Mary Ann Moon

Oral contraceptives containing low- or very low-dose estradiol raised the risks of thrombotic stroke and myocardial infarction by a factor of 1 to 2 in a large Danish cohort study. The results were published in the June 14 issue of the New England Journal of Medicine.

Although these risks were high relative to the nonuse of OCs, the absolute risks of thrombotic stroke and MI remained extremely low, said Dr. Øjvind Lidegaard and his associates at the University of Copenhagen.

"We estimate that among 10,000 women who use desogestrel with ethinyl estradiol at a dose of 20 mg for 1 year, 2 will have arterial thrombosis and 6.8 women ... will have venous thrombosis. Although venous thrombosis is three to four times as frequent as arterial thrombosis among young women, the latter is associated with higher mortality and more serious consequences for survivors. Therefore, these figures should be taken into account when prescribing hormonal contraception," they noted.

Few studies have examined the risks of thrombotic stroke and MI associated with the newer hormonal contraceptives, and those that have examined the issue have produced conflicting results. Dr. Lidegaard and his colleagues assessed this association in a cohort of Danish women aged 15-49 years in 1995 who were followed through 2009.

Among these 1,626,158 study subjects, there were 3,311 first thrombotic strokes and 1,725 first MIs during the 15-year follow-up. The case fatality rates were 1.0% for stroke and 10.8% for MI.

Compared with women who didn’t use hormonal contraceptives, those who used low-dose OCs (30-40 mcg estradiol) had a risk of arterial thrombosis that was 1.3-2.3 times higher, and women who used very-low-dose OCs (20 mcg estradiol) had a risk that was 0.9-1.7 times higher, the investigators said (N. Engl. J. Med. 2012;366:2257-66).

These risks did not vary significantly according to the different types of progestin contained in the OCs.

To put these risk elevations in context, it is useful to note that increasing age raised the risk of arterial thrombosis much more dramatically. The risk of thrombotic stroke was 20 times higher and that of MI was 100 times higher among the oldest study subjects – aged 45-49 years at baseline –compared with the youngest (15-19 years). Several previous studies also have noted the steep rise in thrombotic risk with increasing patient age, the researchers said.

Other hormonal contraceptive products also were assessed in this study. None of the contraceptive products that contained progestin only – such as the levonorgestrel-releasing IUD and subcutaneous implants – raised the risk of thrombotic stroke or MI significantly.

In contrast, contraceptive patches raised the relative risk of thrombotic stroke to 3.15, and vaginal rings raised it to 2.49. "One might expect a higher risk of thrombotic stroke with parenteral administration than with oral administration," Dr. Lidegaard and his associates said.

The number of MIs in these two subgroups of women was too low to allow for reliable estimates of MI risk.

This study was supported by the Danish Heart Association. Dr. Lidegaard reported ties to Bayer Pharma, MSD Denmark, and Theramex. Coinvestigator Ellen Løkkegaard, Ph.D., reported ties to Pfizer.

Oral contraceptives containing low- or very low-dose estradiol raised the risks of thrombotic stroke and myocardial infarction by a factor of 1 to 2 in a large Danish cohort study. The results were published in the June 14 issue of the New England Journal of Medicine.

Although these risks were high relative to the nonuse of OCs, the absolute risks of thrombotic stroke and MI remained extremely low, said Dr. Øjvind Lidegaard and his associates at the University of Copenhagen.

"We estimate that among 10,000 women who use desogestrel with ethinyl estradiol at a dose of 20 mg for 1 year, 2 will have arterial thrombosis and 6.8 women ... will have venous thrombosis. Although venous thrombosis is three to four times as frequent as arterial thrombosis among young women, the latter is associated with higher mortality and more serious consequences for survivors. Therefore, these figures should be taken into account when prescribing hormonal contraception," they noted.

Few studies have examined the risks of thrombotic stroke and MI associated with the newer hormonal contraceptives, and those that have examined the issue have produced conflicting results. Dr. Lidegaard and his colleagues assessed this association in a cohort of Danish women aged 15-49 years in 1995 who were followed through 2009.

Among these 1,626,158 study subjects, there were 3,311 first thrombotic strokes and 1,725 first MIs during the 15-year follow-up. The case fatality rates were 1.0% for stroke and 10.8% for MI.

Compared with women who didn’t use hormonal contraceptives, those who used low-dose OCs (30-40 mcg estradiol) had a risk of arterial thrombosis that was 1.3-2.3 times higher, and women who used very-low-dose OCs (20 mcg estradiol) had a risk that was 0.9-1.7 times higher, the investigators said (N. Engl. J. Med. 2012;366:2257-66).

These risks did not vary significantly according to the different types of progestin contained in the OCs.

To put these risk elevations in context, it is useful to note that increasing age raised the risk of arterial thrombosis much more dramatically. The risk of thrombotic stroke was 20 times higher and that of MI was 100 times higher among the oldest study subjects – aged 45-49 years at baseline –compared with the youngest (15-19 years). Several previous studies also have noted the steep rise in thrombotic risk with increasing patient age, the researchers said.

Other hormonal contraceptive products also were assessed in this study. None of the contraceptive products that contained progestin only – such as the levonorgestrel-releasing IUD and subcutaneous implants – raised the risk of thrombotic stroke or MI significantly.

In contrast, contraceptive patches raised the relative risk of thrombotic stroke to 3.15, and vaginal rings raised it to 2.49. "One might expect a higher risk of thrombotic stroke with parenteral administration than with oral administration," Dr. Lidegaard and his associates said.

The number of MIs in these two subgroups of women was too low to allow for reliable estimates of MI risk.

This study was supported by the Danish Heart Association. Dr. Lidegaard reported ties to Bayer Pharma, MSD Denmark, and Theramex. Coinvestigator Ellen Løkkegaard, Ph.D., reported ties to Pfizer.

Oral contraceptives containing low- or very low-dose estradiol raised the risks of thrombotic stroke and myocardial infarction by a factor of 1 to 2 in a large Danish cohort study. The results were published in the June 14 issue of the New England Journal of Medicine.

Although these risks were high relative to the nonuse of OCs, the absolute risks of thrombotic stroke and MI remained extremely low, said Dr. Øjvind Lidegaard and his associates at the University of Copenhagen.

"We estimate that among 10,000 women who use desogestrel with ethinyl estradiol at a dose of 20 mg for 1 year, 2 will have arterial thrombosis and 6.8 women ... will have venous thrombosis. Although venous thrombosis is three to four times as frequent as arterial thrombosis among young women, the latter is associated with higher mortality and more serious consequences for survivors. Therefore, these figures should be taken into account when prescribing hormonal contraception," they noted.

Few studies have examined the risks of thrombotic stroke and MI associated with the newer hormonal contraceptives, and those that have examined the issue have produced conflicting results. Dr. Lidegaard and his colleagues assessed this association in a cohort of Danish women aged 15-49 years in 1995 who were followed through 2009.

Among these 1,626,158 study subjects, there were 3,311 first thrombotic strokes and 1,725 first MIs during the 15-year follow-up. The case fatality rates were 1.0% for stroke and 10.8% for MI.

Compared with women who didn’t use hormonal contraceptives, those who used low-dose OCs (30-40 mcg estradiol) had a risk of arterial thrombosis that was 1.3-2.3 times higher, and women who used very-low-dose OCs (20 mcg estradiol) had a risk that was 0.9-1.7 times higher, the investigators said (N. Engl. J. Med. 2012;366:2257-66).

These risks did not vary significantly according to the different types of progestin contained in the OCs.

To put these risk elevations in context, it is useful to note that increasing age raised the risk of arterial thrombosis much more dramatically. The risk of thrombotic stroke was 20 times higher and that of MI was 100 times higher among the oldest study subjects – aged 45-49 years at baseline –compared with the youngest (15-19 years). Several previous studies also have noted the steep rise in thrombotic risk with increasing patient age, the researchers said.

Other hormonal contraceptive products also were assessed in this study. None of the contraceptive products that contained progestin only – such as the levonorgestrel-releasing IUD and subcutaneous implants – raised the risk of thrombotic stroke or MI significantly.

In contrast, contraceptive patches raised the relative risk of thrombotic stroke to 3.15, and vaginal rings raised it to 2.49. "One might expect a higher risk of thrombotic stroke with parenteral administration than with oral administration," Dr. Lidegaard and his associates said.

The number of MIs in these two subgroups of women was too low to allow for reliable estimates of MI risk.

This study was supported by the Danish Heart Association. Dr. Lidegaard reported ties to Bayer Pharma, MSD Denmark, and Theramex. Coinvestigator Ellen Løkkegaard, Ph.D., reported ties to Pfizer.

Advanced diagnostic imaging, with its much higher radiation doses than conventional radiography, is being used with increased frequency even within integrated health care delivery systems that are "clinically and fiscally accountable for their members’ outcomes" – in other words, even in the absence of financial incentives to overuse technologies, according to a report in the June 13 issue of JAMA.

The burgeoning use of diagnostic imaging has been well documented in Medicare and in fee-for-service insured populations, but until now no large, multicenter study has assessed time trends in imaging procedures within HMOs, which supposedly put greater limitations on questionable procedures, said Dr. Rebecca Smith-Bindman of the departments of radiology and biomedical imaging, epidemiology and biostatistics, and ob.gyn. and reproductive sciences, University of California, San Francisco, and her coinvestigators.

"Understanding imaging utilization and associated radiation exposure in these settings could help us determine how much of the increase in imaging may be independent of direct financial incentives," they noted (JAMA 307:2400-9).

The marked increase in advanced imaging is a concern because the higher radiation exposures have been linked with the development of radiation-induced cancers.

Dr. Smith-Bindman and her colleagues performed a retrospective population-based study of imaging trends between 1996 and 2010 among members of six geographically diverse U.S. health care delivery systems: Group Health Cooperative in Washington state; Kaiser Permanente in Colorado, Georgia, Hawaii, and Oregon; and Marshfield Clinic and Security Health Plan in Wisconsin.

Between 933,897 and 1,998,650 patients were included during each year of the study, and they underwent a total of 30.9 million imaging examinations. This averages out to 1.18 imaging studies per patient per year.

The investigators estimated the effective dose of ionizing radiation for each procedure, a measure that includes both the amount of radiation to which the patient is exposed and the biologic effect of that radiation on the exposed organs. They then used that data to calculate the total radiation dose each HMO member received each year, as well as the collective effective dose to the entire population.

The rates of conventional radiography and angiography/fluoroscopy remained relatively stable over the 15-year study period, rising just over 1% each year.

In marked contrast, the number of CT studies tripled, from 52 per 1,000 patients in 1996 to 149 per 1,000 in 2010. This represents an annual growth of nearly 8%.

The number of MRIs quadrupled, from 17 to 65 per 1,000 patients, an annual growth of 10%.

The number of ultrasound exams approximately doubled, from 134 to 230 per 1,000 patients, for an annual growth of 4%.

The rates of nuclear medicine exams decreased slightly, with one notable exception: During the last half of the study period, the number of PET scans skyrocketed from 0.24 per 1,000 patients in 2004 to 3.6 per 1,000 in 2010. This represents an annual growth of 57%.

Not surprisingly, the mean per capita effective radiation dose also rose significantly during the study period, effectively doubling from 1.2 mSv to 2.3 mSv. Among patients exposed to any radiation from medical imaging, the average effective dose climbed from 4.8 mSv in 1996 to 7.8 in 2010.

Of particular concern was the finding that the percentage of patients who received high (over 20-50 mSv) or very high (over 50 mSv) radiation exposure during a given year also approximately doubled. "By 2010, 2.5% of enrollees received a high annual dose of greater than 20-50 mSv, and 1.4% received a very high annual dose of greater than 50 mSv," the investigators wrote (JAMA 2012;307:2400-9).

Putting this exposure level in context, "the National Academy of Sciences’ National Research Council concluded, after a comprehensive review of the published literature, that patients who receive radiation exposures in the same range as a single CT – 10mSv – may be at increased risk for developing cancer," they said.

"The number of patients exposed to such levels highlights the need to consider this potential harm when ordering imaging tests and to track radiation exposures for individual patients so that this information is available to physicians who are ordering tests," Dr. Smith-Bindman and her associates said.

Older patients are at particular risk. The use of imaging, particularly of CT and nuclear medicine exams, increased steeply with patient age. "Among enrollees 45 years and older who underwent imaging, nearly 20% received high or very high radiation exposure annually," the researchers said.

Since the potential harm from such exposure may also increase with patient age, "it is particularly important to quantify the benefits of imaging in these patients," they noted.

The increase in the use of CT scanning accounted for much of the overall rise in radiation exposure. In 1996, 30% of patients’ exposure to ionizing radiation was attributed to CT studies; by 2010, 68% of exposure was attributed to CT studies.

"The increase in use of advanced diagnostic imaging has almost certainly contributed to both improved patient care processes and outcomes, but there are remarkably few data to quantify the benefits of imaging. Given the high costs of imaging – estimated at $100 billion annually – and the potential risks of cancer and other harms, these benefits should be quantified, and evidence-based guidelines for using imaging should be developed that clearly balance benefits against financial costs and health risk," Dr. Smith-Bindman and her colleagues said.

This study was funded by the National Cancer Institute and the National Institutes of Health. No financial conflicts of interest were reported by Dr. Smith-Bindman and her coinvestigators.

Advanced diagnostic imaging, with its much higher radiation doses than conventional radiography, is being used with increased frequency even within integrated health care delivery systems that are "clinically and fiscally accountable for their members’ outcomes" – in other words, even in the absence of financial incentives to overuse technologies, according to a report in the June 13 issue of JAMA.

The burgeoning use of diagnostic imaging has been well documented in Medicare and in fee-for-service insured populations, but until now no large, multicenter study has assessed time trends in imaging procedures within HMOs, which supposedly put greater limitations on questionable procedures, said Dr. Rebecca Smith-Bindman of the departments of radiology and biomedical imaging, epidemiology and biostatistics, and ob.gyn. and reproductive sciences, University of California, San Francisco, and her coinvestigators.

"Understanding imaging utilization and associated radiation exposure in these settings could help us determine how much of the increase in imaging may be independent of direct financial incentives," they noted (JAMA 307:2400-9).

The marked increase in advanced imaging is a concern because the higher radiation exposures have been linked with the development of radiation-induced cancers.

Dr. Smith-Bindman and her colleagues performed a retrospective population-based study of imaging trends between 1996 and 2010 among members of six geographically diverse U.S. health care delivery systems: Group Health Cooperative in Washington state; Kaiser Permanente in Colorado, Georgia, Hawaii, and Oregon; and Marshfield Clinic and Security Health Plan in Wisconsin.

Between 933,897 and 1,998,650 patients were included during each year of the study, and they underwent a total of 30.9 million imaging examinations. This averages out to 1.18 imaging studies per patient per year.

The investigators estimated the effective dose of ionizing radiation for each procedure, a measure that includes both the amount of radiation to which the patient is exposed and the biologic effect of that radiation on the exposed organs. They then used that data to calculate the total radiation dose each HMO member received each year, as well as the collective effective dose to the entire population.

The rates of conventional radiography and angiography/fluoroscopy remained relatively stable over the 15-year study period, rising just over 1% each year.

In marked contrast, the number of CT studies tripled, from 52 per 1,000 patients in 1996 to 149 per 1,000 in 2010. This represents an annual growth of nearly 8%.

The number of MRIs quadrupled, from 17 to 65 per 1,000 patients, an annual growth of 10%.

The number of ultrasound exams approximately doubled, from 134 to 230 per 1,000 patients, for an annual growth of 4%.

The rates of nuclear medicine exams decreased slightly, with one notable exception: During the last half of the study period, the number of PET scans skyrocketed from 0.24 per 1,000 patients in 2004 to 3.6 per 1,000 in 2010. This represents an annual growth of 57%.

Not surprisingly, the mean per capita effective radiation dose also rose significantly during the study period, effectively doubling from 1.2 mSv to 2.3 mSv. Among patients exposed to any radiation from medical imaging, the average effective dose climbed from 4.8 mSv in 1996 to 7.8 in 2010.

Of particular concern was the finding that the percentage of patients who received high (over 20-50 mSv) or very high (over 50 mSv) radiation exposure during a given year also approximately doubled. "By 2010, 2.5% of enrollees received a high annual dose of greater than 20-50 mSv, and 1.4% received a very high annual dose of greater than 50 mSv," the investigators wrote (JAMA 2012;307:2400-9).

Putting this exposure level in context, "the National Academy of Sciences’ National Research Council concluded, after a comprehensive review of the published literature, that patients who receive radiation exposures in the same range as a single CT – 10mSv – may be at increased risk for developing cancer," they said.

"The number of patients exposed to such levels highlights the need to consider this potential harm when ordering imaging tests and to track radiation exposures for individual patients so that this information is available to physicians who are ordering tests," Dr. Smith-Bindman and her associates said.

Older patients are at particular risk. The use of imaging, particularly of CT and nuclear medicine exams, increased steeply with patient age. "Among enrollees 45 years and older who underwent imaging, nearly 20% received high or very high radiation exposure annually," the researchers said.

Since the potential harm from such exposure may also increase with patient age, "it is particularly important to quantify the benefits of imaging in these patients," they noted.

The increase in the use of CT scanning accounted for much of the overall rise in radiation exposure. In 1996, 30% of patients’ exposure to ionizing radiation was attributed to CT studies; by 2010, 68% of exposure was attributed to CT studies.

"The increase in use of advanced diagnostic imaging has almost certainly contributed to both improved patient care processes and outcomes, but there are remarkably few data to quantify the benefits of imaging. Given the high costs of imaging – estimated at $100 billion annually – and the potential risks of cancer and other harms, these benefits should be quantified, and evidence-based guidelines for using imaging should be developed that clearly balance benefits against financial costs and health risk," Dr. Smith-Bindman and her colleagues said.

This study was funded by the National Cancer Institute and the National Institutes of Health. No financial conflicts of interest were reported by Dr. Smith-Bindman and her coinvestigators.

Advanced diagnostic imaging, with its much higher radiation doses than conventional radiography, is being used with increased frequency even within integrated health care delivery systems that are "clinically and fiscally accountable for their members’ outcomes" – in other words, even in the absence of financial incentives to overuse technologies, according to a report in the June 13 issue of JAMA.

The burgeoning use of diagnostic imaging has been well documented in Medicare and in fee-for-service insured populations, but until now no large, multicenter study has assessed time trends in imaging procedures within HMOs, which supposedly put greater limitations on questionable procedures, said Dr. Rebecca Smith-Bindman of the departments of radiology and biomedical imaging, epidemiology and biostatistics, and ob.gyn. and reproductive sciences, University of California, San Francisco, and her coinvestigators.

"Understanding imaging utilization and associated radiation exposure in these settings could help us determine how much of the increase in imaging may be independent of direct financial incentives," they noted (JAMA 307:2400-9).

The marked increase in advanced imaging is a concern because the higher radiation exposures have been linked with the development of radiation-induced cancers.

Dr. Smith-Bindman and her colleagues performed a retrospective population-based study of imaging trends between 1996 and 2010 among members of six geographically diverse U.S. health care delivery systems: Group Health Cooperative in Washington state; Kaiser Permanente in Colorado, Georgia, Hawaii, and Oregon; and Marshfield Clinic and Security Health Plan in Wisconsin.

Between 933,897 and 1,998,650 patients were included during each year of the study, and they underwent a total of 30.9 million imaging examinations. This averages out to 1.18 imaging studies per patient per year.

The investigators estimated the effective dose of ionizing radiation for each procedure, a measure that includes both the amount of radiation to which the patient is exposed and the biologic effect of that radiation on the exposed organs. They then used that data to calculate the total radiation dose each HMO member received each year, as well as the collective effective dose to the entire population.

The rates of conventional radiography and angiography/fluoroscopy remained relatively stable over the 15-year study period, rising just over 1% each year.

In marked contrast, the number of CT studies tripled, from 52 per 1,000 patients in 1996 to 149 per 1,000 in 2010. This represents an annual growth of nearly 8%.

The number of MRIs quadrupled, from 17 to 65 per 1,000 patients, an annual growth of 10%.

The number of ultrasound exams approximately doubled, from 134 to 230 per 1,000 patients, for an annual growth of 4%.

The rates of nuclear medicine exams decreased slightly, with one notable exception: During the last half of the study period, the number of PET scans skyrocketed from 0.24 per 1,000 patients in 2004 to 3.6 per 1,000 in 2010. This represents an annual growth of 57%.

Not surprisingly, the mean per capita effective radiation dose also rose significantly during the study period, effectively doubling from 1.2 mSv to 2.3 mSv. Among patients exposed to any radiation from medical imaging, the average effective dose climbed from 4.8 mSv in 1996 to 7.8 in 2010.

Of particular concern was the finding that the percentage of patients who received high (over 20-50 mSv) or very high (over 50 mSv) radiation exposure during a given year also approximately doubled. "By 2010, 2.5% of enrollees received a high annual dose of greater than 20-50 mSv, and 1.4% received a very high annual dose of greater than 50 mSv," the investigators wrote (JAMA 2012;307:2400-9).

Putting this exposure level in context, "the National Academy of Sciences’ National Research Council concluded, after a comprehensive review of the published literature, that patients who receive radiation exposures in the same range as a single CT – 10mSv – may be at increased risk for developing cancer," they said.

"The number of patients exposed to such levels highlights the need to consider this potential harm when ordering imaging tests and to track radiation exposures for individual patients so that this information is available to physicians who are ordering tests," Dr. Smith-Bindman and her associates said.

Older patients are at particular risk. The use of imaging, particularly of CT and nuclear medicine exams, increased steeply with patient age. "Among enrollees 45 years and older who underwent imaging, nearly 20% received high or very high radiation exposure annually," the researchers said.

Since the potential harm from such exposure may also increase with patient age, "it is particularly important to quantify the benefits of imaging in these patients," they noted.

The increase in the use of CT scanning accounted for much of the overall rise in radiation exposure. In 1996, 30% of patients’ exposure to ionizing radiation was attributed to CT studies; by 2010, 68% of exposure was attributed to CT studies.

"The increase in use of advanced diagnostic imaging has almost certainly contributed to both improved patient care processes and outcomes, but there are remarkably few data to quantify the benefits of imaging. Given the high costs of imaging – estimated at $100 billion annually – and the potential risks of cancer and other harms, these benefits should be quantified, and evidence-based guidelines for using imaging should be developed that clearly balance benefits against financial costs and health risk," Dr. Smith-Bindman and her colleagues said.

This study was funded by the National Cancer Institute and the National Institutes of Health. No financial conflicts of interest were reported by Dr. Smith-Bindman and her coinvestigators.

An elimination diet was effective at inducing symptomatic, endoscopic, and histologic improvement in a study of 50 adults with eosinophilic esophagitis, Dr. Nirmala Gonsalves and her colleagues reported in the June issue of Gastroenterology.

Eliminating the six most common food allergens from the diet for 6 weeks reduced by at least half the peak eosinophil counts in 78% of the study subjects. Moreover, 64% of all subjects achieved a reduction to the target level of 5 or fewer eosinophils per high-powered field.

In the prospective clinical trial, reintroducing the food allergens one at a time allowed the investigators to identify the causative dietary agent(s) in all 20 subjects who chose to participate in a reintroduction experiment.

Eosinophilic esophagitis (EOE) is typically characterized by dysphagia, heartburn, and food impaction, and in this study the proportions of patients reporting these symptoms at enrollment were 96%, 94%, and 74%, respectively. The average duration of symptoms was 6 years.

This is the first study to prospectively examine the effectiveness of an elimination diet in adult EOE, and the first to implicate food allergens in the pathogenesis of the disorder in the adult population, said Dr. Gonsalves and her associates at Northwestern University, Chicago (Gastroenterology 2012 June [doi: 10.1053/j.gastro.2012.03.001]).

Food allergens have been proposed as a primary trigger of EOE in the pediatric population, but an elimination diet was found ineffective in a small series of adult patients, and no further research has examined the issue in adults.

In this study, 25 men and 25 women with EOE consulted with a dietitian specifically trained in allergy diet restriction, who provided them with sample menus and shopping guides. The allergens they avoided were milk, soy, egg, wheat, peanuts/tree nuts, and shellfish/fish.

Before and after the 6-week intervention, all the subjects underwent esophagogastroduodenoscopy with biopsy. Those who achieved histologic remission on the diet were invited to undergo sequential reintroduction of each of the six food allergens, with endoscopies and biopsies to confirm their specific food triggers.

The mean peak eosinophil count at baseline was 53 (range, 17-108) per high-powered field. In the patient population as a whole, this decreased significantly, from 34 to 8 in the proximal esophagus and from 48 to 13 in the distal esophagus.

The primary study end point was histologic improvement in esophageal eosinophilia. A complete response was defined as a peak eosinophil count of 5 or fewer per high-powered field, and 64% of the patients achieved this. A near-complete response was 10 or fewer eosinophils per high-powered field (70% of patients), and a partial response was a 50% or greater reduction in peak eosinophil count (78% of patients).

When the results were broken down by level of treatment response, complete responders had a reduction in mean peak eosinophil count from 32 to 3 in the proximal esophagus and from 48 to 3 in the distal esophagus. Partial responders had a reduction from 59 to 9 in the proximal esophagus and from 50 to 16 in the distal esophagus.

Even "nonresponders" had some reductions, from 42 to 30 in the proximal esophagus and from 62 to 55 in the distal esophagus, the investigators said.

At the same time, dysphagia symptom scores decreased in 94% of the study subjects. The frequency, severity, and duration of dysphagia all declined significantly. Endoscopic features also improved in 78% of patients in response to the elimination diet.

Twenty patients completed the dietary reintroduction process, and symptomatic, endoscopic, and histologic abnormalities recurred in all of them after exposure to the causative food. The median time to symptom recurrence was 3 days.

The most common food triggers of EOE were wheat (60% of cases) and milk (50%), followed by soy (10%), nuts (10%), and egg (5%). Three study subjects had more than one food trigger; milk and wheat were the most common combination. These findings parallel those seen in pediatric studies reported in the literature.

Remarkably, none of the study subjects reported having food allergies or intolerances at baseline. And although all of them underwent skin prick testing for an allergic response to the six foods and to aeroallergens at baseline, the results were not predictive of response to the dietary intervention.

"Skin prick testing accurately predicted only 13% of causal agents, and 67% of patients who had a food trigger identified by the reintroduction process had a negative skin prick test to all foods," Dr. Gonsalves and her associates said.

It remains unclear whether eliminating a food trigger from the diet will prove to be a feasible long-term therapy for adults. "A maintenance arm of this study is ongoing to answer this question," the authors said.

The study was not funded, and the authors reported having no financial disclosures.

An elimination diet was effective at inducing symptomatic, endoscopic, and histologic improvement in a study of 50 adults with eosinophilic esophagitis, Dr. Nirmala Gonsalves and her colleagues reported in the June issue of Gastroenterology.

Eliminating the six most common food allergens from the diet for 6 weeks reduced by at least half the peak eosinophil counts in 78% of the study subjects. Moreover, 64% of all subjects achieved a reduction to the target level of 5 or fewer eosinophils per high-powered field.

In the prospective clinical trial, reintroducing the food allergens one at a time allowed the investigators to identify the causative dietary agent(s) in all 20 subjects who chose to participate in a reintroduction experiment.

Eosinophilic esophagitis (EOE) is typically characterized by dysphagia, heartburn, and food impaction, and in this study the proportions of patients reporting these symptoms at enrollment were 96%, 94%, and 74%, respectively. The average duration of symptoms was 6 years.

This is the first study to prospectively examine the effectiveness of an elimination diet in adult EOE, and the first to implicate food allergens in the pathogenesis of the disorder in the adult population, said Dr. Gonsalves and her associates at Northwestern University, Chicago (Gastroenterology 2012 June [doi: 10.1053/j.gastro.2012.03.001]).

Food allergens have been proposed as a primary trigger of EOE in the pediatric population, but an elimination diet was found ineffective in a small series of adult patients, and no further research has examined the issue in adults.

In this study, 25 men and 25 women with EOE consulted with a dietitian specifically trained in allergy diet restriction, who provided them with sample menus and shopping guides. The allergens they avoided were milk, soy, egg, wheat, peanuts/tree nuts, and shellfish/fish.

Before and after the 6-week intervention, all the subjects underwent esophagogastroduodenoscopy with biopsy. Those who achieved histologic remission on the diet were invited to undergo sequential reintroduction of each of the six food allergens, with endoscopies and biopsies to confirm their specific food triggers.

The mean peak eosinophil count at baseline was 53 (range, 17-108) per high-powered field. In the patient population as a whole, this decreased significantly, from 34 to 8 in the proximal esophagus and from 48 to 13 in the distal esophagus.

The primary study end point was histologic improvement in esophageal eosinophilia. A complete response was defined as a peak eosinophil count of 5 or fewer per high-powered field, and 64% of the patients achieved this. A near-complete response was 10 or fewer eosinophils per high-powered field (70% of patients), and a partial response was a 50% or greater reduction in peak eosinophil count (78% of patients).

When the results were broken down by level of treatment response, complete responders had a reduction in mean peak eosinophil count from 32 to 3 in the proximal esophagus and from 48 to 3 in the distal esophagus. Partial responders had a reduction from 59 to 9 in the proximal esophagus and from 50 to 16 in the distal esophagus.

Even "nonresponders" had some reductions, from 42 to 30 in the proximal esophagus and from 62 to 55 in the distal esophagus, the investigators said.

At the same time, dysphagia symptom scores decreased in 94% of the study subjects. The frequency, severity, and duration of dysphagia all declined significantly. Endoscopic features also improved in 78% of patients in response to the elimination diet.

Twenty patients completed the dietary reintroduction process, and symptomatic, endoscopic, and histologic abnormalities recurred in all of them after exposure to the causative food. The median time to symptom recurrence was 3 days.

The most common food triggers of EOE were wheat (60% of cases) and milk (50%), followed by soy (10%), nuts (10%), and egg (5%). Three study subjects had more than one food trigger; milk and wheat were the most common combination. These findings parallel those seen in pediatric studies reported in the literature.

Remarkably, none of the study subjects reported having food allergies or intolerances at baseline. And although all of them underwent skin prick testing for an allergic response to the six foods and to aeroallergens at baseline, the results were not predictive of response to the dietary intervention.

"Skin prick testing accurately predicted only 13% of causal agents, and 67% of patients who had a food trigger identified by the reintroduction process had a negative skin prick test to all foods," Dr. Gonsalves and her associates said.

It remains unclear whether eliminating a food trigger from the diet will prove to be a feasible long-term therapy for adults. "A maintenance arm of this study is ongoing to answer this question," the authors said.

The study was not funded, and the authors reported having no financial disclosures.

An elimination diet was effective at inducing symptomatic, endoscopic, and histologic improvement in a study of 50 adults with eosinophilic esophagitis, Dr. Nirmala Gonsalves and her colleagues reported in the June issue of Gastroenterology.

Eliminating the six most common food allergens from the diet for 6 weeks reduced by at least half the peak eosinophil counts in 78% of the study subjects. Moreover, 64% of all subjects achieved a reduction to the target level of 5 or fewer eosinophils per high-powered field.

In the prospective clinical trial, reintroducing the food allergens one at a time allowed the investigators to identify the causative dietary agent(s) in all 20 subjects who chose to participate in a reintroduction experiment.

Eosinophilic esophagitis (EOE) is typically characterized by dysphagia, heartburn, and food impaction, and in this study the proportions of patients reporting these symptoms at enrollment were 96%, 94%, and 74%, respectively. The average duration of symptoms was 6 years.

This is the first study to prospectively examine the effectiveness of an elimination diet in adult EOE, and the first to implicate food allergens in the pathogenesis of the disorder in the adult population, said Dr. Gonsalves and her associates at Northwestern University, Chicago (Gastroenterology 2012 June [doi: 10.1053/j.gastro.2012.03.001]).

Food allergens have been proposed as a primary trigger of EOE in the pediatric population, but an elimination diet was found ineffective in a small series of adult patients, and no further research has examined the issue in adults.

In this study, 25 men and 25 women with EOE consulted with a dietitian specifically trained in allergy diet restriction, who provided them with sample menus and shopping guides. The allergens they avoided were milk, soy, egg, wheat, peanuts/tree nuts, and shellfish/fish.

Before and after the 6-week intervention, all the subjects underwent esophagogastroduodenoscopy with biopsy. Those who achieved histologic remission on the diet were invited to undergo sequential reintroduction of each of the six food allergens, with endoscopies and biopsies to confirm their specific food triggers.

The mean peak eosinophil count at baseline was 53 (range, 17-108) per high-powered field. In the patient population as a whole, this decreased significantly, from 34 to 8 in the proximal esophagus and from 48 to 13 in the distal esophagus.

The primary study end point was histologic improvement in esophageal eosinophilia. A complete response was defined as a peak eosinophil count of 5 or fewer per high-powered field, and 64% of the patients achieved this. A near-complete response was 10 or fewer eosinophils per high-powered field (70% of patients), and a partial response was a 50% or greater reduction in peak eosinophil count (78% of patients).

When the results were broken down by level of treatment response, complete responders had a reduction in mean peak eosinophil count from 32 to 3 in the proximal esophagus and from 48 to 3 in the distal esophagus. Partial responders had a reduction from 59 to 9 in the proximal esophagus and from 50 to 16 in the distal esophagus.

Even "nonresponders" had some reductions, from 42 to 30 in the proximal esophagus and from 62 to 55 in the distal esophagus, the investigators said.

At the same time, dysphagia symptom scores decreased in 94% of the study subjects. The frequency, severity, and duration of dysphagia all declined significantly. Endoscopic features also improved in 78% of patients in response to the elimination diet.

Twenty patients completed the dietary reintroduction process, and symptomatic, endoscopic, and histologic abnormalities recurred in all of them after exposure to the causative food. The median time to symptom recurrence was 3 days.

The most common food triggers of EOE were wheat (60% of cases) and milk (50%), followed by soy (10%), nuts (10%), and egg (5%). Three study subjects had more than one food trigger; milk and wheat were the most common combination. These findings parallel those seen in pediatric studies reported in the literature.

Remarkably, none of the study subjects reported having food allergies or intolerances at baseline. And although all of them underwent skin prick testing for an allergic response to the six foods and to aeroallergens at baseline, the results were not predictive of response to the dietary intervention.

"Skin prick testing accurately predicted only 13% of causal agents, and 67% of patients who had a food trigger identified by the reintroduction process had a negative skin prick test to all foods," Dr. Gonsalves and her associates said.

It remains unclear whether eliminating a food trigger from the diet will prove to be a feasible long-term therapy for adults. "A maintenance arm of this study is ongoing to answer this question," the authors said.

The study was not funded, and the authors reported having no financial disclosures.

A new practice guideline for diagnosing and managing nonalcoholic fatty liver disease has been released jointly in the June issues of Gastroenterology, the American Journal of Gastroenterology, and Hepatology.

The guideline represents a collaboration among three societies – the American Gastroenterological Association, the American Association for the Study of Liver Diseases, and the American College of Gastroenterology – and it includes 45 recommendations for physicians and other clinicians. These recommendations "suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care." Summaries of the current world literature upon which these recommendations are based are also included.

The recommendations "are intended to be flexible and adjustable for individual patients," said Dr. Naga Chalasani, chair of the writing group and director of the division of gastroenterology and hepatology, Indiana University, Indianapolis, and his associates.

NAFLD is becoming an increasing concern as the obesity epidemic continues. The guideline also includes a discussion of the incidence of NAFLD in the general population and in high-risk groups, as well as a description of the natural history of the disorder, Dr. Chalasani and his colleagues said (Gastroenterol. 2012 May 15 [doi: 10.1053/j.gastro.2012.04.001]).

Screening and Diagnosis in Adults

Among the recommendations concerning diagnosis in the guideline are the following points:

• By definition, NAFLD indicates that patients do not have any ongoing or recent intake of significant quantities of alcohol. But until now, the precise definition of "significant" in this context has been uncertain. The guideline states that when assessing patients suspected of having NAFLD, "significant alcohol consumption" should be defined as more than 21 drinks per week in men and more than 14 drinks per week in women.

• Screening for NAFLD is not recommended at this time, either for adults presenting to primary care practices or for high-risk patients attending diabetes or obesity clinics. There are too many uncertainties concerning diagnostic tests and treatment options, and the long-term benefits and cost-effectiveness of screening are not yet known.

• Screening of family members of patients who have NAFLD is not yet recommended for the same reasons, even though there is some evidence suggesting that the disorder is somewhat heritable and can cluster in certain families.

• When evaluating a patient suspected of having NAFLD, it is essential to exclude other possible causes of steatosis as well as to identify possible comorbid liver disease. Hepatitis, medication toxicity, Wilson’s disease, malnutrition, hemochromatosis, and autoimmune liver disease must be considered in the differential.

• Liver biopsy should be considered in patients at risk for steatohepatitis and advanced fibrosis; in those with persistently high serum ferritin and increased iron saturation, especially if they carry genetic mutations in the C282Y gene; and in patients for whom other etiologies or comorbid liver disease cannot be ascertained without a biopsy. Liver biopsy is not recommended in other patients.

Treatment for Adults

Among the guideline’s recommendations concerning treatment are the following:

• It appears that weight loss of at least 3%-5% of total body weight is necessary to reduce steatosis, and that weight loss of 10% is necessary to improve necroinflammation.

• Metformin is not recommended because it has no significant effect on liver histology.

• Pioglitazone can be used in NAFLD patients who have progressed to nonalcoholic steatohepatitis (NASH), but the long-term safety and efficacy of the drug have not been established, and pioglitazone’s effects in patients with diabetes have never been examined.

• Vitamin E should be considered a first-line therapy for NAFLD patients with NASH, but not those who have concomitant diabetes, NASH cirrhosis, or cryptogenic cirrhosis.

• Ursodeoxycholic acid is not recommended for either NAFLD or NASH. Omega-3 fatty acids are not recommended for NAFLD or NASH but may be first-line agents to treat hypertriglyceridemia in patients who have NAFLD.

• Bariatric surgery is not contraindicated unless patients have established cirrhosis, but "the type, safety, and efficacy of foregut bariatric surgery" in NAFLD have not yet been determined.

• Patients with NASH cirrhosis should be screened for gastroesophageal varices and considered for hepatocellular carcinoma screening.

Pediatric Recommendations

The new guideline contains a section devoted to NAFLD in children and adolescents, since the disorder has been reported in children as young as age 2, and NASH-related cirrhosis has been reported in children as young as age 8.

Among the guideline’s recommendations in the pediatric population are the following:

• No formal recommendation regarding screening of overweight and obese children for NAFLD can yet be made because there is too little evidence to support it, "despite a recent expert committee recommendation for biannual screening for liver disease with liver enzyme measurements in this population."

• Very young or normal-weight children found to have fatty liver should be assessed for monogenic causes of chronic liver disease (such as fatty acid oxidation defects, lysosomal storage diseases, and peroxisomal disorders), as well as the potential causes usually considered among adults.

• High serum titers of autoantibodies, particularly when associated with high aminotransferase and high globulin levels, require a liver biopsy to identify possible autoimmune hepatitis.

• The histopathology of NAFLD in children can differ from that in adults, and can include marked macrovesicular hepatocellular steatosis, portal inflammation, and portal fibrosis in the absence of ballooning.

• Addressing obesity is the first step in treatment, and intensive lifestyle modification is recommended, although no particular diet or exercise program is advocated at this time.

• Metformin is not recommended because it has not been shown to benefit children.

• Vitamin E cannot be recommended for children until confirmatory studies verify that it improves liver histology in NASH.

Dr. Chalasani and his coauthors disclosed relationships with multiple companies; these relationships include research support and paid consulting related to NAFLD.

A new practice guideline for diagnosing and managing nonalcoholic fatty liver disease has been released jointly in the June issues of Gastroenterology, the American Journal of Gastroenterology, and Hepatology.

The guideline represents a collaboration among three societies – the American Gastroenterological Association, the American Association for the Study of Liver Diseases, and the American College of Gastroenterology – and it includes 45 recommendations for physicians and other clinicians. These recommendations "suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care." Summaries of the current world literature upon which these recommendations are based are also included.

The recommendations "are intended to be flexible and adjustable for individual patients," said Dr. Naga Chalasani, chair of the writing group and director of the division of gastroenterology and hepatology, Indiana University, Indianapolis, and his associates.

NAFLD is becoming an increasing concern as the obesity epidemic continues. The guideline also includes a discussion of the incidence of NAFLD in the general population and in high-risk groups, as well as a description of the natural history of the disorder, Dr. Chalasani and his colleagues said (Gastroenterol. 2012 May 15 [doi: 10.1053/j.gastro.2012.04.001]).

Screening and Diagnosis in Adults

Among the recommendations concerning diagnosis in the guideline are the following points:

• By definition, NAFLD indicates that patients do not have any ongoing or recent intake of significant quantities of alcohol. But until now, the precise definition of "significant" in this context has been uncertain. The guideline states that when assessing patients suspected of having NAFLD, "significant alcohol consumption" should be defined as more than 21 drinks per week in men and more than 14 drinks per week in women.

• Screening for NAFLD is not recommended at this time, either for adults presenting to primary care practices or for high-risk patients attending diabetes or obesity clinics. There are too many uncertainties concerning diagnostic tests and treatment options, and the long-term benefits and cost-effectiveness of screening are not yet known.

• Screening of family members of patients who have NAFLD is not yet recommended for the same reasons, even though there is some evidence suggesting that the disorder is somewhat heritable and can cluster in certain families.

• When evaluating a patient suspected of having NAFLD, it is essential to exclude other possible causes of steatosis as well as to identify possible comorbid liver disease. Hepatitis, medication toxicity, Wilson’s disease, malnutrition, hemochromatosis, and autoimmune liver disease must be considered in the differential.

• Liver biopsy should be considered in patients at risk for steatohepatitis and advanced fibrosis; in those with persistently high serum ferritin and increased iron saturation, especially if they carry genetic mutations in the C282Y gene; and in patients for whom other etiologies or comorbid liver disease cannot be ascertained without a biopsy. Liver biopsy is not recommended in other patients.

Treatment for Adults

Among the guideline’s recommendations concerning treatment are the following:

• It appears that weight loss of at least 3%-5% of total body weight is necessary to reduce steatosis, and that weight loss of 10% is necessary to improve necroinflammation.

• Metformin is not recommended because it has no significant effect on liver histology.

• Pioglitazone can be used in NAFLD patients who have progressed to nonalcoholic steatohepatitis (NASH), but the long-term safety and efficacy of the drug have not been established, and pioglitazone’s effects in patients with diabetes have never been examined.

• Vitamin E should be considered a first-line therapy for NAFLD patients with NASH, but not those who have concomitant diabetes, NASH cirrhosis, or cryptogenic cirrhosis.

• Ursodeoxycholic acid is not recommended for either NAFLD or NASH. Omega-3 fatty acids are not recommended for NAFLD or NASH but may be first-line agents to treat hypertriglyceridemia in patients who have NAFLD.

• Bariatric surgery is not contraindicated unless patients have established cirrhosis, but "the type, safety, and efficacy of foregut bariatric surgery" in NAFLD have not yet been determined.

• Patients with NASH cirrhosis should be screened for gastroesophageal varices and considered for hepatocellular carcinoma screening.

Pediatric Recommendations

The new guideline contains a section devoted to NAFLD in children and adolescents, since the disorder has been reported in children as young as age 2, and NASH-related cirrhosis has been reported in children as young as age 8.

Among the guideline’s recommendations in the pediatric population are the following:

• No formal recommendation regarding screening of overweight and obese children for NAFLD can yet be made because there is too little evidence to support it, "despite a recent expert committee recommendation for biannual screening for liver disease with liver enzyme measurements in this population."

• Very young or normal-weight children found to have fatty liver should be assessed for monogenic causes of chronic liver disease (such as fatty acid oxidation defects, lysosomal storage diseases, and peroxisomal disorders), as well as the potential causes usually considered among adults.

• High serum titers of autoantibodies, particularly when associated with high aminotransferase and high globulin levels, require a liver biopsy to identify possible autoimmune hepatitis.

• The histopathology of NAFLD in children can differ from that in adults, and can include marked macrovesicular hepatocellular steatosis, portal inflammation, and portal fibrosis in the absence of ballooning.

• Addressing obesity is the first step in treatment, and intensive lifestyle modification is recommended, although no particular diet or exercise program is advocated at this time.

• Metformin is not recommended because it has not been shown to benefit children.

• Vitamin E cannot be recommended for children until confirmatory studies verify that it improves liver histology in NASH.

Dr. Chalasani and his coauthors disclosed relationships with multiple companies; these relationships include research support and paid consulting related to NAFLD.

A new practice guideline for diagnosing and managing nonalcoholic fatty liver disease has been released jointly in the June issues of Gastroenterology, the American Journal of Gastroenterology, and Hepatology.

The guideline represents a collaboration among three societies – the American Gastroenterological Association, the American Association for the Study of Liver Diseases, and the American College of Gastroenterology – and it includes 45 recommendations for physicians and other clinicians. These recommendations "suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care." Summaries of the current world literature upon which these recommendations are based are also included.

The recommendations "are intended to be flexible and adjustable for individual patients," said Dr. Naga Chalasani, chair of the writing group and director of the division of gastroenterology and hepatology, Indiana University, Indianapolis, and his associates.

NAFLD is becoming an increasing concern as the obesity epidemic continues. The guideline also includes a discussion of the incidence of NAFLD in the general population and in high-risk groups, as well as a description of the natural history of the disorder, Dr. Chalasani and his colleagues said (Gastroenterol. 2012 May 15 [doi: 10.1053/j.gastro.2012.04.001]).

Screening and Diagnosis in Adults

Among the recommendations concerning diagnosis in the guideline are the following points:

• By definition, NAFLD indicates that patients do not have any ongoing or recent intake of significant quantities of alcohol. But until now, the precise definition of "significant" in this context has been uncertain. The guideline states that when assessing patients suspected of having NAFLD, "significant alcohol consumption" should be defined as more than 21 drinks per week in men and more than 14 drinks per week in women.

• Screening for NAFLD is not recommended at this time, either for adults presenting to primary care practices or for high-risk patients attending diabetes or obesity clinics. There are too many uncertainties concerning diagnostic tests and treatment options, and the long-term benefits and cost-effectiveness of screening are not yet known.

• Screening of family members of patients who have NAFLD is not yet recommended for the same reasons, even though there is some evidence suggesting that the disorder is somewhat heritable and can cluster in certain families.

• When evaluating a patient suspected of having NAFLD, it is essential to exclude other possible causes of steatosis as well as to identify possible comorbid liver disease. Hepatitis, medication toxicity, Wilson’s disease, malnutrition, hemochromatosis, and autoimmune liver disease must be considered in the differential.

• Liver biopsy should be considered in patients at risk for steatohepatitis and advanced fibrosis; in those with persistently high serum ferritin and increased iron saturation, especially if they carry genetic mutations in the C282Y gene; and in patients for whom other etiologies or comorbid liver disease cannot be ascertained without a biopsy. Liver biopsy is not recommended in other patients.

Treatment for Adults

Among the guideline’s recommendations concerning treatment are the following:

• It appears that weight loss of at least 3%-5% of total body weight is necessary to reduce steatosis, and that weight loss of 10% is necessary to improve necroinflammation.

• Metformin is not recommended because it has no significant effect on liver histology.

• Pioglitazone can be used in NAFLD patients who have progressed to nonalcoholic steatohepatitis (NASH), but the long-term safety and efficacy of the drug have not been established, and pioglitazone’s effects in patients with diabetes have never been examined.

• Vitamin E should be considered a first-line therapy for NAFLD patients with NASH, but not those who have concomitant diabetes, NASH cirrhosis, or cryptogenic cirrhosis.

• Ursodeoxycholic acid is not recommended for either NAFLD or NASH. Omega-3 fatty acids are not recommended for NAFLD or NASH but may be first-line agents to treat hypertriglyceridemia in patients who have NAFLD.

• Bariatric surgery is not contraindicated unless patients have established cirrhosis, but "the type, safety, and efficacy of foregut bariatric surgery" in NAFLD have not yet been determined.

• Patients with NASH cirrhosis should be screened for gastroesophageal varices and considered for hepatocellular carcinoma screening.

Pediatric Recommendations

The new guideline contains a section devoted to NAFLD in children and adolescents, since the disorder has been reported in children as young as age 2, and NASH-related cirrhosis has been reported in children as young as age 8.

Among the guideline’s recommendations in the pediatric population are the following:

• No formal recommendation regarding screening of overweight and obese children for NAFLD can yet be made because there is too little evidence to support it, "despite a recent expert committee recommendation for biannual screening for liver disease with liver enzyme measurements in this population."

• Very young or normal-weight children found to have fatty liver should be assessed for monogenic causes of chronic liver disease (such as fatty acid oxidation defects, lysosomal storage diseases, and peroxisomal disorders), as well as the potential causes usually considered among adults.

• High serum titers of autoantibodies, particularly when associated with high aminotransferase and high globulin levels, require a liver biopsy to identify possible autoimmune hepatitis.

• The histopathology of NAFLD in children can differ from that in adults, and can include marked macrovesicular hepatocellular steatosis, portal inflammation, and portal fibrosis in the absence of ballooning.

• Addressing obesity is the first step in treatment, and intensive lifestyle modification is recommended, although no particular diet or exercise program is advocated at this time.

• Metformin is not recommended because it has not been shown to benefit children.

• Vitamin E cannot be recommended for children until confirmatory studies verify that it improves liver histology in NASH.

Dr. Chalasani and his coauthors disclosed relationships with multiple companies; these relationships include research support and paid consulting related to NAFLD.

Whole-body hypothermia reduced the rate of death in patients with moderate to severe neonatal encephalopathy without raising the rate of neurodevelopmental deficits in a study that followed 190 children to age 6-7 years, according to a report in the May 31 issue of the New England Journal of Medicine.

Until now, data "have not been available to assess whether the benefits of hypothermia for neonatal hypoxic-ischemic encephalopathy persist after 2 years of age," said Dr. Seetha Shankaran, director of the division of neonatal-perinatal medicine at Wayne State University, Detroit, and her associates.

"These results are reassuring since hypothermia is being used extensively around the world and currently is recommended by health care policymakers," they noted.

The investigators used data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network to assess the long-term rates of death, cognitive impairment, and other neurodevelopmental outcomes in 190 children born in 2000-2003. All the study subjects were diagnosed as having moderate to severe encephalopathy within 6 hours of birth, after an acute perinatal event causing severe acidosis or necessitating resuscitation.

The neonates had been randomly assigned either to undergo whole-body hypothermia at 33.5° C for 72 hours (97 patients) or to usual care (93 patients).

The primary outcome measure – a combination of death or an IQ score below 70 at 6-7 years of age – occurred in 47% of the hypothermia group and 62% of the control group. There were 27 deaths in the hypothermia group and 41 in the control group. In the hypothermia group, 27% of the children attained an IQ score below 70, compared with 33% of the control group. The mean IQ score was 82 with hypothermia and 75 in the control group.

These rates showed a benefit with hypothermia, but the difference between the two groups in the composite primary outcome just failed to reach statistical significance.

When the combined outcome was broken down into its individual parts, however, hypothermia was found to significantly improve mortality, "with no appreciable increase in the risk of neurodevelopmental deficits among survivors," said Dr. Shankaran, who is also director of regional neonatal programs at Children’s Hospital of Michigan, Detroit, and her colleagues.

The secondary composite outcomes of death or severe disability and of death or cerebral palsy were significantly lower in children who had undergone hypothermia. In particular, the rate of cerebral palsy was 17% with hypothermia and 29% in the control group; the rate of blindness was 1% with hypothermia, compared with 4% in the control group, the investigators said (N. Engl. J. Med. 2012;366:2085-92).

"We did not find a decrease in the risk of abnormalities in motor function among nondisabled children in the hypothermia group as compared with those in the control group," the researchers said.

There also were no significant differences between the two groups in measures of attention, executive function, and visuospatial ability.

Children with cerebral palsy are known to have "markedly poor" health, but previous studies have found that "the psychosocial health of children and the emotional impact of the child’s health on the parents tend to be similar regardless of the level of disability," they said.

In this study, parents’ assessments of the child’s health or self-esteem did not differ significantly between children who received hypothermia and the control group, and ratings of the emotional impact of the child’s well-being on the parents also were not significantly different, Dr. Shankaran and her associates said.

With any therapy that reduces mortality in infants at high risk of disability, there is a concern that the number who survive with disability will increase. However, "as reported here, there was no evidence of increased rates of an IQ score below 70, severe disability, or cerebral palsy at 6 to 7 years of age among surviving children treated with hypothermia," the investigators said.

This study was supported by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network. Some of Dr. Shankaran’s associates reported ties to Olympic Medical/Natus Corp., MedImmune, Pfeiffer Research Foundation, and the Robertson Foundation, as well as being recipients of various institutional and governmental grants.

Whole-body hypothermia reduced the rate of death in patients with moderate to severe neonatal encephalopathy without raising the rate of neurodevelopmental deficits in a study that followed 190 children to age 6-7 years, according to a report in the May 31 issue of the New England Journal of Medicine.

Until now, data "have not been available to assess whether the benefits of hypothermia for neonatal hypoxic-ischemic encephalopathy persist after 2 years of age," said Dr. Seetha Shankaran, director of the division of neonatal-perinatal medicine at Wayne State University, Detroit, and her associates.

"These results are reassuring since hypothermia is being used extensively around the world and currently is recommended by health care policymakers," they noted.

The investigators used data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network to assess the long-term rates of death, cognitive impairment, and other neurodevelopmental outcomes in 190 children born in 2000-2003. All the study subjects were diagnosed as having moderate to severe encephalopathy within 6 hours of birth, after an acute perinatal event causing severe acidosis or necessitating resuscitation.

The neonates had been randomly assigned either to undergo whole-body hypothermia at 33.5° C for 72 hours (97 patients) or to usual care (93 patients).

The primary outcome measure – a combination of death or an IQ score below 70 at 6-7 years of age – occurred in 47% of the hypothermia group and 62% of the control group. There were 27 deaths in the hypothermia group and 41 in the control group. In the hypothermia group, 27% of the children attained an IQ score below 70, compared with 33% of the control group. The mean IQ score was 82 with hypothermia and 75 in the control group.

These rates showed a benefit with hypothermia, but the difference between the two groups in the composite primary outcome just failed to reach statistical significance.

When the combined outcome was broken down into its individual parts, however, hypothermia was found to significantly improve mortality, "with no appreciable increase in the risk of neurodevelopmental deficits among survivors," said Dr. Shankaran, who is also director of regional neonatal programs at Children’s Hospital of Michigan, Detroit, and her colleagues.

The secondary composite outcomes of death or severe disability and of death or cerebral palsy were significantly lower in children who had undergone hypothermia. In particular, the rate of cerebral palsy was 17% with hypothermia and 29% in the control group; the rate of blindness was 1% with hypothermia, compared with 4% in the control group, the investigators said (N. Engl. J. Med. 2012;366:2085-92).

"We did not find a decrease in the risk of abnormalities in motor function among nondisabled children in the hypothermia group as compared with those in the control group," the researchers said.

There also were no significant differences between the two groups in measures of attention, executive function, and visuospatial ability.

Children with cerebral palsy are known to have "markedly poor" health, but previous studies have found that "the psychosocial health of children and the emotional impact of the child’s health on the parents tend to be similar regardless of the level of disability," they said.

In this study, parents’ assessments of the child’s health or self-esteem did not differ significantly between children who received hypothermia and the control group, and ratings of the emotional impact of the child’s well-being on the parents also were not significantly different, Dr. Shankaran and her associates said.

With any therapy that reduces mortality in infants at high risk of disability, there is a concern that the number who survive with disability will increase. However, "as reported here, there was no evidence of increased rates of an IQ score below 70, severe disability, or cerebral palsy at 6 to 7 years of age among surviving children treated with hypothermia," the investigators said.

This study was supported by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network. Some of Dr. Shankaran’s associates reported ties to Olympic Medical/Natus Corp., MedImmune, Pfeiffer Research Foundation, and the Robertson Foundation, as well as being recipients of various institutional and governmental grants.

Whole-body hypothermia reduced the rate of death in patients with moderate to severe neonatal encephalopathy without raising the rate of neurodevelopmental deficits in a study that followed 190 children to age 6-7 years, according to a report in the May 31 issue of the New England Journal of Medicine.

Until now, data "have not been available to assess whether the benefits of hypothermia for neonatal hypoxic-ischemic encephalopathy persist after 2 years of age," said Dr. Seetha Shankaran, director of the division of neonatal-perinatal medicine at Wayne State University, Detroit, and her associates.

"These results are reassuring since hypothermia is being used extensively around the world and currently is recommended by health care policymakers," they noted.

The investigators used data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network to assess the long-term rates of death, cognitive impairment, and other neurodevelopmental outcomes in 190 children born in 2000-2003. All the study subjects were diagnosed as having moderate to severe encephalopathy within 6 hours of birth, after an acute perinatal event causing severe acidosis or necessitating resuscitation.

The neonates had been randomly assigned either to undergo whole-body hypothermia at 33.5° C for 72 hours (97 patients) or to usual care (93 patients).

The primary outcome measure – a combination of death or an IQ score below 70 at 6-7 years of age – occurred in 47% of the hypothermia group and 62% of the control group. There were 27 deaths in the hypothermia group and 41 in the control group. In the hypothermia group, 27% of the children attained an IQ score below 70, compared with 33% of the control group. The mean IQ score was 82 with hypothermia and 75 in the control group.

These rates showed a benefit with hypothermia, but the difference between the two groups in the composite primary outcome just failed to reach statistical significance.

When the combined outcome was broken down into its individual parts, however, hypothermia was found to significantly improve mortality, "with no appreciable increase in the risk of neurodevelopmental deficits among survivors," said Dr. Shankaran, who is also director of regional neonatal programs at Children’s Hospital of Michigan, Detroit, and her colleagues.

The secondary composite outcomes of death or severe disability and of death or cerebral palsy were significantly lower in children who had undergone hypothermia. In particular, the rate of cerebral palsy was 17% with hypothermia and 29% in the control group; the rate of blindness was 1% with hypothermia, compared with 4% in the control group, the investigators said (N. Engl. J. Med. 2012;366:2085-92).

"We did not find a decrease in the risk of abnormalities in motor function among nondisabled children in the hypothermia group as compared with those in the control group," the researchers said.

There also were no significant differences between the two groups in measures of attention, executive function, and visuospatial ability.

Children with cerebral palsy are known to have "markedly poor" health, but previous studies have found that "the psychosocial health of children and the emotional impact of the child’s health on the parents tend to be similar regardless of the level of disability," they said.

In this study, parents’ assessments of the child’s health or self-esteem did not differ significantly between children who received hypothermia and the control group, and ratings of the emotional impact of the child’s well-being on the parents also were not significantly different, Dr. Shankaran and her associates said.

With any therapy that reduces mortality in infants at high risk of disability, there is a concern that the number who survive with disability will increase. However, "as reported here, there was no evidence of increased rates of an IQ score below 70, severe disability, or cerebral palsy at 6 to 7 years of age among surviving children treated with hypothermia," the investigators said.

This study was supported by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network. Some of Dr. Shankaran’s associates reported ties to Olympic Medical/Natus Corp., MedImmune, Pfeiffer Research Foundation, and the Robertson Foundation, as well as being recipients of various institutional and governmental grants.

Researchers have developed a simple bedside prediction tool – the CASPRI score – to help clinicians estimate which patients resuscitated from in-hospital cardiac arrest will survive to discharge with favorable neurologic status and which will not, according to a report published in the Archives of Internal Medicine.

"We believe that this tool is simple to use, addresses a critical unmet need for better prognostication after cardiac arrest, and has the potential to enhance communication with patients and families," said Dr. Paul S. Chan of Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., and his associates.

They used data from the Get With the Guidelines Resuscitation registry (formerly known as the National Registry of Cardiopulmonary Resuscitation) to develop this prediction tool, noting that families and caregivers "are eager for more precise information about the likelihood of survival and neurologic outcome" when patients have survived in-hospital resuscitation.

The investigators assessed the cases of 42,957 patients in inpatient wards or intensive care units at 551 U.S. hospitals in 2000-2009 who were successfully resuscitated. The mean patient age was 66 years. Fifty-six percent of the cohort was male, 19% was African American.

The first step in developing their prediction tool, known as the Cardiac Arrest Survival Post-Resuscitation In-Hospital (CASPRI) score, was to determine the value of 37 baseline characteristics in predicting the outcomes of the 28,629 subjects who composed the derivation cohort. These characteristics included patient demographics such as age and sex; the location (within the hospital) of the arrest; the initial cardiac arrest rhythm; the timing of the arrest (during regular work hours or off-hours); the patient’s neurologic status before the cardiac arrest; comorbidities; critical care interventions already in place at the time of the cardiac arrest, such as mechanical ventilation or vasopressor medications; and key cardiac variables such as the duration of resuscitation efforts and time to defibrillation.

From this analysis, the researchers identified the 11 variables with the greatest ability to predict neurologically intact survival. They used those variables to construct a predictive model, and a table for converting the results into a numerical risk score from 1 to 40 points, with higher a total indicating a lower likelihood of favorable neurologic survival.

It was notable that two variables found to have the greatest predictive ability were factors pertaining to the cardiac arrest itself: the initial cardiac arrest rhythm, and the duration of resuscitation until spontaneous circulation was restored. In contrast, many patient factors were not found to be predictive and were discarded from the final model, the investigators said (Arch. Intern. Med. 2012 May 28 [doi:10.1001/archinternmed.2012.2050]).

Dr. Chan and his colleagues then conducted a validation study to test the accuracy of the CASPRI score in the remaining 14,328 subjects. "Patients in the top decile (CASPRI score of less than 10) had a 70.7% mean probability of favorable neurologic survival, whereas patients in the bottom decile (CASPRI score of 28 or higher) had a 2.8% mean probability of favorable neurologic survival," they noted.

"Providing concrete probabilities for favorable neurologic survival after cardiac arrest is an important discussion that clinicians have with patients and their families to manage expectations. By converting our prediction model into a risk score, we have sought to create an infrastructure with which clinicians can identify [the] 10% of patients ... who have a greater than 70% probability of favorable neurologic survival to discharge, compared with another 10% who have less than a 3% chance of this outcome," they added.

This study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association.

Researchers have developed a simple bedside prediction tool – the CASPRI score – to help clinicians estimate which patients resuscitated from in-hospital cardiac arrest will survive to discharge with favorable neurologic status and which will not, according to a report published in the Archives of Internal Medicine.

"We believe that this tool is simple to use, addresses a critical unmet need for better prognostication after cardiac arrest, and has the potential to enhance communication with patients and families," said Dr. Paul S. Chan of Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., and his associates.

They used data from the Get With the Guidelines Resuscitation registry (formerly known as the National Registry of Cardiopulmonary Resuscitation) to develop this prediction tool, noting that families and caregivers "are eager for more precise information about the likelihood of survival and neurologic outcome" when patients have survived in-hospital resuscitation.

The investigators assessed the cases of 42,957 patients in inpatient wards or intensive care units at 551 U.S. hospitals in 2000-2009 who were successfully resuscitated. The mean patient age was 66 years. Fifty-six percent of the cohort was male, 19% was African American.

The first step in developing their prediction tool, known as the Cardiac Arrest Survival Post-Resuscitation In-Hospital (CASPRI) score, was to determine the value of 37 baseline characteristics in predicting the outcomes of the 28,629 subjects who composed the derivation cohort. These characteristics included patient demographics such as age and sex; the location (within the hospital) of the arrest; the initial cardiac arrest rhythm; the timing of the arrest (during regular work hours or off-hours); the patient’s neurologic status before the cardiac arrest; comorbidities; critical care interventions already in place at the time of the cardiac arrest, such as mechanical ventilation or vasopressor medications; and key cardiac variables such as the duration of resuscitation efforts and time to defibrillation.

From this analysis, the researchers identified the 11 variables with the greatest ability to predict neurologically intact survival. They used those variables to construct a predictive model, and a table for converting the results into a numerical risk score from 1 to 40 points, with higher a total indicating a lower likelihood of favorable neurologic survival.

It was notable that two variables found to have the greatest predictive ability were factors pertaining to the cardiac arrest itself: the initial cardiac arrest rhythm, and the duration of resuscitation until spontaneous circulation was restored. In contrast, many patient factors were not found to be predictive and were discarded from the final model, the investigators said (Arch. Intern. Med. 2012 May 28 [doi:10.1001/archinternmed.2012.2050]).

Dr. Chan and his colleagues then conducted a validation study to test the accuracy of the CASPRI score in the remaining 14,328 subjects. "Patients in the top decile (CASPRI score of less than 10) had a 70.7% mean probability of favorable neurologic survival, whereas patients in the bottom decile (CASPRI score of 28 or higher) had a 2.8% mean probability of favorable neurologic survival," they noted.

"Providing concrete probabilities for favorable neurologic survival after cardiac arrest is an important discussion that clinicians have with patients and their families to manage expectations. By converting our prediction model into a risk score, we have sought to create an infrastructure with which clinicians can identify [the] 10% of patients ... who have a greater than 70% probability of favorable neurologic survival to discharge, compared with another 10% who have less than a 3% chance of this outcome," they added.

This study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association.

Researchers have developed a simple bedside prediction tool – the CASPRI score – to help clinicians estimate which patients resuscitated from in-hospital cardiac arrest will survive to discharge with favorable neurologic status and which will not, according to a report published in the Archives of Internal Medicine.

"We believe that this tool is simple to use, addresses a critical unmet need for better prognostication after cardiac arrest, and has the potential to enhance communication with patients and families," said Dr. Paul S. Chan of Saint Luke’s Mid-America Heart Institute, Kansas City, Mo., and his associates.

They used data from the Get With the Guidelines Resuscitation registry (formerly known as the National Registry of Cardiopulmonary Resuscitation) to develop this prediction tool, noting that families and caregivers "are eager for more precise information about the likelihood of survival and neurologic outcome" when patients have survived in-hospital resuscitation.

The investigators assessed the cases of 42,957 patients in inpatient wards or intensive care units at 551 U.S. hospitals in 2000-2009 who were successfully resuscitated. The mean patient age was 66 years. Fifty-six percent of the cohort was male, 19% was African American.

The first step in developing their prediction tool, known as the Cardiac Arrest Survival Post-Resuscitation In-Hospital (CASPRI) score, was to determine the value of 37 baseline characteristics in predicting the outcomes of the 28,629 subjects who composed the derivation cohort. These characteristics included patient demographics such as age and sex; the location (within the hospital) of the arrest; the initial cardiac arrest rhythm; the timing of the arrest (during regular work hours or off-hours); the patient’s neurologic status before the cardiac arrest; comorbidities; critical care interventions already in place at the time of the cardiac arrest, such as mechanical ventilation or vasopressor medications; and key cardiac variables such as the duration of resuscitation efforts and time to defibrillation.

From this analysis, the researchers identified the 11 variables with the greatest ability to predict neurologically intact survival. They used those variables to construct a predictive model, and a table for converting the results into a numerical risk score from 1 to 40 points, with higher a total indicating a lower likelihood of favorable neurologic survival.

It was notable that two variables found to have the greatest predictive ability were factors pertaining to the cardiac arrest itself: the initial cardiac arrest rhythm, and the duration of resuscitation until spontaneous circulation was restored. In contrast, many patient factors were not found to be predictive and were discarded from the final model, the investigators said (Arch. Intern. Med. 2012 May 28 [doi:10.1001/archinternmed.2012.2050]).

Dr. Chan and his colleagues then conducted a validation study to test the accuracy of the CASPRI score in the remaining 14,328 subjects. "Patients in the top decile (CASPRI score of less than 10) had a 70.7% mean probability of favorable neurologic survival, whereas patients in the bottom decile (CASPRI score of 28 or higher) had a 2.8% mean probability of favorable neurologic survival," they noted.

"Providing concrete probabilities for favorable neurologic survival after cardiac arrest is an important discussion that clinicians have with patients and their families to manage expectations. By converting our prediction model into a risk score, we have sought to create an infrastructure with which clinicians can identify [the] 10% of patients ... who have a greater than 70% probability of favorable neurologic survival to discharge, compared with another 10% who have less than a 3% chance of this outcome," they added.

This study was supported by the National Heart, Lung, and Blood Institute and the American Heart Association.

Long-acting contraceptive methods – intrauterine devices and subdermal implants – were superior to oral contraceptives, transdermal patches, and vaginal rings in preventing unintended pregnancies, results from a prospective study of more than 7,000 at-risk women show. The report is in the May 24 issue of the New England Journal of Medicine.

"We found that participants using oral contraceptive pills, a transdermal patch, or a vaginal ring had a risk of contraceptive failure that was 20 times as high as the risk among those using long-acting reversible contraception," said Dr. Brooke Winner of the department of obstetrics and gynecology, Washington University, St. Louis, and her associates.

Photo © EduardoLuzzatti/iStockphoto.com

The researchers attributed this difference to the fact that once IUDs and implants are inserted, they are not user dependent, whereas the other methods in this study depend on correct and consistent usage by the patient.

Approximately 3 million pregnancies each year in the United States, or half of all pregnancies here, are unintended. This rate is significantly higher than that in other developed countries. Half of these unintended pregnancies are due to incorrect or inconsistent use of contraceptives, and the other half to nonuse of contraceptives.

Dr. Winner and her associates conducted a prospective cohort study of women aged 14-45 years who were at risk for unintended pregnancy because they were not using any contraception or were using it only sporadically. The women received counseling regarding all reversible contraceptive methods, which covered the effectiveness, risks, benefits, and side effects of each (N. Engl. J. Med. 2012;366:1998-2007).

They then were given the contraceptive method of their choice at no cost for 2-3 years. The women were allowed to discontinue or switch methods as often as they wished during follow-up.

The 7,486 study subjects were followed via telephone interviews every 6 months, and any changes in their contraceptive use or pregnancy status were documented in a log. This information was corroborated with pharmacy data where the subjects filled their prescriptions.

Between 2007 and 2011, there were 334 unintended pregnancies in these study subjects.

At 1-year, 2-year, and 3-year follow-up, the women using OCs, patches, or vaginal rings had higher rates of unintended pregnancy than did those using IUDs or implants. The contraceptive failure rates were 4.8% vs. 0.3% at 1 year, 7.8% vs. 0.6% at 2 years, and 9.4% vs. 0.9% at 3 years.

The failure rate for depot medroxyprogesterone acetate (DMPA) injections was similar to that with IUDs and implants: 0.1% at 1 year, 0.7% at 2 years, and 0.7% at 3 years.

Looked at from a different perspective, the failure rate for OCs, patches, and rings combined was 4.55 per 100 woman-years, compared with 0.27 per 100 woman-years with IUDs and implants combined.

After the data were adjusted to account for subject age, education level, and number of previous unintended pregnancies, the risk of unintended pregnancy remained markedly higher in women using OCs, patches, or rings than among those using IUDs or implants, with a hazard ratio of 21.8.

The researchers hypothesized that younger women would be less consistent with their use of contraceptives than would older women, so they analyzed the data by subject age to test this hypothesis. They found that subjects younger than 21 years using OCs, patches, or rings were almost twice as likely to have an unintended pregnancy as were older women using those methods.

In contrast, among women using IUDs, implants, or DMPA injections, which do not depend on user consistency, there were no significant differences according to age in the rates of unintended pregnancy.

This finding "underscores the potential benefits of offering adolescents long-acting reversible contraception (which does not require daily, weekly, or monthly compliance) to reduce unintended pregnancies in this high-risk age group," Dr. Winner and her associates said.

They added that their study was somewhat limited in that all contraception was provided at no cost to the women, "which may have improved adherence and led to an underestimation of failure rates."

This study was supported by the Susan Thompson Buffet Foundation. Dr. Winner’s associates reported ties to Omnia Education, Merck, Lippincott, and Bayer HealthCare Pharmaceuticals.

Long-acting contraceptive methods – intrauterine devices and subdermal implants – were superior to oral contraceptives, transdermal patches, and vaginal rings in preventing unintended pregnancies, results from a prospective study of more than 7,000 at-risk women show. The report is in the May 24 issue of the New England Journal of Medicine.

"We found that participants using oral contraceptive pills, a transdermal patch, or a vaginal ring had a risk of contraceptive failure that was 20 times as high as the risk among those using long-acting reversible contraception," said Dr. Brooke Winner of the department of obstetrics and gynecology, Washington University, St. Louis, and her associates.

Photo © EduardoLuzzatti/iStockphoto.com

The researchers attributed this difference to the fact that once IUDs and implants are inserted, they are not user dependent, whereas the other methods in this study depend on correct and consistent usage by the patient.

Approximately 3 million pregnancies each year in the United States, or half of all pregnancies here, are unintended. This rate is significantly higher than that in other developed countries. Half of these unintended pregnancies are due to incorrect or inconsistent use of contraceptives, and the other half to nonuse of contraceptives.

Dr. Winner and her associates conducted a prospective cohort study of women aged 14-45 years who were at risk for unintended pregnancy because they were not using any contraception or were using it only sporadically. The women received counseling regarding all reversible contraceptive methods, which covered the effectiveness, risks, benefits, and side effects of each (N. Engl. J. Med. 2012;366:1998-2007).

They then were given the contraceptive method of their choice at no cost for 2-3 years. The women were allowed to discontinue or switch methods as often as they wished during follow-up.

The 7,486 study subjects were followed via telephone interviews every 6 months, and any changes in their contraceptive use or pregnancy status were documented in a log. This information was corroborated with pharmacy data where the subjects filled their prescriptions.

Between 2007 and 2011, there were 334 unintended pregnancies in these study subjects.

At 1-year, 2-year, and 3-year follow-up, the women using OCs, patches, or vaginal rings had higher rates of unintended pregnancy than did those using IUDs or implants. The contraceptive failure rates were 4.8% vs. 0.3% at 1 year, 7.8% vs. 0.6% at 2 years, and 9.4% vs. 0.9% at 3 years.

The failure rate for depot medroxyprogesterone acetate (DMPA) injections was similar to that with IUDs and implants: 0.1% at 1 year, 0.7% at 2 years, and 0.7% at 3 years.

Looked at from a different perspective, the failure rate for OCs, patches, and rings combined was 4.55 per 100 woman-years, compared with 0.27 per 100 woman-years with IUDs and implants combined.

After the data were adjusted to account for subject age, education level, and number of previous unintended pregnancies, the risk of unintended pregnancy remained markedly higher in women using OCs, patches, or rings than among those using IUDs or implants, with a hazard ratio of 21.8.

The researchers hypothesized that younger women would be less consistent with their use of contraceptives than would older women, so they analyzed the data by subject age to test this hypothesis. They found that subjects younger than 21 years using OCs, patches, or rings were almost twice as likely to have an unintended pregnancy as were older women using those methods.

In contrast, among women using IUDs, implants, or DMPA injections, which do not depend on user consistency, there were no significant differences according to age in the rates of unintended pregnancy.

This finding "underscores the potential benefits of offering adolescents long-acting reversible contraception (which does not require daily, weekly, or monthly compliance) to reduce unintended pregnancies in this high-risk age group," Dr. Winner and her associates said.

They added that their study was somewhat limited in that all contraception was provided at no cost to the women, "which may have improved adherence and led to an underestimation of failure rates."

This study was supported by the Susan Thompson Buffet Foundation. Dr. Winner’s associates reported ties to Omnia Education, Merck, Lippincott, and Bayer HealthCare Pharmaceuticals.

Long-acting contraceptive methods – intrauterine devices and subdermal implants – were superior to oral contraceptives, transdermal patches, and vaginal rings in preventing unintended pregnancies, results from a prospective study of more than 7,000 at-risk women show. The report is in the May 24 issue of the New England Journal of Medicine.

"We found that participants using oral contraceptive pills, a transdermal patch, or a vaginal ring had a risk of contraceptive failure that was 20 times as high as the risk among those using long-acting reversible contraception," said Dr. Brooke Winner of the department of obstetrics and gynecology, Washington University, St. Louis, and her associates.

Photo © EduardoLuzzatti/iStockphoto.com

The researchers attributed this difference to the fact that once IUDs and implants are inserted, they are not user dependent, whereas the other methods in this study depend on correct and consistent usage by the patient.

Approximately 3 million pregnancies each year in the United States, or half of all pregnancies here, are unintended. This rate is significantly higher than that in other developed countries. Half of these unintended pregnancies are due to incorrect or inconsistent use of contraceptives, and the other half to nonuse of contraceptives.

Dr. Winner and her associates conducted a prospective cohort study of women aged 14-45 years who were at risk for unintended pregnancy because they were not using any contraception or were using it only sporadically. The women received counseling regarding all reversible contraceptive methods, which covered the effectiveness, risks, benefits, and side effects of each (N. Engl. J. Med. 2012;366:1998-2007).

They then were given the contraceptive method of their choice at no cost for 2-3 years. The women were allowed to discontinue or switch methods as often as they wished during follow-up.

The 7,486 study subjects were followed via telephone interviews every 6 months, and any changes in their contraceptive use or pregnancy status were documented in a log. This information was corroborated with pharmacy data where the subjects filled their prescriptions.

Between 2007 and 2011, there were 334 unintended pregnancies in these study subjects.

At 1-year, 2-year, and 3-year follow-up, the women using OCs, patches, or vaginal rings had higher rates of unintended pregnancy than did those using IUDs or implants. The contraceptive failure rates were 4.8% vs. 0.3% at 1 year, 7.8% vs. 0.6% at 2 years, and 9.4% vs. 0.9% at 3 years.

The failure rate for depot medroxyprogesterone acetate (DMPA) injections was similar to that with IUDs and implants: 0.1% at 1 year, 0.7% at 2 years, and 0.7% at 3 years.

Looked at from a different perspective, the failure rate for OCs, patches, and rings combined was 4.55 per 100 woman-years, compared with 0.27 per 100 woman-years with IUDs and implants combined.

After the data were adjusted to account for subject age, education level, and number of previous unintended pregnancies, the risk of unintended pregnancy remained markedly higher in women using OCs, patches, or rings than among those using IUDs or implants, with a hazard ratio of 21.8.

The researchers hypothesized that younger women would be less consistent with their use of contraceptives than would older women, so they analyzed the data by subject age to test this hypothesis. They found that subjects younger than 21 years using OCs, patches, or rings were almost twice as likely to have an unintended pregnancy as were older women using those methods.

In contrast, among women using IUDs, implants, or DMPA injections, which do not depend on user consistency, there were no significant differences according to age in the rates of unintended pregnancy.

This finding "underscores the potential benefits of offering adolescents long-acting reversible contraception (which does not require daily, weekly, or monthly compliance) to reduce unintended pregnancies in this high-risk age group," Dr. Winner and her associates said.

They added that their study was somewhat limited in that all contraception was provided at no cost to the women, "which may have improved adherence and led to an underestimation of failure rates."

This study was supported by the Susan Thompson Buffet Foundation. Dr. Winner’s associates reported ties to Omnia Education, Merck, Lippincott, and Bayer HealthCare Pharmaceuticals.

Continuous positive airway pressure therapy was linked to a lower rate of incident hypertension in one study but not in another, separate study reported online in the May 23/30 issue of JAMA.

However, the investigators in the second study discovered methodologic flaws that called their conclusion into question. They performed a post hoc analysis, and the results were similar to those of the first study: CPAP therapy, when adhered to, is associated with a lower rate of incident hypertension.

© David Cannings-Bushell/iStockphoto

Neither study could definitively establish that CPAP itself decreases hypertension; both could only note the strong association between the treatment and a decreased rate of the disorder.

CPAP therapy is known to decrease overall cardiovascular risk and to lower blood pressure in certain groups of patients, but its efficacy in preventing the onset of hypertension has not been adequately studied to date, both groups of researchers noted.

In the first study, Dr. Jose M. Marin of Miguel Servet University Hospital, Zaragoza (Spain), and his associates used data from the observational Zaragoza Sleep Cohort Study to assess whether patients on long-term CPAP were less likely to develop hypertension. The cohort study involved more than 5,000 patients referred by their primary care physicians to a sleep center for assessment of sleep-disordered breathing in 1994-2000.

For his analysis, Dr. Marin and his colleagues studied 1,889 such patients who had no hypertension at baseline and who underwent overnight sleep studies to ascertain the cause of their snoring, daytime fatigue, or daytime sleepiness. A total of 824 subjects were found to have obstructive sleep apnea and then adhered to CPAP therapy; another 462 were found to have obstructive sleep apnea but were ineligible for CPAP, 195 declined to try CPAP, and 98 were nonadherent with CPAP therapy. Another 310 patients who were not found to have obstructive sleep apnea served as control subjects.

During a mean follow-up of 11 years, 705 patients developed incident hypertension.

In unadjusted analyses, the rate of new-onset HT was 3.06 per 100 person-years among patients who adhered to CPAP therapy. It was significantly higher in patients who were ineligible for CPAP (3.34 per 100 person-years), and dramatically higher those who declined CPAP (5.84 per 100 person-years) and those who were nonadherent (5.12 per 100 person-years).

After the data were adjusted to account for several confounders, the risk of new-onset HT was the same between patients who adhered to CPAP and control subjects, but was significantly higher in all other groups (JAMA 2012;307:2169-76).

These findings were independent of the severity of obstructive sleep apnea and of patients’ body mass index. Since almost all the subjects gained weight during follow-up, this suggests that weight gain does not diminish the protective association of CPAP therapy and the development of HT, Dr. Marin and his associates said.

Overall, the study results suggest that obstructive sleep apnea is a modifiable risk factor for new-onset HT. This is highly relevant to clinicians "considering that obstructive sleep apnea, despite a high prevalence in Western populations, remains overwhelmingly unrecognized and untreated," they added.

In the second study, Dr. Ferran Barbe of Arnau de Vilanova University Hospital, Lleida (Spain), and his associates assessed CPAP’s effect on incident hypertension among subjects who had obstructive sleep apnea but did not have symptoms of daytime sleepiness or fatigue. This is a subgroup of apnea patients who have not been shown to benefit from the treatment, with the caveat that research in this patient population has been inadequate.

Dr. Barbe and his colleagues assessed 723 such patients who were randomly assigned to receive CPAP (357 subjects) or no CPAP (366 control subjects). During a median follow-up of 4 years, 147 patients developed incident hypertension and 59 had cardiovascular events.

In the CPAP group there were 68 cases of HT and 28 CV events, and in the control group there were 79 cases of HT and 31 CV events – a nonsignificant difference.

The rate of combined HT/CV events was 11.02 per 100 person-years with CPAP and 9.20 per 100 person-years without CPAP, also a nonsignificant difference. Apnea severity did not affect these findings.

The researchers noted that they had assessed patients who had been prescribed CPAP but not patients who had adhered to CPAP therapy, and that adherence – use of the treatment for at least 4 hours per night – is critical to CPAP’s effectiveness. They therefore performed a post hoc analysis based on a cutoff of 4 hours of actual adherence to CPAP, which they substantiated by examining oxygen saturation data.

This analysis showed that CPAP was associated with a significantly reduced rate of incident HT and CV events as long as patients received 4 hours or more of the treatment each night (JAMA 2012;307:2161-8).

However, as the conclusion of a post hoc analysis, this result must be considered "hypothesis-generating" rather than definitive, they noted.

In addition, Dr. Barbe and his associates realized that they had erred in designing the study and that it likely had insufficient statistical power to detect a significant difference in the rate of HT. "A larger study or longer follow-up might have been able to identify a significant association between treatment and outcome," they said.

Dr. Marin’s study was supported by Instituto Carlos III; the Ministry of Health, Madrid; and the Spanish Society of Respiratory Medicine. Dr. Barbe’s study was funded by Instituto de Salud Carlos III, the Spanish Respiratory Society, Resmed, Air Products-Carburos Metalicos, Respironics, and Breas Medical. Dr. Marin, Dr. Barbe, and their associates reported no financial conflicts of interest.

Continuous positive airway pressure therapy was linked to a lower rate of incident hypertension in one study but not in another, separate study reported online in the May 23/30 issue of JAMA.

However, the investigators in the second study discovered methodologic flaws that called their conclusion into question. They performed a post hoc analysis, and the results were similar to those of the first study: CPAP therapy, when adhered to, is associated with a lower rate of incident hypertension.

© David Cannings-Bushell/iStockphoto

Neither study could definitively establish that CPAP itself decreases hypertension; both could only note the strong association between the treatment and a decreased rate of the disorder.

CPAP therapy is known to decrease overall cardiovascular risk and to lower blood pressure in certain groups of patients, but its efficacy in preventing the onset of hypertension has not been adequately studied to date, both groups of researchers noted.

In the first study, Dr. Jose M. Marin of Miguel Servet University Hospital, Zaragoza (Spain), and his associates used data from the observational Zaragoza Sleep Cohort Study to assess whether patients on long-term CPAP were less likely to develop hypertension. The cohort study involved more than 5,000 patients referred by their primary care physicians to a sleep center for assessment of sleep-disordered breathing in 1994-2000.

For his analysis, Dr. Marin and his colleagues studied 1,889 such patients who had no hypertension at baseline and who underwent overnight sleep studies to ascertain the cause of their snoring, daytime fatigue, or daytime sleepiness. A total of 824 subjects were found to have obstructive sleep apnea and then adhered to CPAP therapy; another 462 were found to have obstructive sleep apnea but were ineligible for CPAP, 195 declined to try CPAP, and 98 were nonadherent with CPAP therapy. Another 310 patients who were not found to have obstructive sleep apnea served as control subjects.

During a mean follow-up of 11 years, 705 patients developed incident hypertension.

In unadjusted analyses, the rate of new-onset HT was 3.06 per 100 person-years among patients who adhered to CPAP therapy. It was significantly higher in patients who were ineligible for CPAP (3.34 per 100 person-years), and dramatically higher those who declined CPAP (5.84 per 100 person-years) and those who were nonadherent (5.12 per 100 person-years).

After the data were adjusted to account for several confounders, the risk of new-onset HT was the same between patients who adhered to CPAP and control subjects, but was significantly higher in all other groups (JAMA 2012;307:2169-76).

These findings were independent of the severity of obstructive sleep apnea and of patients’ body mass index. Since almost all the subjects gained weight during follow-up, this suggests that weight gain does not diminish the protective association of CPAP therapy and the development of HT, Dr. Marin and his associates said.

Overall, the study results suggest that obstructive sleep apnea is a modifiable risk factor for new-onset HT. This is highly relevant to clinicians "considering that obstructive sleep apnea, despite a high prevalence in Western populations, remains overwhelmingly unrecognized and untreated," they added.

In the second study, Dr. Ferran Barbe of Arnau de Vilanova University Hospital, Lleida (Spain), and his associates assessed CPAP’s effect on incident hypertension among subjects who had obstructive sleep apnea but did not have symptoms of daytime sleepiness or fatigue. This is a subgroup of apnea patients who have not been shown to benefit from the treatment, with the caveat that research in this patient population has been inadequate.

Dr. Barbe and his colleagues assessed 723 such patients who were randomly assigned to receive CPAP (357 subjects) or no CPAP (366 control subjects). During a median follow-up of 4 years, 147 patients developed incident hypertension and 59 had cardiovascular events.

In the CPAP group there were 68 cases of HT and 28 CV events, and in the control group there were 79 cases of HT and 31 CV events – a nonsignificant difference.

The rate of combined HT/CV events was 11.02 per 100 person-years with CPAP and 9.20 per 100 person-years without CPAP, also a nonsignificant difference. Apnea severity did not affect these findings.

The researchers noted that they had assessed patients who had been prescribed CPAP but not patients who had adhered to CPAP therapy, and that adherence – use of the treatment for at least 4 hours per night – is critical to CPAP’s effectiveness. They therefore performed a post hoc analysis based on a cutoff of 4 hours of actual adherence to CPAP, which they substantiated by examining oxygen saturation data.

This analysis showed that CPAP was associated with a significantly reduced rate of incident HT and CV events as long as patients received 4 hours or more of the treatment each night (JAMA 2012;307:2161-8).

However, as the conclusion of a post hoc analysis, this result must be considered "hypothesis-generating" rather than definitive, they noted.

In addition, Dr. Barbe and his associates realized that they had erred in designing the study and that it likely had insufficient statistical power to detect a significant difference in the rate of HT. "A larger study or longer follow-up might have been able to identify a significant association between treatment and outcome," they said.

Dr. Marin’s study was supported by Instituto Carlos III; the Ministry of Health, Madrid; and the Spanish Society of Respiratory Medicine. Dr. Barbe’s study was funded by Instituto de Salud Carlos III, the Spanish Respiratory Society, Resmed, Air Products-Carburos Metalicos, Respironics, and Breas Medical. Dr. Marin, Dr. Barbe, and their associates reported no financial conflicts of interest.

Continuous positive airway pressure therapy was linked to a lower rate of incident hypertension in one study but not in another, separate study reported online in the May 23/30 issue of JAMA.

However, the investigators in the second study discovered methodologic flaws that called their conclusion into question. They performed a post hoc analysis, and the results were similar to those of the first study: CPAP therapy, when adhered to, is associated with a lower rate of incident hypertension.

© David Cannings-Bushell/iStockphoto

Neither study could definitively establish that CPAP itself decreases hypertension; both could only note the strong association between the treatment and a decreased rate of the disorder.

CPAP therapy is known to decrease overall cardiovascular risk and to lower blood pressure in certain groups of patients, but its efficacy in preventing the onset of hypertension has not been adequately studied to date, both groups of researchers noted.

In the first study, Dr. Jose M. Marin of Miguel Servet University Hospital, Zaragoza (Spain), and his associates used data from the observational Zaragoza Sleep Cohort Study to assess whether patients on long-term CPAP were less likely to develop hypertension. The cohort study involved more than 5,000 patients referred by their primary care physicians to a sleep center for assessment of sleep-disordered breathing in 1994-2000.

For his analysis, Dr. Marin and his colleagues studied 1,889 such patients who had no hypertension at baseline and who underwent overnight sleep studies to ascertain the cause of their snoring, daytime fatigue, or daytime sleepiness. A total of 824 subjects were found to have obstructive sleep apnea and then adhered to CPAP therapy; another 462 were found to have obstructive sleep apnea but were ineligible for CPAP, 195 declined to try CPAP, and 98 were nonadherent with CPAP therapy. Another 310 patients who were not found to have obstructive sleep apnea served as control subjects.

During a mean follow-up of 11 years, 705 patients developed incident hypertension.

In unadjusted analyses, the rate of new-onset HT was 3.06 per 100 person-years among patients who adhered to CPAP therapy. It was significantly higher in patients who were ineligible for CPAP (3.34 per 100 person-years), and dramatically higher those who declined CPAP (5.84 per 100 person-years) and those who were nonadherent (5.12 per 100 person-years).

After the data were adjusted to account for several confounders, the risk of new-onset HT was the same between patients who adhered to CPAP and control subjects, but was significantly higher in all other groups (JAMA 2012;307:2169-76).

These findings were independent of the severity of obstructive sleep apnea and of patients’ body mass index. Since almost all the subjects gained weight during follow-up, this suggests that weight gain does not diminish the protective association of CPAP therapy and the development of HT, Dr. Marin and his associates said.

Overall, the study results suggest that obstructive sleep apnea is a modifiable risk factor for new-onset HT. This is highly relevant to clinicians "considering that obstructive sleep apnea, despite a high prevalence in Western populations, remains overwhelmingly unrecognized and untreated," they added.

In the second study, Dr. Ferran Barbe of Arnau de Vilanova University Hospital, Lleida (Spain), and his associates assessed CPAP’s effect on incident hypertension among subjects who had obstructive sleep apnea but did not have symptoms of daytime sleepiness or fatigue. This is a subgroup of apnea patients who have not been shown to benefit from the treatment, with the caveat that research in this patient population has been inadequate.

Dr. Barbe and his colleagues assessed 723 such patients who were randomly assigned to receive CPAP (357 subjects) or no CPAP (366 control subjects). During a median follow-up of 4 years, 147 patients developed incident hypertension and 59 had cardiovascular events.

In the CPAP group there were 68 cases of HT and 28 CV events, and in the control group there were 79 cases of HT and 31 CV events – a nonsignificant difference.

The rate of combined HT/CV events was 11.02 per 100 person-years with CPAP and 9.20 per 100 person-years without CPAP, also a nonsignificant difference. Apnea severity did not affect these findings.

The researchers noted that they had assessed patients who had been prescribed CPAP but not patients who had adhered to CPAP therapy, and that adherence – use of the treatment for at least 4 hours per night – is critical to CPAP’s effectiveness. They therefore performed a post hoc analysis based on a cutoff of 4 hours of actual adherence to CPAP, which they substantiated by examining oxygen saturation data.

This analysis showed that CPAP was associated with a significantly reduced rate of incident HT and CV events as long as patients received 4 hours or more of the treatment each night (JAMA 2012;307:2161-8).

However, as the conclusion of a post hoc analysis, this result must be considered "hypothesis-generating" rather than definitive, they noted.

In addition, Dr. Barbe and his associates realized that they had erred in designing the study and that it likely had insufficient statistical power to detect a significant difference in the rate of HT. "A larger study or longer follow-up might have been able to identify a significant association between treatment and outcome," they said.

Dr. Marin’s study was supported by Instituto Carlos III; the Ministry of Health, Madrid; and the Spanish Society of Respiratory Medicine. Dr. Barbe’s study was funded by Instituto de Salud Carlos III, the Spanish Respiratory Society, Resmed, Air Products-Carburos Metalicos, Respironics, and Breas Medical. Dr. Marin, Dr. Barbe, and their associates reported no financial conflicts of interest.

Adding daily low-dose carboplatin chemotherapy to thoracic radiotherapy significantly extended survival in elderly patients with unresectable locally advanced non–small cell lung cancer, according to a study published online May 22 in the Lancet Oncology.

Investigators from the Japan Clinical Oncology Group reported a phase III trial was stopped early after a planned interim analysis showed a 5.5 month gain in median overall survival when this combination was compared with radiotherapy alone.

The addition of low-dose carboplatin did not increase pneumonitis, lung toxicity, or esophageal toxicity; it did increase hematologic toxicity and infections, but these "were manageable with appropriate treatment." Thus, this chemoradiotherapy "is feasible and tolerable for elderly patients with locally advanced" non–small cell lung cancer (NSCLC), and clinicians should consider it, said Dr. Shinji Atagi of the department of thoracic oncology, Kinki-Chuo Chest Medical Center, Osaka, Japan, and his associates.

"This trial is, to the best of our knowledge, the first study to show that combined chemoradiotherapy can improve the outcome of stage III NSCLC in elderly patients," they noted.

The median patient age was 77 years (range 71-93 years), and "the two groups were well-balanced with respect to sex, performance status, and disease and tumor stage," the investigators said. Approximately 80% of the cohort were men, and 90% had a history of smoking.

The appropriate treatment for elderly patients with stage III NSCLC is controversial because few clinical trials have addressed the standard chemoradiotherapy approach specifically in this age group. As cisplatin is considered to be contraindicated in most elderly patients because of its high toxicity, Dr. Atagi and his colleagues assessed a less-toxic analogue, low-dose carboplatin, in the multicenter phase III clinical trial (JCOG0301).

The trial recruited 200 patients aged 71 years or older who had unresectable stage IIIA or IIIB disease and had received no previous chemotherapy or radiotherapy. Participants were randomly assigned to receive 60 Gy of radiotherapy alone (100 patients) in 30 fractions or 60 Gy of radiotherapy in 30 fractions plus a daily 30-minute 30 mg/m² IV infusion of carboplatin (100 patients) 1 hour before the first 20 fractions. Both patients and clinicians were unblinded to treatment assignment.

A planned interim analysis of the data 10 months after patient enrollment was completed, when the median length of follow-up was 19 months, showed that survival was clearly superior with the combined treatment. So the trial was halted early (Lancet Oncol. 2012 [doi:10.1016/S1470-2045(12)70139-0).

At that time, median progression-free survival was 8.9 months with chemoradiotherapy, significantly longer than the 6.8-month progression-free survival with radiotherapy alone.

Median overall survival was 22.4 months with chemoradiotherapy, significantly longer than the 16.9-month overall survival with radiotherapy alone.

The 1-year survival was 70.8% with chemoradiotherapy, compared with 65.2% with radiotherapy alone. The 2-year survival was 46.3% with chemoradiotherapy, compared with 35.1% with radiotherapy alone. These differences also were statistically significant.

At the time of this analysis, 74.7% of the patients in the chemoradiotherapy group showed disease progression, compared with 83.7% of patients in the radiotherapy only group. The sites of recurrence were similar between the two groups.

More patients in the chemoradiotherapy group developed leukopenia, neutropenia, or thrombocytopenia. Grade 4 leukopenia developed in 12 patients and grade 4 neutropenia in 22 patients in the combined-therapy group, compared with 0 patients in the radiotherapy only group. The incidence of grade 3 infections also was higher with chemoradiotherapy.

Investigators reported seven treatment-related deaths: three with chemoradiotherapy and four with radiotherapy.

This study was funded by the Ministry of Health, Labour, and Welfare of Japan. No financial conflicts of interest were reported.

Adding daily low-dose carboplatin chemotherapy to thoracic radiotherapy significantly extended survival in elderly patients with unresectable locally advanced non–small cell lung cancer, according to a study published online May 22 in the Lancet Oncology.

Investigators from the Japan Clinical Oncology Group reported a phase III trial was stopped early after a planned interim analysis showed a 5.5 month gain in median overall survival when this combination was compared with radiotherapy alone.

The addition of low-dose carboplatin did not increase pneumonitis, lung toxicity, or esophageal toxicity; it did increase hematologic toxicity and infections, but these "were manageable with appropriate treatment." Thus, this chemoradiotherapy "is feasible and tolerable for elderly patients with locally advanced" non–small cell lung cancer (NSCLC), and clinicians should consider it, said Dr. Shinji Atagi of the department of thoracic oncology, Kinki-Chuo Chest Medical Center, Osaka, Japan, and his associates.

"This trial is, to the best of our knowledge, the first study to show that combined chemoradiotherapy can improve the outcome of stage III NSCLC in elderly patients," they noted.

The median patient age was 77 years (range 71-93 years), and "the two groups were well-balanced with respect to sex, performance status, and disease and tumor stage," the investigators said. Approximately 80% of the cohort were men, and 90% had a history of smoking.

The appropriate treatment for elderly patients with stage III NSCLC is controversial because few clinical trials have addressed the standard chemoradiotherapy approach specifically in this age group. As cisplatin is considered to be contraindicated in most elderly patients because of its high toxicity, Dr. Atagi and his colleagues assessed a less-toxic analogue, low-dose carboplatin, in the multicenter phase III clinical trial (JCOG0301).

The trial recruited 200 patients aged 71 years or older who had unresectable stage IIIA or IIIB disease and had received no previous chemotherapy or radiotherapy. Participants were randomly assigned to receive 60 Gy of radiotherapy alone (100 patients) in 30 fractions or 60 Gy of radiotherapy in 30 fractions plus a daily 30-minute 30 mg/m² IV infusion of carboplatin (100 patients) 1 hour before the first 20 fractions. Both patients and clinicians were unblinded to treatment assignment.

A planned interim analysis of the data 10 months after patient enrollment was completed, when the median length of follow-up was 19 months, showed that survival was clearly superior with the combined treatment. So the trial was halted early (Lancet Oncol. 2012 [doi:10.1016/S1470-2045(12)70139-0).

At that time, median progression-free survival was 8.9 months with chemoradiotherapy, significantly longer than the 6.8-month progression-free survival with radiotherapy alone.

Median overall survival was 22.4 months with chemoradiotherapy, significantly longer than the 16.9-month overall survival with radiotherapy alone.

The 1-year survival was 70.8% with chemoradiotherapy, compared with 65.2% with radiotherapy alone. The 2-year survival was 46.3% with chemoradiotherapy, compared with 35.1% with radiotherapy alone. These differences also were statistically significant.

At the time of this analysis, 74.7% of the patients in the chemoradiotherapy group showed disease progression, compared with 83.7% of patients in the radiotherapy only group. The sites of recurrence were similar between the two groups.

More patients in the chemoradiotherapy group developed leukopenia, neutropenia, or thrombocytopenia. Grade 4 leukopenia developed in 12 patients and grade 4 neutropenia in 22 patients in the combined-therapy group, compared with 0 patients in the radiotherapy only group. The incidence of grade 3 infections also was higher with chemoradiotherapy.

Investigators reported seven treatment-related deaths: three with chemoradiotherapy and four with radiotherapy.

This study was funded by the Ministry of Health, Labour, and Welfare of Japan. No financial conflicts of interest were reported.

Adding daily low-dose carboplatin chemotherapy to thoracic radiotherapy significantly extended survival in elderly patients with unresectable locally advanced non–small cell lung cancer, according to a study published online May 22 in the Lancet Oncology.

Investigators from the Japan Clinical Oncology Group reported a phase III trial was stopped early after a planned interim analysis showed a 5.5 month gain in median overall survival when this combination was compared with radiotherapy alone.

The addition of low-dose carboplatin did not increase pneumonitis, lung toxicity, or esophageal toxicity; it did increase hematologic toxicity and infections, but these "were manageable with appropriate treatment." Thus, this chemoradiotherapy "is feasible and tolerable for elderly patients with locally advanced" non–small cell lung cancer (NSCLC), and clinicians should consider it, said Dr. Shinji Atagi of the department of thoracic oncology, Kinki-Chuo Chest Medical Center, Osaka, Japan, and his associates.

"This trial is, to the best of our knowledge, the first study to show that combined chemoradiotherapy can improve the outcome of stage III NSCLC in elderly patients," they noted.

The median patient age was 77 years (range 71-93 years), and "the two groups were well-balanced with respect to sex, performance status, and disease and tumor stage," the investigators said. Approximately 80% of the cohort were men, and 90% had a history of smoking.

The appropriate treatment for elderly patients with stage III NSCLC is controversial because few clinical trials have addressed the standard chemoradiotherapy approach specifically in this age group. As cisplatin is considered to be contraindicated in most elderly patients because of its high toxicity, Dr. Atagi and his colleagues assessed a less-toxic analogue, low-dose carboplatin, in the multicenter phase III clinical trial (JCOG0301).

The trial recruited 200 patients aged 71 years or older who had unresectable stage IIIA or IIIB disease and had received no previous chemotherapy or radiotherapy. Participants were randomly assigned to receive 60 Gy of radiotherapy alone (100 patients) in 30 fractions or 60 Gy of radiotherapy in 30 fractions plus a daily 30-minute 30 mg/m² IV infusion of carboplatin (100 patients) 1 hour before the first 20 fractions. Both patients and clinicians were unblinded to treatment assignment.

A planned interim analysis of the data 10 months after patient enrollment was completed, when the median length of follow-up was 19 months, showed that survival was clearly superior with the combined treatment. So the trial was halted early (Lancet Oncol. 2012 [doi:10.1016/S1470-2045(12)70139-0).

At that time, median progression-free survival was 8.9 months with chemoradiotherapy, significantly longer than the 6.8-month progression-free survival with radiotherapy alone.

Median overall survival was 22.4 months with chemoradiotherapy, significantly longer than the 16.9-month overall survival with radiotherapy alone.

The 1-year survival was 70.8% with chemoradiotherapy, compared with 65.2% with radiotherapy alone. The 2-year survival was 46.3% with chemoradiotherapy, compared with 35.1% with radiotherapy alone. These differences also were statistically significant.

At the time of this analysis, 74.7% of the patients in the chemoradiotherapy group showed disease progression, compared with 83.7% of patients in the radiotherapy only group. The sites of recurrence were similar between the two groups.

More patients in the chemoradiotherapy group developed leukopenia, neutropenia, or thrombocytopenia. Grade 4 leukopenia developed in 12 patients and grade 4 neutropenia in 22 patients in the combined-therapy group, compared with 0 patients in the radiotherapy only group. The incidence of grade 3 infections also was higher with chemoradiotherapy.

Investigators reported seven treatment-related deaths: three with chemoradiotherapy and four with radiotherapy.

This study was funded by the Ministry of Health, Labour, and Welfare of Japan. No financial conflicts of interest were reported.

Patients who are obese are more likely than are normal-weight patients to present with advanced papillary thyroid cancer and to have an aggressive subtype of the malignancy, according to a report published online May 21 in the Archives of Surgery.

The reasons for these adverse findings are not yet certain, but the findings are enough to warrant more careful screening for thyroid cancer among obese patients, said Dr. Avital Harari of the section of endocrine surgery, University of California, Los Angeles, and her associates.

Increased body mass index has been linked to an increased incidence of thyroid cancer in several study populations. Higher BMI also has been associated with a more advanced stage of disease at diagnosis in several other types of cancer, including breast and prostate cancers.

To assess a possible relationship between obesity and thyroid cancer, Dr. Harari and her colleagues reviewed the medical records of 443 adults who underwent total thyroidectomy as first-line treatment for papillary thyroid cancer and its variants at their institution during 2004-2011.

The study subjects were categorized as normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg), obese (30-39.9 kg), or morbidly obese (at least 40 kg). The age range was 18-93 years, with a mean age of 48 years.

Obese and morbidly obese patients were significantly more likely than were thinner patients to have stage III or IV disease at diagnosis. In addition, for the study cohort as a whole, higher BMI was a significant predictor of presenting with stage III or IV disease, with an odds ratio (OR) of 1.94 for overweight subjects, an OR of 2.11 for obese subjects, and an OR of 3.67 for morbidly obese patients, compared with normal-weight patients.

Subgroup analysis showed that the percentages of the most-aggressive subtypes of papillary thyroid cancer were higher among patients in the obese and morbidly obese categories than they were among those in the normal-weight and overweight categories, the investigators said (Arch. Surg. 2012 [doi:10.1001/archsurg.2012.713]).

It was noteworthy that patients with higher BMI did not have higher complication rates than did thinner patients. Rates of wound infection, excessive bleeding, hypocalcemia, respiratory problems, and reintubations were similar across all BMI categories. "However, the number of patients was underpowered to detect a less than 3% complication rate," Dr. Harari and her associates noted.

Obese and morbidly obese patients were significantly more likely to have laryngeal nerve dysfunction after thyroidectomy – a rate of 12%, compared with a 2.6% rate in overweight patients and a 2.0% rate in normal-weight patients. But that was because the obese and morbidly obese patients already had vocal cord dysfunction at presentation, concordant with their more advanced local disease.

"We believe that the cause of [the] increase in aggressive papillary thyroid cancer in the overweight and obese population could be multifactorial," the researchers said.

One such factor may be that diagnosis is delayed in patients with higher BMI because it is more difficult to palpate thyroid nodules in the obese neck, so tumors are more advanced when they are finally detected. Another possibility is that certain biomarkers common in obesity, such as high leptin levels, are associated with cancer development and progression.

It is also likely that obesity and thyroid cancer are both linked to third biological factor, such as diabetes. A recent study of diet and health in older Americans found an increased risk of papillary thyroid cancer among women with diabetes, Dr. Harari and her colleagues said.

"Given our findings, we believe that obese patients are at a higher risk of developing aggressive thyroid cancers and thus should be screened ... by sonography, which has been shown to be more sensitive in detecting thyroid cancer than physical examination alone," they said.

No potential financial conflicts of interest were reported.

Patients who are obese are more likely than are normal-weight patients to present with advanced papillary thyroid cancer and to have an aggressive subtype of the malignancy, according to a report published online May 21 in the Archives of Surgery.

The reasons for these adverse findings are not yet certain, but the findings are enough to warrant more careful screening for thyroid cancer among obese patients, said Dr. Avital Harari of the section of endocrine surgery, University of California, Los Angeles, and her associates.

Increased body mass index has been linked to an increased incidence of thyroid cancer in several study populations. Higher BMI also has been associated with a more advanced stage of disease at diagnosis in several other types of cancer, including breast and prostate cancers.

To assess a possible relationship between obesity and thyroid cancer, Dr. Harari and her colleagues reviewed the medical records of 443 adults who underwent total thyroidectomy as first-line treatment for papillary thyroid cancer and its variants at their institution during 2004-2011.

The study subjects were categorized as normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg), obese (30-39.9 kg), or morbidly obese (at least 40 kg). The age range was 18-93 years, with a mean age of 48 years.

Obese and morbidly obese patients were significantly more likely than were thinner patients to have stage III or IV disease at diagnosis. In addition, for the study cohort as a whole, higher BMI was a significant predictor of presenting with stage III or IV disease, with an odds ratio (OR) of 1.94 for overweight subjects, an OR of 2.11 for obese subjects, and an OR of 3.67 for morbidly obese patients, compared with normal-weight patients.

Subgroup analysis showed that the percentages of the most-aggressive subtypes of papillary thyroid cancer were higher among patients in the obese and morbidly obese categories than they were among those in the normal-weight and overweight categories, the investigators said (Arch. Surg. 2012 [doi:10.1001/archsurg.2012.713]).

It was noteworthy that patients with higher BMI did not have higher complication rates than did thinner patients. Rates of wound infection, excessive bleeding, hypocalcemia, respiratory problems, and reintubations were similar across all BMI categories. "However, the number of patients was underpowered to detect a less than 3% complication rate," Dr. Harari and her associates noted.

Obese and morbidly obese patients were significantly more likely to have laryngeal nerve dysfunction after thyroidectomy – a rate of 12%, compared with a 2.6% rate in overweight patients and a 2.0% rate in normal-weight patients. But that was because the obese and morbidly obese patients already had vocal cord dysfunction at presentation, concordant with their more advanced local disease.

"We believe that the cause of [the] increase in aggressive papillary thyroid cancer in the overweight and obese population could be multifactorial," the researchers said.

One such factor may be that diagnosis is delayed in patients with higher BMI because it is more difficult to palpate thyroid nodules in the obese neck, so tumors are more advanced when they are finally detected. Another possibility is that certain biomarkers common in obesity, such as high leptin levels, are associated with cancer development and progression.

It is also likely that obesity and thyroid cancer are both linked to third biological factor, such as diabetes. A recent study of diet and health in older Americans found an increased risk of papillary thyroid cancer among women with diabetes, Dr. Harari and her colleagues said.

"Given our findings, we believe that obese patients are at a higher risk of developing aggressive thyroid cancers and thus should be screened ... by sonography, which has been shown to be more sensitive in detecting thyroid cancer than physical examination alone," they said.

No potential financial conflicts of interest were reported.

Patients who are obese are more likely than are normal-weight patients to present with advanced papillary thyroid cancer and to have an aggressive subtype of the malignancy, according to a report published online May 21 in the Archives of Surgery.

The reasons for these adverse findings are not yet certain, but the findings are enough to warrant more careful screening for thyroid cancer among obese patients, said Dr. Avital Harari of the section of endocrine surgery, University of California, Los Angeles, and her associates.

Increased body mass index has been linked to an increased incidence of thyroid cancer in several study populations. Higher BMI also has been associated with a more advanced stage of disease at diagnosis in several other types of cancer, including breast and prostate cancers.

To assess a possible relationship between obesity and thyroid cancer, Dr. Harari and her colleagues reviewed the medical records of 443 adults who underwent total thyroidectomy as first-line treatment for papillary thyroid cancer and its variants at their institution during 2004-2011.

The study subjects were categorized as normal weight (18.5-24.9 kg/m²), overweight (25-29.9 kg), obese (30-39.9 kg), or morbidly obese (at least 40 kg). The age range was 18-93 years, with a mean age of 48 years.

Obese and morbidly obese patients were significantly more likely than were thinner patients to have stage III or IV disease at diagnosis. In addition, for the study cohort as a whole, higher BMI was a significant predictor of presenting with stage III or IV disease, with an odds ratio (OR) of 1.94 for overweight subjects, an OR of 2.11 for obese subjects, and an OR of 3.67 for morbidly obese patients, compared with normal-weight patients.

Subgroup analysis showed that the percentages of the most-aggressive subtypes of papillary thyroid cancer were higher among patients in the obese and morbidly obese categories than they were among those in the normal-weight and overweight categories, the investigators said (Arch. Surg. 2012 [doi:10.1001/archsurg.2012.713]).

It was noteworthy that patients with higher BMI did not have higher complication rates than did thinner patients. Rates of wound infection, excessive bleeding, hypocalcemia, respiratory problems, and reintubations were similar across all BMI categories. "However, the number of patients was underpowered to detect a less than 3% complication rate," Dr. Harari and her associates noted.

Obese and morbidly obese patients were significantly more likely to have laryngeal nerve dysfunction after thyroidectomy – a rate of 12%, compared with a 2.6% rate in overweight patients and a 2.0% rate in normal-weight patients. But that was because the obese and morbidly obese patients already had vocal cord dysfunction at presentation, concordant with their more advanced local disease.

"We believe that the cause of [the] increase in aggressive papillary thyroid cancer in the overweight and obese population could be multifactorial," the researchers said.

One such factor may be that diagnosis is delayed in patients with higher BMI because it is more difficult to palpate thyroid nodules in the obese neck, so tumors are more advanced when they are finally detected. Another possibility is that certain biomarkers common in obesity, such as high leptin levels, are associated with cancer development and progression.

It is also likely that obesity and thyroid cancer are both linked to third biological factor, such as diabetes. A recent study of diet and health in older Americans found an increased risk of papillary thyroid cancer among women with diabetes, Dr. Harari and her colleagues said.

"Given our findings, we believe that obese patients are at a higher risk of developing aggressive thyroid cancers and thus should be screened ... by sonography, which has been shown to be more sensitive in detecting thyroid cancer than physical examination alone," they said.

No potential financial conflicts of interest were reported.