Larry Hand

NEW YORK (Reuters Health) - Type 2 diabetes risk appears to be increased in youth who are treated with antipsychotics, according to new research.

"We believe that clinicians should take away from our study that type 2 diabetes is a risk when treating youth with antipsychotics, especially long-term," said senior author Dr. Christoff U. Correll of Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York.

"Therefore, antipsychotics should be used judiciously and for as short a period as necessary and possible," he told Reuters Health by email. "Importantly, clinicians should routinely and proactively monitor the efficacy and need for ongoing antipsychotic treatment as well as the potential emergence of adverse effects. Specifically, clinicians and patients, as well as parents, should monitor weight change monthly, and fasting blood work for blood sugar and blood lipids

should be obtained before starting an antipsychotic, three months later, and every six months thereafter."

Dr. Correll and colleagues conducted a systematic review of studies reporting on type 2 diabetes incidence in youth up to 24 years old who were exposed to antipsychotics for at least three months. They did a meta-analysis of thirteen studies involving more than 185,000 youth exposed to antipsychotics, representing some 310,000 patient-years.

Seven studies included psychiatric controls and eight studies included healthy controls.

During a mean follow-up of 1.7 years, the cumulative type 2 diabetes risk was 5.72 per 1,000 patient-years (p<0.001). The overall incidence rate was 3.09 cases per 1,000 patient-years (p<0.001), according to an article online January 20 in JAMA Psychiatry.

Compared with healthy controls, antipsychotic-exposed youth had significantly higher cumulative type 2 diabetes risk (odds ratio, 2.58; p<0.0001) and incidence rate ratio (IRR, 3.02; p<0.0001). Compared with psychiatric controls, they had significantly higher risks (OR 2.09, p<0.0001, IRR 1.79,p<0.0001).

In multivariate regression analysis of 10 studies, diabetes was associated with longer follow-up, use of olanzapine, and male sex. Greater diabetes incidence was tied to use of second-generation antipsychotics, while it was inversely related to diagnosis of autism spectrum disorder.

"Although our findings cannot comment on the individual risk with any specific antipsychotic other than the significantly higher risk associated with olanzapine, other studies equally suggest the much increased cardiovascular risk associates with olanzapine than with other antipsychotics in youth. Based on all of these data, I personally believe that olanzapine should not be used first- or second-line in youth, but likely be reserved or treatment-resistant patients who cannot benefit sufficiently from antipsychotics with lower cardiometabolic risk," Dr. Correll told Reuters Health.

"Clearly, additional research is needed to identify the specific mechanisms of antipsychotic-related weight gain and development of diabetes in order to either counter these effects or develop medications that do not adversely affect cardiometabolic health," he added. "Moreover, research is needed seeking to identify patients who are at particularly high risk for weight gain and diabetes and those who seem to be protected against these antipsychotic-related side effects to help individualize treatment selection."

"Finally," he concluded, "research is required that tests lower-risk pharmacologic and nonpharmacologic interventions that may be used effectively before or instead of an antipsychotic when treating nonpsychotic conditions. This need pertains especially to youth presenting with severe mood or behavioral dysregulation, irritability, and aggression for whom antipsychotics are used a lot, often without even providing psychosocial treatments."

NEW YORK (Reuters Health) - Type 2 diabetes risk appears to be increased in youth who are treated with antipsychotics, according to new research.

"We believe that clinicians should take away from our study that type 2 diabetes is a risk when treating youth with antipsychotics, especially long-term," said senior author Dr. Christoff U. Correll of Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York.

"Therefore, antipsychotics should be used judiciously and for as short a period as necessary and possible," he told Reuters Health by email. "Importantly, clinicians should routinely and proactively monitor the efficacy and need for ongoing antipsychotic treatment as well as the potential emergence of adverse effects. Specifically, clinicians and patients, as well as parents, should monitor weight change monthly, and fasting blood work for blood sugar and blood lipids

should be obtained before starting an antipsychotic, three months later, and every six months thereafter."

Dr. Correll and colleagues conducted a systematic review of studies reporting on type 2 diabetes incidence in youth up to 24 years old who were exposed to antipsychotics for at least three months. They did a meta-analysis of thirteen studies involving more than 185,000 youth exposed to antipsychotics, representing some 310,000 patient-years.

Seven studies included psychiatric controls and eight studies included healthy controls.

During a mean follow-up of 1.7 years, the cumulative type 2 diabetes risk was 5.72 per 1,000 patient-years (p<0.001). The overall incidence rate was 3.09 cases per 1,000 patient-years (p<0.001), according to an article online January 20 in JAMA Psychiatry.

Compared with healthy controls, antipsychotic-exposed youth had significantly higher cumulative type 2 diabetes risk (odds ratio, 2.58; p<0.0001) and incidence rate ratio (IRR, 3.02; p<0.0001). Compared with psychiatric controls, they had significantly higher risks (OR 2.09, p<0.0001, IRR 1.79,p<0.0001).

In multivariate regression analysis of 10 studies, diabetes was associated with longer follow-up, use of olanzapine, and male sex. Greater diabetes incidence was tied to use of second-generation antipsychotics, while it was inversely related to diagnosis of autism spectrum disorder.

"Although our findings cannot comment on the individual risk with any specific antipsychotic other than the significantly higher risk associated with olanzapine, other studies equally suggest the much increased cardiovascular risk associates with olanzapine than with other antipsychotics in youth. Based on all of these data, I personally believe that olanzapine should not be used first- or second-line in youth, but likely be reserved or treatment-resistant patients who cannot benefit sufficiently from antipsychotics with lower cardiometabolic risk," Dr. Correll told Reuters Health.

"Clearly, additional research is needed to identify the specific mechanisms of antipsychotic-related weight gain and development of diabetes in order to either counter these effects or develop medications that do not adversely affect cardiometabolic health," he added. "Moreover, research is needed seeking to identify patients who are at particularly high risk for weight gain and diabetes and those who seem to be protected against these antipsychotic-related side effects to help individualize treatment selection."

"Finally," he concluded, "research is required that tests lower-risk pharmacologic and nonpharmacologic interventions that may be used effectively before or instead of an antipsychotic when treating nonpsychotic conditions. This need pertains especially to youth presenting with severe mood or behavioral dysregulation, irritability, and aggression for whom antipsychotics are used a lot, often without even providing psychosocial treatments."

NEW YORK (Reuters Health) - Type 2 diabetes risk appears to be increased in youth who are treated with antipsychotics, according to new research.

"We believe that clinicians should take away from our study that type 2 diabetes is a risk when treating youth with antipsychotics, especially long-term," said senior author Dr. Christoff U. Correll of Zucker Hillside Hospital, North Shore-Long Island Jewish Health System, Glen Oaks, New York.

"Therefore, antipsychotics should be used judiciously and for as short a period as necessary and possible," he told Reuters Health by email. "Importantly, clinicians should routinely and proactively monitor the efficacy and need for ongoing antipsychotic treatment as well as the potential emergence of adverse effects. Specifically, clinicians and patients, as well as parents, should monitor weight change monthly, and fasting blood work for blood sugar and blood lipids

should be obtained before starting an antipsychotic, three months later, and every six months thereafter."

Dr. Correll and colleagues conducted a systematic review of studies reporting on type 2 diabetes incidence in youth up to 24 years old who were exposed to antipsychotics for at least three months. They did a meta-analysis of thirteen studies involving more than 185,000 youth exposed to antipsychotics, representing some 310,000 patient-years.

Seven studies included psychiatric controls and eight studies included healthy controls.

During a mean follow-up of 1.7 years, the cumulative type 2 diabetes risk was 5.72 per 1,000 patient-years (p<0.001). The overall incidence rate was 3.09 cases per 1,000 patient-years (p<0.001), according to an article online January 20 in JAMA Psychiatry.

Compared with healthy controls, antipsychotic-exposed youth had significantly higher cumulative type 2 diabetes risk (odds ratio, 2.58; p<0.0001) and incidence rate ratio (IRR, 3.02; p<0.0001). Compared with psychiatric controls, they had significantly higher risks (OR 2.09, p<0.0001, IRR 1.79,p<0.0001).

In multivariate regression analysis of 10 studies, diabetes was associated with longer follow-up, use of olanzapine, and male sex. Greater diabetes incidence was tied to use of second-generation antipsychotics, while it was inversely related to diagnosis of autism spectrum disorder.

"Although our findings cannot comment on the individual risk with any specific antipsychotic other than the significantly higher risk associated with olanzapine, other studies equally suggest the much increased cardiovascular risk associates with olanzapine than with other antipsychotics in youth. Based on all of these data, I personally believe that olanzapine should not be used first- or second-line in youth, but likely be reserved or treatment-resistant patients who cannot benefit sufficiently from antipsychotics with lower cardiometabolic risk," Dr. Correll told Reuters Health.

"Clearly, additional research is needed to identify the specific mechanisms of antipsychotic-related weight gain and development of diabetes in order to either counter these effects or develop medications that do not adversely affect cardiometabolic health," he added. "Moreover, research is needed seeking to identify patients who are at particularly high risk for weight gain and diabetes and those who seem to be protected against these antipsychotic-related side effects to help individualize treatment selection."

"Finally," he concluded, "research is required that tests lower-risk pharmacologic and nonpharmacologic interventions that may be used effectively before or instead of an antipsychotic when treating nonpsychotic conditions. This need pertains especially to youth presenting with severe mood or behavioral dysregulation, irritability, and aggression for whom antipsychotics are used a lot, often without even providing psychosocial treatments."

NEW YORK - Hospital resources, and not necessarily patient characteristics, may be causing safety-net hospitals to deliver inferior surgical outcomes at increased cost in elective surgical procedures, according to a new study.

"Analysis of Medicare Hospital Compare data revealed that safety-net hospitals perform worse on Surgical Care Improvement Project (SCIP) measures and have less efficient emergency departments throughput," first author Dr. Richard S. Hoehn from the University of Cincinnati, Ohio, said by email. "This last category indicates that these hospitals have insufficient staffing and/or resources to handle their patient burden."

"Safety-net hospitals care for a vulnerable population and maintain an open door to all patients, regardless of their ability to pay. Our study of nine major surgical procedures at academic medical centers in the United States found that hospitals with the highest safety net burden have the most patients of low socioeconomic status, extreme severity of illness, and in need of urgent surgery," Dr. Hoehn said.

"These hospitals also had the worst mortality and readmission rates and highest costs for most procedures. After controlling for patient age, race, severity of illness, and socioeconomic status, safety-net hospitals still had worse outcomes. Their inferior mortality and readmission rates were somewhat reduced, but the increased costs observed at these centers persisted, implying that other characteristics intrinsic to safety-net hospitals are associated with increased costs," he added.

Dr. Hoehn and colleagues analyzed outcomes for nine surgical procedures at 231 hospitals in the University HealthSystem Consortium over a four-year period ending in 2012, accounting for more than 12.6 million patient encounters. They sorted the hospitals into high safety-net burden (HBH) versus hospitals with low (LBH) or medium (MBH) safety-net burden.

They found the HBHs overall to have the most patients likely to be young, black, have the lowest socioeconomic status, and have the highest severity of illness and the highest cost for surgical care (p<0.01 for all). They also had the highest proportion of patient-emergent cases and the longest lengths of stay (p<0.01 for all).

After the researchers adjusted for patient characteristics and hospital volume, the HBHs still had higher odds ratios of mortality for three procedures (OR, 1.81 to 2.08, p<0.05), readmission for two procedures (OR, 1.19 to 1.30, p<0.05), and the highest cost of care for seven procedures (risk ratios, 1.23 to 1.35, p<0.05).

Postoperative mortality was worse for colectomy, esophagectomy, pancreaticoduodenectomy, and ventral hernia repair. Readmission odds were higher for coronary artery bypass, colectomy, kidney transplant, and ventral hernia repair.

"[W]hen assessing markers of emergency department throughput, HBHs were inferior to LBHs in all measures, including time from arrival to evaluation, admission decision time, times from arrival to departure for discharged and admitted patients, time for pain medicine administration to patients with long-bone fractures, and patients who left without being seen (p <= 0.002 for all)," the researchers write in JAMA Surgery, online October 14.

In an accompanying editorial, Dr. Larry R. Kaiser of Temple University School of Medicine, Philadelphia, and colleagues note, "At best, emergency department throughput as a surrogate for staffing adequacy and systems efficiency is an indirect estimate of these important hospital factors. Deficiencies in documentation and coding may or may not be influenced by overall hospital performance but could have a significant influence on expected rates of death and complications."

Dr. Kaiser said by email, "Physicians and surgeons should be very careful in drawing substantive conclusions from the study because of factors we don't know about these patients. Let the message be greater resources should be provided to those hospitals bearing the burden of caring for this underserved population of patients who, if anything, are more complex than commercially insured patients with similar problems."

"It's important to acknowledge that this study is not trying to criticize safety-net hospitals," Dr. Hoehn emphasized. "We are trying to highlight the unique situation these providers face, and also show that current policy changes that financially penalize these hospitals may adversely impact surgical care and further exacerbate the disparities in health care that already exist in our country. Safety-net hospitals in America have always been important institutions that train doctors and care for indigent patients, and our goal is to find a way to preserve this model in the face of changing healthcare policy."

Dr. Hoehn continued, "There are two options to improve the care at these centers: either close these hospitals and send their patients elsewhere or invest in initiatives that will allow these hospitals to improve not only their outcomes but also their efficiency. To do this, we must better understand their needs."

Dr. Kaiser said, "Continued scrutiny of outcomes with transparency and sharing of data with all those involved in the care of patients will result in continued quality improvement. Participation in [universal health care] that allows institutions to benchmark their data with similar institutions will tend to push those who need improvement to continue to improve."

"There must be a concerted effort among all involved in caring for patients at an institution to continue to improve quality. The designation of a chief quality officer working in concert with the chief medical officer also is critically important in working toward improved quality. But all of this depends on accurate recording and reporting of quality metrics," he concluded.

NEW YORK - Hospital resources, and not necessarily patient characteristics, may be causing safety-net hospitals to deliver inferior surgical outcomes at increased cost in elective surgical procedures, according to a new study.

"Analysis of Medicare Hospital Compare data revealed that safety-net hospitals perform worse on Surgical Care Improvement Project (SCIP) measures and have less efficient emergency departments throughput," first author Dr. Richard S. Hoehn from the University of Cincinnati, Ohio, said by email. "This last category indicates that these hospitals have insufficient staffing and/or resources to handle their patient burden."

"Safety-net hospitals care for a vulnerable population and maintain an open door to all patients, regardless of their ability to pay. Our study of nine major surgical procedures at academic medical centers in the United States found that hospitals with the highest safety net burden have the most patients of low socioeconomic status, extreme severity of illness, and in need of urgent surgery," Dr. Hoehn said.

"These hospitals also had the worst mortality and readmission rates and highest costs for most procedures. After controlling for patient age, race, severity of illness, and socioeconomic status, safety-net hospitals still had worse outcomes. Their inferior mortality and readmission rates were somewhat reduced, but the increased costs observed at these centers persisted, implying that other characteristics intrinsic to safety-net hospitals are associated with increased costs," he added.

Dr. Hoehn and colleagues analyzed outcomes for nine surgical procedures at 231 hospitals in the University HealthSystem Consortium over a four-year period ending in 2012, accounting for more than 12.6 million patient encounters. They sorted the hospitals into high safety-net burden (HBH) versus hospitals with low (LBH) or medium (MBH) safety-net burden.

They found the HBHs overall to have the most patients likely to be young, black, have the lowest socioeconomic status, and have the highest severity of illness and the highest cost for surgical care (p<0.01 for all). They also had the highest proportion of patient-emergent cases and the longest lengths of stay (p<0.01 for all).

After the researchers adjusted for patient characteristics and hospital volume, the HBHs still had higher odds ratios of mortality for three procedures (OR, 1.81 to 2.08, p<0.05), readmission for two procedures (OR, 1.19 to 1.30, p<0.05), and the highest cost of care for seven procedures (risk ratios, 1.23 to 1.35, p<0.05).

Postoperative mortality was worse for colectomy, esophagectomy, pancreaticoduodenectomy, and ventral hernia repair. Readmission odds were higher for coronary artery bypass, colectomy, kidney transplant, and ventral hernia repair.

"[W]hen assessing markers of emergency department throughput, HBHs were inferior to LBHs in all measures, including time from arrival to evaluation, admission decision time, times from arrival to departure for discharged and admitted patients, time for pain medicine administration to patients with long-bone fractures, and patients who left without being seen (p <= 0.002 for all)," the researchers write in JAMA Surgery, online October 14.

In an accompanying editorial, Dr. Larry R. Kaiser of Temple University School of Medicine, Philadelphia, and colleagues note, "At best, emergency department throughput as a surrogate for staffing adequacy and systems efficiency is an indirect estimate of these important hospital factors. Deficiencies in documentation and coding may or may not be influenced by overall hospital performance but could have a significant influence on expected rates of death and complications."

Dr. Kaiser said by email, "Physicians and surgeons should be very careful in drawing substantive conclusions from the study because of factors we don't know about these patients. Let the message be greater resources should be provided to those hospitals bearing the burden of caring for this underserved population of patients who, if anything, are more complex than commercially insured patients with similar problems."

"It's important to acknowledge that this study is not trying to criticize safety-net hospitals," Dr. Hoehn emphasized. "We are trying to highlight the unique situation these providers face, and also show that current policy changes that financially penalize these hospitals may adversely impact surgical care and further exacerbate the disparities in health care that already exist in our country. Safety-net hospitals in America have always been important institutions that train doctors and care for indigent patients, and our goal is to find a way to preserve this model in the face of changing healthcare policy."

Dr. Hoehn continued, "There are two options to improve the care at these centers: either close these hospitals and send their patients elsewhere or invest in initiatives that will allow these hospitals to improve not only their outcomes but also their efficiency. To do this, we must better understand their needs."

Dr. Kaiser said, "Continued scrutiny of outcomes with transparency and sharing of data with all those involved in the care of patients will result in continued quality improvement. Participation in [universal health care] that allows institutions to benchmark their data with similar institutions will tend to push those who need improvement to continue to improve."

"There must be a concerted effort among all involved in caring for patients at an institution to continue to improve quality. The designation of a chief quality officer working in concert with the chief medical officer also is critically important in working toward improved quality. But all of this depends on accurate recording and reporting of quality metrics," he concluded.

NEW YORK - Hospital resources, and not necessarily patient characteristics, may be causing safety-net hospitals to deliver inferior surgical outcomes at increased cost in elective surgical procedures, according to a new study.

"Analysis of Medicare Hospital Compare data revealed that safety-net hospitals perform worse on Surgical Care Improvement Project (SCIP) measures and have less efficient emergency departments throughput," first author Dr. Richard S. Hoehn from the University of Cincinnati, Ohio, said by email. "This last category indicates that these hospitals have insufficient staffing and/or resources to handle their patient burden."

"Safety-net hospitals care for a vulnerable population and maintain an open door to all patients, regardless of their ability to pay. Our study of nine major surgical procedures at academic medical centers in the United States found that hospitals with the highest safety net burden have the most patients of low socioeconomic status, extreme severity of illness, and in need of urgent surgery," Dr. Hoehn said.

"These hospitals also had the worst mortality and readmission rates and highest costs for most procedures. After controlling for patient age, race, severity of illness, and socioeconomic status, safety-net hospitals still had worse outcomes. Their inferior mortality and readmission rates were somewhat reduced, but the increased costs observed at these centers persisted, implying that other characteristics intrinsic to safety-net hospitals are associated with increased costs," he added.

Dr. Hoehn and colleagues analyzed outcomes for nine surgical procedures at 231 hospitals in the University HealthSystem Consortium over a four-year period ending in 2012, accounting for more than 12.6 million patient encounters. They sorted the hospitals into high safety-net burden (HBH) versus hospitals with low (LBH) or medium (MBH) safety-net burden.

They found the HBHs overall to have the most patients likely to be young, black, have the lowest socioeconomic status, and have the highest severity of illness and the highest cost for surgical care (p<0.01 for all). They also had the highest proportion of patient-emergent cases and the longest lengths of stay (p<0.01 for all).

After the researchers adjusted for patient characteristics and hospital volume, the HBHs still had higher odds ratios of mortality for three procedures (OR, 1.81 to 2.08, p<0.05), readmission for two procedures (OR, 1.19 to 1.30, p<0.05), and the highest cost of care for seven procedures (risk ratios, 1.23 to 1.35, p<0.05).

Postoperative mortality was worse for colectomy, esophagectomy, pancreaticoduodenectomy, and ventral hernia repair. Readmission odds were higher for coronary artery bypass, colectomy, kidney transplant, and ventral hernia repair.

"[W]hen assessing markers of emergency department throughput, HBHs were inferior to LBHs in all measures, including time from arrival to evaluation, admission decision time, times from arrival to departure for discharged and admitted patients, time for pain medicine administration to patients with long-bone fractures, and patients who left without being seen (p <= 0.002 for all)," the researchers write in JAMA Surgery, online October 14.

In an accompanying editorial, Dr. Larry R. Kaiser of Temple University School of Medicine, Philadelphia, and colleagues note, "At best, emergency department throughput as a surrogate for staffing adequacy and systems efficiency is an indirect estimate of these important hospital factors. Deficiencies in documentation and coding may or may not be influenced by overall hospital performance but could have a significant influence on expected rates of death and complications."

Dr. Kaiser said by email, "Physicians and surgeons should be very careful in drawing substantive conclusions from the study because of factors we don't know about these patients. Let the message be greater resources should be provided to those hospitals bearing the burden of caring for this underserved population of patients who, if anything, are more complex than commercially insured patients with similar problems."

"It's important to acknowledge that this study is not trying to criticize safety-net hospitals," Dr. Hoehn emphasized. "We are trying to highlight the unique situation these providers face, and also show that current policy changes that financially penalize these hospitals may adversely impact surgical care and further exacerbate the disparities in health care that already exist in our country. Safety-net hospitals in America have always been important institutions that train doctors and care for indigent patients, and our goal is to find a way to preserve this model in the face of changing healthcare policy."

Dr. Hoehn continued, "There are two options to improve the care at these centers: either close these hospitals and send their patients elsewhere or invest in initiatives that will allow these hospitals to improve not only their outcomes but also their efficiency. To do this, we must better understand their needs."

Dr. Kaiser said, "Continued scrutiny of outcomes with transparency and sharing of data with all those involved in the care of patients will result in continued quality improvement. Participation in [universal health care] that allows institutions to benchmark their data with similar institutions will tend to push those who need improvement to continue to improve."

"There must be a concerted effort among all involved in caring for patients at an institution to continue to improve quality. The designation of a chief quality officer working in concert with the chief medical officer also is critically important in working toward improved quality. But all of this depends on accurate recording and reporting of quality metrics," he concluded.

NEW YORK - Initiation of antipsychotic or antidepressant drug treatment is linked to a reduction in hospitalizations for patients with schizophrenia, according to a new study.

"Use of sulpiride, mirtazapine, venlafaxine, and clozapine-aripiprazole and clozapine amisulpride combinations were associated with fewer subsequent admission-days in patients with schizophrenia," Dr. Rudolf N. Cardinal of the Behavioral and Clinical Neuroscience Institute, University of Cambridge, UK, said by email.

"These studies are correlative and do not prove causation," he cautioned.

Dr. Cardinal and colleagues analyzed eight years' of admission records at a secondary mental health care institution in Cambridgeshire. The analysis included nearly 1,500 patients with a diagnosis of schizophrenia and a median follow-up of five years.

In mirror-image analysis covering two years before and after therapy initiation, the researchers found treatment with amisulpride, aripiprazole, clozapine, fluoxetine, mirtazapine, olanzapine, quetiapine, and sulpiride was associated with fewer subsequent admissions in one year.

The association persisted in a "more stringent" two-year analysis for aripiprazole, clozapine, and sulpiride.

Using regression analysis, the researchers found a continued reduction in admissions with sulpiride and mirtazapine (estimated mean change, -20.4 and -11.6 days/year, respectively).

Treatment with clozapine-aripiprazole and clozapine-amisulpride combinations as well as venlafaxine was associated with significantly fewer hospitalized days (-17.7, -13.8, and -12.3 days/year, respectively).

Overall, the mean admission rate was 26.8 days/year.

"This analysis focused on patients with more severe disease, in that they had at least one hospital admission in the pre-drug period," the researchers note in the article online October 21 in NPJ Schizophrenia.

"Larger correlative studies are required to corroborate these effects, followed by randomized controlled trials if appropriate," Dr. Cardinal said. "We are all very keen that these are not misrepresented as causal-grade findings."

The authors reported no funding. One coauthor reported receiving research funding from Genus Pharmaceuticals and consulting fees from Roche/Genentech.

NEW YORK - Initiation of antipsychotic or antidepressant drug treatment is linked to a reduction in hospitalizations for patients with schizophrenia, according to a new study.

"Use of sulpiride, mirtazapine, venlafaxine, and clozapine-aripiprazole and clozapine amisulpride combinations were associated with fewer subsequent admission-days in patients with schizophrenia," Dr. Rudolf N. Cardinal of the Behavioral and Clinical Neuroscience Institute, University of Cambridge, UK, said by email.

"These studies are correlative and do not prove causation," he cautioned.

Dr. Cardinal and colleagues analyzed eight years' of admission records at a secondary mental health care institution in Cambridgeshire. The analysis included nearly 1,500 patients with a diagnosis of schizophrenia and a median follow-up of five years.

In mirror-image analysis covering two years before and after therapy initiation, the researchers found treatment with amisulpride, aripiprazole, clozapine, fluoxetine, mirtazapine, olanzapine, quetiapine, and sulpiride was associated with fewer subsequent admissions in one year.

The association persisted in a "more stringent" two-year analysis for aripiprazole, clozapine, and sulpiride.

Using regression analysis, the researchers found a continued reduction in admissions with sulpiride and mirtazapine (estimated mean change, -20.4 and -11.6 days/year, respectively).

Treatment with clozapine-aripiprazole and clozapine-amisulpride combinations as well as venlafaxine was associated with significantly fewer hospitalized days (-17.7, -13.8, and -12.3 days/year, respectively).

Overall, the mean admission rate was 26.8 days/year.

"This analysis focused on patients with more severe disease, in that they had at least one hospital admission in the pre-drug period," the researchers note in the article online October 21 in NPJ Schizophrenia.

"Larger correlative studies are required to corroborate these effects, followed by randomized controlled trials if appropriate," Dr. Cardinal said. "We are all very keen that these are not misrepresented as causal-grade findings."

The authors reported no funding. One coauthor reported receiving research funding from Genus Pharmaceuticals and consulting fees from Roche/Genentech.

NEW YORK - Initiation of antipsychotic or antidepressant drug treatment is linked to a reduction in hospitalizations for patients with schizophrenia, according to a new study.

"Use of sulpiride, mirtazapine, venlafaxine, and clozapine-aripiprazole and clozapine amisulpride combinations were associated with fewer subsequent admission-days in patients with schizophrenia," Dr. Rudolf N. Cardinal of the Behavioral and Clinical Neuroscience Institute, University of Cambridge, UK, said by email.

"These studies are correlative and do not prove causation," he cautioned.

Dr. Cardinal and colleagues analyzed eight years' of admission records at a secondary mental health care institution in Cambridgeshire. The analysis included nearly 1,500 patients with a diagnosis of schizophrenia and a median follow-up of five years.

In mirror-image analysis covering two years before and after therapy initiation, the researchers found treatment with amisulpride, aripiprazole, clozapine, fluoxetine, mirtazapine, olanzapine, quetiapine, and sulpiride was associated with fewer subsequent admissions in one year.

The association persisted in a "more stringent" two-year analysis for aripiprazole, clozapine, and sulpiride.

Using regression analysis, the researchers found a continued reduction in admissions with sulpiride and mirtazapine (estimated mean change, -20.4 and -11.6 days/year, respectively).

Treatment with clozapine-aripiprazole and clozapine-amisulpride combinations as well as venlafaxine was associated with significantly fewer hospitalized days (-17.7, -13.8, and -12.3 days/year, respectively).

Overall, the mean admission rate was 26.8 days/year.

"This analysis focused on patients with more severe disease, in that they had at least one hospital admission in the pre-drug period," the researchers note in the article online October 21 in NPJ Schizophrenia.

"Larger correlative studies are required to corroborate these effects, followed by randomized controlled trials if appropriate," Dr. Cardinal said. "We are all very keen that these are not misrepresented as causal-grade findings."

The authors reported no funding. One coauthor reported receiving research funding from Genus Pharmaceuticals and consulting fees from Roche/Genentech.

NEW YORK - Patients with lymphedema may reduce their risk of cellulitis, as well as the number of outpatient visits, by using an advanced pneumatic compression device (APCD), according to a new study.

"Our study demonstrates, for the first time, that receipt of an advanced pneumatic compression device is associated with significant improvements in key clinical endpoints for lymphedema patients, both for those with cancer and those without," Dr. Pinar Karaca-Mandic of the University of Minnesota School of Public Health in Minneapolis said by email.

"This finding has important implications for the patients who suffer from the disease, especially for those who have high rates of cellulitis. These devices serve as a viable self-management option and can reduce the need for more intensive outpatient care in rehabilitative settings," she added.

Advanced devices have more garment chambers and greater adjustability than earlier devices, the researchers wrote.

Dr. Karaca-Mandic and colleagues used a commercial insurance claims database to compare outcomes for 12 months before and 12 months after APCD purchase (Flexitouch System, Tactile Medical) by 718 patients (374 with cancer) between 2008 and 2012.

Lymphedema-related outcomes had either primary or secondary diagnosis codes.

The patients' mean age was 54.2, 84.8% were female, and 71.6% were non-Hispanic white. Just over half (52.2%) had hypertension, and breast cancer (39.6%) was the predominant disease in the cancer group.

As reported online October 7 in JAMA Dermatology, the adjusted rate of cellulitis diagnoses fell from 21.1% before APCD use to 4.5% afterward (p<0.001), a 79% decline. The noncancer group had a 75% decline, from 28.8% to 7.3% (p<0.001).

The noncancer group also had a 54% decline in adjusted rate of hospitalizations, from 7.0% to 3.2% (p=0.02), the authors reported.

Both groups had declines in receipt of manual therapy, from an adjusted rate of 35.6% before APCD use to 24.9% afterward for cancer patients (p<0.001) and from 32.3% to 21.2% for noncancer patients (p<0.001).

The adjusted rate of outpatient visits fell from 58.6% to 41.4% in the cancer cohort and from 52.6% to 31.4% in the noncancer group (p<0.001 for both).

Total costs per patient, excluding medical equipment, declined from $2597 to $1642 for cancer patients (p=0.002) and from $2937 to $1883 (p=0.007) for noncancer patients.

"While our findings are based upon the outcomes from one specific device, it is possible other such devices may also reduce patient burden. This warrants explorations in future studies. In addition, our study was not designed to assess the long term effectiveness of the device. That should be studied in future work," Dr. Karaca-Mandic explained.

Also, she pointed out, her team didn't look at nonmonetary expenses such as productivity loss and caretaker costs. "To the extent that device use improves physical functioning and lowers such costs as well, the impact is likely much larger than we can measure," she added.

Dr. Peter J. Franks, of the Center for Research and Implementation of Clinical Practice in London, UK, said by email, "We have these devices that appear to work. The problem is that the evidence on efficacy and cost effectiveness is so poor. The article gave some retrospective observational data that implied that the incidence of infection (cellulitis) was reduced. This is important, as infections lead to further deterioration of the lymphatic system, making the situation worse for the patient and increasing the risk of further infections."

"It is hard to say how generalizable the results are to other devices, though fundamentally they all work in similar ways," said Dr. Franks, who coauthored an accompanying editorial. "I think that this is an important step in how we consider the use of medical devices."

Cynthia Shechter, an occupational therapist in New York City who is a lymphedema specialist for cancer patients, said by email, "When looking for the right device, look for a pump that contains multiple chambers, operates on a short thirty-second cycle time, and applies graduated compression."

"The body operates on a pressure gradient system, so it is imperative to obtain a gradient or graduated compression pump. Pressure at the feet or hand is greater than the thigh or shoulder," she added.

"Clinicians practicing in the treatment of lymphedema need to be open-minded regarding less traditional treatment options for this insidious condition, including the use of traditional and advanced pneumatic compression devices," Shechter said.

"This study indicates that use of an APCD reduces the necessity for therapy. However, rehabilitation therapy for primary and secondary lymphedema, at least a short course of

treatment, is important, especially in order to ensure patients are adequately educated in lymphedema care, management, and precautions," she said.

"There should be a follow-up study performed to discuss a patient's ability to sustain use of the APCD versus a traditional pneumatic pump, and the long-term success in both preventing infection and in reduction of therapy visits," Shechter said.

Tactile Medical partially supported this research and employs one coauthor as chief medical officer. Dr. Karaca-Mandic, Dr. Franks, and his coauthor reported consulting for the company.

NEW YORK - Patients with lymphedema may reduce their risk of cellulitis, as well as the number of outpatient visits, by using an advanced pneumatic compression device (APCD), according to a new study.

"Our study demonstrates, for the first time, that receipt of an advanced pneumatic compression device is associated with significant improvements in key clinical endpoints for lymphedema patients, both for those with cancer and those without," Dr. Pinar Karaca-Mandic of the University of Minnesota School of Public Health in Minneapolis said by email.

"This finding has important implications for the patients who suffer from the disease, especially for those who have high rates of cellulitis. These devices serve as a viable self-management option and can reduce the need for more intensive outpatient care in rehabilitative settings," she added.

Advanced devices have more garment chambers and greater adjustability than earlier devices, the researchers wrote.

Dr. Karaca-Mandic and colleagues used a commercial insurance claims database to compare outcomes for 12 months before and 12 months after APCD purchase (Flexitouch System, Tactile Medical) by 718 patients (374 with cancer) between 2008 and 2012.

Lymphedema-related outcomes had either primary or secondary diagnosis codes.

The patients' mean age was 54.2, 84.8% were female, and 71.6% were non-Hispanic white. Just over half (52.2%) had hypertension, and breast cancer (39.6%) was the predominant disease in the cancer group.

As reported online October 7 in JAMA Dermatology, the adjusted rate of cellulitis diagnoses fell from 21.1% before APCD use to 4.5% afterward (p<0.001), a 79% decline. The noncancer group had a 75% decline, from 28.8% to 7.3% (p<0.001).

The noncancer group also had a 54% decline in adjusted rate of hospitalizations, from 7.0% to 3.2% (p=0.02), the authors reported.

Both groups had declines in receipt of manual therapy, from an adjusted rate of 35.6% before APCD use to 24.9% afterward for cancer patients (p<0.001) and from 32.3% to 21.2% for noncancer patients (p<0.001).

The adjusted rate of outpatient visits fell from 58.6% to 41.4% in the cancer cohort and from 52.6% to 31.4% in the noncancer group (p<0.001 for both).

Total costs per patient, excluding medical equipment, declined from $2597 to $1642 for cancer patients (p=0.002) and from $2937 to $1883 (p=0.007) for noncancer patients.

"While our findings are based upon the outcomes from one specific device, it is possible other such devices may also reduce patient burden. This warrants explorations in future studies. In addition, our study was not designed to assess the long term effectiveness of the device. That should be studied in future work," Dr. Karaca-Mandic explained.

Also, she pointed out, her team didn't look at nonmonetary expenses such as productivity loss and caretaker costs. "To the extent that device use improves physical functioning and lowers such costs as well, the impact is likely much larger than we can measure," she added.

Dr. Peter J. Franks, of the Center for Research and Implementation of Clinical Practice in London, UK, said by email, "We have these devices that appear to work. The problem is that the evidence on efficacy and cost effectiveness is so poor. The article gave some retrospective observational data that implied that the incidence of infection (cellulitis) was reduced. This is important, as infections lead to further deterioration of the lymphatic system, making the situation worse for the patient and increasing the risk of further infections."

"It is hard to say how generalizable the results are to other devices, though fundamentally they all work in similar ways," said Dr. Franks, who coauthored an accompanying editorial. "I think that this is an important step in how we consider the use of medical devices."

Cynthia Shechter, an occupational therapist in New York City who is a lymphedema specialist for cancer patients, said by email, "When looking for the right device, look for a pump that contains multiple chambers, operates on a short thirty-second cycle time, and applies graduated compression."

"The body operates on a pressure gradient system, so it is imperative to obtain a gradient or graduated compression pump. Pressure at the feet or hand is greater than the thigh or shoulder," she added.

"Clinicians practicing in the treatment of lymphedema need to be open-minded regarding less traditional treatment options for this insidious condition, including the use of traditional and advanced pneumatic compression devices," Shechter said.

"This study indicates that use of an APCD reduces the necessity for therapy. However, rehabilitation therapy for primary and secondary lymphedema, at least a short course of

treatment, is important, especially in order to ensure patients are adequately educated in lymphedema care, management, and precautions," she said.

"There should be a follow-up study performed to discuss a patient's ability to sustain use of the APCD versus a traditional pneumatic pump, and the long-term success in both preventing infection and in reduction of therapy visits," Shechter said.

Tactile Medical partially supported this research and employs one coauthor as chief medical officer. Dr. Karaca-Mandic, Dr. Franks, and his coauthor reported consulting for the company.

NEW YORK - Patients with lymphedema may reduce their risk of cellulitis, as well as the number of outpatient visits, by using an advanced pneumatic compression device (APCD), according to a new study.

"Our study demonstrates, for the first time, that receipt of an advanced pneumatic compression device is associated with significant improvements in key clinical endpoints for lymphedema patients, both for those with cancer and those without," Dr. Pinar Karaca-Mandic of the University of Minnesota School of Public Health in Minneapolis said by email.

"This finding has important implications for the patients who suffer from the disease, especially for those who have high rates of cellulitis. These devices serve as a viable self-management option and can reduce the need for more intensive outpatient care in rehabilitative settings," she added.

Advanced devices have more garment chambers and greater adjustability than earlier devices, the researchers wrote.

Dr. Karaca-Mandic and colleagues used a commercial insurance claims database to compare outcomes for 12 months before and 12 months after APCD purchase (Flexitouch System, Tactile Medical) by 718 patients (374 with cancer) between 2008 and 2012.

Lymphedema-related outcomes had either primary or secondary diagnosis codes.

The patients' mean age was 54.2, 84.8% were female, and 71.6% were non-Hispanic white. Just over half (52.2%) had hypertension, and breast cancer (39.6%) was the predominant disease in the cancer group.

As reported online October 7 in JAMA Dermatology, the adjusted rate of cellulitis diagnoses fell from 21.1% before APCD use to 4.5% afterward (p<0.001), a 79% decline. The noncancer group had a 75% decline, from 28.8% to 7.3% (p<0.001).

The noncancer group also had a 54% decline in adjusted rate of hospitalizations, from 7.0% to 3.2% (p=0.02), the authors reported.

Both groups had declines in receipt of manual therapy, from an adjusted rate of 35.6% before APCD use to 24.9% afterward for cancer patients (p<0.001) and from 32.3% to 21.2% for noncancer patients (p<0.001).

The adjusted rate of outpatient visits fell from 58.6% to 41.4% in the cancer cohort and from 52.6% to 31.4% in the noncancer group (p<0.001 for both).

Total costs per patient, excluding medical equipment, declined from $2597 to $1642 for cancer patients (p=0.002) and from $2937 to $1883 (p=0.007) for noncancer patients.

"While our findings are based upon the outcomes from one specific device, it is possible other such devices may also reduce patient burden. This warrants explorations in future studies. In addition, our study was not designed to assess the long term effectiveness of the device. That should be studied in future work," Dr. Karaca-Mandic explained.

Also, she pointed out, her team didn't look at nonmonetary expenses such as productivity loss and caretaker costs. "To the extent that device use improves physical functioning and lowers such costs as well, the impact is likely much larger than we can measure," she added.

Dr. Peter J. Franks, of the Center for Research and Implementation of Clinical Practice in London, UK, said by email, "We have these devices that appear to work. The problem is that the evidence on efficacy and cost effectiveness is so poor. The article gave some retrospective observational data that implied that the incidence of infection (cellulitis) was reduced. This is important, as infections lead to further deterioration of the lymphatic system, making the situation worse for the patient and increasing the risk of further infections."

"It is hard to say how generalizable the results are to other devices, though fundamentally they all work in similar ways," said Dr. Franks, who coauthored an accompanying editorial. "I think that this is an important step in how we consider the use of medical devices."

Cynthia Shechter, an occupational therapist in New York City who is a lymphedema specialist for cancer patients, said by email, "When looking for the right device, look for a pump that contains multiple chambers, operates on a short thirty-second cycle time, and applies graduated compression."

"The body operates on a pressure gradient system, so it is imperative to obtain a gradient or graduated compression pump. Pressure at the feet or hand is greater than the thigh or shoulder," she added.

"Clinicians practicing in the treatment of lymphedema need to be open-minded regarding less traditional treatment options for this insidious condition, including the use of traditional and advanced pneumatic compression devices," Shechter said.

"This study indicates that use of an APCD reduces the necessity for therapy. However, rehabilitation therapy for primary and secondary lymphedema, at least a short course of

treatment, is important, especially in order to ensure patients are adequately educated in lymphedema care, management, and precautions," she said.

"There should be a follow-up study performed to discuss a patient's ability to sustain use of the APCD versus a traditional pneumatic pump, and the long-term success in both preventing infection and in reduction of therapy visits," Shechter said.

Tactile Medical partially supported this research and employs one coauthor as chief medical officer. Dr. Karaca-Mandic, Dr. Franks, and his coauthor reported consulting for the company.

NEW YORK  - Health care professionals should be highly suspicious of megacolon in Clostridium difficile-infected patients and have a low threshold for transferring infected patients to intensive care units, Veterans Affairs researchers warn.

"The incidence of Clostridium difficile-associated megacolon has nearly tripled and mortality has nearly doubled over the past decade," Dr. SreyRam Kuy from the Overton Brooks VA Medical Center in Shreveport, Louisiana, said by email.

"It could be argued that this increased incidence may be due in part to improvements in detection of Clostridium difficile," she said. "However, this increase over the past decade . . . correlates with prior work by the Agency for Healthcare Research and Quality, which showed a 74% increase in the overall number of hospital discharges with Clostridium difficile infections from 1993-2001, in the decade prior to our study."

Dr. Kuy and colleagues analyzed records in the Nationwide Inpatient Sample (2000-2010) and identified patients with both C. difficile infection and megacolon.

They identified 28,219 cases of C. difficile infection, or 0.38% of all hospitalized patients, in 2000. That grew to more than 68,600 cases, or 0.88% of hospitalized patients, in 2010.

While the overall incidence of megacolon remained steady at 0.02% of hospitalized patients from 2000 to 2010, the rate of megacolon cases tied to C. diff infection increased from 3.61% in 2000 to 9.39% in 2010 (p<0.05).

"Compared with patients with megacolon but without C. difficile infection, patients with C. difficile-associated megacolon are significantly older, are more likely to have an urgent or emergent admission, are more likely to be admitted from the emergency department or transferred from another hospital, and are more likely to be treated at large, urban, teaching hospitals," the researchers write in an article online Oct. 7 in JAMA Surgery.

They report that the mean length of hospital stay for patients with C. difficile-associated megacolon was 16.13 days, the mean cost of hospitalization came to $41,968, and 50.7% required transitional care after hospital discharge. The mortality among these patients went up from 13.56% in 2000 to 24.45% in 2010, and peaked at 30.03% in 2007 (p<0.05).

"The rise in mortality is also alarming," Dr. Kuy said. "Potentially, this rise in mortality could be attributed to changes in virulence of Clostridium difficile strains, though we are unable to determine this due to limitations of the dataset utilized for this research. Other factors that can affect mortality are antibiotic regimen, severity of disease, physical exam findings, immunosuppression, presence of end organ failure, patient frailty status, APACHE (Acute Physiology and Chronic Health Evaluation) score, signs of sepsis, and leukocytosis, which have been identified as factors associated with mortality in prior published reports."

"This study draws attention to the tremendous burden of Clostridium difficile on patient mortality, health care costs and resources, transitional care utilization, and the extremely important need for aggressive prevention of this iatrogenic disease," she concluded.

The authors reported no funding or disclosures.

NEW YORK  - Health care professionals should be highly suspicious of megacolon in Clostridium difficile-infected patients and have a low threshold for transferring infected patients to intensive care units, Veterans Affairs researchers warn.

"The incidence of Clostridium difficile-associated megacolon has nearly tripled and mortality has nearly doubled over the past decade," Dr. SreyRam Kuy from the Overton Brooks VA Medical Center in Shreveport, Louisiana, said by email.

"It could be argued that this increased incidence may be due in part to improvements in detection of Clostridium difficile," she said. "However, this increase over the past decade . . . correlates with prior work by the Agency for Healthcare Research and Quality, which showed a 74% increase in the overall number of hospital discharges with Clostridium difficile infections from 1993-2001, in the decade prior to our study."

Dr. Kuy and colleagues analyzed records in the Nationwide Inpatient Sample (2000-2010) and identified patients with both C. difficile infection and megacolon.

They identified 28,219 cases of C. difficile infection, or 0.38% of all hospitalized patients, in 2000. That grew to more than 68,600 cases, or 0.88% of hospitalized patients, in 2010.

While the overall incidence of megacolon remained steady at 0.02% of hospitalized patients from 2000 to 2010, the rate of megacolon cases tied to C. diff infection increased from 3.61% in 2000 to 9.39% in 2010 (p<0.05).

"Compared with patients with megacolon but without C. difficile infection, patients with C. difficile-associated megacolon are significantly older, are more likely to have an urgent or emergent admission, are more likely to be admitted from the emergency department or transferred from another hospital, and are more likely to be treated at large, urban, teaching hospitals," the researchers write in an article online Oct. 7 in JAMA Surgery.

They report that the mean length of hospital stay for patients with C. difficile-associated megacolon was 16.13 days, the mean cost of hospitalization came to $41,968, and 50.7% required transitional care after hospital discharge. The mortality among these patients went up from 13.56% in 2000 to 24.45% in 2010, and peaked at 30.03% in 2007 (p<0.05).

"The rise in mortality is also alarming," Dr. Kuy said. "Potentially, this rise in mortality could be attributed to changes in virulence of Clostridium difficile strains, though we are unable to determine this due to limitations of the dataset utilized for this research. Other factors that can affect mortality are antibiotic regimen, severity of disease, physical exam findings, immunosuppression, presence of end organ failure, patient frailty status, APACHE (Acute Physiology and Chronic Health Evaluation) score, signs of sepsis, and leukocytosis, which have been identified as factors associated with mortality in prior published reports."

"This study draws attention to the tremendous burden of Clostridium difficile on patient mortality, health care costs and resources, transitional care utilization, and the extremely important need for aggressive prevention of this iatrogenic disease," she concluded.

The authors reported no funding or disclosures.

NEW YORK  - Health care professionals should be highly suspicious of megacolon in Clostridium difficile-infected patients and have a low threshold for transferring infected patients to intensive care units, Veterans Affairs researchers warn.

"The incidence of Clostridium difficile-associated megacolon has nearly tripled and mortality has nearly doubled over the past decade," Dr. SreyRam Kuy from the Overton Brooks VA Medical Center in Shreveport, Louisiana, said by email.

"It could be argued that this increased incidence may be due in part to improvements in detection of Clostridium difficile," she said. "However, this increase over the past decade . . . correlates with prior work by the Agency for Healthcare Research and Quality, which showed a 74% increase in the overall number of hospital discharges with Clostridium difficile infections from 1993-2001, in the decade prior to our study."

Dr. Kuy and colleagues analyzed records in the Nationwide Inpatient Sample (2000-2010) and identified patients with both C. difficile infection and megacolon.

They identified 28,219 cases of C. difficile infection, or 0.38% of all hospitalized patients, in 2000. That grew to more than 68,600 cases, or 0.88% of hospitalized patients, in 2010.

While the overall incidence of megacolon remained steady at 0.02% of hospitalized patients from 2000 to 2010, the rate of megacolon cases tied to C. diff infection increased from 3.61% in 2000 to 9.39% in 2010 (p<0.05).

"Compared with patients with megacolon but without C. difficile infection, patients with C. difficile-associated megacolon are significantly older, are more likely to have an urgent or emergent admission, are more likely to be admitted from the emergency department or transferred from another hospital, and are more likely to be treated at large, urban, teaching hospitals," the researchers write in an article online Oct. 7 in JAMA Surgery.

They report that the mean length of hospital stay for patients with C. difficile-associated megacolon was 16.13 days, the mean cost of hospitalization came to $41,968, and 50.7% required transitional care after hospital discharge. The mortality among these patients went up from 13.56% in 2000 to 24.45% in 2010, and peaked at 30.03% in 2007 (p<0.05).

"The rise in mortality is also alarming," Dr. Kuy said. "Potentially, this rise in mortality could be attributed to changes in virulence of Clostridium difficile strains, though we are unable to determine this due to limitations of the dataset utilized for this research. Other factors that can affect mortality are antibiotic regimen, severity of disease, physical exam findings, immunosuppression, presence of end organ failure, patient frailty status, APACHE (Acute Physiology and Chronic Health Evaluation) score, signs of sepsis, and leukocytosis, which have been identified as factors associated with mortality in prior published reports."

"This study draws attention to the tremendous burden of Clostridium difficile on patient mortality, health care costs and resources, transitional care utilization, and the extremely important need for aggressive prevention of this iatrogenic disease," she concluded.

The authors reported no funding or disclosures.