Editors’ Note: Patients are part of family systems, and understanding these systems can help psychiatrists advance treatment. That’s why we’re launching a new column we are calling Families in Psychiatry. In this column, Dr. Alison M. Heru will examine issues faced by psychiatrists who are involved in family therapy and psychoeducation. She will also look at family research and at the impact that caring for patients with mental illness has on caregivers. Often, she will also offer a global perspective on these issues. If you have an idea for Dr. Heru, e-mail her at [email protected].

At age 7, Maggie Jarry watched her mother "walk around the apartment trying to catch her eyes because she believed they had floated out of her face." Her mother often locked herself in the bathroom and talked to herself in the mirror because she believed that had telepathic powers.

"We lived like this for a year, until a babysitter and her mother figured out what was going on" and got professional help for Maggie’s mother. Her mother was diagnosed with schizoaffective disorder, and after she died in 2007, Maggie Jarry felt free to share her experience (Psychiatr. Serv. 2009;60:1587-8). "During these years, no one asked me about my experiences of living with my mom while she was ill. I was expected to just go play and be a child while she was in the hospital," Maggie wrote.

Maggie, now a community organizer, is part of a new consumer organization that seeks to provide support and resources to those who have a parent with mental illness. In the organization’s blog, called "Daughters and Sons," one writer expressed the burden of children living with parents with mental illness this way:

"People can be told that your family member is ‘sick’ but until they have concrete examples of how a day becomes an eternity as a child sits unknowingly, waiting for a storm to pass that has no time limit, they really have no idea what it is like. Until people ‘get it,’ they won’t be inclined to help change it and deal with it on a societal level. Unlike the adults who can get away from dysfunction, the child growing up in a crooked house has no escape."

In Maggie’s case, when her mother was doing well, the two had a good relationship. The bond that existed between the two underscores the essential human role that parenting can have in helping patients with mental illness reach wellness.

Many resources are available for children of parents with mental illness, although there are more in Europe, Australia, and New Zealand than in the United States. In the Netherlands, an online group course for Parents With Mental Illness has been piloted, and in Finland, clinician training has been studied. In the United States, the National Research Council and the Institute of Medicine produced a report on Depression in Parents, Parenting and Children: Opportunities to Improve Identification, Treatment, and Prevention. In addition, excellent web resources are listed at end of the column.

What can individual adult psychiatrists do? We can include children in family meetings about the parent’s illness. We can answer their questions about psychiatric illness. Children can also provide great insight into family functioning – strengths and weaknesses. We can provide age-appropriate literature when they visit the hospital or come with their parent to our office. We can ask our patients, their spouses, and other caregiving adults about their children. We can ask if they need help with parenting, and provide appropriate resources. We can reassure our patients that we want to help them become better parents, not remove their children! Families can be referred for help and support. If you see your patient as being part of a family, then you have a family or systems perspective of health care.

There are many family psychiatrists and many of us are members of the Association of Family Psychiatrists, which is an organization allied with the American Psychiatric Association. We have a website and a newsletter. Family psychiatrists are found in diverse settings, such as child and adolescent inpatient units, geriatric clinics, and psychosomatic medicine services. Those of us in outpatient practice may use family therapy as a single modality. Most of us, however, incorporate a family approach in our care of the patient. We use medication, individual therapy, and family interventions.

Several international family psychiatry resources are available online. Among them are the "Mental Health and Growing Up" leaflets, the "Children of Parents With a Mental Illness" website, and the Effective Family Programme.

I look forward to bringing you updates on family psychiatry, the latest in evidence-based family interventions, and other information aimed at helping you keep an updated family systems approach in your practice. Let me hear from you.

Editors’ Note: Patients are part of family systems, and understanding these systems can help psychiatrists advance treatment. That’s why we’re launching a new column we are calling Families in Psychiatry. In this column, Dr. Alison M. Heru will examine issues faced by psychiatrists who are involved in family therapy and psychoeducation. She will also look at family research and at the impact that caring for patients with mental illness has on caregivers. Often, she will also offer a global perspective on these issues. If you have an idea for Dr. Heru, e-mail her at [email protected].

At age 7, Maggie Jarry watched her mother "walk around the apartment trying to catch her eyes because she believed they had floated out of her face." Her mother often locked herself in the bathroom and talked to herself in the mirror because she believed that had telepathic powers.

"We lived like this for a year, until a babysitter and her mother figured out what was going on" and got professional help for Maggie’s mother. Her mother was diagnosed with schizoaffective disorder, and after she died in 2007, Maggie Jarry felt free to share her experience (Psychiatr. Serv. 2009;60:1587-8). "During these years, no one asked me about my experiences of living with my mom while she was ill. I was expected to just go play and be a child while she was in the hospital," Maggie wrote.

Maggie, now a community organizer, is part of a new consumer organization that seeks to provide support and resources to those who have a parent with mental illness. In the organization’s blog, called "Daughters and Sons," one writer expressed the burden of children living with parents with mental illness this way:

"People can be told that your family member is ‘sick’ but until they have concrete examples of how a day becomes an eternity as a child sits unknowingly, waiting for a storm to pass that has no time limit, they really have no idea what it is like. Until people ‘get it,’ they won’t be inclined to help change it and deal with it on a societal level. Unlike the adults who can get away from dysfunction, the child growing up in a crooked house has no escape."

In Maggie’s case, when her mother was doing well, the two had a good relationship. The bond that existed between the two underscores the essential human role that parenting can have in helping patients with mental illness reach wellness.

Many resources are available for children of parents with mental illness, although there are more in Europe, Australia, and New Zealand than in the United States. In the Netherlands, an online group course for Parents With Mental Illness has been piloted, and in Finland, clinician training has been studied. In the United States, the National Research Council and the Institute of Medicine produced a report on Depression in Parents, Parenting and Children: Opportunities to Improve Identification, Treatment, and Prevention. In addition, excellent web resources are listed at end of the column.

What can individual adult psychiatrists do? We can include children in family meetings about the parent’s illness. We can answer their questions about psychiatric illness. Children can also provide great insight into family functioning – strengths and weaknesses. We can provide age-appropriate literature when they visit the hospital or come with their parent to our office. We can ask our patients, their spouses, and other caregiving adults about their children. We can ask if they need help with parenting, and provide appropriate resources. We can reassure our patients that we want to help them become better parents, not remove their children! Families can be referred for help and support. If you see your patient as being part of a family, then you have a family or systems perspective of health care.

There are many family psychiatrists and many of us are members of the Association of Family Psychiatrists, which is an organization allied with the American Psychiatric Association. We have a website and a newsletter. Family psychiatrists are found in diverse settings, such as child and adolescent inpatient units, geriatric clinics, and psychosomatic medicine services. Those of us in outpatient practice may use family therapy as a single modality. Most of us, however, incorporate a family approach in our care of the patient. We use medication, individual therapy, and family interventions.

Several international family psychiatry resources are available online. Among them are the "Mental Health and Growing Up" leaflets, the "Children of Parents With a Mental Illness" website, and the Effective Family Programme.

I look forward to bringing you updates on family psychiatry, the latest in evidence-based family interventions, and other information aimed at helping you keep an updated family systems approach in your practice. Let me hear from you.

Editors’ Note: Patients are part of family systems, and understanding these systems can help psychiatrists advance treatment. That’s why we’re launching a new column we are calling Families in Psychiatry. In this column, Dr. Alison M. Heru will examine issues faced by psychiatrists who are involved in family therapy and psychoeducation. She will also look at family research and at the impact that caring for patients with mental illness has on caregivers. Often, she will also offer a global perspective on these issues. If you have an idea for Dr. Heru, e-mail her at [email protected].

At age 7, Maggie Jarry watched her mother "walk around the apartment trying to catch her eyes because she believed they had floated out of her face." Her mother often locked herself in the bathroom and talked to herself in the mirror because she believed that had telepathic powers.

"We lived like this for a year, until a babysitter and her mother figured out what was going on" and got professional help for Maggie’s mother. Her mother was diagnosed with schizoaffective disorder, and after she died in 2007, Maggie Jarry felt free to share her experience (Psychiatr. Serv. 2009;60:1587-8). "During these years, no one asked me about my experiences of living with my mom while she was ill. I was expected to just go play and be a child while she was in the hospital," Maggie wrote.

Maggie, now a community organizer, is part of a new consumer organization that seeks to provide support and resources to those who have a parent with mental illness. In the organization’s blog, called "Daughters and Sons," one writer expressed the burden of children living with parents with mental illness this way:

"People can be told that your family member is ‘sick’ but until they have concrete examples of how a day becomes an eternity as a child sits unknowingly, waiting for a storm to pass that has no time limit, they really have no idea what it is like. Until people ‘get it,’ they won’t be inclined to help change it and deal with it on a societal level. Unlike the adults who can get away from dysfunction, the child growing up in a crooked house has no escape."

In Maggie’s case, when her mother was doing well, the two had a good relationship. The bond that existed between the two underscores the essential human role that parenting can have in helping patients with mental illness reach wellness.

Many resources are available for children of parents with mental illness, although there are more in Europe, Australia, and New Zealand than in the United States. In the Netherlands, an online group course for Parents With Mental Illness has been piloted, and in Finland, clinician training has been studied. In the United States, the National Research Council and the Institute of Medicine produced a report on Depression in Parents, Parenting and Children: Opportunities to Improve Identification, Treatment, and Prevention. In addition, excellent web resources are listed at end of the column.

What can individual adult psychiatrists do? We can include children in family meetings about the parent’s illness. We can answer their questions about psychiatric illness. Children can also provide great insight into family functioning – strengths and weaknesses. We can provide age-appropriate literature when they visit the hospital or come with their parent to our office. We can ask our patients, their spouses, and other caregiving adults about their children. We can ask if they need help with parenting, and provide appropriate resources. We can reassure our patients that we want to help them become better parents, not remove their children! Families can be referred for help and support. If you see your patient as being part of a family, then you have a family or systems perspective of health care.

There are many family psychiatrists and many of us are members of the Association of Family Psychiatrists, which is an organization allied with the American Psychiatric Association. We have a website and a newsletter. Family psychiatrists are found in diverse settings, such as child and adolescent inpatient units, geriatric clinics, and psychosomatic medicine services. Those of us in outpatient practice may use family therapy as a single modality. Most of us, however, incorporate a family approach in our care of the patient. We use medication, individual therapy, and family interventions.

Several international family psychiatry resources are available online. Among them are the "Mental Health and Growing Up" leaflets, the "Children of Parents With a Mental Illness" website, and the Effective Family Programme.

I look forward to bringing you updates on family psychiatry, the latest in evidence-based family interventions, and other information aimed at helping you keep an updated family systems approach in your practice. Let me hear from you.

STOCKHOLM – Adding pemetrexed to bevacizumab maintenance therapy cut the relative risk of disease progression for patients with advanced nonsquamous non–small cell lung cancer in a phase III clinical trial.

Patients on the combination had a median progression-free survival of 10.2 months from the start of first-line induction therapy vs. 6.6 months with solo bevacizumab maintenance in the randomized open label study (hazard ratio, 0.50; P less than.001).

The same measure from randomization to maintenance therapy was twice as long with the combination therapy as with bevacizumab alone – 7.4 months vs. 3.7 months (HR = 0.48; P less than.001).

"First-line cisplatin/pemetrexed/bevacizumab followed by continuation maintenance with bevacizumab and pemetrexed achieved a patient PFS [progression-free survival] benefit of unprecedented magnitude," said Dr. Fabrice Barlesi, who presented the results of the AVAPERL trial at the European Multidisciplinary Cancer Congress.

The researchers recruited patients with previously untreated stage IIIB-IV advanced nonsquamous non–small cell lung cancer (nsNSCLC). All patients received four 3-week cycles of first-line induction with bevacizumab, pemetrexed (Alimta), and cisplatin.

Patients with complete response, partial response, or stable disease at the end of this treatment were randomized to continuation maintenance with bevacizumab or bevacizumab and pemetrexed in 3-week cycles until disease progression. Progression-free survival was assessed from the beginning of induction therapy to first progressive disease or death from any cause.

A total of 376 patients started first-line induction therapy; 123 were not eligible for randomization due to disease progression. Of the remainder, 253 patients were randomized to maintenance therapy with bevacizumab alone (125) or bevacizumab plus pemetrexed (128). Three patients did not receive maintenance treatment.

Median follow-up was 11 months for this analysis presented at the joint congress of the European Cancer Organization (ECCO), the European Society for Medical Oncology (ESMO), and the European Society for Radiotherapy and Oncology (ESTRO).

Overall survival from induction was 15.7 months with bevacizumab alone but has not been reached yet with the combination maintenance therapy, according to Dr. Barlesi of the multidisciplinary oncology and therapeutic innovations department at the Assistance Publique Hôpitaux de Marseille, France.

First-line therapy with cisplatin, pemetrexed, and bevacizumab was well tolerated with no new or unexpected toxicities.

Notably, grade 3-5 hematologic adverse events were greater with the bevacizumab plus pemetrexed arm vs. the control group (10% vs. 0%). Grade 3-5 nonhematologic events also were greater with the combination maintenance treatment (31% vs. 22%).

Pemetrexed is approved in the United States for maintenance treatment of nonsquamous locally advanced or metastatic non–small cell lung cancer that has not progressed after four cycles of platinum-based chemotherapy. AVAPERL was the first phase III trial to investigate the combination of pemetrexed and bevacizumab as maintenance therapy in this disease.

The study was funded by Hoffman-La Roche. Dr. Barlesi reported that he has been a consultant for and received research funding from Roche and Lilly. One of the study authors is an employee for Hoffman-La Roche.

STOCKHOLM – Adding pemetrexed to bevacizumab maintenance therapy cut the relative risk of disease progression for patients with advanced nonsquamous non–small cell lung cancer in a phase III clinical trial.

Patients on the combination had a median progression-free survival of 10.2 months from the start of first-line induction therapy vs. 6.6 months with solo bevacizumab maintenance in the randomized open label study (hazard ratio, 0.50; P less than.001).

The same measure from randomization to maintenance therapy was twice as long with the combination therapy as with bevacizumab alone – 7.4 months vs. 3.7 months (HR = 0.48; P less than.001).

"First-line cisplatin/pemetrexed/bevacizumab followed by continuation maintenance with bevacizumab and pemetrexed achieved a patient PFS [progression-free survival] benefit of unprecedented magnitude," said Dr. Fabrice Barlesi, who presented the results of the AVAPERL trial at the European Multidisciplinary Cancer Congress.

The researchers recruited patients with previously untreated stage IIIB-IV advanced nonsquamous non–small cell lung cancer (nsNSCLC). All patients received four 3-week cycles of first-line induction with bevacizumab, pemetrexed (Alimta), and cisplatin.

Patients with complete response, partial response, or stable disease at the end of this treatment were randomized to continuation maintenance with bevacizumab or bevacizumab and pemetrexed in 3-week cycles until disease progression. Progression-free survival was assessed from the beginning of induction therapy to first progressive disease or death from any cause.

A total of 376 patients started first-line induction therapy; 123 were not eligible for randomization due to disease progression. Of the remainder, 253 patients were randomized to maintenance therapy with bevacizumab alone (125) or bevacizumab plus pemetrexed (128). Three patients did not receive maintenance treatment.

Median follow-up was 11 months for this analysis presented at the joint congress of the European Cancer Organization (ECCO), the European Society for Medical Oncology (ESMO), and the European Society for Radiotherapy and Oncology (ESTRO).

Overall survival from induction was 15.7 months with bevacizumab alone but has not been reached yet with the combination maintenance therapy, according to Dr. Barlesi of the multidisciplinary oncology and therapeutic innovations department at the Assistance Publique Hôpitaux de Marseille, France.

First-line therapy with cisplatin, pemetrexed, and bevacizumab was well tolerated with no new or unexpected toxicities.

Notably, grade 3-5 hematologic adverse events were greater with the bevacizumab plus pemetrexed arm vs. the control group (10% vs. 0%). Grade 3-5 nonhematologic events also were greater with the combination maintenance treatment (31% vs. 22%).

Pemetrexed is approved in the United States for maintenance treatment of nonsquamous locally advanced or metastatic non–small cell lung cancer that has not progressed after four cycles of platinum-based chemotherapy. AVAPERL was the first phase III trial to investigate the combination of pemetrexed and bevacizumab as maintenance therapy in this disease.

The study was funded by Hoffman-La Roche. Dr. Barlesi reported that he has been a consultant for and received research funding from Roche and Lilly. One of the study authors is an employee for Hoffman-La Roche.

STOCKHOLM – Adding pemetrexed to bevacizumab maintenance therapy cut the relative risk of disease progression for patients with advanced nonsquamous non–small cell lung cancer in a phase III clinical trial.

Patients on the combination had a median progression-free survival of 10.2 months from the start of first-line induction therapy vs. 6.6 months with solo bevacizumab maintenance in the randomized open label study (hazard ratio, 0.50; P less than.001).

The same measure from randomization to maintenance therapy was twice as long with the combination therapy as with bevacizumab alone – 7.4 months vs. 3.7 months (HR = 0.48; P less than.001).

"First-line cisplatin/pemetrexed/bevacizumab followed by continuation maintenance with bevacizumab and pemetrexed achieved a patient PFS [progression-free survival] benefit of unprecedented magnitude," said Dr. Fabrice Barlesi, who presented the results of the AVAPERL trial at the European Multidisciplinary Cancer Congress.

The researchers recruited patients with previously untreated stage IIIB-IV advanced nonsquamous non–small cell lung cancer (nsNSCLC). All patients received four 3-week cycles of first-line induction with bevacizumab, pemetrexed (Alimta), and cisplatin.

Patients with complete response, partial response, or stable disease at the end of this treatment were randomized to continuation maintenance with bevacizumab or bevacizumab and pemetrexed in 3-week cycles until disease progression. Progression-free survival was assessed from the beginning of induction therapy to first progressive disease or death from any cause.

A total of 376 patients started first-line induction therapy; 123 were not eligible for randomization due to disease progression. Of the remainder, 253 patients were randomized to maintenance therapy with bevacizumab alone (125) or bevacizumab plus pemetrexed (128). Three patients did not receive maintenance treatment.

Median follow-up was 11 months for this analysis presented at the joint congress of the European Cancer Organization (ECCO), the European Society for Medical Oncology (ESMO), and the European Society for Radiotherapy and Oncology (ESTRO).

Overall survival from induction was 15.7 months with bevacizumab alone but has not been reached yet with the combination maintenance therapy, according to Dr. Barlesi of the multidisciplinary oncology and therapeutic innovations department at the Assistance Publique Hôpitaux de Marseille, France.

First-line therapy with cisplatin, pemetrexed, and bevacizumab was well tolerated with no new or unexpected toxicities.

Notably, grade 3-5 hematologic adverse events were greater with the bevacizumab plus pemetrexed arm vs. the control group (10% vs. 0%). Grade 3-5 nonhematologic events also were greater with the combination maintenance treatment (31% vs. 22%).

Pemetrexed is approved in the United States for maintenance treatment of nonsquamous locally advanced or metastatic non–small cell lung cancer that has not progressed after four cycles of platinum-based chemotherapy. AVAPERL was the first phase III trial to investigate the combination of pemetrexed and bevacizumab as maintenance therapy in this disease.

The study was funded by Hoffman-La Roche. Dr. Barlesi reported that he has been a consultant for and received research funding from Roche and Lilly. One of the study authors is an employee for Hoffman-La Roche.

If our readers have any doubt, all they need do is casually scan the program for the recent VAM in Chicago or examine the content and Editorial Board of a current copy of the JVS to realize that the Society for Vascular Surgery is unquestionably an international organization. This sort of globalization, in contrast to the variety that, according to Tom Friedman, makes the world flat instead makes our specialty more vibrant and interesting than ever.

Because of this world change we believe that our journals should better represent the people that write and read our journals, and so, too, this newspaper. For this reason, we introduce in this issue our two newest members of the Vascular Specialist Editorial Board: From England, we have Professor Cliff Shearman, and from Australia, Professor Rob Fitridge. Both have a well-deserved preeminence and will broaden the view and the viewpoint of your SVS newspaper.

Professor Shearman is professor of vascular surgery at the University of Southampton and a consultant vascular surgeon at Southampton University Hospitals NHS Trust. He was on the Council and Chairman of the Training and Education Committee of the Vascular Society of Great Britain and Ireland, and President of the Society (2009-2010) He has a long time interest in training and was appointed head of the Wessex Post Graduate School of Surgery in 2007. He is currently president elect of the Society for Academic Research Surgery and Director of Professional Practice for the Association of Surgeons of Great Britain and Ireland. His main clinical interest is in the vascular complications of diabetes and in particular trying to reduce the rate of amputation in this group.

Professor Fitridge is professor of vascular surgery at the University of Adelaide and Head of Vascular Surgery at The Queen Elizabeth Hospital. He became chairman of the Board of Vascular Surgery in 2002 and during his tenure the online curriculum was developed. In collaboration with Matt Thompson he edited "Mechanisms of Vascular Disease: A Textbook for Vascular Surgeons" published by Cambridge University Press. His research interests include the systemic effects of skeletal muscle reperfusion injury and outcome modelling in aortic surgery. He recently was elected president of the ANZSVS and is president of the World Federation of Vascular Societies.

We welcome these new additions to our editorial team.

George Andros, M.D.

Medical Editor

If our readers have any doubt, all they need do is casually scan the program for the recent VAM in Chicago or examine the content and Editorial Board of a current copy of the JVS to realize that the Society for Vascular Surgery is unquestionably an international organization. This sort of globalization, in contrast to the variety that, according to Tom Friedman, makes the world flat instead makes our specialty more vibrant and interesting than ever.

Because of this world change we believe that our journals should better represent the people that write and read our journals, and so, too, this newspaper. For this reason, we introduce in this issue our two newest members of the Vascular Specialist Editorial Board: From England, we have Professor Cliff Shearman, and from Australia, Professor Rob Fitridge. Both have a well-deserved preeminence and will broaden the view and the viewpoint of your SVS newspaper.

Professor Shearman is professor of vascular surgery at the University of Southampton and a consultant vascular surgeon at Southampton University Hospitals NHS Trust. He was on the Council and Chairman of the Training and Education Committee of the Vascular Society of Great Britain and Ireland, and President of the Society (2009-2010) He has a long time interest in training and was appointed head of the Wessex Post Graduate School of Surgery in 2007. He is currently president elect of the Society for Academic Research Surgery and Director of Professional Practice for the Association of Surgeons of Great Britain and Ireland. His main clinical interest is in the vascular complications of diabetes and in particular trying to reduce the rate of amputation in this group.

Professor Fitridge is professor of vascular surgery at the University of Adelaide and Head of Vascular Surgery at The Queen Elizabeth Hospital. He became chairman of the Board of Vascular Surgery in 2002 and during his tenure the online curriculum was developed. In collaboration with Matt Thompson he edited "Mechanisms of Vascular Disease: A Textbook for Vascular Surgeons" published by Cambridge University Press. His research interests include the systemic effects of skeletal muscle reperfusion injury and outcome modelling in aortic surgery. He recently was elected president of the ANZSVS and is president of the World Federation of Vascular Societies.

We welcome these new additions to our editorial team.

George Andros, M.D.

Medical Editor

If our readers have any doubt, all they need do is casually scan the program for the recent VAM in Chicago or examine the content and Editorial Board of a current copy of the JVS to realize that the Society for Vascular Surgery is unquestionably an international organization. This sort of globalization, in contrast to the variety that, according to Tom Friedman, makes the world flat instead makes our specialty more vibrant and interesting than ever.

Because of this world change we believe that our journals should better represent the people that write and read our journals, and so, too, this newspaper. For this reason, we introduce in this issue our two newest members of the Vascular Specialist Editorial Board: From England, we have Professor Cliff Shearman, and from Australia, Professor Rob Fitridge. Both have a well-deserved preeminence and will broaden the view and the viewpoint of your SVS newspaper.

Professor Shearman is professor of vascular surgery at the University of Southampton and a consultant vascular surgeon at Southampton University Hospitals NHS Trust. He was on the Council and Chairman of the Training and Education Committee of the Vascular Society of Great Britain and Ireland, and President of the Society (2009-2010) He has a long time interest in training and was appointed head of the Wessex Post Graduate School of Surgery in 2007. He is currently president elect of the Society for Academic Research Surgery and Director of Professional Practice for the Association of Surgeons of Great Britain and Ireland. His main clinical interest is in the vascular complications of diabetes and in particular trying to reduce the rate of amputation in this group.

Professor Fitridge is professor of vascular surgery at the University of Adelaide and Head of Vascular Surgery at The Queen Elizabeth Hospital. He became chairman of the Board of Vascular Surgery in 2002 and during his tenure the online curriculum was developed. In collaboration with Matt Thompson he edited "Mechanisms of Vascular Disease: A Textbook for Vascular Surgeons" published by Cambridge University Press. His research interests include the systemic effects of skeletal muscle reperfusion injury and outcome modelling in aortic surgery. He recently was elected president of the ANZSVS and is president of the World Federation of Vascular Societies.

We welcome these new additions to our editorial team.

George Andros, M.D.

Medical Editor

Randomized controlled trials (RCTs) constitute level 1 evidence, which is widely considered the best data upon which to base medical practice. This is particularly true when the RCTs are published in leading journals like the New England Journal of Medicine or Lancet. Such trials are viewed by many as the Holy Grail of medicine and thus infallible and inviolate.

However, RCTs can have many flaws that render them obsolete, non-applicable or outright misleading. More importantly RCTs can be misinterpreted or spun by their authors or others so that they exert an effect on practice trends or standards unjustified by their data.

Possible flaws in RCTs are of two types:

1. Timeliness flaws can occur when progress is made in the treatment under evaluation arm or the control arm. Examples would be the early trials of carotid stenting (CAS) vs. carotid endarterectomy (CEA). If progress in CAS technology or patient selection occurs, a trial showing CAS inferiority becomes invalid. In contrast, the landmark trials showing CEA to be superior to medical treatment in preventing strokes have become obsolete because dramatic progress has been made with medical treatment.

2. Many design flaws can impair the validity of RCTs. These include patient selection flaws (e.g. in SAPPHIRE, patients were selected for randomization only if they were high risk for CEA). SAPPHIRE also included 71% asymptomatic patients in whom the high adverse event rates for both CEA and CAS were unjustified. Good medical treatment would have served these patients better. CREST also had patient selection flaws. It was originally designed to compare CAS and CEA only in symptomatic patients. When adequate numbers of patients could not be recruited, asymptomatic patients were added, thereby diluting the power of the study and impairing the statistical significance of some of its results.

Other design flaws include questionable competence of operators in a trial (e.g. the CAS operators in the EVA-3S and ICSS trials); problems with randomization (e.g. SAPPHIRE in which only 10% of eligible patients were randomized); and questionable applicability of RCT results to real world practice (e.g. CAS operators in CREST were highly vetted and more skilled than others performing the procedure).

There are also idiosyncratic flaws, as in the EVAR 2 trial in patients unfit for open repair. Although this trial, published in Lancet, showed EVAR to have similar mortality to no treatment, half the deaths in the group randomized to EVAR occurred from rupture during a lengthy (average 57 days) waiting period before treatment. Had these deaths been prevented by a more timely EVAR, the conclusion of EVAR 2 might have been different.

Inappropriate or questionable primary endpoints in RCTS are another design flaw that can lead to misleading conclusions. An example is the inclusion of minor myocardial infarctions (MIs) with strokes and deaths as a composite endpoint in a CAS vs. CEA trial (e.g. SAPPHIRE and CREST).

The components of the primary endpoint in the CAS and CEA arms of CREST were death, stroke, and myocardial infarction. Total stroke and minor strokes were both significantly different in the two groups in favor of CEA, and death and major strokes, although not significantly different between the two groups were both numerically higher for CAS. (See complete table oline at www. vascularspecialistonline.com)

Although it is arguable, it is hard to understand how minor MIs are the equivalent of strokes and deaths, and only when MIs were included were the adverse event rates in the two groups similar (7.2% for CAS vs 6.8% for CEA, P = .051).

So much for the flaws in RCTs. What about good trials or those with only minor weaknesses? Even these can result in misleading conclusions when the authors reach conclusions unjustified by their own data. SAPPHIRE and CREST are two recent examples.

Despite the flaws in these trials, both of which were reported in the New England Journal of Medicine, the authors concluded that "with high risk patients CAS and CEA are equivalent treatments" (SAPPHIRE) and "among patients with symptomatic and asymptomatic carotid stenosis, the risk of the composite primary end-point ... did not differ significantly in the group undergoing CAS and the group undergoing CEA" (CREST).

Although the CREST authors pointed out the higher incidence of stroke with stenting, others have used the CREST study to claim equivalence of CAS and CEA. Nowhere is this more apparent than in the recent American Heart Association (AHA) Guideline on the management of patients with extracranial carotid and vertebral artery disease.

This important and influential document, which was also approved by 13 other organizations including the SVS, stated that "CAS is indicated as an alternative to CEA for symptomatic patients at average or low risk of complications associated from endovascular interventions...." In Webster’s Dictionary one definition of "alternative" is "a choice between 2 things".

This clearly implies equivalence, and it has been so interpreted by many others, particularly those biased toward catheter based treatment. Of note, the AHA Guideline appears to be based largely on CREST, and did not even consider the findings of the ICSS trial, published in Lancet the same day as the main article reporting CREST.

Although ICSS may also have flaws, it showed, in a large group of only symptomatic patients, that CAS produced significantly more strokes and diffusion weighted MRI defects than did CEA. It is hard to understand why these ICSS results did not have more of an influence on the AHA Guideline.

Although my bias as a CAS enthusiast makes me believe that CAS will ultimately have a major role in the treatment of carotid stenosis patients, that bias is not yet sufficient for me to spin the data and believe we are now there. One has to wonder if bias more intense than mine was involved in the conclusion reached in the AHA Guideline.

Thus, it is apparent that misleading conclusions can be reached in articles reporting RCTs in leading journals. These can be the result of flaws in the RCTs and/or unrecognized author bias. More importantly, the results of even good trials can be further misinterpreted by others to guide practice standards in a way unjustified by the data.

It is important for all to recognize the possible role of bias in these misinterpretations. By recognizing the possible flaws in RCTs and that physicians, like all other people, are influenced by bias, we can exercise the judgment to use RCTs fairly to help us treat individual patients optimally.n

Dr. Frank J. Veith is professor of surgery at New York University Medical Center and professor of surgery and William J. von Liebig Chair in vascular surgery at Case Western Reserve University and The Cleveland Clinic.

Randomized controlled trials (RCTs) constitute level 1 evidence, which is widely considered the best data upon which to base medical practice. This is particularly true when the RCTs are published in leading journals like the New England Journal of Medicine or Lancet. Such trials are viewed by many as the Holy Grail of medicine and thus infallible and inviolate.

However, RCTs can have many flaws that render them obsolete, non-applicable or outright misleading. More importantly RCTs can be misinterpreted or spun by their authors or others so that they exert an effect on practice trends or standards unjustified by their data.

Possible flaws in RCTs are of two types:

1. Timeliness flaws can occur when progress is made in the treatment under evaluation arm or the control arm. Examples would be the early trials of carotid stenting (CAS) vs. carotid endarterectomy (CEA). If progress in CAS technology or patient selection occurs, a trial showing CAS inferiority becomes invalid. In contrast, the landmark trials showing CEA to be superior to medical treatment in preventing strokes have become obsolete because dramatic progress has been made with medical treatment.

2. Many design flaws can impair the validity of RCTs. These include patient selection flaws (e.g. in SAPPHIRE, patients were selected for randomization only if they were high risk for CEA). SAPPHIRE also included 71% asymptomatic patients in whom the high adverse event rates for both CEA and CAS were unjustified. Good medical treatment would have served these patients better. CREST also had patient selection flaws. It was originally designed to compare CAS and CEA only in symptomatic patients. When adequate numbers of patients could not be recruited, asymptomatic patients were added, thereby diluting the power of the study and impairing the statistical significance of some of its results.

Other design flaws include questionable competence of operators in a trial (e.g. the CAS operators in the EVA-3S and ICSS trials); problems with randomization (e.g. SAPPHIRE in which only 10% of eligible patients were randomized); and questionable applicability of RCT results to real world practice (e.g. CAS operators in CREST were highly vetted and more skilled than others performing the procedure).

There are also idiosyncratic flaws, as in the EVAR 2 trial in patients unfit for open repair. Although this trial, published in Lancet, showed EVAR to have similar mortality to no treatment, half the deaths in the group randomized to EVAR occurred from rupture during a lengthy (average 57 days) waiting period before treatment. Had these deaths been prevented by a more timely EVAR, the conclusion of EVAR 2 might have been different.

Inappropriate or questionable primary endpoints in RCTS are another design flaw that can lead to misleading conclusions. An example is the inclusion of minor myocardial infarctions (MIs) with strokes and deaths as a composite endpoint in a CAS vs. CEA trial (e.g. SAPPHIRE and CREST).

The components of the primary endpoint in the CAS and CEA arms of CREST were death, stroke, and myocardial infarction. Total stroke and minor strokes were both significantly different in the two groups in favor of CEA, and death and major strokes, although not significantly different between the two groups were both numerically higher for CAS. (See complete table oline at www. vascularspecialistonline.com)

Although it is arguable, it is hard to understand how minor MIs are the equivalent of strokes and deaths, and only when MIs were included were the adverse event rates in the two groups similar (7.2% for CAS vs 6.8% for CEA, P = .051).

So much for the flaws in RCTs. What about good trials or those with only minor weaknesses? Even these can result in misleading conclusions when the authors reach conclusions unjustified by their own data. SAPPHIRE and CREST are two recent examples.

Despite the flaws in these trials, both of which were reported in the New England Journal of Medicine, the authors concluded that "with high risk patients CAS and CEA are equivalent treatments" (SAPPHIRE) and "among patients with symptomatic and asymptomatic carotid stenosis, the risk of the composite primary end-point ... did not differ significantly in the group undergoing CAS and the group undergoing CEA" (CREST).

Although the CREST authors pointed out the higher incidence of stroke with stenting, others have used the CREST study to claim equivalence of CAS and CEA. Nowhere is this more apparent than in the recent American Heart Association (AHA) Guideline on the management of patients with extracranial carotid and vertebral artery disease.

This important and influential document, which was also approved by 13 other organizations including the SVS, stated that "CAS is indicated as an alternative to CEA for symptomatic patients at average or low risk of complications associated from endovascular interventions...." In Webster’s Dictionary one definition of "alternative" is "a choice between 2 things".

This clearly implies equivalence, and it has been so interpreted by many others, particularly those biased toward catheter based treatment. Of note, the AHA Guideline appears to be based largely on CREST, and did not even consider the findings of the ICSS trial, published in Lancet the same day as the main article reporting CREST.

Although ICSS may also have flaws, it showed, in a large group of only symptomatic patients, that CAS produced significantly more strokes and diffusion weighted MRI defects than did CEA. It is hard to understand why these ICSS results did not have more of an influence on the AHA Guideline.

Although my bias as a CAS enthusiast makes me believe that CAS will ultimately have a major role in the treatment of carotid stenosis patients, that bias is not yet sufficient for me to spin the data and believe we are now there. One has to wonder if bias more intense than mine was involved in the conclusion reached in the AHA Guideline.

Thus, it is apparent that misleading conclusions can be reached in articles reporting RCTs in leading journals. These can be the result of flaws in the RCTs and/or unrecognized author bias. More importantly, the results of even good trials can be further misinterpreted by others to guide practice standards in a way unjustified by the data.

It is important for all to recognize the possible role of bias in these misinterpretations. By recognizing the possible flaws in RCTs and that physicians, like all other people, are influenced by bias, we can exercise the judgment to use RCTs fairly to help us treat individual patients optimally.n

Dr. Frank J. Veith is professor of surgery at New York University Medical Center and professor of surgery and William J. von Liebig Chair in vascular surgery at Case Western Reserve University and The Cleveland Clinic.

Randomized controlled trials (RCTs) constitute level 1 evidence, which is widely considered the best data upon which to base medical practice. This is particularly true when the RCTs are published in leading journals like the New England Journal of Medicine or Lancet. Such trials are viewed by many as the Holy Grail of medicine and thus infallible and inviolate.

However, RCTs can have many flaws that render them obsolete, non-applicable or outright misleading. More importantly RCTs can be misinterpreted or spun by their authors or others so that they exert an effect on practice trends or standards unjustified by their data.

Possible flaws in RCTs are of two types:

1. Timeliness flaws can occur when progress is made in the treatment under evaluation arm or the control arm. Examples would be the early trials of carotid stenting (CAS) vs. carotid endarterectomy (CEA). If progress in CAS technology or patient selection occurs, a trial showing CAS inferiority becomes invalid. In contrast, the landmark trials showing CEA to be superior to medical treatment in preventing strokes have become obsolete because dramatic progress has been made with medical treatment.

2. Many design flaws can impair the validity of RCTs. These include patient selection flaws (e.g. in SAPPHIRE, patients were selected for randomization only if they were high risk for CEA). SAPPHIRE also included 71% asymptomatic patients in whom the high adverse event rates for both CEA and CAS were unjustified. Good medical treatment would have served these patients better. CREST also had patient selection flaws. It was originally designed to compare CAS and CEA only in symptomatic patients. When adequate numbers of patients could not be recruited, asymptomatic patients were added, thereby diluting the power of the study and impairing the statistical significance of some of its results.

Other design flaws include questionable competence of operators in a trial (e.g. the CAS operators in the EVA-3S and ICSS trials); problems with randomization (e.g. SAPPHIRE in which only 10% of eligible patients were randomized); and questionable applicability of RCT results to real world practice (e.g. CAS operators in CREST were highly vetted and more skilled than others performing the procedure).

There are also idiosyncratic flaws, as in the EVAR 2 trial in patients unfit for open repair. Although this trial, published in Lancet, showed EVAR to have similar mortality to no treatment, half the deaths in the group randomized to EVAR occurred from rupture during a lengthy (average 57 days) waiting period before treatment. Had these deaths been prevented by a more timely EVAR, the conclusion of EVAR 2 might have been different.

Inappropriate or questionable primary endpoints in RCTS are another design flaw that can lead to misleading conclusions. An example is the inclusion of minor myocardial infarctions (MIs) with strokes and deaths as a composite endpoint in a CAS vs. CEA trial (e.g. SAPPHIRE and CREST).

The components of the primary endpoint in the CAS and CEA arms of CREST were death, stroke, and myocardial infarction. Total stroke and minor strokes were both significantly different in the two groups in favor of CEA, and death and major strokes, although not significantly different between the two groups were both numerically higher for CAS. (See complete table oline at www. vascularspecialistonline.com)

Although it is arguable, it is hard to understand how minor MIs are the equivalent of strokes and deaths, and only when MIs were included were the adverse event rates in the two groups similar (7.2% for CAS vs 6.8% for CEA, P = .051).

So much for the flaws in RCTs. What about good trials or those with only minor weaknesses? Even these can result in misleading conclusions when the authors reach conclusions unjustified by their own data. SAPPHIRE and CREST are two recent examples.

Despite the flaws in these trials, both of which were reported in the New England Journal of Medicine, the authors concluded that "with high risk patients CAS and CEA are equivalent treatments" (SAPPHIRE) and "among patients with symptomatic and asymptomatic carotid stenosis, the risk of the composite primary end-point ... did not differ significantly in the group undergoing CAS and the group undergoing CEA" (CREST).

Although the CREST authors pointed out the higher incidence of stroke with stenting, others have used the CREST study to claim equivalence of CAS and CEA. Nowhere is this more apparent than in the recent American Heart Association (AHA) Guideline on the management of patients with extracranial carotid and vertebral artery disease.

This important and influential document, which was also approved by 13 other organizations including the SVS, stated that "CAS is indicated as an alternative to CEA for symptomatic patients at average or low risk of complications associated from endovascular interventions...." In Webster’s Dictionary one definition of "alternative" is "a choice between 2 things".

This clearly implies equivalence, and it has been so interpreted by many others, particularly those biased toward catheter based treatment. Of note, the AHA Guideline appears to be based largely on CREST, and did not even consider the findings of the ICSS trial, published in Lancet the same day as the main article reporting CREST.

Although ICSS may also have flaws, it showed, in a large group of only symptomatic patients, that CAS produced significantly more strokes and diffusion weighted MRI defects than did CEA. It is hard to understand why these ICSS results did not have more of an influence on the AHA Guideline.

Although my bias as a CAS enthusiast makes me believe that CAS will ultimately have a major role in the treatment of carotid stenosis patients, that bias is not yet sufficient for me to spin the data and believe we are now there. One has to wonder if bias more intense than mine was involved in the conclusion reached in the AHA Guideline.

Thus, it is apparent that misleading conclusions can be reached in articles reporting RCTs in leading journals. These can be the result of flaws in the RCTs and/or unrecognized author bias. More importantly, the results of even good trials can be further misinterpreted by others to guide practice standards in a way unjustified by the data.

It is important for all to recognize the possible role of bias in these misinterpretations. By recognizing the possible flaws in RCTs and that physicians, like all other people, are influenced by bias, we can exercise the judgment to use RCTs fairly to help us treat individual patients optimally.n

Dr. Frank J. Veith is professor of surgery at New York University Medical Center and professor of surgery and William J. von Liebig Chair in vascular surgery at Case Western Reserve University and The Cleveland Clinic.

Americans are living longer – but not healthier – lives, researchers have found.

While average life expectancy is now higher than ever, the number of years Americans can expect to live without type 2 diabetes is decreasing. A prolonged period of morbidity is more likely to characterize people’s later years now than it was in the 1980s.

The difference was driven by a marked increase in the number of Americans who are obese, according to findings published Sept. 23 by Solveig A. Cunningham, Ph.D., an epidemiologist at Emory University in Atlanta, and colleagues. More than one-third of American adults now have a body-mass index of 30 kg/m² or higher.

"All of the observed reductions in diabetes-free life expectancy at the population level were actually due to increases in diabetes only among obese individuals," Dr. Cunningham and colleagues reported (Diabetes Care 2011;34:2225-30 [doi:10.2337/dc11-0462]).

The fact that obese individuals would be more likely to be diagnosed with diabetes in the 2000s than in the 1980s, they wrote, may be because obese adults were 3.4% heavier in the latter period, or it may reflect better diagnosis of diabetes in this population group, the researchers hypothesized. Another possible explanation "is that diabetes risks are higher with younger age of obesity onset; indeed, the prevalence of obesity has tripled among children since the 1970s."

For other weight groups, including people classified as overweight (BMI, 25-30), the diabetes-free life expectancy actually improved from the 1980s to the 2000s. However, this was largely thanks to overall mortality decreasing. Life expectancy as a whole was 70.6 years for men and 77.4 years for women in the 1980s, and had increased to 74.3 for men and 79 years for women by 2000-2004.

The proportion of obese individuals had grown enough in the same time period to alter estimates of disease-free life expectancy for the population as a whole, the investigators found.

All together, diabetes-free life expectancy for an 18-year-old U.S. man was 1.7 years longer in the 1980s than it was during 2000-2004; for a woman, it was 1.5 years longer in the 1980s. The proportion of 18-year-olds who would be diagnosed with diabetes in their lifetimes increased by almost 50% among women between 1980-1989 and 2000-2004, and almost doubled among men, Dr. Cunningham and colleagues found.

Obese men lost an average of 5.6 years of diabetes-free life between the 1980s and the early 2000s, whereas women lost 2.5 years in the same interval. "In 2000-2004, obese 18-year-old men and women could expect to live 13.7 and 19.1 fewer years without diabetes, respectively, compared with normal/underweight 18-year-old men and women," the investigators wrote.

For their research, Dr. Cunningham and colleagues examined data from the National Vital Statistics System and the National Health Interview Survey, which collects self-reported health information from the noninstitutionalized, nonmilitary population.

The 1980-1989 NHIS surveys analyzed by Dr. Cunningham and colleagues contained responses from 143,765 adults (507 diagnosed diabetic in the previous year), and the 2000-2004 period surveys contained responses from 150,718 (1,366 diagnosed diabetic in the previous year).

Dr. Cunningham and colleagues examined diabetes and obesity incidence in the survey population in the context of changes in national mortality rates and population aging between the time periods.

Limitations of the study included its reliance on self-reported information about diabetes diagnosis, weight, and height, which is susceptible to bias. However, the investigators wrote that "NHIS data are collected via rigorous in-person interviews, and the differences in reported and measured BMI are not large and do not affect health risk estimates, including those associated with diabetes."

The researchers concluded that their results "suggest that in the face of budgetary or logistic constraints, new efforts to prevent diabetes can have the greatest impact among obese individuals," as all other groups were shown to have improved diabetes-free life expectancy over the decades studied.

Dr. Cunningham and colleagues reported no conflicts of interest.

Americans are living longer – but not healthier – lives, researchers have found.

While average life expectancy is now higher than ever, the number of years Americans can expect to live without type 2 diabetes is decreasing. A prolonged period of morbidity is more likely to characterize people’s later years now than it was in the 1980s.

The difference was driven by a marked increase in the number of Americans who are obese, according to findings published Sept. 23 by Solveig A. Cunningham, Ph.D., an epidemiologist at Emory University in Atlanta, and colleagues. More than one-third of American adults now have a body-mass index of 30 kg/m² or higher.

"All of the observed reductions in diabetes-free life expectancy at the population level were actually due to increases in diabetes only among obese individuals," Dr. Cunningham and colleagues reported (Diabetes Care 2011;34:2225-30 [doi:10.2337/dc11-0462]).

The fact that obese individuals would be more likely to be diagnosed with diabetes in the 2000s than in the 1980s, they wrote, may be because obese adults were 3.4% heavier in the latter period, or it may reflect better diagnosis of diabetes in this population group, the researchers hypothesized. Another possible explanation "is that diabetes risks are higher with younger age of obesity onset; indeed, the prevalence of obesity has tripled among children since the 1970s."

For other weight groups, including people classified as overweight (BMI, 25-30), the diabetes-free life expectancy actually improved from the 1980s to the 2000s. However, this was largely thanks to overall mortality decreasing. Life expectancy as a whole was 70.6 years for men and 77.4 years for women in the 1980s, and had increased to 74.3 for men and 79 years for women by 2000-2004.

The proportion of obese individuals had grown enough in the same time period to alter estimates of disease-free life expectancy for the population as a whole, the investigators found.

All together, diabetes-free life expectancy for an 18-year-old U.S. man was 1.7 years longer in the 1980s than it was during 2000-2004; for a woman, it was 1.5 years longer in the 1980s. The proportion of 18-year-olds who would be diagnosed with diabetes in their lifetimes increased by almost 50% among women between 1980-1989 and 2000-2004, and almost doubled among men, Dr. Cunningham and colleagues found.

Obese men lost an average of 5.6 years of diabetes-free life between the 1980s and the early 2000s, whereas women lost 2.5 years in the same interval. "In 2000-2004, obese 18-year-old men and women could expect to live 13.7 and 19.1 fewer years without diabetes, respectively, compared with normal/underweight 18-year-old men and women," the investigators wrote.

For their research, Dr. Cunningham and colleagues examined data from the National Vital Statistics System and the National Health Interview Survey, which collects self-reported health information from the noninstitutionalized, nonmilitary population.

The 1980-1989 NHIS surveys analyzed by Dr. Cunningham and colleagues contained responses from 143,765 adults (507 diagnosed diabetic in the previous year), and the 2000-2004 period surveys contained responses from 150,718 (1,366 diagnosed diabetic in the previous year).

Dr. Cunningham and colleagues examined diabetes and obesity incidence in the survey population in the context of changes in national mortality rates and population aging between the time periods.

Limitations of the study included its reliance on self-reported information about diabetes diagnosis, weight, and height, which is susceptible to bias. However, the investigators wrote that "NHIS data are collected via rigorous in-person interviews, and the differences in reported and measured BMI are not large and do not affect health risk estimates, including those associated with diabetes."

The researchers concluded that their results "suggest that in the face of budgetary or logistic constraints, new efforts to prevent diabetes can have the greatest impact among obese individuals," as all other groups were shown to have improved diabetes-free life expectancy over the decades studied.

Dr. Cunningham and colleagues reported no conflicts of interest.

Americans are living longer – but not healthier – lives, researchers have found.

While average life expectancy is now higher than ever, the number of years Americans can expect to live without type 2 diabetes is decreasing. A prolonged period of morbidity is more likely to characterize people’s later years now than it was in the 1980s.

The difference was driven by a marked increase in the number of Americans who are obese, according to findings published Sept. 23 by Solveig A. Cunningham, Ph.D., an epidemiologist at Emory University in Atlanta, and colleagues. More than one-third of American adults now have a body-mass index of 30 kg/m² or higher.

"All of the observed reductions in diabetes-free life expectancy at the population level were actually due to increases in diabetes only among obese individuals," Dr. Cunningham and colleagues reported (Diabetes Care 2011;34:2225-30 [doi:10.2337/dc11-0462]).

The fact that obese individuals would be more likely to be diagnosed with diabetes in the 2000s than in the 1980s, they wrote, may be because obese adults were 3.4% heavier in the latter period, or it may reflect better diagnosis of diabetes in this population group, the researchers hypothesized. Another possible explanation "is that diabetes risks are higher with younger age of obesity onset; indeed, the prevalence of obesity has tripled among children since the 1970s."

For other weight groups, including people classified as overweight (BMI, 25-30), the diabetes-free life expectancy actually improved from the 1980s to the 2000s. However, this was largely thanks to overall mortality decreasing. Life expectancy as a whole was 70.6 years for men and 77.4 years for women in the 1980s, and had increased to 74.3 for men and 79 years for women by 2000-2004.

The proportion of obese individuals had grown enough in the same time period to alter estimates of disease-free life expectancy for the population as a whole, the investigators found.

All together, diabetes-free life expectancy for an 18-year-old U.S. man was 1.7 years longer in the 1980s than it was during 2000-2004; for a woman, it was 1.5 years longer in the 1980s. The proportion of 18-year-olds who would be diagnosed with diabetes in their lifetimes increased by almost 50% among women between 1980-1989 and 2000-2004, and almost doubled among men, Dr. Cunningham and colleagues found.

Obese men lost an average of 5.6 years of diabetes-free life between the 1980s and the early 2000s, whereas women lost 2.5 years in the same interval. "In 2000-2004, obese 18-year-old men and women could expect to live 13.7 and 19.1 fewer years without diabetes, respectively, compared with normal/underweight 18-year-old men and women," the investigators wrote.

For their research, Dr. Cunningham and colleagues examined data from the National Vital Statistics System and the National Health Interview Survey, which collects self-reported health information from the noninstitutionalized, nonmilitary population.

The 1980-1989 NHIS surveys analyzed by Dr. Cunningham and colleagues contained responses from 143,765 adults (507 diagnosed diabetic in the previous year), and the 2000-2004 period surveys contained responses from 150,718 (1,366 diagnosed diabetic in the previous year).

Dr. Cunningham and colleagues examined diabetes and obesity incidence in the survey population in the context of changes in national mortality rates and population aging between the time periods.

Limitations of the study included its reliance on self-reported information about diabetes diagnosis, weight, and height, which is susceptible to bias. However, the investigators wrote that "NHIS data are collected via rigorous in-person interviews, and the differences in reported and measured BMI are not large and do not affect health risk estimates, including those associated with diabetes."

The researchers concluded that their results "suggest that in the face of budgetary or logistic constraints, new efforts to prevent diabetes can have the greatest impact among obese individuals," as all other groups were shown to have improved diabetes-free life expectancy over the decades studied.

Dr. Cunningham and colleagues reported no conflicts of interest.

Establishing mutual respect and trust between hospitalists and nurses is an important part of ensuring patient safety, whether you’re on your first job or your 20th, says Angela Beck, RN, director of critical-care services at Nebraska Medical Center in Omaha.

“Nurses are important coordinators of care,” she says. “Recognizing and valuing nurses for that is truly the most important thing for the patient, and can also help hospitalists build relationships.”

Key Partners

Forming a collaborative relationship with the nursing service might depend on where you start. At Northwestern Memorial Hospital in Chicago, the nursing service enjoys a “close and collaborative relationship” with hospitalists, according to Kristin Ramsey, RN, MSN, MPPM, NE-BC, associate chief nurse and executive director of operations. New hospitalists are oriented to the care-delivery models on the inpatient care units. In addition, hospitalists are acculturated into the hospital’s coleadership model.

“We have partnered with our hospitalists to create a model in which the physician and nurse leader collaboratively lead the development of multidisciplinary, subspecialty teams to ensure quality outcomes,” Ramsey says. “The model is so successful with the hospitalists that we are now extending it to other areas in the organization.”

Round Sharing

Absent a formalized training protocol for partnering with nursing, hospitalists still can learn a great deal by listening to and communicating with the nursing staff, says Connie Ogden, RN, MSN, NEA-BC, executive director of adult acute services at Nebraska Medical Center. “Nurses are there around the clock caring for patients and may have a different insight” about patients’ evolving conditions, she says.

Care for the patient improves if everyone is on the same page, Ogden adds. That’s why it makes sense, she says, to include nurses during rounds. Beck agrees: “If nurses aren’t there to hear how the plan of care comes about, there is no reason to believe they can effectively describe it once the physician turns around and walks away to see another patient.”

In critical-care units, according to Beck, nurses can function as a bridge between patients and physicians. For example, they can help patients define and express their goals. Some of these goals can be incremental, she notes, such as “I really want to get out of bed this afternoon,” or “I really want my family here to listen to this message.”

Different Role, Same Goal

As director of adult acute services, Ogden often receives complaints from physicians about calls they receive from nurses. Often, these calls emanate from a concern for the patient (e.g. a 2 a.m. call for a Tylenol order to address a headache) or from the requirement that nurses follow policy and clarify orders. If hospitalists understand the back story of the call, their perception of its purpose can change.

Although there have been strides toward better nurse-physician collaboration, “we still have a lot of opportunities for improvement,” Beck asserts.

Establishing mutual respect and trust is not an overnight accomplishment. As Ogden explains, physicians and nurses have different roles, but they share the same goal: quality outcomes in patient care.

Gretchen Henkel is a freelance writer based in southern California.

► For more career-related articles, visit the SHM Career Center.

Establishing mutual respect and trust between hospitalists and nurses is an important part of ensuring patient safety, whether you’re on your first job or your 20th, says Angela Beck, RN, director of critical-care services at Nebraska Medical Center in Omaha.

“Nurses are important coordinators of care,” she says. “Recognizing and valuing nurses for that is truly the most important thing for the patient, and can also help hospitalists build relationships.”

Key Partners

Forming a collaborative relationship with the nursing service might depend on where you start. At Northwestern Memorial Hospital in Chicago, the nursing service enjoys a “close and collaborative relationship” with hospitalists, according to Kristin Ramsey, RN, MSN, MPPM, NE-BC, associate chief nurse and executive director of operations. New hospitalists are oriented to the care-delivery models on the inpatient care units. In addition, hospitalists are acculturated into the hospital’s coleadership model.

“We have partnered with our hospitalists to create a model in which the physician and nurse leader collaboratively lead the development of multidisciplinary, subspecialty teams to ensure quality outcomes,” Ramsey says. “The model is so successful with the hospitalists that we are now extending it to other areas in the organization.”

Round Sharing

Absent a formalized training protocol for partnering with nursing, hospitalists still can learn a great deal by listening to and communicating with the nursing staff, says Connie Ogden, RN, MSN, NEA-BC, executive director of adult acute services at Nebraska Medical Center. “Nurses are there around the clock caring for patients and may have a different insight” about patients’ evolving conditions, she says.

Care for the patient improves if everyone is on the same page, Ogden adds. That’s why it makes sense, she says, to include nurses during rounds. Beck agrees: “If nurses aren’t there to hear how the plan of care comes about, there is no reason to believe they can effectively describe it once the physician turns around and walks away to see another patient.”

In critical-care units, according to Beck, nurses can function as a bridge between patients and physicians. For example, they can help patients define and express their goals. Some of these goals can be incremental, she notes, such as “I really want to get out of bed this afternoon,” or “I really want my family here to listen to this message.”

Different Role, Same Goal

As director of adult acute services, Ogden often receives complaints from physicians about calls they receive from nurses. Often, these calls emanate from a concern for the patient (e.g. a 2 a.m. call for a Tylenol order to address a headache) or from the requirement that nurses follow policy and clarify orders. If hospitalists understand the back story of the call, their perception of its purpose can change.

Although there have been strides toward better nurse-physician collaboration, “we still have a lot of opportunities for improvement,” Beck asserts.

Establishing mutual respect and trust is not an overnight accomplishment. As Ogden explains, physicians and nurses have different roles, but they share the same goal: quality outcomes in patient care.

Gretchen Henkel is a freelance writer based in southern California.

► For more career-related articles, visit the SHM Career Center.

Establishing mutual respect and trust between hospitalists and nurses is an important part of ensuring patient safety, whether you’re on your first job or your 20th, says Angela Beck, RN, director of critical-care services at Nebraska Medical Center in Omaha.

“Nurses are important coordinators of care,” she says. “Recognizing and valuing nurses for that is truly the most important thing for the patient, and can also help hospitalists build relationships.”

Key Partners

Forming a collaborative relationship with the nursing service might depend on where you start. At Northwestern Memorial Hospital in Chicago, the nursing service enjoys a “close and collaborative relationship” with hospitalists, according to Kristin Ramsey, RN, MSN, MPPM, NE-BC, associate chief nurse and executive director of operations. New hospitalists are oriented to the care-delivery models on the inpatient care units. In addition, hospitalists are acculturated into the hospital’s coleadership model.

“We have partnered with our hospitalists to create a model in which the physician and nurse leader collaboratively lead the development of multidisciplinary, subspecialty teams to ensure quality outcomes,” Ramsey says. “The model is so successful with the hospitalists that we are now extending it to other areas in the organization.”

Round Sharing

Absent a formalized training protocol for partnering with nursing, hospitalists still can learn a great deal by listening to and communicating with the nursing staff, says Connie Ogden, RN, MSN, NEA-BC, executive director of adult acute services at Nebraska Medical Center. “Nurses are there around the clock caring for patients and may have a different insight” about patients’ evolving conditions, she says.

Care for the patient improves if everyone is on the same page, Ogden adds. That’s why it makes sense, she says, to include nurses during rounds. Beck agrees: “If nurses aren’t there to hear how the plan of care comes about, there is no reason to believe they can effectively describe it once the physician turns around and walks away to see another patient.”

In critical-care units, according to Beck, nurses can function as a bridge between patients and physicians. For example, they can help patients define and express their goals. Some of these goals can be incremental, she notes, such as “I really want to get out of bed this afternoon,” or “I really want my family here to listen to this message.”

Different Role, Same Goal

As director of adult acute services, Ogden often receives complaints from physicians about calls they receive from nurses. Often, these calls emanate from a concern for the patient (e.g. a 2 a.m. call for a Tylenol order to address a headache) or from the requirement that nurses follow policy and clarify orders. If hospitalists understand the back story of the call, their perception of its purpose can change.

Although there have been strides toward better nurse-physician collaboration, “we still have a lot of opportunities for improvement,” Beck asserts.

Establishing mutual respect and trust is not an overnight accomplishment. As Ogden explains, physicians and nurses have different roles, but they share the same goal: quality outcomes in patient care.

Gretchen Henkel is a freelance writer based in southern California.

► For more career-related articles, visit the SHM Career Center.

The US Food and Drug Administration (FDA) has granted accelerated approval for eculizumab (Soliris) to treat patients with atypical hemolytic uremic syndrome (aHUS).

This rare and chronic disease can lead to renal failure and is associated with an increased risk of death and stroke. It accounts for 5% to 10% of all cases of hemolytic uremic syndrome and disproportionately affects children.

Eculizumab is a targeted therapy that works by inhibiting proteins that play a role in aHUS. The FDA granted accelerated approval for eculizumab based on data suggesting the drug likely confers a clinical benefit for patients with aHUS.

The FDA’s Accelerated Approval Program allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint that is thought to predict clinical benefit. The makers of eculizumab, Alexion Pharmaceuticals, are still required to conduct research to confirm the anticipated clinical benefit.

If this research indicates that eculizumab does provide a clinical benefit, the FDA will grant traditional approval for the drug. If research suggests eculizumab does not provide a clinical benefit, the FDA has regulatory procedures in place that could lead to removing the drug from the market.

There are no other FDA-approved treatments for aHUS. The safety and efficacy of the current standard treatment, plasma therapy (plasma exchange or fresh frozen plasma infusion), have not been studied in well-controlled trials.

Researchers have examined the safety and efficacy of eculizumab in 2 single-arm trials of 37 adult and adolescent patients with aHUS and 1 retrospective study of 19 pediatric and 11 adult patients with aHUS.
 
Patients treated with eculizumab in these studies experienced a favorable improvement in kidney function, including elimination of the requirement for dialysis in several patients who did not respond to plasma therapy.

Patients treated with eculizumab also exhibited improvement in platelet counts and other blood parameters that correlate with aHUS disease activity.

The most common side effects included hypertension, diarrhea, headache, anemia, vomiting, nausea, upper respiratory and urinary tract infections, and leukopenia.

Eculizumab will continue to be available only through a restricted program. Prescribers must enroll in a registration program and provide a medication guide to patients who receive the drug.

Eculizumab is marketed as Soliris by Alexion Pharmaceuticals, located in Cheshire, Connecticut.

The US Food and Drug Administration (FDA) has granted accelerated approval for eculizumab (Soliris) to treat patients with atypical hemolytic uremic syndrome (aHUS).

This rare and chronic disease can lead to renal failure and is associated with an increased risk of death and stroke. It accounts for 5% to 10% of all cases of hemolytic uremic syndrome and disproportionately affects children.

Eculizumab is a targeted therapy that works by inhibiting proteins that play a role in aHUS. The FDA granted accelerated approval for eculizumab based on data suggesting the drug likely confers a clinical benefit for patients with aHUS.

The FDA’s Accelerated Approval Program allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint that is thought to predict clinical benefit. The makers of eculizumab, Alexion Pharmaceuticals, are still required to conduct research to confirm the anticipated clinical benefit.

If this research indicates that eculizumab does provide a clinical benefit, the FDA will grant traditional approval for the drug. If research suggests eculizumab does not provide a clinical benefit, the FDA has regulatory procedures in place that could lead to removing the drug from the market.

There are no other FDA-approved treatments for aHUS. The safety and efficacy of the current standard treatment, plasma therapy (plasma exchange or fresh frozen plasma infusion), have not been studied in well-controlled trials.

Researchers have examined the safety and efficacy of eculizumab in 2 single-arm trials of 37 adult and adolescent patients with aHUS and 1 retrospective study of 19 pediatric and 11 adult patients with aHUS.
 
Patients treated with eculizumab in these studies experienced a favorable improvement in kidney function, including elimination of the requirement for dialysis in several patients who did not respond to plasma therapy.

Patients treated with eculizumab also exhibited improvement in platelet counts and other blood parameters that correlate with aHUS disease activity.

The most common side effects included hypertension, diarrhea, headache, anemia, vomiting, nausea, upper respiratory and urinary tract infections, and leukopenia.

Eculizumab will continue to be available only through a restricted program. Prescribers must enroll in a registration program and provide a medication guide to patients who receive the drug.

Eculizumab is marketed as Soliris by Alexion Pharmaceuticals, located in Cheshire, Connecticut.

The US Food and Drug Administration (FDA) has granted accelerated approval for eculizumab (Soliris) to treat patients with atypical hemolytic uremic syndrome (aHUS).

This rare and chronic disease can lead to renal failure and is associated with an increased risk of death and stroke. It accounts for 5% to 10% of all cases of hemolytic uremic syndrome and disproportionately affects children.

Eculizumab is a targeted therapy that works by inhibiting proteins that play a role in aHUS. The FDA granted accelerated approval for eculizumab based on data suggesting the drug likely confers a clinical benefit for patients with aHUS.

The FDA’s Accelerated Approval Program allows for earlier approval of drugs that treat serious conditions and fill an unmet medical need based on a surrogate endpoint that is thought to predict clinical benefit. The makers of eculizumab, Alexion Pharmaceuticals, are still required to conduct research to confirm the anticipated clinical benefit.

If this research indicates that eculizumab does provide a clinical benefit, the FDA will grant traditional approval for the drug. If research suggests eculizumab does not provide a clinical benefit, the FDA has regulatory procedures in place that could lead to removing the drug from the market.

There are no other FDA-approved treatments for aHUS. The safety and efficacy of the current standard treatment, plasma therapy (plasma exchange or fresh frozen plasma infusion), have not been studied in well-controlled trials.

Researchers have examined the safety and efficacy of eculizumab in 2 single-arm trials of 37 adult and adolescent patients with aHUS and 1 retrospective study of 19 pediatric and 11 adult patients with aHUS.
 
Patients treated with eculizumab in these studies experienced a favorable improvement in kidney function, including elimination of the requirement for dialysis in several patients who did not respond to plasma therapy.

Patients treated with eculizumab also exhibited improvement in platelet counts and other blood parameters that correlate with aHUS disease activity.

The most common side effects included hypertension, diarrhea, headache, anemia, vomiting, nausea, upper respiratory and urinary tract infections, and leukopenia.

Eculizumab will continue to be available only through a restricted program. Prescribers must enroll in a registration program and provide a medication guide to patients who receive the drug.

Eculizumab is marketed as Soliris by Alexion Pharmaceuticals, located in Cheshire, Connecticut.

LISBON – A new meta-analysis offers some tantalizing hints that DPP-4 inhibitors may offer some level of protection against major cardiovascular events in type 2 diabetes patients.

The analysis, which included data on more than 33,000 patients, found a consistent 31% reduction in major cardiovascular events among those who took dipeptidyl peptidase–4 (DPP-4) inhibitors, compared with those taking placebo or other treatments, Dr. Edoardo Mannucci reported at the annual meeting of the European Association for the Study of Diabetes.

Despite the positive findings, Dr. Mannucci, of the Careggi Teaching Hospital in Florence, Italy, warned against taking the data as gospel.

"The limitations here are clear," he said. "Cardiovascular events were not end points in any of these trials, and were [reported only] as major adverse events. Also, since they were not prespecified end points, there is a possibility that some of the cases could have been misclassified."

Additionally, none of the trials enrolled patients who were at a high risk of cardiovascular events. "These subjects are not very likely to be included in trials with metabolic outcomes, so we really don’t know the effect on those people."

Still, he said, the consistency of the findings "suggests the possibility of some unconventional cardiovascular protective effect that deserves further investigation."

Dr. Mannucci and his colleagues examined 42 phase III trials completed through March 2011 that included one of four DPP-4 inhibitors: saxagliptin, sitagliptin, alogliptin, and vildagliptin. (The latter two are not available in the United States.) Among placebo-controlled trials, 137 events occurred, and in comparator trials, 120 occurred.

Overall, the hazard ratios for a major cardiovascular event were 0.63 for alogliptin, 0.66 for saxagliptin, 0.74 for sitagliptin, and 0.67 for vildagliptin, compared with placebo. All the comparisons were statistically significant, he said.

In the comparator trials, none of the difference in cardiovascular events between drug regimens reached statistical significance, but the trend in favor of the DPP-4 inhibitors was similar to the findings in the placebo-controlled studies, he said.

Dr. Mannucci speculated that the lack of significance could be related to the low incidence of a major cardiovascular event in these trials, ranging from one event in an acarbose study to five each in studies with metformin and sulfonylureas.

Considering all of the 26 placebo-controlled and 16 comparator studies, the odds ratio in favor of the DPP-4 drugs was 0.69, "easily reaching statistical significance," with a P value of .006, Dr. Mannucci said.

When the trials were divided by duration, those less than 52 weeks (30) were significantly in favor of the drugs (OR, 0.62). For those 52 weeks or longer, the result was not significant (OR, 0.83).

Despite the analysis’s limitations, the unexpected observation raises intriguing questions, Dr. Mannucci said, including the possible rapidity of a cardiovascular benefit in the shorter trials. "Usually when we treat any risk factor for cardiovascular disease, we need several years to see any effect on major cardiovascular events. This is true for blood pressure, blood lipids, and blood glucose, and here we see agents that work on blood glucose and show an effect in a few months. This points to speculation that some unconventional cardioprotective effect occurs, which does not require a lot of incubation."

There are no proven mechanistic actions for the observed risk reductions, but Dr. Mannucci said that preclinical studies of the DPP-4 drugs provide some hints, including a direct myocardial effect, GLP-1 stimulation, myocardial protection from ischemia, and recruitment of endothelial cell progenitors."

"We are somewhat stretching the data here, because these trials were not designed for this end point," he acknowledged. "These findings are not fully reliable and we must admit that. But we won’t have any data with credible reliability for the next 4-5 years, so in the meanwhile, even data with some problems could give us some further information."

Dr. Carolyn Deacon, a medical physiologist at Panum Institute in Copenhagen, said that the meta-analysis offers some reassurance to those who are concerned about the cardiovascular safety of any drug. "When we get all the data for the DPP-4–inhibitor trials and the GLP-1 analogues, and examine cardiovascular events for these outcomes, we’ll know much more. But we are getting preclinical data that look positive, so we’re moving in the right direction," she noted.

The preclinical data suggest that the DPP-4 inhibitors may act directly on the heart, induce vasodilation, and improve endothelial function, Dr. Deacon added. "But right now, we cannot separate those benefits from the improved metabolic profile that the drugs induce, so I don’t want to raise hopes too much."

Dr. Mannucci disclosed relationships with Astra Zeneca, Boehringer Ingelheim, Eli Lilly Merck, Bristol-Myers Squibb, Novartis, and Takeda. Dr. Deacon disclosed a number of relationships with pharmaceutical companies involved in diabetes research.

LISBON – A new meta-analysis offers some tantalizing hints that DPP-4 inhibitors may offer some level of protection against major cardiovascular events in type 2 diabetes patients.

The analysis, which included data on more than 33,000 patients, found a consistent 31% reduction in major cardiovascular events among those who took dipeptidyl peptidase–4 (DPP-4) inhibitors, compared with those taking placebo or other treatments, Dr. Edoardo Mannucci reported at the annual meeting of the European Association for the Study of Diabetes.

Despite the positive findings, Dr. Mannucci, of the Careggi Teaching Hospital in Florence, Italy, warned against taking the data as gospel.

"The limitations here are clear," he said. "Cardiovascular events were not end points in any of these trials, and were [reported only] as major adverse events. Also, since they were not prespecified end points, there is a possibility that some of the cases could have been misclassified."

Additionally, none of the trials enrolled patients who were at a high risk of cardiovascular events. "These subjects are not very likely to be included in trials with metabolic outcomes, so we really don’t know the effect on those people."

Still, he said, the consistency of the findings "suggests the possibility of some unconventional cardiovascular protective effect that deserves further investigation."

Dr. Mannucci and his colleagues examined 42 phase III trials completed through March 2011 that included one of four DPP-4 inhibitors: saxagliptin, sitagliptin, alogliptin, and vildagliptin. (The latter two are not available in the United States.) Among placebo-controlled trials, 137 events occurred, and in comparator trials, 120 occurred.

Overall, the hazard ratios for a major cardiovascular event were 0.63 for alogliptin, 0.66 for saxagliptin, 0.74 for sitagliptin, and 0.67 for vildagliptin, compared with placebo. All the comparisons were statistically significant, he said.

In the comparator trials, none of the difference in cardiovascular events between drug regimens reached statistical significance, but the trend in favor of the DPP-4 inhibitors was similar to the findings in the placebo-controlled studies, he said.

Dr. Mannucci speculated that the lack of significance could be related to the low incidence of a major cardiovascular event in these trials, ranging from one event in an acarbose study to five each in studies with metformin and sulfonylureas.

Considering all of the 26 placebo-controlled and 16 comparator studies, the odds ratio in favor of the DPP-4 drugs was 0.69, "easily reaching statistical significance," with a P value of .006, Dr. Mannucci said.

When the trials were divided by duration, those less than 52 weeks (30) were significantly in favor of the drugs (OR, 0.62). For those 52 weeks or longer, the result was not significant (OR, 0.83).

Despite the analysis’s limitations, the unexpected observation raises intriguing questions, Dr. Mannucci said, including the possible rapidity of a cardiovascular benefit in the shorter trials. "Usually when we treat any risk factor for cardiovascular disease, we need several years to see any effect on major cardiovascular events. This is true for blood pressure, blood lipids, and blood glucose, and here we see agents that work on blood glucose and show an effect in a few months. This points to speculation that some unconventional cardioprotective effect occurs, which does not require a lot of incubation."

There are no proven mechanistic actions for the observed risk reductions, but Dr. Mannucci said that preclinical studies of the DPP-4 drugs provide some hints, including a direct myocardial effect, GLP-1 stimulation, myocardial protection from ischemia, and recruitment of endothelial cell progenitors."

"We are somewhat stretching the data here, because these trials were not designed for this end point," he acknowledged. "These findings are not fully reliable and we must admit that. But we won’t have any data with credible reliability for the next 4-5 years, so in the meanwhile, even data with some problems could give us some further information."

Dr. Carolyn Deacon, a medical physiologist at Panum Institute in Copenhagen, said that the meta-analysis offers some reassurance to those who are concerned about the cardiovascular safety of any drug. "When we get all the data for the DPP-4–inhibitor trials and the GLP-1 analogues, and examine cardiovascular events for these outcomes, we’ll know much more. But we are getting preclinical data that look positive, so we’re moving in the right direction," she noted.

The preclinical data suggest that the DPP-4 inhibitors may act directly on the heart, induce vasodilation, and improve endothelial function, Dr. Deacon added. "But right now, we cannot separate those benefits from the improved metabolic profile that the drugs induce, so I don’t want to raise hopes too much."

Dr. Mannucci disclosed relationships with Astra Zeneca, Boehringer Ingelheim, Eli Lilly Merck, Bristol-Myers Squibb, Novartis, and Takeda. Dr. Deacon disclosed a number of relationships with pharmaceutical companies involved in diabetes research.

LISBON – A new meta-analysis offers some tantalizing hints that DPP-4 inhibitors may offer some level of protection against major cardiovascular events in type 2 diabetes patients.

The analysis, which included data on more than 33,000 patients, found a consistent 31% reduction in major cardiovascular events among those who took dipeptidyl peptidase–4 (DPP-4) inhibitors, compared with those taking placebo or other treatments, Dr. Edoardo Mannucci reported at the annual meeting of the European Association for the Study of Diabetes.

Despite the positive findings, Dr. Mannucci, of the Careggi Teaching Hospital in Florence, Italy, warned against taking the data as gospel.

"The limitations here are clear," he said. "Cardiovascular events were not end points in any of these trials, and were [reported only] as major adverse events. Also, since they were not prespecified end points, there is a possibility that some of the cases could have been misclassified."

Additionally, none of the trials enrolled patients who were at a high risk of cardiovascular events. "These subjects are not very likely to be included in trials with metabolic outcomes, so we really don’t know the effect on those people."

Still, he said, the consistency of the findings "suggests the possibility of some unconventional cardiovascular protective effect that deserves further investigation."

Dr. Mannucci and his colleagues examined 42 phase III trials completed through March 2011 that included one of four DPP-4 inhibitors: saxagliptin, sitagliptin, alogliptin, and vildagliptin. (The latter two are not available in the United States.) Among placebo-controlled trials, 137 events occurred, and in comparator trials, 120 occurred.

Overall, the hazard ratios for a major cardiovascular event were 0.63 for alogliptin, 0.66 for saxagliptin, 0.74 for sitagliptin, and 0.67 for vildagliptin, compared with placebo. All the comparisons were statistically significant, he said.

In the comparator trials, none of the difference in cardiovascular events between drug regimens reached statistical significance, but the trend in favor of the DPP-4 inhibitors was similar to the findings in the placebo-controlled studies, he said.

Dr. Mannucci speculated that the lack of significance could be related to the low incidence of a major cardiovascular event in these trials, ranging from one event in an acarbose study to five each in studies with metformin and sulfonylureas.

Considering all of the 26 placebo-controlled and 16 comparator studies, the odds ratio in favor of the DPP-4 drugs was 0.69, "easily reaching statistical significance," with a P value of .006, Dr. Mannucci said.

When the trials were divided by duration, those less than 52 weeks (30) were significantly in favor of the drugs (OR, 0.62). For those 52 weeks or longer, the result was not significant (OR, 0.83).

Despite the analysis’s limitations, the unexpected observation raises intriguing questions, Dr. Mannucci said, including the possible rapidity of a cardiovascular benefit in the shorter trials. "Usually when we treat any risk factor for cardiovascular disease, we need several years to see any effect on major cardiovascular events. This is true for blood pressure, blood lipids, and blood glucose, and here we see agents that work on blood glucose and show an effect in a few months. This points to speculation that some unconventional cardioprotective effect occurs, which does not require a lot of incubation."

There are no proven mechanistic actions for the observed risk reductions, but Dr. Mannucci said that preclinical studies of the DPP-4 drugs provide some hints, including a direct myocardial effect, GLP-1 stimulation, myocardial protection from ischemia, and recruitment of endothelial cell progenitors."

"We are somewhat stretching the data here, because these trials were not designed for this end point," he acknowledged. "These findings are not fully reliable and we must admit that. But we won’t have any data with credible reliability for the next 4-5 years, so in the meanwhile, even data with some problems could give us some further information."

Dr. Carolyn Deacon, a medical physiologist at Panum Institute in Copenhagen, said that the meta-analysis offers some reassurance to those who are concerned about the cardiovascular safety of any drug. "When we get all the data for the DPP-4–inhibitor trials and the GLP-1 analogues, and examine cardiovascular events for these outcomes, we’ll know much more. But we are getting preclinical data that look positive, so we’re moving in the right direction," she noted.

The preclinical data suggest that the DPP-4 inhibitors may act directly on the heart, induce vasodilation, and improve endothelial function, Dr. Deacon added. "But right now, we cannot separate those benefits from the improved metabolic profile that the drugs induce, so I don’t want to raise hopes too much."

Dr. Mannucci disclosed relationships with Astra Zeneca, Boehringer Ingelheim, Eli Lilly Merck, Bristol-Myers Squibb, Novartis, and Takeda. Dr. Deacon disclosed a number of relationships with pharmaceutical companies involved in diabetes research.

When you assess a patient with a swollen joint, limited range of motion, and/or pain, consider a diagnosis of juvenile idiopathic arthritis.

Start with a detailed history and physical examination. Questions to ask include: How long have the symptoms been present? Was the onset acute or gradual? What is its severity? Ask the patient to rate the severity of pain. Use a 0-10 rating scale in older children and a faces scale in younger kids. Remember that not all children with oligoarticular juvenile idiopathic arthritis (JIA) experience pain.

Is there interference with school or any other activities? Are the symptoms improving or getting worse?

Also inquire about diurnal variation: Are symptoms more problematic in the morning or evening? Stiffness in the morning or following prolonged inactivity is a classic sign of arthritis in children as well as in adults. Also, what medications or other strategies has the patient tried, and how successful where they?

Inquire about associated symptoms. Fever, cutaneous eruption, weight loss, abdominal pain, diarrhea, and behavioral or visual changes are examples. Ocular inflammation is a common feature of some of the subtypes of juvenile arthritis.

Ask the patient or family about a history of trauma to rule out a fracture or significant intraarticular injury. Keep in mind that even chronic swelling of a joint sometimes may be an orthopedic issue.

One diagnosis you don’t want to miss is malignancy. You think automatically about arthritis when a child presents with joint pain, but all pediatric rheumatologists see a few children each year who turn out to have cancer instead. So be sure that pain truly is localized to the joint, and it’s not bone pain which may reflect the presence of leukemia, lymphoma, or another malignancy.

Remember arthritis is not always the primary disorder. During the initial evaluation you might see a child with inflammation of two of three joints. If you don’t ask about recurrent abdominal pain and/or low-grade fever, you may miss the fact that their arthritis is part of inflammatory bowel disease. If you have any questions about the primary vs. secondary nature of a child’s arthritis, refer the patient to a pediatric rheumatologist for further evaluation. The differential diagnosis for juvenile idiopathic arthritis (now the preferred name replacing "juvenile rheumatoid arthritis") can be lengthy.

Once a diagnosis of JIA is confirmed, a pediatric rheumatologist is best qualified to oversee ongoing care of the patient. Compared with 20 years ago, there are now a great many new agents specifically tailored to treat JIA (particularly biologics), and these medications require that those familiar with dosing schedules and side effects direct their administration. A medication that works well for one subtype of JIA may not work as well for another.

Physical and occupational therapists are critical for a successful approach to children with chronic arthritis. Their involvement helps to maintain range of motion, muscle strength, and endurance while preventing joint contractures and abnormalities of bone growth. The overall goal is to "mainstream" children back to their usual activities. However, if they participated in rugby, ice hockey, or tackle football, we will try to steer these patients to activities with a lower potential for direct trauma. We don’t want a child to be isolated from their peers.

It also is important not to overtest children with suspected arthritis. Laboratory testing is indicated if you strongly suspect an inflammatory process rather than for a child with vague aches and pains. Appropriate initial assays often include a complete blood count, urinalysis, sedimentation rate, and measurement of the C-reactive protein.

Tests such as an ANA (antinuclear antibody) and rheumatoid factor should be reserved for those children with symptoms and signs more likely to be associated with an inflammatory condition. These tests may be misleading with frequent false-positive results that cause undue anxiety for the patient and their family.

For more information on when to refer your patient, see the American College of Rheumatology’s 2010 Guidelines for the Referral of Children and Adolescents to Pediatric Rheumatologists.

Dr. Goldsmith is professor of pediatrics at Drexel University and chief of the rheumatology section at St. Christopher’s Hospital for Children, both in Philadelphia. Dr. Goldsmith said that he has no relevant financial disclosures.

This column, "Subspecialist Consult," appears regularly in Pediatric News, a publication of Elsevier.

When you assess a patient with a swollen joint, limited range of motion, and/or pain, consider a diagnosis of juvenile idiopathic arthritis.

Start with a detailed history and physical examination. Questions to ask include: How long have the symptoms been present? Was the onset acute or gradual? What is its severity? Ask the patient to rate the severity of pain. Use a 0-10 rating scale in older children and a faces scale in younger kids. Remember that not all children with oligoarticular juvenile idiopathic arthritis (JIA) experience pain.

Is there interference with school or any other activities? Are the symptoms improving or getting worse?

Also inquire about diurnal variation: Are symptoms more problematic in the morning or evening? Stiffness in the morning or following prolonged inactivity is a classic sign of arthritis in children as well as in adults. Also, what medications or other strategies has the patient tried, and how successful where they?

Inquire about associated symptoms. Fever, cutaneous eruption, weight loss, abdominal pain, diarrhea, and behavioral or visual changes are examples. Ocular inflammation is a common feature of some of the subtypes of juvenile arthritis.

Ask the patient or family about a history of trauma to rule out a fracture or significant intraarticular injury. Keep in mind that even chronic swelling of a joint sometimes may be an orthopedic issue.

One diagnosis you don’t want to miss is malignancy. You think automatically about arthritis when a child presents with joint pain, but all pediatric rheumatologists see a few children each year who turn out to have cancer instead. So be sure that pain truly is localized to the joint, and it’s not bone pain which may reflect the presence of leukemia, lymphoma, or another malignancy.

Remember arthritis is not always the primary disorder. During the initial evaluation you might see a child with inflammation of two of three joints. If you don’t ask about recurrent abdominal pain and/or low-grade fever, you may miss the fact that their arthritis is part of inflammatory bowel disease. If you have any questions about the primary vs. secondary nature of a child’s arthritis, refer the patient to a pediatric rheumatologist for further evaluation. The differential diagnosis for juvenile idiopathic arthritis (now the preferred name replacing "juvenile rheumatoid arthritis") can be lengthy.

Once a diagnosis of JIA is confirmed, a pediatric rheumatologist is best qualified to oversee ongoing care of the patient. Compared with 20 years ago, there are now a great many new agents specifically tailored to treat JIA (particularly biologics), and these medications require that those familiar with dosing schedules and side effects direct their administration. A medication that works well for one subtype of JIA may not work as well for another.

Physical and occupational therapists are critical for a successful approach to children with chronic arthritis. Their involvement helps to maintain range of motion, muscle strength, and endurance while preventing joint contractures and abnormalities of bone growth. The overall goal is to "mainstream" children back to their usual activities. However, if they participated in rugby, ice hockey, or tackle football, we will try to steer these patients to activities with a lower potential for direct trauma. We don’t want a child to be isolated from their peers.

It also is important not to overtest children with suspected arthritis. Laboratory testing is indicated if you strongly suspect an inflammatory process rather than for a child with vague aches and pains. Appropriate initial assays often include a complete blood count, urinalysis, sedimentation rate, and measurement of the C-reactive protein.

Tests such as an ANA (antinuclear antibody) and rheumatoid factor should be reserved for those children with symptoms and signs more likely to be associated with an inflammatory condition. These tests may be misleading with frequent false-positive results that cause undue anxiety for the patient and their family.

For more information on when to refer your patient, see the American College of Rheumatology’s 2010 Guidelines for the Referral of Children and Adolescents to Pediatric Rheumatologists.

Dr. Goldsmith is professor of pediatrics at Drexel University and chief of the rheumatology section at St. Christopher’s Hospital for Children, both in Philadelphia. Dr. Goldsmith said that he has no relevant financial disclosures.

This column, "Subspecialist Consult," appears regularly in Pediatric News, a publication of Elsevier.

When you assess a patient with a swollen joint, limited range of motion, and/or pain, consider a diagnosis of juvenile idiopathic arthritis.

Start with a detailed history and physical examination. Questions to ask include: How long have the symptoms been present? Was the onset acute or gradual? What is its severity? Ask the patient to rate the severity of pain. Use a 0-10 rating scale in older children and a faces scale in younger kids. Remember that not all children with oligoarticular juvenile idiopathic arthritis (JIA) experience pain.

Is there interference with school or any other activities? Are the symptoms improving or getting worse?

Also inquire about diurnal variation: Are symptoms more problematic in the morning or evening? Stiffness in the morning or following prolonged inactivity is a classic sign of arthritis in children as well as in adults. Also, what medications or other strategies has the patient tried, and how successful where they?

Inquire about associated symptoms. Fever, cutaneous eruption, weight loss, abdominal pain, diarrhea, and behavioral or visual changes are examples. Ocular inflammation is a common feature of some of the subtypes of juvenile arthritis.

Ask the patient or family about a history of trauma to rule out a fracture or significant intraarticular injury. Keep in mind that even chronic swelling of a joint sometimes may be an orthopedic issue.

One diagnosis you don’t want to miss is malignancy. You think automatically about arthritis when a child presents with joint pain, but all pediatric rheumatologists see a few children each year who turn out to have cancer instead. So be sure that pain truly is localized to the joint, and it’s not bone pain which may reflect the presence of leukemia, lymphoma, or another malignancy.

Remember arthritis is not always the primary disorder. During the initial evaluation you might see a child with inflammation of two of three joints. If you don’t ask about recurrent abdominal pain and/or low-grade fever, you may miss the fact that their arthritis is part of inflammatory bowel disease. If you have any questions about the primary vs. secondary nature of a child’s arthritis, refer the patient to a pediatric rheumatologist for further evaluation. The differential diagnosis for juvenile idiopathic arthritis (now the preferred name replacing "juvenile rheumatoid arthritis") can be lengthy.

Once a diagnosis of JIA is confirmed, a pediatric rheumatologist is best qualified to oversee ongoing care of the patient. Compared with 20 years ago, there are now a great many new agents specifically tailored to treat JIA (particularly biologics), and these medications require that those familiar with dosing schedules and side effects direct their administration. A medication that works well for one subtype of JIA may not work as well for another.

Physical and occupational therapists are critical for a successful approach to children with chronic arthritis. Their involvement helps to maintain range of motion, muscle strength, and endurance while preventing joint contractures and abnormalities of bone growth. The overall goal is to "mainstream" children back to their usual activities. However, if they participated in rugby, ice hockey, or tackle football, we will try to steer these patients to activities with a lower potential for direct trauma. We don’t want a child to be isolated from their peers.

It also is important not to overtest children with suspected arthritis. Laboratory testing is indicated if you strongly suspect an inflammatory process rather than for a child with vague aches and pains. Appropriate initial assays often include a complete blood count, urinalysis, sedimentation rate, and measurement of the C-reactive protein.

Tests such as an ANA (antinuclear antibody) and rheumatoid factor should be reserved for those children with symptoms and signs more likely to be associated with an inflammatory condition. These tests may be misleading with frequent false-positive results that cause undue anxiety for the patient and their family.

For more information on when to refer your patient, see the American College of Rheumatology’s 2010 Guidelines for the Referral of Children and Adolescents to Pediatric Rheumatologists.

Dr. Goldsmith is professor of pediatrics at Drexel University and chief of the rheumatology section at St. Christopher’s Hospital for Children, both in Philadelphia. Dr. Goldsmith said that he has no relevant financial disclosures.

This column, "Subspecialist Consult," appears regularly in Pediatric News, a publication of Elsevier.