Reuters Health

(Reuters Health) - Having sleep apnea may increase the risk of chronic kidney disease, according to a report from Taiwan.

Researchers analyzed data from 2000 through 2010 on 8,600 adults diagnosed with sleep apnea and four times as many adults of similar age, sex and monthly income without sleep apnea, using Taiwan's National Health Insurance Research Database.

They found 157 new cases of chronic kidney disease among people with sleep apnea and 298 cases in the comparison group, according to Yung-Tai Chen of Taipei City Hospital Heping Fuyou Branch in Taiwan and coauthors.

After taking other health factors into account, sleep apnea increased the risk of kidney disease by 58%. By comparison, hypertension (a known risk factor for kidney disease) increased the risk by 17%. Diabetes was a stronger predictor than both other factors, more than doubling the risk of kidney disease, the research team reported online February 1 in Respirology.

Intermittent low oxygen levels during the night and fragmented sleep patterns may activate higher blood pressure, which would damage the kidneys and could make individuals more susceptible to chronic kidney disease, said Tetyana Kendzerska of the University of Toronto Institute for Clinical Evaluative Sciences, who was not part of the study in Taiwan.

But, "the findings from this study are limited by lack of information on sleep apnea and chronic kidney disease severity given that these conditions were defined through the health administrative data," Kendzerska said.

Factors like obesity and smoking status are also important for kidney risk but were not included in the assessment, she told Reuters Health by email.

"So, instead of concluding that sleep apnea has the same impact as high blood pressure on the kidney, I would rather conclude that this study suggests that the association between sleep apnea and chronic kidney disease may exist," and should be validated with more powerful studies, she said.

Moderate to severe obstructive sleep apnea can be treated with continuous positive airway pressure (CPAP) at night which may decrease high blood pressure and mitigate kidney risk, Kendzerska said.

"These findings raise the issue of whether the relationship between sleep apnea and chronic kidney disease is unidirectional or bidirectional," she said. "If the importance of sleep apnea and preventive effect of treatment will be confirmed in further studies, sleep apnea should be added to the list of modifiable risk factors considered in (chronic kidney disease) risk assessment."

The authors of the study did not respond to a request for comment.

(Reuters Health) - Having sleep apnea may increase the risk of chronic kidney disease, according to a report from Taiwan.

Researchers analyzed data from 2000 through 2010 on 8,600 adults diagnosed with sleep apnea and four times as many adults of similar age, sex and monthly income without sleep apnea, using Taiwan's National Health Insurance Research Database.

They found 157 new cases of chronic kidney disease among people with sleep apnea and 298 cases in the comparison group, according to Yung-Tai Chen of Taipei City Hospital Heping Fuyou Branch in Taiwan and coauthors.

After taking other health factors into account, sleep apnea increased the risk of kidney disease by 58%. By comparison, hypertension (a known risk factor for kidney disease) increased the risk by 17%. Diabetes was a stronger predictor than both other factors, more than doubling the risk of kidney disease, the research team reported online February 1 in Respirology.

Intermittent low oxygen levels during the night and fragmented sleep patterns may activate higher blood pressure, which would damage the kidneys and could make individuals more susceptible to chronic kidney disease, said Tetyana Kendzerska of the University of Toronto Institute for Clinical Evaluative Sciences, who was not part of the study in Taiwan.

But, "the findings from this study are limited by lack of information on sleep apnea and chronic kidney disease severity given that these conditions were defined through the health administrative data," Kendzerska said.

Factors like obesity and smoking status are also important for kidney risk but were not included in the assessment, she told Reuters Health by email.

"So, instead of concluding that sleep apnea has the same impact as high blood pressure on the kidney, I would rather conclude that this study suggests that the association between sleep apnea and chronic kidney disease may exist," and should be validated with more powerful studies, she said.

Moderate to severe obstructive sleep apnea can be treated with continuous positive airway pressure (CPAP) at night which may decrease high blood pressure and mitigate kidney risk, Kendzerska said.

"These findings raise the issue of whether the relationship between sleep apnea and chronic kidney disease is unidirectional or bidirectional," she said. "If the importance of sleep apnea and preventive effect of treatment will be confirmed in further studies, sleep apnea should be added to the list of modifiable risk factors considered in (chronic kidney disease) risk assessment."

The authors of the study did not respond to a request for comment.

(Reuters Health) - Having sleep apnea may increase the risk of chronic kidney disease, according to a report from Taiwan.

Researchers analyzed data from 2000 through 2010 on 8,600 adults diagnosed with sleep apnea and four times as many adults of similar age, sex and monthly income without sleep apnea, using Taiwan's National Health Insurance Research Database.

They found 157 new cases of chronic kidney disease among people with sleep apnea and 298 cases in the comparison group, according to Yung-Tai Chen of Taipei City Hospital Heping Fuyou Branch in Taiwan and coauthors.

After taking other health factors into account, sleep apnea increased the risk of kidney disease by 58%. By comparison, hypertension (a known risk factor for kidney disease) increased the risk by 17%. Diabetes was a stronger predictor than both other factors, more than doubling the risk of kidney disease, the research team reported online February 1 in Respirology.

Intermittent low oxygen levels during the night and fragmented sleep patterns may activate higher blood pressure, which would damage the kidneys and could make individuals more susceptible to chronic kidney disease, said Tetyana Kendzerska of the University of Toronto Institute for Clinical Evaluative Sciences, who was not part of the study in Taiwan.

But, "the findings from this study are limited by lack of information on sleep apnea and chronic kidney disease severity given that these conditions were defined through the health administrative data," Kendzerska said.

Factors like obesity and smoking status are also important for kidney risk but were not included in the assessment, she told Reuters Health by email.

"So, instead of concluding that sleep apnea has the same impact as high blood pressure on the kidney, I would rather conclude that this study suggests that the association between sleep apnea and chronic kidney disease may exist," and should be validated with more powerful studies, she said.

Moderate to severe obstructive sleep apnea can be treated with continuous positive airway pressure (CPAP) at night which may decrease high blood pressure and mitigate kidney risk, Kendzerska said.

"These findings raise the issue of whether the relationship between sleep apnea and chronic kidney disease is unidirectional or bidirectional," she said. "If the importance of sleep apnea and preventive effect of treatment will be confirmed in further studies, sleep apnea should be added to the list of modifiable risk factors considered in (chronic kidney disease) risk assessment."

The authors of the study did not respond to a request for comment.

NEW YORK (Reuters Health) - Opioid modulation with the combination of buprenorphine and samidorphan (ALKS 5461) improves symptoms in patients whose depression has not responded adequately to antidepressant treatment, researchers report.

"If the findings are confirmed in phase 3 studies, ALKS 5461 could be used as an augmenting agent in patients not responding to standard antidepressant therapies as an alternative to the atypical antipsychotic agents currently approved for the treatment of this population," Dr. Maurizio Fava, from Massachusetts General Hospital and Harvard Medical School, Boston, told Reuters Health by email.

Buprenorphine is a mu- and kappa-opioid partial agonist, and samidorphan blocks the mu agonist effects of buprenorphine associated with its abuse and addictive potential. A growing body of evidence implicates dysregulation of the endogenous mu- and kappa-opioid system in mood disorders.

Dr. Fava and colleagues at 31 sites in the U.S. used a sequential parallel comparison design to investigate the efficacy of buprenorphine/samidorphan (2 mg/2 mg or 8 mg/8 mg) in 142 patients with major depression inadequately responsive to antidepressant therapy.

At the end of four weeks of treatment, patients in the ALKS 5461 2 mg/2 mg group showed significantly greater improvements in Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression severity scores, compared with patients in the placebo group. The ALKS 5461 8 mg/8 mg group showed smaller, nonsignificant improvements.

"The overall effect sizes for the 2/2 dosage were 0.50 for HAM-D and 0.54 for MADRS," the researchers noted. "The result compares favorably with results from a meta-analysis of 14 studies with atypical antipsychotics as adjunctive therapy for major depression, with reported effect sizes of 0.35 to 0.48 for individual drugs."

Treatment response rates according to HAM-D and MADRS (at least 50% reduction in scores) were highest with ALKS 5461 2 mg/2 mg treatment group, according to the February 12 onlinereport in the American Journal of Psychiatry.

Two patients (1.6%) in the placebo group and 17 patients (19.3%) in the ALKS 5461 groups discontinued because of treatment-emergent adverse events, but there was no evidence of opioid withdrawal in any patient.

"When depressed patients do not respond to standard monoamine-based therapies for depression, consider the use of an augmenting agent that modulates other systems, such as the opioid one," Dr. Fava concluded.

Dr. Jeffrey F. Scherrer, from Saint Louis University School of Medicine, St. Louis, Missouri, recently examined the association between opioid use and increased depression rates. He told Reuters Health by email, "Our analysis of opioid use and depression did not include buprenorphine among the opioid exposure variable. Therefore, it is difficult to extrapolate our results to a trial of buprenorphine/samidorphan and major depression."

"As the authors noted, the clinical trial was of short duration and the risks of depression that we have observed appears to be greatest among those patients remaining on opioids for more than 90 days," he explained. "Additional work is currently being done to determine if some opioid medications have a greater depressogenic effect than others, which further limits direct comparison of our findings to the current study."

"I will say that it is unlikely for oxycodone, codeine, and hydrocodone (which together account for more than 90% of prescribed opioids) would help depressed patients and be more likely to worsen their depression with chronic treatment," Dr. Scherrer concluded.

Alkermes sponsored the trial, employed seven coauthors, and had various relationships with the other four coauthors.

NEW YORK (Reuters Health) - Opioid modulation with the combination of buprenorphine and samidorphan (ALKS 5461) improves symptoms in patients whose depression has not responded adequately to antidepressant treatment, researchers report.

"If the findings are confirmed in phase 3 studies, ALKS 5461 could be used as an augmenting agent in patients not responding to standard antidepressant therapies as an alternative to the atypical antipsychotic agents currently approved for the treatment of this population," Dr. Maurizio Fava, from Massachusetts General Hospital and Harvard Medical School, Boston, told Reuters Health by email.

Buprenorphine is a mu- and kappa-opioid partial agonist, and samidorphan blocks the mu agonist effects of buprenorphine associated with its abuse and addictive potential. A growing body of evidence implicates dysregulation of the endogenous mu- and kappa-opioid system in mood disorders.

Dr. Fava and colleagues at 31 sites in the U.S. used a sequential parallel comparison design to investigate the efficacy of buprenorphine/samidorphan (2 mg/2 mg or 8 mg/8 mg) in 142 patients with major depression inadequately responsive to antidepressant therapy.

At the end of four weeks of treatment, patients in the ALKS 5461 2 mg/2 mg group showed significantly greater improvements in Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression severity scores, compared with patients in the placebo group. The ALKS 5461 8 mg/8 mg group showed smaller, nonsignificant improvements.

"The overall effect sizes for the 2/2 dosage were 0.50 for HAM-D and 0.54 for MADRS," the researchers noted. "The result compares favorably with results from a meta-analysis of 14 studies with atypical antipsychotics as adjunctive therapy for major depression, with reported effect sizes of 0.35 to 0.48 for individual drugs."

Treatment response rates according to HAM-D and MADRS (at least 50% reduction in scores) were highest with ALKS 5461 2 mg/2 mg treatment group, according to the February 12 onlinereport in the American Journal of Psychiatry.

Two patients (1.6%) in the placebo group and 17 patients (19.3%) in the ALKS 5461 groups discontinued because of treatment-emergent adverse events, but there was no evidence of opioid withdrawal in any patient.

"When depressed patients do not respond to standard monoamine-based therapies for depression, consider the use of an augmenting agent that modulates other systems, such as the opioid one," Dr. Fava concluded.

Dr. Jeffrey F. Scherrer, from Saint Louis University School of Medicine, St. Louis, Missouri, recently examined the association between opioid use and increased depression rates. He told Reuters Health by email, "Our analysis of opioid use and depression did not include buprenorphine among the opioid exposure variable. Therefore, it is difficult to extrapolate our results to a trial of buprenorphine/samidorphan and major depression."

"As the authors noted, the clinical trial was of short duration and the risks of depression that we have observed appears to be greatest among those patients remaining on opioids for more than 90 days," he explained. "Additional work is currently being done to determine if some opioid medications have a greater depressogenic effect than others, which further limits direct comparison of our findings to the current study."

"I will say that it is unlikely for oxycodone, codeine, and hydrocodone (which together account for more than 90% of prescribed opioids) would help depressed patients and be more likely to worsen their depression with chronic treatment," Dr. Scherrer concluded.

Alkermes sponsored the trial, employed seven coauthors, and had various relationships with the other four coauthors.

NEW YORK (Reuters Health) - Opioid modulation with the combination of buprenorphine and samidorphan (ALKS 5461) improves symptoms in patients whose depression has not responded adequately to antidepressant treatment, researchers report.

"If the findings are confirmed in phase 3 studies, ALKS 5461 could be used as an augmenting agent in patients not responding to standard antidepressant therapies as an alternative to the atypical antipsychotic agents currently approved for the treatment of this population," Dr. Maurizio Fava, from Massachusetts General Hospital and Harvard Medical School, Boston, told Reuters Health by email.

Buprenorphine is a mu- and kappa-opioid partial agonist, and samidorphan blocks the mu agonist effects of buprenorphine associated with its abuse and addictive potential. A growing body of evidence implicates dysregulation of the endogenous mu- and kappa-opioid system in mood disorders.

Dr. Fava and colleagues at 31 sites in the U.S. used a sequential parallel comparison design to investigate the efficacy of buprenorphine/samidorphan (2 mg/2 mg or 8 mg/8 mg) in 142 patients with major depression inadequately responsive to antidepressant therapy.

At the end of four weeks of treatment, patients in the ALKS 5461 2 mg/2 mg group showed significantly greater improvements in Hamilton Depression Rating Scale (HAM-D), Montgomery-Asberg Depression Rating Scale (MADRS), and Clinical Global Impression severity scores, compared with patients in the placebo group. The ALKS 5461 8 mg/8 mg group showed smaller, nonsignificant improvements.

"The overall effect sizes for the 2/2 dosage were 0.50 for HAM-D and 0.54 for MADRS," the researchers noted. "The result compares favorably with results from a meta-analysis of 14 studies with atypical antipsychotics as adjunctive therapy for major depression, with reported effect sizes of 0.35 to 0.48 for individual drugs."

Treatment response rates according to HAM-D and MADRS (at least 50% reduction in scores) were highest with ALKS 5461 2 mg/2 mg treatment group, according to the February 12 onlinereport in the American Journal of Psychiatry.

Two patients (1.6%) in the placebo group and 17 patients (19.3%) in the ALKS 5461 groups discontinued because of treatment-emergent adverse events, but there was no evidence of opioid withdrawal in any patient.

"When depressed patients do not respond to standard monoamine-based therapies for depression, consider the use of an augmenting agent that modulates other systems, such as the opioid one," Dr. Fava concluded.

Dr. Jeffrey F. Scherrer, from Saint Louis University School of Medicine, St. Louis, Missouri, recently examined the association between opioid use and increased depression rates. He told Reuters Health by email, "Our analysis of opioid use and depression did not include buprenorphine among the opioid exposure variable. Therefore, it is difficult to extrapolate our results to a trial of buprenorphine/samidorphan and major depression."

"As the authors noted, the clinical trial was of short duration and the risks of depression that we have observed appears to be greatest among those patients remaining on opioids for more than 90 days," he explained. "Additional work is currently being done to determine if some opioid medications have a greater depressogenic effect than others, which further limits direct comparison of our findings to the current study."

"I will say that it is unlikely for oxycodone, codeine, and hydrocodone (which together account for more than 90% of prescribed opioids) would help depressed patients and be more likely to worsen their depression with chronic treatment," Dr. Scherrer concluded.

Alkermes sponsored the trial, employed seven coauthors, and had various relationships with the other four coauthors.

NEW YORK (Reuters Health) - The diabetes drug pioglitazone, given to non-diabetics with a recent history of stroke or transient ischemic attack (TIA), prevented subsequent strokes and reduced their odds of developing type 2 diabetes, a long-term multicenter study has concluded.

But the drug also increased the risk of fracture, weight gain, and edema.

After nearly five years of follow-up, the rate of stroke or heart attack was 11.8% with placebo and 9.0% with the drug (p=0.007). The target dose was 45 mg daily.

"That 25% relative reduction is a huge effect for a stroke trial," coauthor Dr. Wayne Clark, director of the Oregon Stroke Center at Oregon Health and Science University, told Reuters Health by phone. "That's on the same realm as aspirin and a big effect for stroke.

"We're always expecting negative results these days," because so many stroke drugs have failed in previous tests, he said. "This was a positive surprise."

Dr. Clark said he was particularly taken aback by the rate that diabetes developed in pioglitazone recipients. It manifested in 3.8% of drug recipients versus 7.7% of placebo

recipients (p<0.001).

"I didn't expect that at all," he said. "That has much wider implications and might take confirmatory studies."

The 3,876 volunteers studied at 179 sites worldwide were not diabetic but they had developed insulin resistance at the time of enrollment.

Drug therapy did not reduce mortality.The results of the study, known as IRIS, were presented February 17 at the American Heart Association and the American

Stroke Association's International Stroke Conference in Los Angeles, and online in the New England Journal of Medicine.

"The findings suggest that the administration of pioglitazone in 100 patients similar to those in our trial for about five years could prevent three patients from having a

stroke or myocardial infarction," the researchers wrote in the Journal. "However, during the same period, the treatment would be expected to result in bone fractures requiring surgery or hospitalization in two patients.

"It seems reasonable to consider individual treatment preference and risk of drug-related adverse events in addition to potential benefits when making patient-specific decisions regarding therapy," they concluded.

Serious fractures occurred in 5.1% of drug recipients versus 3.2% among placebo patients (p=0.003). A weight gain of more than 4.5 kg was seen in 52.2% of pioglitazone recipientscompared with 33.7% for placebo, and rates of edema were 35.6% with the drug versus 24.9% with placebo (both p<0.001).

The drug has been plagued by suspicions that it might increase the risk of heart failure and bladder cancer. In this study, 74 pioglitazone recipients developed heart failure versus 71 in the placebo group (p=0.80). A dozen drug recipients were diagnosed with bladder cancer compared with eight cases in the placebo group (p=0.37).

Dr. Clark said, "All of the stuff we're doing for risk-factor reduction -- blood pressure reduction, stop smoking and giving aspirin -- they're all on the same level of relative improvement, and all of those are widely used. Aspirin has a list of side effects that will fill up three pages."

At the start of the study, all of the volunteers were insulin resistant, at least 40 years old, and had experienced an ischemic stroke or TIA in the previous six months. Diabetics were excluded as were patients with heart failure, active liver disease, and an increased risk of bladder cancer.

By the end of the study, 60% of the pioglitazone patients were still taking their medicine compared with 67% of placebo recipients. The most common reason for discontinuing was edema or weight gain.

The National Institute of Neurological Disorders and Stroke funded this study. Eleven coauthors reported disclosures.

NEW YORK (Reuters Health) - The diabetes drug pioglitazone, given to non-diabetics with a recent history of stroke or transient ischemic attack (TIA), prevented subsequent strokes and reduced their odds of developing type 2 diabetes, a long-term multicenter study has concluded.

But the drug also increased the risk of fracture, weight gain, and edema.

After nearly five years of follow-up, the rate of stroke or heart attack was 11.8% with placebo and 9.0% with the drug (p=0.007). The target dose was 45 mg daily.

"That 25% relative reduction is a huge effect for a stroke trial," coauthor Dr. Wayne Clark, director of the Oregon Stroke Center at Oregon Health and Science University, told Reuters Health by phone. "That's on the same realm as aspirin and a big effect for stroke.

"We're always expecting negative results these days," because so many stroke drugs have failed in previous tests, he said. "This was a positive surprise."

Dr. Clark said he was particularly taken aback by the rate that diabetes developed in pioglitazone recipients. It manifested in 3.8% of drug recipients versus 7.7% of placebo

recipients (p<0.001).

"I didn't expect that at all," he said. "That has much wider implications and might take confirmatory studies."

The 3,876 volunteers studied at 179 sites worldwide were not diabetic but they had developed insulin resistance at the time of enrollment.

Drug therapy did not reduce mortality.The results of the study, known as IRIS, were presented February 17 at the American Heart Association and the American

Stroke Association's International Stroke Conference in Los Angeles, and online in the New England Journal of Medicine.

"The findings suggest that the administration of pioglitazone in 100 patients similar to those in our trial for about five years could prevent three patients from having a

stroke or myocardial infarction," the researchers wrote in the Journal. "However, during the same period, the treatment would be expected to result in bone fractures requiring surgery or hospitalization in two patients.

"It seems reasonable to consider individual treatment preference and risk of drug-related adverse events in addition to potential benefits when making patient-specific decisions regarding therapy," they concluded.

Serious fractures occurred in 5.1% of drug recipients versus 3.2% among placebo patients (p=0.003). A weight gain of more than 4.5 kg was seen in 52.2% of pioglitazone recipientscompared with 33.7% for placebo, and rates of edema were 35.6% with the drug versus 24.9% with placebo (both p<0.001).

The drug has been plagued by suspicions that it might increase the risk of heart failure and bladder cancer. In this study, 74 pioglitazone recipients developed heart failure versus 71 in the placebo group (p=0.80). A dozen drug recipients were diagnosed with bladder cancer compared with eight cases in the placebo group (p=0.37).

Dr. Clark said, "All of the stuff we're doing for risk-factor reduction -- blood pressure reduction, stop smoking and giving aspirin -- they're all on the same level of relative improvement, and all of those are widely used. Aspirin has a list of side effects that will fill up three pages."

At the start of the study, all of the volunteers were insulin resistant, at least 40 years old, and had experienced an ischemic stroke or TIA in the previous six months. Diabetics were excluded as were patients with heart failure, active liver disease, and an increased risk of bladder cancer.

By the end of the study, 60% of the pioglitazone patients were still taking their medicine compared with 67% of placebo recipients. The most common reason for discontinuing was edema or weight gain.

The National Institute of Neurological Disorders and Stroke funded this study. Eleven coauthors reported disclosures.

NEW YORK (Reuters Health) - The diabetes drug pioglitazone, given to non-diabetics with a recent history of stroke or transient ischemic attack (TIA), prevented subsequent strokes and reduced their odds of developing type 2 diabetes, a long-term multicenter study has concluded.

But the drug also increased the risk of fracture, weight gain, and edema.

After nearly five years of follow-up, the rate of stroke or heart attack was 11.8% with placebo and 9.0% with the drug (p=0.007). The target dose was 45 mg daily.

"That 25% relative reduction is a huge effect for a stroke trial," coauthor Dr. Wayne Clark, director of the Oregon Stroke Center at Oregon Health and Science University, told Reuters Health by phone. "That's on the same realm as aspirin and a big effect for stroke.

"We're always expecting negative results these days," because so many stroke drugs have failed in previous tests, he said. "This was a positive surprise."

Dr. Clark said he was particularly taken aback by the rate that diabetes developed in pioglitazone recipients. It manifested in 3.8% of drug recipients versus 7.7% of placebo

recipients (p<0.001).

"I didn't expect that at all," he said. "That has much wider implications and might take confirmatory studies."

The 3,876 volunteers studied at 179 sites worldwide were not diabetic but they had developed insulin resistance at the time of enrollment.

Drug therapy did not reduce mortality.The results of the study, known as IRIS, were presented February 17 at the American Heart Association and the American

Stroke Association's International Stroke Conference in Los Angeles, and online in the New England Journal of Medicine.

"The findings suggest that the administration of pioglitazone in 100 patients similar to those in our trial for about five years could prevent three patients from having a

stroke or myocardial infarction," the researchers wrote in the Journal. "However, during the same period, the treatment would be expected to result in bone fractures requiring surgery or hospitalization in two patients.

"It seems reasonable to consider individual treatment preference and risk of drug-related adverse events in addition to potential benefits when making patient-specific decisions regarding therapy," they concluded.

Serious fractures occurred in 5.1% of drug recipients versus 3.2% among placebo patients (p=0.003). A weight gain of more than 4.5 kg was seen in 52.2% of pioglitazone recipientscompared with 33.7% for placebo, and rates of edema were 35.6% with the drug versus 24.9% with placebo (both p<0.001).

The drug has been plagued by suspicions that it might increase the risk of heart failure and bladder cancer. In this study, 74 pioglitazone recipients developed heart failure versus 71 in the placebo group (p=0.80). A dozen drug recipients were diagnosed with bladder cancer compared with eight cases in the placebo group (p=0.37).

Dr. Clark said, "All of the stuff we're doing for risk-factor reduction -- blood pressure reduction, stop smoking and giving aspirin -- they're all on the same level of relative improvement, and all of those are widely used. Aspirin has a list of side effects that will fill up three pages."

At the start of the study, all of the volunteers were insulin resistant, at least 40 years old, and had experienced an ischemic stroke or TIA in the previous six months. Diabetics were excluded as were patients with heart failure, active liver disease, and an increased risk of bladder cancer.

By the end of the study, 60% of the pioglitazone patients were still taking their medicine compared with 67% of placebo recipients. The most common reason for discontinuing was edema or weight gain.

The National Institute of Neurological Disorders and Stroke funded this study. Eleven coauthors reported disclosures.

(Reuters Health) - Elderly patients hospitalized for cancer surgery are more likely to have complications afterward compared to the middle-aged, particularly when they have several other health problems, a U.S. study suggests.

Overall, almost one in 10 adults age 55 and older had at least one post-operative issue like delirium, dehydration, falls, fractures, pressure ulcers or unusual weight loss, the study of nearly 1 million cancer surgery patients found.

These setbacks were even more common when patients were at least 65 years old, had two or more other serious health problems in addition to malignancies, or had surgeries for tumors of the digestive system or nearby organs.

But the odds were worst for people over 75 - about 46 percent of them had at least one complication, compared with 22 percent of adults aged 55 to 64.

"With the population aging, it's becoming increasingly important to consider not only the survival benefits of cancer surgery but the impact on functionality, vitality and quality of life," said lead study author Dr. Hung-Jui Tan, a researcher in urologic oncology at the University of California, Los Angeles.

While the events studied here are specific to the initial hospitalization, they can carry potential long-term ramifications," Tan added by email.

To see how age influences the risk of post-operative complications, Tan and colleagues reviewed hospital admission records for a nationwide sample of 940,000 adults age 55 and older who had cancer surgery from 2009 to 2011.

Compared with patients who were under age 65, those who were 65 to 74 years old were 23 percent more likely to have complications, while the over-75 group had 66 percent higher odds, researchers report in the Journal of Clinical Oncology.

Complications were most likely when patients were having surgery for cancers of the bladder, ovary, colon, rectum, pancreas or stomach.

After suffering post-operative setbacks, patients were also more likely to have further complications during their hospital stay, to remain in the hospital longer and to have more costly care. They were also more likely to die in the hospital and less likely to be discharged to home.

One limitation of the study is its reliance on administrative claims data, which is designed for billing purposes and might not always reflect the nuances of patients' medical conditions, the authors note. In addition, it's possible that some complications may have resulted from conditions patients had before they arrived at the hospital for cancer surgery.

The study can't prove that advanced age directly causes post-operative problems. But the findings suggest doctors and patients should consider these potential risks when deciding the best course of treatment, Tan said.

Patients should also understand that not all complications are equally devastating to quality of life. Dehydration and weight loss, for example, are nutritional problems that might be treated with fluids, noted Dr. Siri Rostoft, a geriatric medicine researcher at Oslo University Hospital in Norway.

"Cancer is often a lethal disease if left untreated that causes conditions such as bleeding, obstruction of the intestines, and pain," Rostoft, who wasn't involved in the study, said by email. "Not treating patients may be worse for their quality of life than operating."

Still, the findings add to a growing body of data on post-operative complications that may help doctors and patients decide if the potential benefits of surgery outweigh the possible risks, Dr. Steven Cunningham, a researcher at Saint Agnes Hospital and Cancer Institute in Baltimore who wasn't involved in the study, said by email.

Complications in the study were more likely at non-teaching hospitals and facilities that did fewer cancer surgeries, a factor that patients should also consider when they have a choice about where to go for surgery, noted Dr. Kwok-Leung Cheung, a researcher at the University of Nottingham in the U.K. and member of the surgical task force for the International Society of Geriatric Oncology.

Knowing when not to operate also matters, Cheung, who wasn't involved in the study, added by email.

"The surgeon should seriously consider the intensity of surgery, which has been identified as one of the important factors with post operative problems," Cheung added. "The use of minimally invasive techniques including laparoscopic and robotic surgery should be considered wherever appropriate."

(Reuters Health) - Elderly patients hospitalized for cancer surgery are more likely to have complications afterward compared to the middle-aged, particularly when they have several other health problems, a U.S. study suggests.

Overall, almost one in 10 adults age 55 and older had at least one post-operative issue like delirium, dehydration, falls, fractures, pressure ulcers or unusual weight loss, the study of nearly 1 million cancer surgery patients found.

These setbacks were even more common when patients were at least 65 years old, had two or more other serious health problems in addition to malignancies, or had surgeries for tumors of the digestive system or nearby organs.

But the odds were worst for people over 75 - about 46 percent of them had at least one complication, compared with 22 percent of adults aged 55 to 64.

"With the population aging, it's becoming increasingly important to consider not only the survival benefits of cancer surgery but the impact on functionality, vitality and quality of life," said lead study author Dr. Hung-Jui Tan, a researcher in urologic oncology at the University of California, Los Angeles.

While the events studied here are specific to the initial hospitalization, they can carry potential long-term ramifications," Tan added by email.

To see how age influences the risk of post-operative complications, Tan and colleagues reviewed hospital admission records for a nationwide sample of 940,000 adults age 55 and older who had cancer surgery from 2009 to 2011.

Compared with patients who were under age 65, those who were 65 to 74 years old were 23 percent more likely to have complications, while the over-75 group had 66 percent higher odds, researchers report in the Journal of Clinical Oncology.

Complications were most likely when patients were having surgery for cancers of the bladder, ovary, colon, rectum, pancreas or stomach.

After suffering post-operative setbacks, patients were also more likely to have further complications during their hospital stay, to remain in the hospital longer and to have more costly care. They were also more likely to die in the hospital and less likely to be discharged to home.

One limitation of the study is its reliance on administrative claims data, which is designed for billing purposes and might not always reflect the nuances of patients' medical conditions, the authors note. In addition, it's possible that some complications may have resulted from conditions patients had before they arrived at the hospital for cancer surgery.

The study can't prove that advanced age directly causes post-operative problems. But the findings suggest doctors and patients should consider these potential risks when deciding the best course of treatment, Tan said.

Patients should also understand that not all complications are equally devastating to quality of life. Dehydration and weight loss, for example, are nutritional problems that might be treated with fluids, noted Dr. Siri Rostoft, a geriatric medicine researcher at Oslo University Hospital in Norway.

"Cancer is often a lethal disease if left untreated that causes conditions such as bleeding, obstruction of the intestines, and pain," Rostoft, who wasn't involved in the study, said by email. "Not treating patients may be worse for their quality of life than operating."

Still, the findings add to a growing body of data on post-operative complications that may help doctors and patients decide if the potential benefits of surgery outweigh the possible risks, Dr. Steven Cunningham, a researcher at Saint Agnes Hospital and Cancer Institute in Baltimore who wasn't involved in the study, said by email.

Complications in the study were more likely at non-teaching hospitals and facilities that did fewer cancer surgeries, a factor that patients should also consider when they have a choice about where to go for surgery, noted Dr. Kwok-Leung Cheung, a researcher at the University of Nottingham in the U.K. and member of the surgical task force for the International Society of Geriatric Oncology.

Knowing when not to operate also matters, Cheung, who wasn't involved in the study, added by email.

"The surgeon should seriously consider the intensity of surgery, which has been identified as one of the important factors with post operative problems," Cheung added. "The use of minimally invasive techniques including laparoscopic and robotic surgery should be considered wherever appropriate."

(Reuters Health) - Elderly patients hospitalized for cancer surgery are more likely to have complications afterward compared to the middle-aged, particularly when they have several other health problems, a U.S. study suggests.

Overall, almost one in 10 adults age 55 and older had at least one post-operative issue like delirium, dehydration, falls, fractures, pressure ulcers or unusual weight loss, the study of nearly 1 million cancer surgery patients found.

These setbacks were even more common when patients were at least 65 years old, had two or more other serious health problems in addition to malignancies, or had surgeries for tumors of the digestive system or nearby organs.

But the odds were worst for people over 75 - about 46 percent of them had at least one complication, compared with 22 percent of adults aged 55 to 64.

"With the population aging, it's becoming increasingly important to consider not only the survival benefits of cancer surgery but the impact on functionality, vitality and quality of life," said lead study author Dr. Hung-Jui Tan, a researcher in urologic oncology at the University of California, Los Angeles.

While the events studied here are specific to the initial hospitalization, they can carry potential long-term ramifications," Tan added by email.

To see how age influences the risk of post-operative complications, Tan and colleagues reviewed hospital admission records for a nationwide sample of 940,000 adults age 55 and older who had cancer surgery from 2009 to 2011.

Compared with patients who were under age 65, those who were 65 to 74 years old were 23 percent more likely to have complications, while the over-75 group had 66 percent higher odds, researchers report in the Journal of Clinical Oncology.

Complications were most likely when patients were having surgery for cancers of the bladder, ovary, colon, rectum, pancreas or stomach.

After suffering post-operative setbacks, patients were also more likely to have further complications during their hospital stay, to remain in the hospital longer and to have more costly care. They were also more likely to die in the hospital and less likely to be discharged to home.

One limitation of the study is its reliance on administrative claims data, which is designed for billing purposes and might not always reflect the nuances of patients' medical conditions, the authors note. In addition, it's possible that some complications may have resulted from conditions patients had before they arrived at the hospital for cancer surgery.

The study can't prove that advanced age directly causes post-operative problems. But the findings suggest doctors and patients should consider these potential risks when deciding the best course of treatment, Tan said.

Patients should also understand that not all complications are equally devastating to quality of life. Dehydration and weight loss, for example, are nutritional problems that might be treated with fluids, noted Dr. Siri Rostoft, a geriatric medicine researcher at Oslo University Hospital in Norway.

"Cancer is often a lethal disease if left untreated that causes conditions such as bleeding, obstruction of the intestines, and pain," Rostoft, who wasn't involved in the study, said by email. "Not treating patients may be worse for their quality of life than operating."

Still, the findings add to a growing body of data on post-operative complications that may help doctors and patients decide if the potential benefits of surgery outweigh the possible risks, Dr. Steven Cunningham, a researcher at Saint Agnes Hospital and Cancer Institute in Baltimore who wasn't involved in the study, said by email.

Complications in the study were more likely at non-teaching hospitals and facilities that did fewer cancer surgeries, a factor that patients should also consider when they have a choice about where to go for surgery, noted Dr. Kwok-Leung Cheung, a researcher at the University of Nottingham in the U.K. and member of the surgical task force for the International Society of Geriatric Oncology.

Knowing when not to operate also matters, Cheung, who wasn't involved in the study, added by email.

"The surgeon should seriously consider the intensity of surgery, which has been identified as one of the important factors with post operative problems," Cheung added. "The use of minimally invasive techniques including laparoscopic and robotic surgery should be considered wherever appropriate."

NEW YORK (Reuters Health) - Outcomes of inpatient laparoscopic cholecystectomy in Medicare patients vary widely among hospitals, and most adverse outcomes occur well after patients have been discharged, new findings show.

While the overall adverse outcome rate was 20.7%, risk-adjusted adverse outcomes ranged from 10% in the best-performing decile of hospitals to 32.1% for the worst-performing decile, Dr. Donald E. Fry of MPA Healthcare Solutions in Chicago and colleagues found.

"These differences indicate that a significant number of readmissions and overall adverse outcomes of care after laparoscopic cholecystectomy are potentially preventable," Dr. Fry and his team state in their report, online February 1 in the Annals of Surgery.

Risk-adjusted measurement of care has typically been limited to inpatient events and 30-day mortality rates, they note, but declines in mortality rates, shorter patient stays and a shift toward ambulatory procedures have made this measurement more difficult.

"Surgery for gallbladder disease has experienced one of the most dramatic transitions from extended inpatient care to outpatient or limited inpatient care," they write.

To compare outcomes among hospitals, Dr. Fry and his team looked at Medicare data for 2010-2012 including both inpatient and 90-day post-discharge adverse outcomes for inpatient laparoscopic cholecystectomy.

They created a developmental database including more than 73,000 patients to construct predictive models for adverse outcomes, and a database of more than 83,000 patients treated at 1,570 hospitals, each with 20 or more qualifying cases and 4.5 or more predicted total adverse outcomes, to compare performance.

A total of 509 patients (0.6%) died in the hospital, 5,761 (6.9%) had prolonged length of stay, 1,154 (1.4%) died within 90 days of discharge without being readmitted, and 12,038 (14.5%) were readmitted at least once in the 90 days after discharge.

Gastrointestinal, infectious and cardiovascular events were the most common readmission causes.

"Strategies for improvement begin with hospitals and surgeons knowing what the results of their care happen to be," Dr. Fry told Reuters Health by email. "Since many readmissions and Emergency Department visits of post-discharge surgical cases occur at hospitals other than the facility of the index

hospitalization, the actual results of care may not be appreciated by the providers."

He added: "Improvement strategies need to focus on the reasons patients were readmitted. Better pain management will reduce readmissions for constipation, abdominal distention, nausea and vomiting. Increased contact by clinicians with their patients after discharge can identify early evidence of

pulmonary problems or potential urinary tract infection. Earlier recognition of evolving issues can provide interventions that avoid readmissions. Better overall strategies to avoid cardiac events and hypovolemia that may play in central nervous system events and renal failure should be of benefit."

Dr. Fry and his colleagues are now investigating whether similar differences in outcomes occur with other types of surgical procedures, as well as the frequency of and reasons for post-discharge emergency room visits.

"A final message for surgeons in this research is that Medicare has begun an initiative into bundled payments," Dr. Fry said. "Surgeons and hospitals need to establish better trackingmethods for post-discharge patients so that they know the results of care and so that they can develop focused strategies for better outcomes. There will be a substantial financial penalty for those who cannot adapt to the new payment model that CMS is implementing."

NEW YORK (Reuters Health) - Outcomes of inpatient laparoscopic cholecystectomy in Medicare patients vary widely among hospitals, and most adverse outcomes occur well after patients have been discharged, new findings show.

While the overall adverse outcome rate was 20.7%, risk-adjusted adverse outcomes ranged from 10% in the best-performing decile of hospitals to 32.1% for the worst-performing decile, Dr. Donald E. Fry of MPA Healthcare Solutions in Chicago and colleagues found.

"These differences indicate that a significant number of readmissions and overall adverse outcomes of care after laparoscopic cholecystectomy are potentially preventable," Dr. Fry and his team state in their report, online February 1 in the Annals of Surgery.

Risk-adjusted measurement of care has typically been limited to inpatient events and 30-day mortality rates, they note, but declines in mortality rates, shorter patient stays and a shift toward ambulatory procedures have made this measurement more difficult.

"Surgery for gallbladder disease has experienced one of the most dramatic transitions from extended inpatient care to outpatient or limited inpatient care," they write.

To compare outcomes among hospitals, Dr. Fry and his team looked at Medicare data for 2010-2012 including both inpatient and 90-day post-discharge adverse outcomes for inpatient laparoscopic cholecystectomy.

They created a developmental database including more than 73,000 patients to construct predictive models for adverse outcomes, and a database of more than 83,000 patients treated at 1,570 hospitals, each with 20 or more qualifying cases and 4.5 or more predicted total adverse outcomes, to compare performance.

A total of 509 patients (0.6%) died in the hospital, 5,761 (6.9%) had prolonged length of stay, 1,154 (1.4%) died within 90 days of discharge without being readmitted, and 12,038 (14.5%) were readmitted at least once in the 90 days after discharge.

Gastrointestinal, infectious and cardiovascular events were the most common readmission causes.

"Strategies for improvement begin with hospitals and surgeons knowing what the results of their care happen to be," Dr. Fry told Reuters Health by email. "Since many readmissions and Emergency Department visits of post-discharge surgical cases occur at hospitals other than the facility of the index

hospitalization, the actual results of care may not be appreciated by the providers."

He added: "Improvement strategies need to focus on the reasons patients were readmitted. Better pain management will reduce readmissions for constipation, abdominal distention, nausea and vomiting. Increased contact by clinicians with their patients after discharge can identify early evidence of

pulmonary problems or potential urinary tract infection. Earlier recognition of evolving issues can provide interventions that avoid readmissions. Better overall strategies to avoid cardiac events and hypovolemia that may play in central nervous system events and renal failure should be of benefit."

Dr. Fry and his colleagues are now investigating whether similar differences in outcomes occur with other types of surgical procedures, as well as the frequency of and reasons for post-discharge emergency room visits.

"A final message for surgeons in this research is that Medicare has begun an initiative into bundled payments," Dr. Fry said. "Surgeons and hospitals need to establish better trackingmethods for post-discharge patients so that they know the results of care and so that they can develop focused strategies for better outcomes. There will be a substantial financial penalty for those who cannot adapt to the new payment model that CMS is implementing."

NEW YORK (Reuters Health) - Outcomes of inpatient laparoscopic cholecystectomy in Medicare patients vary widely among hospitals, and most adverse outcomes occur well after patients have been discharged, new findings show.

While the overall adverse outcome rate was 20.7%, risk-adjusted adverse outcomes ranged from 10% in the best-performing decile of hospitals to 32.1% for the worst-performing decile, Dr. Donald E. Fry of MPA Healthcare Solutions in Chicago and colleagues found.

"These differences indicate that a significant number of readmissions and overall adverse outcomes of care after laparoscopic cholecystectomy are potentially preventable," Dr. Fry and his team state in their report, online February 1 in the Annals of Surgery.

Risk-adjusted measurement of care has typically been limited to inpatient events and 30-day mortality rates, they note, but declines in mortality rates, shorter patient stays and a shift toward ambulatory procedures have made this measurement more difficult.

"Surgery for gallbladder disease has experienced one of the most dramatic transitions from extended inpatient care to outpatient or limited inpatient care," they write.

To compare outcomes among hospitals, Dr. Fry and his team looked at Medicare data for 2010-2012 including both inpatient and 90-day post-discharge adverse outcomes for inpatient laparoscopic cholecystectomy.

They created a developmental database including more than 73,000 patients to construct predictive models for adverse outcomes, and a database of more than 83,000 patients treated at 1,570 hospitals, each with 20 or more qualifying cases and 4.5 or more predicted total adverse outcomes, to compare performance.

A total of 509 patients (0.6%) died in the hospital, 5,761 (6.9%) had prolonged length of stay, 1,154 (1.4%) died within 90 days of discharge without being readmitted, and 12,038 (14.5%) were readmitted at least once in the 90 days after discharge.

Gastrointestinal, infectious and cardiovascular events were the most common readmission causes.

"Strategies for improvement begin with hospitals and surgeons knowing what the results of their care happen to be," Dr. Fry told Reuters Health by email. "Since many readmissions and Emergency Department visits of post-discharge surgical cases occur at hospitals other than the facility of the index

hospitalization, the actual results of care may not be appreciated by the providers."

He added: "Improvement strategies need to focus on the reasons patients were readmitted. Better pain management will reduce readmissions for constipation, abdominal distention, nausea and vomiting. Increased contact by clinicians with their patients after discharge can identify early evidence of

pulmonary problems or potential urinary tract infection. Earlier recognition of evolving issues can provide interventions that avoid readmissions. Better overall strategies to avoid cardiac events and hypovolemia that may play in central nervous system events and renal failure should be of benefit."

Dr. Fry and his colleagues are now investigating whether similar differences in outcomes occur with other types of surgical procedures, as well as the frequency of and reasons for post-discharge emergency room visits.

"A final message for surgeons in this research is that Medicare has begun an initiative into bundled payments," Dr. Fry said. "Surgeons and hospitals need to establish better trackingmethods for post-discharge patients so that they know the results of care and so that they can develop focused strategies for better outcomes. There will be a substantial financial penalty for those who cannot adapt to the new payment model that CMS is implementing."

NEW YORK (Reuters Health) - Implementation of a patient-centered medical home (PCMH) resulted in small changes in utilization patterns and modest quality improvements over a three-year period, according to a new report.

Dr. Lisa M. Kern of Weill Cornell Medical College in New York City and colleagues found more primary care visits, fewer specialist visits, fewer lab and radiologic tests, and fewer hospitalizations and rehospitalizations in the practices that adopted the PCMH.

Most changes occurred in the last year of the study, three years after PCMH implementation, they report in the Annals of Internal Medicine, online February 15.

The PCMH model "attempts to shift the medical paradigm from care for individual patients to care for populations, from care by physicians to care by a team of providers, from a focus on acute illness to an emphasis on chronic disease management, and from care at a single site to coordinated care across providers and settings," Dr. Kern and her team write. However, they add, studies looking at the effectiveness of the approach have had mixed results.

To date, most studies attempting to look at PCMH have had follow-up periods lasting just 1.5 to 2 years after implementation, the researchers note. "These changes take time, and studies with relatively short follow-up may have underestimated the effects of the intervention," they add.

The new study included 438 primary care physicians in 226 practices with more than 136,000 patients enrolled in five health plans. Insurers offered incentives of $2 to $10 per patient per month to practices that achieved level III PCMH recognition from the National Committee for Quality Assurance

(NCQA).

Twelve practices including 125 physicians volunteered for the PCMH initiative, and were assisted by two outside consulting groups. All of these practices achieved level III PCMH recognition. Among the remaining physicians, 87 doctors in 45 practices adopted electronic health records (EHR) without the

PCMH intervention, and 226 physicians in 169 practices continued using paper records.

For the eight quality measures the researchers looked at, two showed greater improvements over time in the PCMH group compared to one or both of the control groups: eye examination and hemoglobin A1c testing for patients with diabetes.

From 2008 to 2012, the PCMH group showed improvements over the paper group and the EHR group for six of seven utilization measures.

NCQA recognition was one aspect of the PCMH intervention in the new study, but this doesn't represent the entire intervention, Dr. Mark W. Friedberg of RAND Corporation and Brigham and Women's Hospital in Boston, who wrote an editorial accompanying the study, told Reuters Health.

"What they evaluated was a different way of paying practices, combined with some technical assistance, combined with some shared savings in the last year of the pilot," Dr. Friedberg explained. And this also requires defining what improving care means, he added, for example "better technical quality of care, better patient experience, better effectiveness of care, better professional satisfaction and lower burnout for people working in the practices. It's also hard to measure all of those, and most studies don't."

The new study is well done, according to Dr. Friedberg, but the challenge will be to understand how it fits in with the rest of the medical home literature, he said. "There's a lot of trials still out there and the results are still coming in, including some very large Medicare medical home pilots. I think we'll have a much better sense of what works in a year or two as those results come back."

Dr. Kern did not respond to an interview request by press time.

The study was funded by The Commonwealth Fund and the New York State Department of Health.

NEW YORK (Reuters Health) - Implementation of a patient-centered medical home (PCMH) resulted in small changes in utilization patterns and modest quality improvements over a three-year period, according to a new report.

Dr. Lisa M. Kern of Weill Cornell Medical College in New York City and colleagues found more primary care visits, fewer specialist visits, fewer lab and radiologic tests, and fewer hospitalizations and rehospitalizations in the practices that adopted the PCMH.

Most changes occurred in the last year of the study, three years after PCMH implementation, they report in the Annals of Internal Medicine, online February 15.

The PCMH model "attempts to shift the medical paradigm from care for individual patients to care for populations, from care by physicians to care by a team of providers, from a focus on acute illness to an emphasis on chronic disease management, and from care at a single site to coordinated care across providers and settings," Dr. Kern and her team write. However, they add, studies looking at the effectiveness of the approach have had mixed results.

To date, most studies attempting to look at PCMH have had follow-up periods lasting just 1.5 to 2 years after implementation, the researchers note. "These changes take time, and studies with relatively short follow-up may have underestimated the effects of the intervention," they add.

The new study included 438 primary care physicians in 226 practices with more than 136,000 patients enrolled in five health plans. Insurers offered incentives of $2 to $10 per patient per month to practices that achieved level III PCMH recognition from the National Committee for Quality Assurance

(NCQA).

Twelve practices including 125 physicians volunteered for the PCMH initiative, and were assisted by two outside consulting groups. All of these practices achieved level III PCMH recognition. Among the remaining physicians, 87 doctors in 45 practices adopted electronic health records (EHR) without the

PCMH intervention, and 226 physicians in 169 practices continued using paper records.

For the eight quality measures the researchers looked at, two showed greater improvements over time in the PCMH group compared to one or both of the control groups: eye examination and hemoglobin A1c testing for patients with diabetes.

From 2008 to 2012, the PCMH group showed improvements over the paper group and the EHR group for six of seven utilization measures.

NCQA recognition was one aspect of the PCMH intervention in the new study, but this doesn't represent the entire intervention, Dr. Mark W. Friedberg of RAND Corporation and Brigham and Women's Hospital in Boston, who wrote an editorial accompanying the study, told Reuters Health.

"What they evaluated was a different way of paying practices, combined with some technical assistance, combined with some shared savings in the last year of the pilot," Dr. Friedberg explained. And this also requires defining what improving care means, he added, for example "better technical quality of care, better patient experience, better effectiveness of care, better professional satisfaction and lower burnout for people working in the practices. It's also hard to measure all of those, and most studies don't."

The new study is well done, according to Dr. Friedberg, but the challenge will be to understand how it fits in with the rest of the medical home literature, he said. "There's a lot of trials still out there and the results are still coming in, including some very large Medicare medical home pilots. I think we'll have a much better sense of what works in a year or two as those results come back."

Dr. Kern did not respond to an interview request by press time.

The study was funded by The Commonwealth Fund and the New York State Department of Health.

NEW YORK (Reuters Health) - Implementation of a patient-centered medical home (PCMH) resulted in small changes in utilization patterns and modest quality improvements over a three-year period, according to a new report.

Dr. Lisa M. Kern of Weill Cornell Medical College in New York City and colleagues found more primary care visits, fewer specialist visits, fewer lab and radiologic tests, and fewer hospitalizations and rehospitalizations in the practices that adopted the PCMH.

Most changes occurred in the last year of the study, three years after PCMH implementation, they report in the Annals of Internal Medicine, online February 15.

The PCMH model "attempts to shift the medical paradigm from care for individual patients to care for populations, from care by physicians to care by a team of providers, from a focus on acute illness to an emphasis on chronic disease management, and from care at a single site to coordinated care across providers and settings," Dr. Kern and her team write. However, they add, studies looking at the effectiveness of the approach have had mixed results.

To date, most studies attempting to look at PCMH have had follow-up periods lasting just 1.5 to 2 years after implementation, the researchers note. "These changes take time, and studies with relatively short follow-up may have underestimated the effects of the intervention," they add.

The new study included 438 primary care physicians in 226 practices with more than 136,000 patients enrolled in five health plans. Insurers offered incentives of $2 to $10 per patient per month to practices that achieved level III PCMH recognition from the National Committee for Quality Assurance

(NCQA).

Twelve practices including 125 physicians volunteered for the PCMH initiative, and were assisted by two outside consulting groups. All of these practices achieved level III PCMH recognition. Among the remaining physicians, 87 doctors in 45 practices adopted electronic health records (EHR) without the

PCMH intervention, and 226 physicians in 169 practices continued using paper records.

For the eight quality measures the researchers looked at, two showed greater improvements over time in the PCMH group compared to one or both of the control groups: eye examination and hemoglobin A1c testing for patients with diabetes.

From 2008 to 2012, the PCMH group showed improvements over the paper group and the EHR group for six of seven utilization measures.

NCQA recognition was one aspect of the PCMH intervention in the new study, but this doesn't represent the entire intervention, Dr. Mark W. Friedberg of RAND Corporation and Brigham and Women's Hospital in Boston, who wrote an editorial accompanying the study, told Reuters Health.

"What they evaluated was a different way of paying practices, combined with some technical assistance, combined with some shared savings in the last year of the pilot," Dr. Friedberg explained. And this also requires defining what improving care means, he added, for example "better technical quality of care, better patient experience, better effectiveness of care, better professional satisfaction and lower burnout for people working in the practices. It's also hard to measure all of those, and most studies don't."

The new study is well done, according to Dr. Friedberg, but the challenge will be to understand how it fits in with the rest of the medical home literature, he said. "There's a lot of trials still out there and the results are still coming in, including some very large Medicare medical home pilots. I think we'll have a much better sense of what works in a year or two as those results come back."

Dr. Kern did not respond to an interview request by press time.

The study was funded by The Commonwealth Fund and the New York State Department of Health.

NEW YORK (Reuters Health) - Only two strategies offer some effectiveness in preventing contrast-induced nephropathy (CIN), according to a systematic review and meta-analysis of 86 randomized, controlled trials.

Those are use of N-acetylcysteine (NAc) in patients receiving low-osmolar contrast media (LOCM), and statins plus NAc.

The reported incidence of CIN, defined as an increase in serum creatinine levels >25% or 44.2 mmol/L (0.5 mg/dL) within three days of IV administration of contrast media, ranges from 7% to 11% and adds an average $10,345 to a CIN-related hospital stay. There is no clear consensus about the most effective intervention to prevent or reduce CIN.

Dr. Rathan M. Subramaniam and colleagues from Johns Hopkins University in Baltimore compared five strategies for preventing CIN in their systematic review and meta-analysis: IV NAc plus saline versus IV saline alone; IV sodium bicarbonate versus IV saline; NAc plus IV saline versus IV sodium bicarbonate; statins with or without NAc versus IV saline; and ascorbic acid versus NAc or IV saline.

In the NAc studies, all of which had low strength of evidence, NAc had a clinically important benefit in reducing CIN risk only when LOCM were used.

Low-dose NAc had a borderline clinically important effect on preventing CIN, whereas high-dose NAc had a statistically significant (but clinically unimportant) effect on reducing CIN risk (with low strength of evidence).

Similarly, statins when added to NAc showed a clinically important reduction in CIN risk, although with low strength of evidence.

IV sodium bicarbonate (versus IV saline), NAc (versus IV sodium bicarbonate), and ascorbic acid (versus other strategies) showed no statistically significant, clinically important benefit in reducing CIN risk, according to the report onine February 1 in Annals of Internal Medicine online.

"The studies span over two decades, and there may have been changes in the practice of CIN prevention, such as increased screening, variation in definition of acute kidney injury, and variation in hydration, over time," the researchers noted. "Such changes could contribute to differences in outcomes."

"This comprehensive review highlights the generally low strength of evidence on interventions for preventing CIN while indicating that the greatest reduction in CIN risk has been achieved with low-dose N-acetylcysteine in patients receiving LOCM or with statins plus N-acetylcysteine," they concluded.

In a related article, the group from Johns Hopkins University found no differences in CIN risk among the different types of LOCM. Iodixanol had a slightly lower risk of CIN than LOCM did, but the difference was not clinically important.

Dr. Guillaume Mahe from CHU de Rennes, Rennes, France recently reviewed remote ischemic preconditioning, another proposed method for preventing CIN (http://bit.ly/23EU40a). He told Reuters Health by email, "It seems of interest to use N-acetylcysteine, which is a low cost drug. Statins might be also a good option. This is another interesting effect of the statins, which is unknown by most physicians."

Even more important, Dr. Mahe said, is to "be sure that the patients need a computed tomography angiography with contrast media."

He expressed surprise that the authors did not assess the role of remote ischemic preconditioning in their review.

Dr. Subramaniam did not respond to a request for comments. The Agency for Healthcare Research and Quality funded both studies.

NEW YORK (Reuters Health) - Only two strategies offer some effectiveness in preventing contrast-induced nephropathy (CIN), according to a systematic review and meta-analysis of 86 randomized, controlled trials.

Those are use of N-acetylcysteine (NAc) in patients receiving low-osmolar contrast media (LOCM), and statins plus NAc.

The reported incidence of CIN, defined as an increase in serum creatinine levels >25% or 44.2 mmol/L (0.5 mg/dL) within three days of IV administration of contrast media, ranges from 7% to 11% and adds an average $10,345 to a CIN-related hospital stay. There is no clear consensus about the most effective intervention to prevent or reduce CIN.

Dr. Rathan M. Subramaniam and colleagues from Johns Hopkins University in Baltimore compared five strategies for preventing CIN in their systematic review and meta-analysis: IV NAc plus saline versus IV saline alone; IV sodium bicarbonate versus IV saline; NAc plus IV saline versus IV sodium bicarbonate; statins with or without NAc versus IV saline; and ascorbic acid versus NAc or IV saline.

In the NAc studies, all of which had low strength of evidence, NAc had a clinically important benefit in reducing CIN risk only when LOCM were used.

Low-dose NAc had a borderline clinically important effect on preventing CIN, whereas high-dose NAc had a statistically significant (but clinically unimportant) effect on reducing CIN risk (with low strength of evidence).

Similarly, statins when added to NAc showed a clinically important reduction in CIN risk, although with low strength of evidence.

IV sodium bicarbonate (versus IV saline), NAc (versus IV sodium bicarbonate), and ascorbic acid (versus other strategies) showed no statistically significant, clinically important benefit in reducing CIN risk, according to the report onine February 1 in Annals of Internal Medicine online.

"The studies span over two decades, and there may have been changes in the practice of CIN prevention, such as increased screening, variation in definition of acute kidney injury, and variation in hydration, over time," the researchers noted. "Such changes could contribute to differences in outcomes."

"This comprehensive review highlights the generally low strength of evidence on interventions for preventing CIN while indicating that the greatest reduction in CIN risk has been achieved with low-dose N-acetylcysteine in patients receiving LOCM or with statins plus N-acetylcysteine," they concluded.

In a related article, the group from Johns Hopkins University found no differences in CIN risk among the different types of LOCM. Iodixanol had a slightly lower risk of CIN than LOCM did, but the difference was not clinically important.

Dr. Guillaume Mahe from CHU de Rennes, Rennes, France recently reviewed remote ischemic preconditioning, another proposed method for preventing CIN (http://bit.ly/23EU40a). He told Reuters Health by email, "It seems of interest to use N-acetylcysteine, which is a low cost drug. Statins might be also a good option. This is another interesting effect of the statins, which is unknown by most physicians."

Even more important, Dr. Mahe said, is to "be sure that the patients need a computed tomography angiography with contrast media."

He expressed surprise that the authors did not assess the role of remote ischemic preconditioning in their review.

Dr. Subramaniam did not respond to a request for comments. The Agency for Healthcare Research and Quality funded both studies.

NEW YORK (Reuters Health) - Only two strategies offer some effectiveness in preventing contrast-induced nephropathy (CIN), according to a systematic review and meta-analysis of 86 randomized, controlled trials.

Those are use of N-acetylcysteine (NAc) in patients receiving low-osmolar contrast media (LOCM), and statins plus NAc.

The reported incidence of CIN, defined as an increase in serum creatinine levels >25% or 44.2 mmol/L (0.5 mg/dL) within three days of IV administration of contrast media, ranges from 7% to 11% and adds an average $10,345 to a CIN-related hospital stay. There is no clear consensus about the most effective intervention to prevent or reduce CIN.

Dr. Rathan M. Subramaniam and colleagues from Johns Hopkins University in Baltimore compared five strategies for preventing CIN in their systematic review and meta-analysis: IV NAc plus saline versus IV saline alone; IV sodium bicarbonate versus IV saline; NAc plus IV saline versus IV sodium bicarbonate; statins with or without NAc versus IV saline; and ascorbic acid versus NAc or IV saline.

In the NAc studies, all of which had low strength of evidence, NAc had a clinically important benefit in reducing CIN risk only when LOCM were used.

Low-dose NAc had a borderline clinically important effect on preventing CIN, whereas high-dose NAc had a statistically significant (but clinically unimportant) effect on reducing CIN risk (with low strength of evidence).

Similarly, statins when added to NAc showed a clinically important reduction in CIN risk, although with low strength of evidence.

IV sodium bicarbonate (versus IV saline), NAc (versus IV sodium bicarbonate), and ascorbic acid (versus other strategies) showed no statistically significant, clinically important benefit in reducing CIN risk, according to the report onine February 1 in Annals of Internal Medicine online.

"The studies span over two decades, and there may have been changes in the practice of CIN prevention, such as increased screening, variation in definition of acute kidney injury, and variation in hydration, over time," the researchers noted. "Such changes could contribute to differences in outcomes."

"This comprehensive review highlights the generally low strength of evidence on interventions for preventing CIN while indicating that the greatest reduction in CIN risk has been achieved with low-dose N-acetylcysteine in patients receiving LOCM or with statins plus N-acetylcysteine," they concluded.

In a related article, the group from Johns Hopkins University found no differences in CIN risk among the different types of LOCM. Iodixanol had a slightly lower risk of CIN than LOCM did, but the difference was not clinically important.

Dr. Guillaume Mahe from CHU de Rennes, Rennes, France recently reviewed remote ischemic preconditioning, another proposed method for preventing CIN (http://bit.ly/23EU40a). He told Reuters Health by email, "It seems of interest to use N-acetylcysteine, which is a low cost drug. Statins might be also a good option. This is another interesting effect of the statins, which is unknown by most physicians."

Even more important, Dr. Mahe said, is to "be sure that the patients need a computed tomography angiography with contrast media."

He expressed surprise that the authors did not assess the role of remote ischemic preconditioning in their review.

Dr. Subramaniam did not respond to a request for comments. The Agency for Healthcare Research and Quality funded both studies.

(Reuters Health) - Medicaid, the U.S. health program for the poor, pays far less for common surgical procedures in many states than does Medicare, the federal insurance plan for the elderly, according to a new study.

Some of the discounts are so steep that they may threaten access to care, the authors argue.

Medicaid is the biggest public health program in the U.S. and currently accounts for about $1 out of every $6 spent on medical care. Medicaid expenditures also represent almost half of all federal funds spent by states.

When Medicaid fees are too low relative to payments from Medicare, doctors may refuse to treat Medicaid patients, potentially making it much harder for poor people to get treatment, argue Dr. Charles Mabry of the University of Arkansas in Little Rock and colleagues in a paper released online January 13 in the Journal of the American College of Surgeons.

"Lack of proper payment can cause some Medicaid patients to have needed surgical procedures delayed," Mabry told Reuters Health by email. "Our hope was that by researching and publishing on these wide variations in payment, it would spur states to rethink the methodology for how they determine payment."

Even though the federal government picks up part of the tab for care, Medicaid payment rates as well as enrollment eligibility and covered benefits are determined by individual states.

To assess the degree of variation between Medicare and Medicaid payments for surgery, Mabry and colleagues calculated how much fees varied for some of the most common procedures done by general surgeons in nearly every state across the country.

The analysis excluded only Kansas and Tennessee.

The largest discount they found was in New Jersey, where Medicaid paid $1,011 (about 933 euros) less than Medicare for surgery to remove all or part of the small intestine.

At the other extreme, the biggest premium was in Alaska, which paid $1,382 more for insertion of a tunneled central venous port under Medicaid than Medicare would pay for the procedure.

When they looked at mastectomy, Medicaid paid $226.47 in Connecticut, 69% less than the $725.35 Medicare payment for the same procedure in the same state.

For an enterectomy, New Jersey's Medicaid payment of $332 was 75% less than the $1,343.16 payment under Medicare.

To fix a ventral hernia, Medicaid in New Hampshire pays $300, 61% less than the $762.28 Medicare payment in the state.

The analysis has several limitations, including the narrow focus on a handful of surgical procedures and the reliance on published payment schedules in each state, which may not necessarily reflect what surgeons actually get paid, the authors note. The analysis also lacked data on certain bulk payments or additional funds paid by Medicaid that might minimize the apparent discounts in some cases.

The paper didn't examine how access to care might be adversely affected by steep discounts in Medicaid payments relative to Medicare or private insurance. But, the authors conclude, it's likely some people struggle to find surgeons or experience delays in care as a direct result of low fees that motivate doctors to refuse Medicaid patients.

One woman with sickle-cell disease and Medicaid coverage is a case-in-point for Dr. Constantine Manthous, who retired from Yale University and works in private practice in New London, Connecticut.

He recalled meeting her after she had spent a decade in a wheelchair because she couldn't find a surgeon to repair her hip. She didn't receive surgery until the hip fell out of its socket, requiring constant hospitalization and morphine.

"By that time she was so ill she died of late complications from the decade delay," Manthous, who wasn't involved in the study, said by email. "You and I would have gotten the hip immediately."

(Reuters Health) - Medicaid, the U.S. health program for the poor, pays far less for common surgical procedures in many states than does Medicare, the federal insurance plan for the elderly, according to a new study.

Some of the discounts are so steep that they may threaten access to care, the authors argue.

Medicaid is the biggest public health program in the U.S. and currently accounts for about $1 out of every $6 spent on medical care. Medicaid expenditures also represent almost half of all federal funds spent by states.

When Medicaid fees are too low relative to payments from Medicare, doctors may refuse to treat Medicaid patients, potentially making it much harder for poor people to get treatment, argue Dr. Charles Mabry of the University of Arkansas in Little Rock and colleagues in a paper released online January 13 in the Journal of the American College of Surgeons.

"Lack of proper payment can cause some Medicaid patients to have needed surgical procedures delayed," Mabry told Reuters Health by email. "Our hope was that by researching and publishing on these wide variations in payment, it would spur states to rethink the methodology for how they determine payment."

Even though the federal government picks up part of the tab for care, Medicaid payment rates as well as enrollment eligibility and covered benefits are determined by individual states.

To assess the degree of variation between Medicare and Medicaid payments for surgery, Mabry and colleagues calculated how much fees varied for some of the most common procedures done by general surgeons in nearly every state across the country.

The analysis excluded only Kansas and Tennessee.

The largest discount they found was in New Jersey, where Medicaid paid $1,011 (about 933 euros) less than Medicare for surgery to remove all or part of the small intestine.

At the other extreme, the biggest premium was in Alaska, which paid $1,382 more for insertion of a tunneled central venous port under Medicaid than Medicare would pay for the procedure.

When they looked at mastectomy, Medicaid paid $226.47 in Connecticut, 69% less than the $725.35 Medicare payment for the same procedure in the same state.

For an enterectomy, New Jersey's Medicaid payment of $332 was 75% less than the $1,343.16 payment under Medicare.

To fix a ventral hernia, Medicaid in New Hampshire pays $300, 61% less than the $762.28 Medicare payment in the state.

The analysis has several limitations, including the narrow focus on a handful of surgical procedures and the reliance on published payment schedules in each state, which may not necessarily reflect what surgeons actually get paid, the authors note. The analysis also lacked data on certain bulk payments or additional funds paid by Medicaid that might minimize the apparent discounts in some cases.

The paper didn't examine how access to care might be adversely affected by steep discounts in Medicaid payments relative to Medicare or private insurance. But, the authors conclude, it's likely some people struggle to find surgeons or experience delays in care as a direct result of low fees that motivate doctors to refuse Medicaid patients.

One woman with sickle-cell disease and Medicaid coverage is a case-in-point for Dr. Constantine Manthous, who retired from Yale University and works in private practice in New London, Connecticut.

He recalled meeting her after she had spent a decade in a wheelchair because she couldn't find a surgeon to repair her hip. She didn't receive surgery until the hip fell out of its socket, requiring constant hospitalization and morphine.

"By that time she was so ill she died of late complications from the decade delay," Manthous, who wasn't involved in the study, said by email. "You and I would have gotten the hip immediately."

(Reuters Health) - Medicaid, the U.S. health program for the poor, pays far less for common surgical procedures in many states than does Medicare, the federal insurance plan for the elderly, according to a new study.

Some of the discounts are so steep that they may threaten access to care, the authors argue.

Medicaid is the biggest public health program in the U.S. and currently accounts for about $1 out of every $6 spent on medical care. Medicaid expenditures also represent almost half of all federal funds spent by states.

When Medicaid fees are too low relative to payments from Medicare, doctors may refuse to treat Medicaid patients, potentially making it much harder for poor people to get treatment, argue Dr. Charles Mabry of the University of Arkansas in Little Rock and colleagues in a paper released online January 13 in the Journal of the American College of Surgeons.

"Lack of proper payment can cause some Medicaid patients to have needed surgical procedures delayed," Mabry told Reuters Health by email. "Our hope was that by researching and publishing on these wide variations in payment, it would spur states to rethink the methodology for how they determine payment."

Even though the federal government picks up part of the tab for care, Medicaid payment rates as well as enrollment eligibility and covered benefits are determined by individual states.

To assess the degree of variation between Medicare and Medicaid payments for surgery, Mabry and colleagues calculated how much fees varied for some of the most common procedures done by general surgeons in nearly every state across the country.

The analysis excluded only Kansas and Tennessee.

The largest discount they found was in New Jersey, where Medicaid paid $1,011 (about 933 euros) less than Medicare for surgery to remove all or part of the small intestine.

At the other extreme, the biggest premium was in Alaska, which paid $1,382 more for insertion of a tunneled central venous port under Medicaid than Medicare would pay for the procedure.

When they looked at mastectomy, Medicaid paid $226.47 in Connecticut, 69% less than the $725.35 Medicare payment for the same procedure in the same state.

For an enterectomy, New Jersey's Medicaid payment of $332 was 75% less than the $1,343.16 payment under Medicare.

To fix a ventral hernia, Medicaid in New Hampshire pays $300, 61% less than the $762.28 Medicare payment in the state.

The analysis has several limitations, including the narrow focus on a handful of surgical procedures and the reliance on published payment schedules in each state, which may not necessarily reflect what surgeons actually get paid, the authors note. The analysis also lacked data on certain bulk payments or additional funds paid by Medicaid that might minimize the apparent discounts in some cases.

The paper didn't examine how access to care might be adversely affected by steep discounts in Medicaid payments relative to Medicare or private insurance. But, the authors conclude, it's likely some people struggle to find surgeons or experience delays in care as a direct result of low fees that motivate doctors to refuse Medicaid patients.

One woman with sickle-cell disease and Medicaid coverage is a case-in-point for Dr. Constantine Manthous, who retired from Yale University and works in private practice in New London, Connecticut.

He recalled meeting her after she had spent a decade in a wheelchair because she couldn't find a surgeon to repair her hip. She didn't receive surgery until the hip fell out of its socket, requiring constant hospitalization and morphine.

"By that time she was so ill she died of late complications from the decade delay," Manthous, who wasn't involved in the study, said by email. "You and I would have gotten the hip immediately."

NEW YORK (Reuters Health) - Dabigatran and warfarin offer similar stroke-prevention efficacy in patients with atrial fibrillation (AF), but their side effect profiles differ, according to a systematic review and meta-analysis of real-world clinical practice.

"There could be many reasons for the differences in our findings, such as differences in the quality of evidence of observational studies and randomized controlled trials (RCTs) or differences in the included study populations between the observational studies in our review and the RE-LY trial," Dr. Robert J. Romanelli from Palo Alto Medical Foundation Research Institute, California, told Reuters Health by email.

The RE-LY trial is the only RCT to have evaluated dabigatran in stroke prevention, and RCTs are prone to selection biases less likely to be present in well designed observational studies, Dr. Romanelli and colleagues note in Circulation:Cardiovascular and Quality Outcomes, online January 26.

The team used data from seven retrospective cohort studies to compare the effectiveness and safety of dabigatran and warfarin among more than 348,750 patients with nonvalvular AF.

During an overall mean follow-up of 794 days, dabigatran 150mg or 110 mg was similar to warfarin in ischemic stroke prevention.

Both the higher and lower dabigatran doses had significantly lower hazards of intracranial bleeding compared with warfarin (pooled hazard ratio, 0.44 and 0.49, respectively). But the hazard of gastrointestinal bleeding was significantly greater for dabigatran 150 mg (but not for 110 mg) than for warfarin (pHR, 1.23). The 110 mg dose of dabigatran was only available during the trial; it's now sold in 150 mg or 75 mg capsules.

The increased risk of gastrointestinal bleeding with the higher dose of dabigatran was significant only in older populations (75 years or older).

"Data presented in this review reflect relative risk, which is not always clinically meaningful," the researchers caution. "It is important to bear in mind that event rates for the outcome of interest are low under standard treatment."

"I don't think the findings from this one reviewshould change clinical practice," Dr. Romanelli said. "If anything, this study revealed areas for future research.

NEW YORK (Reuters Health) - Dabigatran and warfarin offer similar stroke-prevention efficacy in patients with atrial fibrillation (AF), but their side effect profiles differ, according to a systematic review and meta-analysis of real-world clinical practice.

"There could be many reasons for the differences in our findings, such as differences in the quality of evidence of observational studies and randomized controlled trials (RCTs) or differences in the included study populations between the observational studies in our review and the RE-LY trial," Dr. Robert J. Romanelli from Palo Alto Medical Foundation Research Institute, California, told Reuters Health by email.

The RE-LY trial is the only RCT to have evaluated dabigatran in stroke prevention, and RCTs are prone to selection biases less likely to be present in well designed observational studies, Dr. Romanelli and colleagues note in Circulation:Cardiovascular and Quality Outcomes, online January 26.

The team used data from seven retrospective cohort studies to compare the effectiveness and safety of dabigatran and warfarin among more than 348,750 patients with nonvalvular AF.

During an overall mean follow-up of 794 days, dabigatran 150mg or 110 mg was similar to warfarin in ischemic stroke prevention.

Both the higher and lower dabigatran doses had significantly lower hazards of intracranial bleeding compared with warfarin (pooled hazard ratio, 0.44 and 0.49, respectively). But the hazard of gastrointestinal bleeding was significantly greater for dabigatran 150 mg (but not for 110 mg) than for warfarin (pHR, 1.23). The 110 mg dose of dabigatran was only available during the trial; it's now sold in 150 mg or 75 mg capsules.

The increased risk of gastrointestinal bleeding with the higher dose of dabigatran was significant only in older populations (75 years or older).

"Data presented in this review reflect relative risk, which is not always clinically meaningful," the researchers caution. "It is important to bear in mind that event rates for the outcome of interest are low under standard treatment."

"I don't think the findings from this one reviewshould change clinical practice," Dr. Romanelli said. "If anything, this study revealed areas for future research.

NEW YORK (Reuters Health) - Dabigatran and warfarin offer similar stroke-prevention efficacy in patients with atrial fibrillation (AF), but their side effect profiles differ, according to a systematic review and meta-analysis of real-world clinical practice.

"There could be many reasons for the differences in our findings, such as differences in the quality of evidence of observational studies and randomized controlled trials (RCTs) or differences in the included study populations between the observational studies in our review and the RE-LY trial," Dr. Robert J. Romanelli from Palo Alto Medical Foundation Research Institute, California, told Reuters Health by email.

The RE-LY trial is the only RCT to have evaluated dabigatran in stroke prevention, and RCTs are prone to selection biases less likely to be present in well designed observational studies, Dr. Romanelli and colleagues note in Circulation:Cardiovascular and Quality Outcomes, online January 26.

The team used data from seven retrospective cohort studies to compare the effectiveness and safety of dabigatran and warfarin among more than 348,750 patients with nonvalvular AF.

During an overall mean follow-up of 794 days, dabigatran 150mg or 110 mg was similar to warfarin in ischemic stroke prevention.

Both the higher and lower dabigatran doses had significantly lower hazards of intracranial bleeding compared with warfarin (pooled hazard ratio, 0.44 and 0.49, respectively). But the hazard of gastrointestinal bleeding was significantly greater for dabigatran 150 mg (but not for 110 mg) than for warfarin (pHR, 1.23). The 110 mg dose of dabigatran was only available during the trial; it's now sold in 150 mg or 75 mg capsules.

The increased risk of gastrointestinal bleeding with the higher dose of dabigatran was significant only in older populations (75 years or older).

"Data presented in this review reflect relative risk, which is not always clinically meaningful," the researchers caution. "It is important to bear in mind that event rates for the outcome of interest are low under standard treatment."

"I don't think the findings from this one reviewshould change clinical practice," Dr. Romanelli said. "If anything, this study revealed areas for future research.

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."