling in the risk of chronic kidney disease (HR, 1.90) and almost a tripling in the risk of end stage renal disease (HR, 2.97), after adjusting for age, gender, comorbidities, and use of nonsteroidal anti-inflammatory drugs (J Dermatol Sci. 2015 Jun;78[3]:232-8).

Ms. Grewal and her coinvestigators used data from The Health Improvement Network in the United Kingdom – the same database used in the 2013 study. The study group comprised 206,000 patients with psoriasis and about 1 million controls.

In the overall group of patients, the risk of IgAN was not significantly increased. Nor was there a significant overall association with glomerular disease. And when the group was divided by disease severity, there were no significant associations with either IgAN or glomerular disease in the group with mild psoriasis.

Among those with severe psoriasis, however, the risk of IgAN was almost five times higher (HR, 4.75) and the risk of glomerular disease was doubled (HR, 2.05).

But although the hazard ratios look impressive, the clinical reality shouldn’t spark too much concern, Ms. Grewal said. “To keep things in context, it’s very important to remember that the excess risk of nephropathy attributed to severe psoriasis was still quite small – similar to the chance of a spontaneous pregnancy resulting in triplets.”

Still, she said, the link is intriguing, and something clinicians should keep in mind when managing patients with severe psoriasis.

Ms. Grewal had no financial disclosures. She is a medical student at the Commonwealth Medical College (Scranton, Pa.), and is currently spending a year at the Gelfand Clinical Research Lab at the University of Pennsylvania, Philadelphia.

WASHINGTON – Another population-based study has found a link between severe psoriasis and kidney disease – this one discovering almost a fivefold increase in the risk of immunoglobulin A nephropathy (IgAN) and a doubling in the risk of glomerular disease.

The findings suggest yet again that psoriasis is a systemic illness, and not something that affects only the skin, Sungat Grewal said at the annual meeting of the American Academy of Dermatology.

©Waldemarus/Thinkstock

“Numerous case reports have generated a hypothesis that psoriasis may be associated,” with an increased risk of IgAN, said Ms. Grewal, of the department of dermatology at the University of Pennsylvania, Philadelphia. “Our study is the first to test this, and it supports the notion that this is no coincidence. Now we need further research to determine if this association is due to causality or to a shared pathophysiology.”

The link between psoriasis and kidney disease has long been noted, but the first study formally investigating this association was published in 2013 (BMJ. 2013 Oct;347:f5961). The study, also conducted by University of Pennsylvania investigators, used a large patient database in the United Kingdom, matched about 143,000 patients with psoriasis with up to five controls without psoriasis each, and found the risk of chronic kidney disease was nearly doubled for those with severe psoriasis (hazard ratio, 1.93).

A similar finding emerged from Taiwan in 2015. Using the national healthcare database, researchers matched about 4,600 patients with psoriasis with about 923,000 controls. They found that having severe psoriasis was associated with almost a doubling in the risk of chronic kidney disease (HR, 1.90) and almost a tripling in the risk of end stage renal disease (HR, 2.97), after adjusting for age, gender, comorbidities, and use of nonsteroidal anti-inflammatory drugs (J Dermatol Sci. 2015 Jun;78[3]:232-8).

Ms. Grewal and her coinvestigators used data from The Health Improvement Network in the United Kingdom – the same database used in the 2013 study. The study group comprised 206,000 patients with psoriasis and about 1 million controls.

In the overall group of patients, the risk of IgAN was not significantly increased. Nor was there a significant overall association with glomerular disease. And when the group was divided by disease severity, there were no significant associations with either IgAN or glomerular disease in the group with mild psoriasis.

Among those with severe psoriasis, however, the risk of IgAN was almost five times higher (HR, 4.75) and the risk of glomerular disease was doubled (HR, 2.05).

But although the hazard ratios look impressive, the clinical reality shouldn’t spark too much concern, Ms. Grewal said. “To keep things in context, it’s very important to remember that the excess risk of nephropathy attributed to severe psoriasis was still quite small – similar to the chance of a spontaneous pregnancy resulting in triplets.”

Still, she said, the link is intriguing, and something clinicians should keep in mind when managing patients with severe psoriasis.

Ms. Grewal had no financial disclosures. She is a medical student at the Commonwealth Medical College (Scranton, Pa.), and is currently spending a year at the Gelfand Clinical Research Lab at the University of Pennsylvania, Philadelphia.

[email protected]

WASHINGTON – Another population-based study has found a link between severe psoriasis and kidney disease – this one discovering almost a fivefold increase in the risk of immunoglobulin A nephropathy (IgAN) and a doubling in the risk of glomerular disease.

The findings suggest yet again that psoriasis is a systemic illness, and not something that affects only the skin, Sungat Grewal said at the annual meeting of the American Academy of Dermatology.

©Waldemarus/Thinkstock

“Numerous case reports have generated a hypothesis that psoriasis may be associated,” with an increased risk of IgAN, said Ms. Grewal, of the department of dermatology at the University of Pennsylvania, Philadelphia. “Our study is the first to test this, and it supports the notion that this is no coincidence. Now we need further research to determine if this association is due to causality or to a shared pathophysiology.”

The link between psoriasis and kidney disease has long been noted, but the first study formally investigating this association was published in 2013 (BMJ. 2013 Oct;347:f5961). The study, also conducted by University of Pennsylvania investigators, used a large patient database in the United Kingdom, matched about 143,000 patients with psoriasis with up to five controls without psoriasis each, and found the risk of chronic kidney disease was nearly doubled for those with severe psoriasis (hazard ratio, 1.93).

A similar finding emerged from Taiwan in 2015. Using the national healthcare database, researchers matched about 4,600 patients with psoriasis with about 923,000 controls. They found that having severe psoriasis was associated with almost a doubling in the risk of chronic kidney disease (HR, 1.90) and almost a tripling in the risk of end stage renal disease (HR, 2.97), after adjusting for age, gender, comorbidities, and use of nonsteroidal anti-inflammatory drugs (J Dermatol Sci. 2015 Jun;78[3]:232-8).

Ms. Grewal and her coinvestigators used data from The Health Improvement Network in the United Kingdom – the same database used in the 2013 study. The study group comprised 206,000 patients with psoriasis and about 1 million controls.

In the overall group of patients, the risk of IgAN was not significantly increased. Nor was there a significant overall association with glomerular disease. And when the group was divided by disease severity, there were no significant associations with either IgAN or glomerular disease in the group with mild psoriasis.

Among those with severe psoriasis, however, the risk of IgAN was almost five times higher (HR, 4.75) and the risk of glomerular disease was doubled (HR, 2.05).

But although the hazard ratios look impressive, the clinical reality shouldn’t spark too much concern, Ms. Grewal said. “To keep things in context, it’s very important to remember that the excess risk of nephropathy attributed to severe psoriasis was still quite small – similar to the chance of a spontaneous pregnancy resulting in triplets.”

Still, she said, the link is intriguing, and something clinicians should keep in mind when managing patients with severe psoriasis.

Ms. Grewal had no financial disclosures. She is a medical student at the Commonwealth Medical College (Scranton, Pa.), and is currently spending a year at the Gelfand Clinical Research Lab at the University of Pennsylvania, Philadelphia.

[email protected]

WASHINGTON – Another population-based study has found a link between severe psoriasis and kidney disease – this one discovering almost a fivefold increase in the risk of immunoglobulin A nephropathy (IgAN) and a doubling in the risk of glomerular disease.

The findings suggest yet again that psoriasis is a systemic illness, and not something that affects only the skin, Sungat Grewal said at the annual meeting of the American Academy of Dermatology.

©Waldemarus/Thinkstock

“Numerous case reports have generated a hypothesis that psoriasis may be associated,” with an increased risk of IgAN, said Ms. Grewal, of the department of dermatology at the University of Pennsylvania, Philadelphia. “Our study is the first to test this, and it supports the notion that this is no coincidence. Now we need further research to determine if this association is due to causality or to a shared pathophysiology.”

The link between psoriasis and kidney disease has long been noted, but the first study formally investigating this association was published in 2013 (BMJ. 2013 Oct;347:f5961). The study, also conducted by University of Pennsylvania investigators, used a large patient database in the United Kingdom, matched about 143,000 patients with psoriasis with up to five controls without psoriasis each, and found the risk of chronic kidney disease was nearly doubled for those with severe psoriasis (hazard ratio, 1.93).

A similar finding emerged from Taiwan in 2015. Using the national healthcare database, researchers matched about 4,600 patients with psoriasis with about 923,000 controls. They found that having severe psoriasis was associated with almost a doubling in the risk of chronic kidney disease (HR, 1.90) and almost a tripling in the risk of end stage renal disease (HR, 2.97), after adjusting for age, gender, comorbidities, and use of nonsteroidal anti-inflammatory drugs (J Dermatol Sci. 2015 Jun;78[3]:232-8).

Ms. Grewal and her coinvestigators used data from The Health Improvement Network in the United Kingdom – the same database used in the 2013 study. The study group comprised 206,000 patients with psoriasis and about 1 million controls.

In the overall group of patients, the risk of IgAN was not significantly increased. Nor was there a significant overall association with glomerular disease. And when the group was divided by disease severity, there were no significant associations with either IgAN or glomerular disease in the group with mild psoriasis.

Among those with severe psoriasis, however, the risk of IgAN was almost five times higher (HR, 4.75) and the risk of glomerular disease was doubled (HR, 2.05).

But although the hazard ratios look impressive, the clinical reality shouldn’t spark too much concern, Ms. Grewal said. “To keep things in context, it’s very important to remember that the excess risk of nephropathy attributed to severe psoriasis was still quite small – similar to the chance of a spontaneous pregnancy resulting in triplets.”

Still, she said, the link is intriguing, and something clinicians should keep in mind when managing patients with severe psoriasis.

Ms. Grewal had no financial disclosures. She is a medical student at the Commonwealth Medical College (Scranton, Pa.), and is currently spending a year at the Gelfand Clinical Research Lab at the University of Pennsylvania, Philadelphia.

[email protected]

MADRID – Untreated people at high risk for developing psychosis also showed an increased prevalence of certain components of metabolic syndrome in data collected from 163 German study participants, a finding that gives new insight into the well-documented but poorly delineated link between schizophrenia and metabolic syndrome.

“The findings point out that a high risk for schizophrenia implies a certain risk for patients to develop metabolic syndrome independent of treatment effects,” said Dr. Joachim Cordes, a psychiatrist at the LVR Clinic of the Heinrich-Heine University in Düsseldorf, Germany. He assumed that genetic factors underlie the shared risk some people face for both developing schizophrenia and metabolic syndrome. “I think there is a direct connection between schizophrenia and metabolic syndrome, an inherent factor like a genetic factor,” Dr. Cordes said in an interview. This understanding should influence how patients with newly diagnosed schizophrenia or those at risk for psychosis are managed, he added.

Dr. Cordes’s report was one of several at the meeting sponsored by the European Psychiatric Association that examined different facets of the complex links that tie schizophrenia to metabolic syndrome, an association that already had lots of evidence, including a recent meta-analysis (Schizophr Bull. 2013 March;39[2]:306-18).

He used data collected on 163 people enrolled in the PREVENT study and at high risk for a first psychotic episode. Run at nine German centers, PREVENT primarily tested very early intervention with drug and behavioral therapy to improve outcomes. Dr. Cordes took data collected from these prepsychosis, high-risk patients to assess their prevalence of metabolic syndrome and of the various individual features that define metabolic syndrome, using a definition published by the American Heart Association and the U.S. National Heart, Lung, and Blood Institute (Circulation. 2005 Oct 18;112[17]:2735-52). He compared these metabolic syndrome rates with the general German population, using data from 35,869 randomly selected German adults in more than 1,500 German primary care practices, the German Metabolic and Cardiovascular Risk Project (GEMCAS).

The findings showed a 9.2% prevalence of metabolic syndrome in the prepsychosis group and a 7.4% rate among the general adult population, Dr. Cordes reported. Among men in the prepsychosis group, the metabolic syndrome definers with the largest increments in prevalence were low HDL, in 21% of the prepsychosis people and in 12% of the general population, and elevated blood glucose in 11%, compared with 6%. Among women, the metabolic syndrome definers with the greatest between-group differences were elevated waist circumference, in 30% of those with prepsychosis, compared with 17% in the general population, and low HDL in 19%, compared with 14%.

This apparently inherent link between a tendency toward psychosis and schizophrenia and a tendency to develop features of metabolic syndrome suggests that patients with newly diagnosed schizophrenia need a preventive approach to weight management, Dr. Cordes said. He also suggested prescribing antipsychotic medications that pose the lowest risk for causing further metabolic derangements in patients.

A second report at the meeting came from an assessment of cognitive function and its relationship to metabolic syndrome in 54 women diagnosed with schizophrenia and on stable treatment. The schizophrenia patients with metabolic syndrome, nearly half of the total group, performed significantly worse than those without metabolic syndrome in tests of verbal memory, executive function, and attention and processing speed, findings that support an increased incidence of selective cognitive impairment in patients with schizophrenia and metabolic syndrome, said Dr. Adela C. Botis, a psychiatrist and researcher at the University of Medicine and Pharmacy in Cluj-Napoca, Romania.

Dr. Botis and her associates studied 54 women diagnosed with schizophrenia who had remitted symptoms for at least 6 months on stable antipsychotic treatment. Using the metabolic syndrome definition of the International Diabetes Federation 25 (46%) had metabolic syndrome, and the other 29 (54%) did not. These numbers document the high prevalence of metabolic syndrome in schizophrenia patients.

A multivariate analysis identified demographic and metabolic factors that significantly linked with decrements in several cognitive domains. Economic status and living situation linked with deficits in verbal memory; elevated systolic blood pressure significantly linked with worsened attention and processing speed; high body mass index linked with loss of motor speed; and less education significantly linked with all these increments as well as four other domains,

A third report used a post-hoc analysis of data from two separate trials to show that treatment with a relatively new antipsychotic drug, lurasidone (Latuda), produced less metabolic syndrome, compared with risperidone or extended-release quetiapine (Seroquel XR), said Dr. Andrei Pikalov, head of global medical affairs at Sunovion Pharmaceuticals, the company that markets Latuda. Lurasidone received approval for treating schizophrenia in 2010.

He took data from two studies designed to assess lurasidone’s efficacy for treating adults with schizophrenia for 12 months, compared with either risperidone in a study with 621 patients, or with quetiapine XR in a study with 292 patients. He applied the same metabolic syndrome definition used by Dr. Cordes to clinical measurements taken at baseline and after 12 months on treatment.

The results showed that treatment with lurasidone produced less than half the rate of new metabolic syndrome cases, compared with risperidone, a statistically significant difference, and less than two-thirds the rate of quetiapine XR, a difference that did not reach statistical significance.

Dr. Cordes said he has been a speaker for Servier. Dr. Botis had no disclosures. Dr. Pikalov is an employee of Sunovion, which markets lurasidone (Latuda).

[email protected]

On Twitter @mitchelzoler

MADRID – Untreated people at high risk for developing psychosis also showed an increased prevalence of certain components of metabolic syndrome in data collected from 163 German study participants, a finding that gives new insight into the well-documented but poorly delineated link between schizophrenia and metabolic syndrome.

“The findings point out that a high risk for schizophrenia implies a certain risk for patients to develop metabolic syndrome independent of treatment effects,” said Dr. Joachim Cordes, a psychiatrist at the LVR Clinic of the Heinrich-Heine University in Düsseldorf, Germany. He assumed that genetic factors underlie the shared risk some people face for both developing schizophrenia and metabolic syndrome. “I think there is a direct connection between schizophrenia and metabolic syndrome, an inherent factor like a genetic factor,” Dr. Cordes said in an interview. This understanding should influence how patients with newly diagnosed schizophrenia or those at risk for psychosis are managed, he added.

Dr. Cordes’s report was one of several at the meeting sponsored by the European Psychiatric Association that examined different facets of the complex links that tie schizophrenia to metabolic syndrome, an association that already had lots of evidence, including a recent meta-analysis (Schizophr Bull. 2013 March;39[2]:306-18).

He used data collected on 163 people enrolled in the PREVENT study and at high risk for a first psychotic episode. Run at nine German centers, PREVENT primarily tested very early intervention with drug and behavioral therapy to improve outcomes. Dr. Cordes took data collected from these prepsychosis, high-risk patients to assess their prevalence of metabolic syndrome and of the various individual features that define metabolic syndrome, using a definition published by the American Heart Association and the U.S. National Heart, Lung, and Blood Institute (Circulation. 2005 Oct 18;112[17]:2735-52). He compared these metabolic syndrome rates with the general German population, using data from 35,869 randomly selected German adults in more than 1,500 German primary care practices, the German Metabolic and Cardiovascular Risk Project (GEMCAS).

The findings showed a 9.2% prevalence of metabolic syndrome in the prepsychosis group and a 7.4% rate among the general adult population, Dr. Cordes reported. Among men in the prepsychosis group, the metabolic syndrome definers with the largest increments in prevalence were low HDL, in 21% of the prepsychosis people and in 12% of the general population, and elevated blood glucose in 11%, compared with 6%. Among women, the metabolic syndrome definers with the greatest between-group differences were elevated waist circumference, in 30% of those with prepsychosis, compared with 17% in the general population, and low HDL in 19%, compared with 14%.

This apparently inherent link between a tendency toward psychosis and schizophrenia and a tendency to develop features of metabolic syndrome suggests that patients with newly diagnosed schizophrenia need a preventive approach to weight management, Dr. Cordes said. He also suggested prescribing antipsychotic medications that pose the lowest risk for causing further metabolic derangements in patients.

A second report at the meeting came from an assessment of cognitive function and its relationship to metabolic syndrome in 54 women diagnosed with schizophrenia and on stable treatment. The schizophrenia patients with metabolic syndrome, nearly half of the total group, performed significantly worse than those without metabolic syndrome in tests of verbal memory, executive function, and attention and processing speed, findings that support an increased incidence of selective cognitive impairment in patients with schizophrenia and metabolic syndrome, said Dr. Adela C. Botis, a psychiatrist and researcher at the University of Medicine and Pharmacy in Cluj-Napoca, Romania.

Dr. Botis and her associates studied 54 women diagnosed with schizophrenia who had remitted symptoms for at least 6 months on stable antipsychotic treatment. Using the metabolic syndrome definition of the International Diabetes Federation 25 (46%) had metabolic syndrome, and the other 29 (54%) did not. These numbers document the high prevalence of metabolic syndrome in schizophrenia patients.

A multivariate analysis identified demographic and metabolic factors that significantly linked with decrements in several cognitive domains. Economic status and living situation linked with deficits in verbal memory; elevated systolic blood pressure significantly linked with worsened attention and processing speed; high body mass index linked with loss of motor speed; and less education significantly linked with all these increments as well as four other domains,

A third report used a post-hoc analysis of data from two separate trials to show that treatment with a relatively new antipsychotic drug, lurasidone (Latuda), produced less metabolic syndrome, compared with risperidone or extended-release quetiapine (Seroquel XR), said Dr. Andrei Pikalov, head of global medical affairs at Sunovion Pharmaceuticals, the company that markets Latuda. Lurasidone received approval for treating schizophrenia in 2010.

He took data from two studies designed to assess lurasidone’s efficacy for treating adults with schizophrenia for 12 months, compared with either risperidone in a study with 621 patients, or with quetiapine XR in a study with 292 patients. He applied the same metabolic syndrome definition used by Dr. Cordes to clinical measurements taken at baseline and after 12 months on treatment.

The results showed that treatment with lurasidone produced less than half the rate of new metabolic syndrome cases, compared with risperidone, a statistically significant difference, and less than two-thirds the rate of quetiapine XR, a difference that did not reach statistical significance.

Dr. Cordes said he has been a speaker for Servier. Dr. Botis had no disclosures. Dr. Pikalov is an employee of Sunovion, which markets lurasidone (Latuda).

[email protected]

On Twitter @mitchelzoler

MADRID – Untreated people at high risk for developing psychosis also showed an increased prevalence of certain components of metabolic syndrome in data collected from 163 German study participants, a finding that gives new insight into the well-documented but poorly delineated link between schizophrenia and metabolic syndrome.

“The findings point out that a high risk for schizophrenia implies a certain risk for patients to develop metabolic syndrome independent of treatment effects,” said Dr. Joachim Cordes, a psychiatrist at the LVR Clinic of the Heinrich-Heine University in Düsseldorf, Germany. He assumed that genetic factors underlie the shared risk some people face for both developing schizophrenia and metabolic syndrome. “I think there is a direct connection between schizophrenia and metabolic syndrome, an inherent factor like a genetic factor,” Dr. Cordes said in an interview. This understanding should influence how patients with newly diagnosed schizophrenia or those at risk for psychosis are managed, he added.

Dr. Cordes’s report was one of several at the meeting sponsored by the European Psychiatric Association that examined different facets of the complex links that tie schizophrenia to metabolic syndrome, an association that already had lots of evidence, including a recent meta-analysis (Schizophr Bull. 2013 March;39[2]:306-18).

He used data collected on 163 people enrolled in the PREVENT study and at high risk for a first psychotic episode. Run at nine German centers, PREVENT primarily tested very early intervention with drug and behavioral therapy to improve outcomes. Dr. Cordes took data collected from these prepsychosis, high-risk patients to assess their prevalence of metabolic syndrome and of the various individual features that define metabolic syndrome, using a definition published by the American Heart Association and the U.S. National Heart, Lung, and Blood Institute (Circulation. 2005 Oct 18;112[17]:2735-52). He compared these metabolic syndrome rates with the general German population, using data from 35,869 randomly selected German adults in more than 1,500 German primary care practices, the German Metabolic and Cardiovascular Risk Project (GEMCAS).

The findings showed a 9.2% prevalence of metabolic syndrome in the prepsychosis group and a 7.4% rate among the general adult population, Dr. Cordes reported. Among men in the prepsychosis group, the metabolic syndrome definers with the largest increments in prevalence were low HDL, in 21% of the prepsychosis people and in 12% of the general population, and elevated blood glucose in 11%, compared with 6%. Among women, the metabolic syndrome definers with the greatest between-group differences were elevated waist circumference, in 30% of those with prepsychosis, compared with 17% in the general population, and low HDL in 19%, compared with 14%.

This apparently inherent link between a tendency toward psychosis and schizophrenia and a tendency to develop features of metabolic syndrome suggests that patients with newly diagnosed schizophrenia need a preventive approach to weight management, Dr. Cordes said. He also suggested prescribing antipsychotic medications that pose the lowest risk for causing further metabolic derangements in patients.

A second report at the meeting came from an assessment of cognitive function and its relationship to metabolic syndrome in 54 women diagnosed with schizophrenia and on stable treatment. The schizophrenia patients with metabolic syndrome, nearly half of the total group, performed significantly worse than those without metabolic syndrome in tests of verbal memory, executive function, and attention and processing speed, findings that support an increased incidence of selective cognitive impairment in patients with schizophrenia and metabolic syndrome, said Dr. Adela C. Botis, a psychiatrist and researcher at the University of Medicine and Pharmacy in Cluj-Napoca, Romania.

Dr. Botis and her associates studied 54 women diagnosed with schizophrenia who had remitted symptoms for at least 6 months on stable antipsychotic treatment. Using the metabolic syndrome definition of the International Diabetes Federation 25 (46%) had metabolic syndrome, and the other 29 (54%) did not. These numbers document the high prevalence of metabolic syndrome in schizophrenia patients.

A multivariate analysis identified demographic and metabolic factors that significantly linked with decrements in several cognitive domains. Economic status and living situation linked with deficits in verbal memory; elevated systolic blood pressure significantly linked with worsened attention and processing speed; high body mass index linked with loss of motor speed; and less education significantly linked with all these increments as well as four other domains,

A third report used a post-hoc analysis of data from two separate trials to show that treatment with a relatively new antipsychotic drug, lurasidone (Latuda), produced less metabolic syndrome, compared with risperidone or extended-release quetiapine (Seroquel XR), said Dr. Andrei Pikalov, head of global medical affairs at Sunovion Pharmaceuticals, the company that markets Latuda. Lurasidone received approval for treating schizophrenia in 2010.

He took data from two studies designed to assess lurasidone’s efficacy for treating adults with schizophrenia for 12 months, compared with either risperidone in a study with 621 patients, or with quetiapine XR in a study with 292 patients. He applied the same metabolic syndrome definition used by Dr. Cordes to clinical measurements taken at baseline and after 12 months on treatment.

The results showed that treatment with lurasidone produced less than half the rate of new metabolic syndrome cases, compared with risperidone, a statistically significant difference, and less than two-thirds the rate of quetiapine XR, a difference that did not reach statistical significance.

Dr. Cordes said he has been a speaker for Servier. Dr. Botis had no disclosures. Dr. Pikalov is an employee of Sunovion, which markets lurasidone (Latuda).

[email protected]

On Twitter @mitchelzoler

BOSTON – The longer that estrogen therapy is delayed in girls with Turner syndrome, the lower their bone density will be in subsequent years, based on results of a retrospective, cross-sectional study from Monash University, in Melbourne, Australia.

For every year after age 11 that Turner patients went without estrogen – generally due to delayed initiation, but sometimes noncompliance – there was a significant reduction in bone mineral density in both the lumbar spine (Beta -0.582, P less than 0.001) and femoral neck (Beta -0.383, P = 0.008).

Estrogen deficiency and subsequent suboptimal bone mass accrual are known to contribute to the increased risk of osteoporosis in women with Turner syndrome, and about a doubling of the risk of fragility fractures, mostly of the forearm. About a third of the 76 women in the study had at least one fracture, explained investigator Dr. Amanda Vincent, head of the Midlife Health and Menopause Program at Monash.

“Avoiding estrogen deficiency is important to optimize bone health in Turner syndrome.” It “depends on early diagnosis, age-appropriate pubertal induction, and optimization of compliance,” Dr. Vincent said at the Endocrine Society annual meeting.

The median age of Turner syndrome diagnosis was 11 years, but estrogen treatments didn’t begin until a median age of 15. The women in the study were a median of about 30 years old, which means that they were adolescents at the time when estrogen treatment was often delayed in the mistaken belief that growth hormone therapy would be more effective before puberty was induced.

It’s now known that estrogen replacement works synergistically with, and even potentiates, the effects of growth hormone. Current guidelines recommend pubertal induction by age 13 (J Clin Endocrinol Metab. 2007 Jan;92(1):10-25).

The women had at least one dual-energy x-ray absorptiometry scan at Monash since 1998. Z-scores below - 2, indicating low bone density, were found in the lumbar spines of about a quarter the subjects, and in the femoral necks of about 8%. Primary amenorrhea and premature menopause, followed by vitamin D deficiency, were the most common risk factors for low bone mass. Almost 40% of the women reported non-continuous use of estrogen. About half had undergone growth hormone therapy.

At a median height of 149 cm, the subjects were about 15 cm shorter than age-matched, healthy controls, and also had a slightly higher median body mass index of 25.6 kg/m². Lumbar spine bone area, bone mineral content, areal bone mineral density, and bone mineral apparent density were significantly lower in Turner syndrome patients. In the femoral neck, areal bone mineral density was significantly lower.

There was no relationship between bone markers and growth hormone use or Turner syndrome karyotype; the predominant karyotype was 45XO, but the study also included mosaic karyotypes.

The investigators had no disclosures.

[email protected]

BOSTON – The longer that estrogen therapy is delayed in girls with Turner syndrome, the lower their bone density will be in subsequent years, based on results of a retrospective, cross-sectional study from Monash University, in Melbourne, Australia.

For every year after age 11 that Turner patients went without estrogen – generally due to delayed initiation, but sometimes noncompliance – there was a significant reduction in bone mineral density in both the lumbar spine (Beta -0.582, P less than 0.001) and femoral neck (Beta -0.383, P = 0.008).

Estrogen deficiency and subsequent suboptimal bone mass accrual are known to contribute to the increased risk of osteoporosis in women with Turner syndrome, and about a doubling of the risk of fragility fractures, mostly of the forearm. About a third of the 76 women in the study had at least one fracture, explained investigator Dr. Amanda Vincent, head of the Midlife Health and Menopause Program at Monash.

“Avoiding estrogen deficiency is important to optimize bone health in Turner syndrome.” It “depends on early diagnosis, age-appropriate pubertal induction, and optimization of compliance,” Dr. Vincent said at the Endocrine Society annual meeting.

The median age of Turner syndrome diagnosis was 11 years, but estrogen treatments didn’t begin until a median age of 15. The women in the study were a median of about 30 years old, which means that they were adolescents at the time when estrogen treatment was often delayed in the mistaken belief that growth hormone therapy would be more effective before puberty was induced.

It’s now known that estrogen replacement works synergistically with, and even potentiates, the effects of growth hormone. Current guidelines recommend pubertal induction by age 13 (J Clin Endocrinol Metab. 2007 Jan;92(1):10-25).

The women had at least one dual-energy x-ray absorptiometry scan at Monash since 1998. Z-scores below - 2, indicating low bone density, were found in the lumbar spines of about a quarter the subjects, and in the femoral necks of about 8%. Primary amenorrhea and premature menopause, followed by vitamin D deficiency, were the most common risk factors for low bone mass. Almost 40% of the women reported non-continuous use of estrogen. About half had undergone growth hormone therapy.

At a median height of 149 cm, the subjects were about 15 cm shorter than age-matched, healthy controls, and also had a slightly higher median body mass index of 25.6 kg/m². Lumbar spine bone area, bone mineral content, areal bone mineral density, and bone mineral apparent density were significantly lower in Turner syndrome patients. In the femoral neck, areal bone mineral density was significantly lower.

There was no relationship between bone markers and growth hormone use or Turner syndrome karyotype; the predominant karyotype was 45XO, but the study also included mosaic karyotypes.

The investigators had no disclosures.

[email protected]

BOSTON – The longer that estrogen therapy is delayed in girls with Turner syndrome, the lower their bone density will be in subsequent years, based on results of a retrospective, cross-sectional study from Monash University, in Melbourne, Australia.

For every year after age 11 that Turner patients went without estrogen – generally due to delayed initiation, but sometimes noncompliance – there was a significant reduction in bone mineral density in both the lumbar spine (Beta -0.582, P less than 0.001) and femoral neck (Beta -0.383, P = 0.008).

Estrogen deficiency and subsequent suboptimal bone mass accrual are known to contribute to the increased risk of osteoporosis in women with Turner syndrome, and about a doubling of the risk of fragility fractures, mostly of the forearm. About a third of the 76 women in the study had at least one fracture, explained investigator Dr. Amanda Vincent, head of the Midlife Health and Menopause Program at Monash.

“Avoiding estrogen deficiency is important to optimize bone health in Turner syndrome.” It “depends on early diagnosis, age-appropriate pubertal induction, and optimization of compliance,” Dr. Vincent said at the Endocrine Society annual meeting.

The median age of Turner syndrome diagnosis was 11 years, but estrogen treatments didn’t begin until a median age of 15. The women in the study were a median of about 30 years old, which means that they were adolescents at the time when estrogen treatment was often delayed in the mistaken belief that growth hormone therapy would be more effective before puberty was induced.

It’s now known that estrogen replacement works synergistically with, and even potentiates, the effects of growth hormone. Current guidelines recommend pubertal induction by age 13 (J Clin Endocrinol Metab. 2007 Jan;92(1):10-25).

The women had at least one dual-energy x-ray absorptiometry scan at Monash since 1998. Z-scores below - 2, indicating low bone density, were found in the lumbar spines of about a quarter the subjects, and in the femoral necks of about 8%. Primary amenorrhea and premature menopause, followed by vitamin D deficiency, were the most common risk factors for low bone mass. Almost 40% of the women reported non-continuous use of estrogen. About half had undergone growth hormone therapy.

At a median height of 149 cm, the subjects were about 15 cm shorter than age-matched, healthy controls, and also had a slightly higher median body mass index of 25.6 kg/m². Lumbar spine bone area, bone mineral content, areal bone mineral density, and bone mineral apparent density were significantly lower in Turner syndrome patients. In the femoral neck, areal bone mineral density was significantly lower.

There was no relationship between bone markers and growth hormone use or Turner syndrome karyotype; the predominant karyotype was 45XO, but the study also included mosaic karyotypes.

The investigators had no disclosures.

[email protected]

SAN DIEGO — Hospital medicine’s annual extravaganza nestled into the southwestern corner of the country in March, with a record 4,000 hospitalists and others expanding their knowledge of clinical care, management, leadership, technology, and quality improvement.

They listened, they laughed, they learned.

Read more about the knowledge, experiences hospitalists shared at HM16.

Between the nitty-gritty of the workshops, expert panels, and forums, three high-profile speakers offered broad and insightful perspectives:

• U.S. Surgeon General Vivek Murthy, MD, MBA, a hospitalist by training, on his experiences as a hospitalist and his thoughts on the importance of public health in America;
• New SHM President Brian Harte, MD, SFHM, on the role of hospital medicine in cultivating leadership; and
• Hospitalist pioneer Robert Wachter, MD, MHM, on the future of hospital medicine as it reaches its 20th year since he introduced the term “hospitalist” in a New England Journal of Medicine article.

Dr. Murthy, formerly a hospitalist at Brigham and Women’s Hospital in Boston who in 2009 founded Doctors for America, an organization for healthcare improvement in the U.S., said his career as a hospitalist came as a surprise to him.

“When I was in medical school, I didn’t even know what a hospitalist was,” he said. “When I became a hospitalist, I thought it would be a temporary gig, something I did for a couple of years while I figured out what I really wanted to do. But as it turned out, I really loved what I did as a hospitalist. I love teaching. I love caring for patients. I love being part of a tight-knit team.”

He called good health “the key to opportunity,” explaining health is “intrinsically connected to the American dream.”

Hospitalists can play a role in building a “foundation for health,” he said. Four ingredients to this, he said, are creating a culture in which “healthy is equated with happiness” rather than associated with an attitude of “suck it up and eat your spinach”; changing our environment, such as adding sidewalks to encourage walking, to promote healthy behavior change; focusing on the spirit and mind as well as the body; and cultivating our ability to give and receive kindness, which he called “a source of healing.”

Dr. Harte described hospital medicine as “fertile ground” for leadership development.

“Our day-to-day experiences provide a leadership incubator that really no other specialty can claim,” he said.

He said he hopes that over the next several years, hospitalists and SHM make strides in these areas:

• Continuing and expanding membership;
• Continuing to push members and projects to focus on the Triple Aim, particularly patient- and family-centered care; and
• Better understanding hospitalists’ role in the era of risk.

“We need to clarify our position regarding specialty training and our training programs,” he added.

Dr. Harte recognized that such a discussion can get “difficult and contentious and political,” but that “when we look at what we have to do to be clinically effective, and what our current training programs and family medicine, internal medicine, and pediatrics provide for us, that gap to me only appears to be increasing.”

He said SHM has and will “continue to step up with curricula to fill those gaps.” However, he also said hospitalists “have to question what is the best way to train physicians for the roles of providers in the acute-care setting.”

Dr. Wachter, keeping his tradition of giving the final talk of the four-day conference, retraced the roots and successes of the field over the last 20 years. It was part history lesson, part report card, and part prognostication.

What the field has gotten wrong, so far, amounts to “an amazingly short list,” he said, but it’s not a nonexistent list.

“I think one thing we got wrong was a 7-days-on/7-days-off schedule,” he said, drawing applause. While it might be appealing to a 35-year-old doctor, he added, “I don’t believe this is a viable schedule for a 60-year-old.”

HM modeled itself after its closest cousin, emergency medicine, in which doctors frequently work 10- to 12-hour shifts every other day. Since that every-other-day schedule is not good for continuity, HM essentially strung together shifts for as many consecutive days as possible, leading to the 7-on/7-off. Now, many clinicians won’t consider positions without such a schedule even though it’s not a schedule suitable for everyone.

“I think we’ve shot ourselves in the foot,” he said. “Because what it means is you take all the work that needs to be done and you shove it into a very small amount of space. Therefore, the amount of intensity in that work that you have is, I think, undoable over time. I hope we rethink that.”

He cautioned that SHM is near the age when, all too often, societies begin to be complacent and needs to guard against the instinct to keep doing things as they have always been done.

“We need to instinctively say, ‘Wait a second, am I turning into all of those other societies that have become irrelevant—or less relevant—because of that reflex?’” he questioned.

He predicted that, even though value in care is now becoming an obsession, the digitization of healthcare ultimately will have a deeper impact on medicine.

“You ask me 10 years from now, I’m guessing that the fact that we’ve just gone from analog to digital will have turned out to be a bigger transformation,” he explained. “And the reason I say that is if you look at the history of every other industry that went from analog to digital, eventually the industries got turned upside down.”

Burnout, a prominent topic at the meeting, still doesn’t seem to be worse in hospital medicine than in many other specialties, he said, but it is a concern.

“We need to rethink this. We need to come up with some new practice models using information technology in new ways, collaborating with members of the team in different ways,” he said. “We have to take this issue and figure out a way of solving it.”

Dr. Wachter said hospital medicine needs to keep innovating and finding ways to add value; otherwise, the financial support hospitals give to hospital medicine could begin to shrink.

The field is facing challenges, he said, but he is clearly proud of its accomplishments. He said that before he went out on the stage at an early conference he organized in 1998, during the early days of hospital medicine, his wife asked him, “Are you sure this is a good idea?”

“What I said to her was, ‘It is a good idea, and it will be a good idea if we are successful in recruiting and retaining young people, innovative people who want to change the world,’” he said. “I think we have done that, and I thank all of you for turning this into a good idea.” TH

Thomas R. Collins is a freelance writer in South Florida.

SAN DIEGO — Hospital medicine’s annual extravaganza nestled into the southwestern corner of the country in March, with a record 4,000 hospitalists and others expanding their knowledge of clinical care, management, leadership, technology, and quality improvement.

They listened, they laughed, they learned.

Read more about the knowledge, experiences hospitalists shared at HM16.

Between the nitty-gritty of the workshops, expert panels, and forums, three high-profile speakers offered broad and insightful perspectives:

• U.S. Surgeon General Vivek Murthy, MD, MBA, a hospitalist by training, on his experiences as a hospitalist and his thoughts on the importance of public health in America;
• New SHM President Brian Harte, MD, SFHM, on the role of hospital medicine in cultivating leadership; and
• Hospitalist pioneer Robert Wachter, MD, MHM, on the future of hospital medicine as it reaches its 20th year since he introduced the term “hospitalist” in a New England Journal of Medicine article.

Dr. Murthy, formerly a hospitalist at Brigham and Women’s Hospital in Boston who in 2009 founded Doctors for America, an organization for healthcare improvement in the U.S., said his career as a hospitalist came as a surprise to him.

“When I was in medical school, I didn’t even know what a hospitalist was,” he said. “When I became a hospitalist, I thought it would be a temporary gig, something I did for a couple of years while I figured out what I really wanted to do. But as it turned out, I really loved what I did as a hospitalist. I love teaching. I love caring for patients. I love being part of a tight-knit team.”

He called good health “the key to opportunity,” explaining health is “intrinsically connected to the American dream.”

Hospitalists can play a role in building a “foundation for health,” he said. Four ingredients to this, he said, are creating a culture in which “healthy is equated with happiness” rather than associated with an attitude of “suck it up and eat your spinach”; changing our environment, such as adding sidewalks to encourage walking, to promote healthy behavior change; focusing on the spirit and mind as well as the body; and cultivating our ability to give and receive kindness, which he called “a source of healing.”

Dr. Harte described hospital medicine as “fertile ground” for leadership development.

“Our day-to-day experiences provide a leadership incubator that really no other specialty can claim,” he said.

He said he hopes that over the next several years, hospitalists and SHM make strides in these areas:

• Continuing and expanding membership;
• Continuing to push members and projects to focus on the Triple Aim, particularly patient- and family-centered care; and
• Better understanding hospitalists’ role in the era of risk.

“We need to clarify our position regarding specialty training and our training programs,” he added.

Dr. Harte recognized that such a discussion can get “difficult and contentious and political,” but that “when we look at what we have to do to be clinically effective, and what our current training programs and family medicine, internal medicine, and pediatrics provide for us, that gap to me only appears to be increasing.”

He said SHM has and will “continue to step up with curricula to fill those gaps.” However, he also said hospitalists “have to question what is the best way to train physicians for the roles of providers in the acute-care setting.”

Dr. Wachter, keeping his tradition of giving the final talk of the four-day conference, retraced the roots and successes of the field over the last 20 years. It was part history lesson, part report card, and part prognostication.

What the field has gotten wrong, so far, amounts to “an amazingly short list,” he said, but it’s not a nonexistent list.

“I think one thing we got wrong was a 7-days-on/7-days-off schedule,” he said, drawing applause. While it might be appealing to a 35-year-old doctor, he added, “I don’t believe this is a viable schedule for a 60-year-old.”

HM modeled itself after its closest cousin, emergency medicine, in which doctors frequently work 10- to 12-hour shifts every other day. Since that every-other-day schedule is not good for continuity, HM essentially strung together shifts for as many consecutive days as possible, leading to the 7-on/7-off. Now, many clinicians won’t consider positions without such a schedule even though it’s not a schedule suitable for everyone.

“I think we’ve shot ourselves in the foot,” he said. “Because what it means is you take all the work that needs to be done and you shove it into a very small amount of space. Therefore, the amount of intensity in that work that you have is, I think, undoable over time. I hope we rethink that.”

He cautioned that SHM is near the age when, all too often, societies begin to be complacent and needs to guard against the instinct to keep doing things as they have always been done.

“We need to instinctively say, ‘Wait a second, am I turning into all of those other societies that have become irrelevant—or less relevant—because of that reflex?’” he questioned.

He predicted that, even though value in care is now becoming an obsession, the digitization of healthcare ultimately will have a deeper impact on medicine.

“You ask me 10 years from now, I’m guessing that the fact that we’ve just gone from analog to digital will have turned out to be a bigger transformation,” he explained. “And the reason I say that is if you look at the history of every other industry that went from analog to digital, eventually the industries got turned upside down.”

Burnout, a prominent topic at the meeting, still doesn’t seem to be worse in hospital medicine than in many other specialties, he said, but it is a concern.

“We need to rethink this. We need to come up with some new practice models using information technology in new ways, collaborating with members of the team in different ways,” he said. “We have to take this issue and figure out a way of solving it.”

Dr. Wachter said hospital medicine needs to keep innovating and finding ways to add value; otherwise, the financial support hospitals give to hospital medicine could begin to shrink.

The field is facing challenges, he said, but he is clearly proud of its accomplishments. He said that before he went out on the stage at an early conference he organized in 1998, during the early days of hospital medicine, his wife asked him, “Are you sure this is a good idea?”

“What I said to her was, ‘It is a good idea, and it will be a good idea if we are successful in recruiting and retaining young people, innovative people who want to change the world,’” he said. “I think we have done that, and I thank all of you for turning this into a good idea.” TH

Thomas R. Collins is a freelance writer in South Florida.

SAN DIEGO — Hospital medicine’s annual extravaganza nestled into the southwestern corner of the country in March, with a record 4,000 hospitalists and others expanding their knowledge of clinical care, management, leadership, technology, and quality improvement.

They listened, they laughed, they learned.

Read more about the knowledge, experiences hospitalists shared at HM16.

Between the nitty-gritty of the workshops, expert panels, and forums, three high-profile speakers offered broad and insightful perspectives:

• U.S. Surgeon General Vivek Murthy, MD, MBA, a hospitalist by training, on his experiences as a hospitalist and his thoughts on the importance of public health in America;
• New SHM President Brian Harte, MD, SFHM, on the role of hospital medicine in cultivating leadership; and
• Hospitalist pioneer Robert Wachter, MD, MHM, on the future of hospital medicine as it reaches its 20th year since he introduced the term “hospitalist” in a New England Journal of Medicine article.

Dr. Murthy, formerly a hospitalist at Brigham and Women’s Hospital in Boston who in 2009 founded Doctors for America, an organization for healthcare improvement in the U.S., said his career as a hospitalist came as a surprise to him.

“When I was in medical school, I didn’t even know what a hospitalist was,” he said. “When I became a hospitalist, I thought it would be a temporary gig, something I did for a couple of years while I figured out what I really wanted to do. But as it turned out, I really loved what I did as a hospitalist. I love teaching. I love caring for patients. I love being part of a tight-knit team.”

He called good health “the key to opportunity,” explaining health is “intrinsically connected to the American dream.”

Hospitalists can play a role in building a “foundation for health,” he said. Four ingredients to this, he said, are creating a culture in which “healthy is equated with happiness” rather than associated with an attitude of “suck it up and eat your spinach”; changing our environment, such as adding sidewalks to encourage walking, to promote healthy behavior change; focusing on the spirit and mind as well as the body; and cultivating our ability to give and receive kindness, which he called “a source of healing.”

Dr. Harte described hospital medicine as “fertile ground” for leadership development.

“Our day-to-day experiences provide a leadership incubator that really no other specialty can claim,” he said.

He said he hopes that over the next several years, hospitalists and SHM make strides in these areas:

• Continuing and expanding membership;
• Continuing to push members and projects to focus on the Triple Aim, particularly patient- and family-centered care; and
• Better understanding hospitalists’ role in the era of risk.

“We need to clarify our position regarding specialty training and our training programs,” he added.

Dr. Harte recognized that such a discussion can get “difficult and contentious and political,” but that “when we look at what we have to do to be clinically effective, and what our current training programs and family medicine, internal medicine, and pediatrics provide for us, that gap to me only appears to be increasing.”

He said SHM has and will “continue to step up with curricula to fill those gaps.” However, he also said hospitalists “have to question what is the best way to train physicians for the roles of providers in the acute-care setting.”

Dr. Wachter, keeping his tradition of giving the final talk of the four-day conference, retraced the roots and successes of the field over the last 20 years. It was part history lesson, part report card, and part prognostication.

What the field has gotten wrong, so far, amounts to “an amazingly short list,” he said, but it’s not a nonexistent list.

“I think one thing we got wrong was a 7-days-on/7-days-off schedule,” he said, drawing applause. While it might be appealing to a 35-year-old doctor, he added, “I don’t believe this is a viable schedule for a 60-year-old.”

HM modeled itself after its closest cousin, emergency medicine, in which doctors frequently work 10- to 12-hour shifts every other day. Since that every-other-day schedule is not good for continuity, HM essentially strung together shifts for as many consecutive days as possible, leading to the 7-on/7-off. Now, many clinicians won’t consider positions without such a schedule even though it’s not a schedule suitable for everyone.

“I think we’ve shot ourselves in the foot,” he said. “Because what it means is you take all the work that needs to be done and you shove it into a very small amount of space. Therefore, the amount of intensity in that work that you have is, I think, undoable over time. I hope we rethink that.”

He cautioned that SHM is near the age when, all too often, societies begin to be complacent and needs to guard against the instinct to keep doing things as they have always been done.

“We need to instinctively say, ‘Wait a second, am I turning into all of those other societies that have become irrelevant—or less relevant—because of that reflex?’” he questioned.

He predicted that, even though value in care is now becoming an obsession, the digitization of healthcare ultimately will have a deeper impact on medicine.

“You ask me 10 years from now, I’m guessing that the fact that we’ve just gone from analog to digital will have turned out to be a bigger transformation,” he explained. “And the reason I say that is if you look at the history of every other industry that went from analog to digital, eventually the industries got turned upside down.”

Burnout, a prominent topic at the meeting, still doesn’t seem to be worse in hospital medicine than in many other specialties, he said, but it is a concern.

“We need to rethink this. We need to come up with some new practice models using information technology in new ways, collaborating with members of the team in different ways,” he said. “We have to take this issue and figure out a way of solving it.”

Dr. Wachter said hospital medicine needs to keep innovating and finding ways to add value; otherwise, the financial support hospitals give to hospital medicine could begin to shrink.

The field is facing challenges, he said, but he is clearly proud of its accomplishments. He said that before he went out on the stage at an early conference he organized in 1998, during the early days of hospital medicine, his wife asked him, “Are you sure this is a good idea?”

“What I said to her was, ‘It is a good idea, and it will be a good idea if we are successful in recruiting and retaining young people, innovative people who want to change the world,’” he said. “I think we have done that, and I thank all of you for turning this into a good idea.” TH

Thomas R. Collins is a freelance writer in South Florida.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for daratumumab (Darzalex), a first-in-class monoclonal antibody targeting CD38.

The recommended indication for daratumumab is as monotherapy for adults with relapsed and refractory multiple myeloma (MM).

The patients must have progressed on their last therapy and have received treatment with both a proteasome inhibitor and an immunomodulatory agent.

The CHMP’s positive opinion will now be reviewed by the European Commission, which has the authority to grant marketing authorization for medicines in the European Economic Area.

The European Commission’s final decision on daratumumab is anticipated in the coming months.

About conditional authorization

A product may receive conditional marketing authorization if the CHMP finds that, although comprehensive clinical data on the safety and efficacy of the product are not available, all of the following requirements are met:

• The risk-benefit balance of the product is positive
• The company developing the product will likely be in a position to provide comprehensive clinical data in the future
• Unmet medical needs will be fulfilled
• The benefit to public health of the immediate availability of the product outweighs the risk inherent in the fact that additional data are still required.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder will be required to complete ongoing studies or to conduct new studies with a view to confirming that the benefit-risk balance of a product is positive. In addition, specific obligations may be imposed in relation to the collection of pharmacovigilance data.

About daratumumab

Daratumumab is the first CD38-directed monoclonal antibody recommended for approval in Europe. It works by binding to CD38, a signaling molecule highly expressed on the surface of MM cells regardless of stage of disease.

In binding to CD38, daratumumab triggers the patient’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple, immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death via apoptosis.

The CHMP’s positive opinion of daratumumab was based on a review of data from the phase 2 SIRIUS study, the phase 1/2 GEN501 study, and 3 additional supportive studies.

The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.

The results suggested daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%. Most adverse events in this study were grade 1 or 2, although serious events did occur.

The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 patients received the drug at 16 mg/kg.

Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.

Findings from a combined efficacy analysis of the GEN501 and SIRIUS trials demonstrated that, after a mean follow-up of 14.8 months, the estimated median overall survival for patients who received single-agent daratumumab at 16 mg/kg was 20 months.

Five phase 3 clinical studies with daratumumab in MM patients—in relapsed and frontline settings—are ongoing. Additional studies are ongoing or planned to assess the drug’s potential in other malignant and pre-malignant diseases in which CD38 is expressed.

Janssen has exclusive worldwide rights to the development, manufacturing, and commercialization of daratumumab for all potential indications. Janssen licensed daratumumab from Genmab A/S in August 2012.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for daratumumab (Darzalex), a first-in-class monoclonal antibody targeting CD38.

The recommended indication for daratumumab is as monotherapy for adults with relapsed and refractory multiple myeloma (MM).

The patients must have progressed on their last therapy and have received treatment with both a proteasome inhibitor and an immunomodulatory agent.

The CHMP’s positive opinion will now be reviewed by the European Commission, which has the authority to grant marketing authorization for medicines in the European Economic Area.

The European Commission’s final decision on daratumumab is anticipated in the coming months.

About conditional authorization

A product may receive conditional marketing authorization if the CHMP finds that, although comprehensive clinical data on the safety and efficacy of the product are not available, all of the following requirements are met:

• The risk-benefit balance of the product is positive
• The company developing the product will likely be in a position to provide comprehensive clinical data in the future
• Unmet medical needs will be fulfilled
• The benefit to public health of the immediate availability of the product outweighs the risk inherent in the fact that additional data are still required.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder will be required to complete ongoing studies or to conduct new studies with a view to confirming that the benefit-risk balance of a product is positive. In addition, specific obligations may be imposed in relation to the collection of pharmacovigilance data.

About daratumumab

Daratumumab is the first CD38-directed monoclonal antibody recommended for approval in Europe. It works by binding to CD38, a signaling molecule highly expressed on the surface of MM cells regardless of stage of disease.

In binding to CD38, daratumumab triggers the patient’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple, immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death via apoptosis.

The CHMP’s positive opinion of daratumumab was based on a review of data from the phase 2 SIRIUS study, the phase 1/2 GEN501 study, and 3 additional supportive studies.

The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.

The results suggested daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%. Most adverse events in this study were grade 1 or 2, although serious events did occur.

The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 patients received the drug at 16 mg/kg.

Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.

Findings from a combined efficacy analysis of the GEN501 and SIRIUS trials demonstrated that, after a mean follow-up of 14.8 months, the estimated median overall survival for patients who received single-agent daratumumab at 16 mg/kg was 20 months.

Five phase 3 clinical studies with daratumumab in MM patients—in relapsed and frontline settings—are ongoing. Additional studies are ongoing or planned to assess the drug’s potential in other malignant and pre-malignant diseases in which CD38 is expressed.

Janssen has exclusive worldwide rights to the development, manufacturing, and commercialization of daratumumab for all potential indications. Janssen licensed daratumumab from Genmab A/S in August 2012.

Daratumumab (Darzalex)

Photo courtesy of Janssen

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended conditional marketing authorization for daratumumab (Darzalex), a first-in-class monoclonal antibody targeting CD38.

The recommended indication for daratumumab is as monotherapy for adults with relapsed and refractory multiple myeloma (MM).

The patients must have progressed on their last therapy and have received treatment with both a proteasome inhibitor and an immunomodulatory agent.

The CHMP’s positive opinion will now be reviewed by the European Commission, which has the authority to grant marketing authorization for medicines in the European Economic Area.

The European Commission’s final decision on daratumumab is anticipated in the coming months.

About conditional authorization

A product may receive conditional marketing authorization if the CHMP finds that, although comprehensive clinical data on the safety and efficacy of the product are not available, all of the following requirements are met:

• The risk-benefit balance of the product is positive
• The company developing the product will likely be in a position to provide comprehensive clinical data in the future
• Unmet medical needs will be fulfilled
• The benefit to public health of the immediate availability of the product outweighs the risk inherent in the fact that additional data are still required.

Conditional marketing authorizations are valid for 1 year, on a renewable basis. The holder will be required to complete ongoing studies or to conduct new studies with a view to confirming that the benefit-risk balance of a product is positive. In addition, specific obligations may be imposed in relation to the collection of pharmacovigilance data.

About daratumumab

Daratumumab is the first CD38-directed monoclonal antibody recommended for approval in Europe. It works by binding to CD38, a signaling molecule highly expressed on the surface of MM cells regardless of stage of disease.

In binding to CD38, daratumumab triggers the patient’s own immune system to attack the cancer cells, resulting in rapid tumor cell death through multiple, immune-mediated mechanisms of action and through immunomodulatory effects, in addition to direct tumor cell death via apoptosis.

The CHMP’s positive opinion of daratumumab was based on a review of data from the phase 2 SIRIUS study, the phase 1/2 GEN501 study, and 3 additional supportive studies.

The GEN501 study enrolled 102 patients with relapsed MM or relapsed MM that was refractory to 2 or more prior lines of therapy. The patients received daratumumab at a range of doses and on a number of different schedules.

The results suggested daratumumab is most effective at a dose of 16 mg/kg. At this dose, the overall response rate was 36%. Most adverse events in this study were grade 1 or 2, although serious events did occur.

The SIRIUS study enrolled 124 MM patients who had received 3 or more prior lines of therapy. They received daratumumab at different doses and on different schedules, but 106 patients received the drug at 16 mg/kg.

Twenty-nine percent of the 106 patients responded to treatment, and the median duration of response was 7 months. Thirty percent of patients experienced serious adverse events.

Findings from a combined efficacy analysis of the GEN501 and SIRIUS trials demonstrated that, after a mean follow-up of 14.8 months, the estimated median overall survival for patients who received single-agent daratumumab at 16 mg/kg was 20 months.

Five phase 3 clinical studies with daratumumab in MM patients—in relapsed and frontline settings—are ongoing. Additional studies are ongoing or planned to assess the drug’s potential in other malignant and pre-malignant diseases in which CD38 is expressed.

Janssen has exclusive worldwide rights to the development, manufacturing, and commercialization of daratumumab for all potential indications. Janssen licensed daratumumab from Genmab A/S in August 2012.