Mary Ann Moon

When physicians tell patients directly that they are overweight, it raises the odds that the patients will perceive their weight realistically, will want to lose weight, and will try to lose weight, according to a report in the Feb. 28 issue of Archives of Internal Medicine.

However, fewer than half of overweight patients and fewer than two-thirds of obese patients say they have been told by their physicians that they are overweight.

"This is an important intervention point that is being missed by many physicians. Physicians need to tell more overweight and obese patients that they are overweight because this may help encourage them to change their behavior to lose weight and lower their risk for many diseases," said Dr. Robert E. Post of the department of family medicine, Medical University of South Carolina, Charleston, and his associates.

Today’s overweight and obese patients are more likely to consider themselves to be of normal weight than their counterparts of 20 years ago were, in part because the current obesity epidemic has made higher weights and larger sizes seem more normal. Patients who don’t perceive their weight accurately won’t recognize their health risks and won’t work to reduce them, the investigators said.

They analyzed data from the 2005-2008 National Health and Nutrition Examination Survey in a cross-sectional study to assess the effect of physician acknowledgment of weight status on patient behavior. The study included data for 7,790 men and women aged 20-64 years who constituted a nationally representative sample of the U.S. population.

A total of 5,474 of these subjects qualified as overweight, with a BMI of 25 kg/m² or greater, including 2,874 who qualified as obese, with a BMI of 30 or greater.

Of the overweight subjects, 45% reported that their physicians had told them they were overweight, as did 66% of the obese subjects. These subjects were much more likely to identify themselves as overweight (94%) or obese (97%) than were overweight subjects whose physicians had not so informed them (63% and 81%, respectively). They also were much more likely to report that they wanted to lose weight and had attempted to lose weight during the preceding year.

However, about 37% of overweight and 19% of obese subjects had not been told they were overweight by their physicians and did not consider themselves to be. In comparison, only 6% of overweight and 3% of obese subjects who had been told by their physicians that they were overweight continued to consider themselves to be of normal weight.

"This speaks strongly to the influence that physicians’ words have on their patients," Dr. Post and his colleagues said (Arch. Intern. Med. 2011;171:316-21).

Extrapolating this finding to the general U.S. adult population, "this equates to more than 74 million overweight individuals, including nearly 23 million obese individuals, who have never been told that they are overweight," they added.

Telling patients that they are overweight was associated with an eightfold increase in the odds that they would accurately see themselves as overweight and a sixfold increase in the odds that they would accurately see themselves as obese. This recognition is essential because being aware of the problem is the first step in changing behavior to overcome it, the investigators noted.

This study could not assess why physicians fail to identify patients as overweight. It is possible that some patients didn’t "hear" this even though their physicians did tell them.

Alternatively, some physicians may not bother to inform patients of weight status because they see patients as lacking in self-control or motivation to change. Some may feel that labeling patients as overweight or obese is simply stating the obvious and won’t make much difference. Still others may cite time constraints, feeling that if they don’t have the time, they should "avoid starting a potentially long conversation" during a patient visit.

The strong association found in this study between physicians’ remarks and patients’ beliefs "should help to change these negative perceptions among physicians and encourage incorporating extra time into visits to discuss weight management with their patients," Dr. Post and his associates said.

No financial conflicts of interest were reported.

When physicians tell patients directly that they are overweight, it raises the odds that the patients will perceive their weight realistically, will want to lose weight, and will try to lose weight, according to a report in the Feb. 28 issue of Archives of Internal Medicine.

However, fewer than half of overweight patients and fewer than two-thirds of obese patients say they have been told by their physicians that they are overweight.

"This is an important intervention point that is being missed by many physicians. Physicians need to tell more overweight and obese patients that they are overweight because this may help encourage them to change their behavior to lose weight and lower their risk for many diseases," said Dr. Robert E. Post of the department of family medicine, Medical University of South Carolina, Charleston, and his associates.

Today’s overweight and obese patients are more likely to consider themselves to be of normal weight than their counterparts of 20 years ago were, in part because the current obesity epidemic has made higher weights and larger sizes seem more normal. Patients who don’t perceive their weight accurately won’t recognize their health risks and won’t work to reduce them, the investigators said.

They analyzed data from the 2005-2008 National Health and Nutrition Examination Survey in a cross-sectional study to assess the effect of physician acknowledgment of weight status on patient behavior. The study included data for 7,790 men and women aged 20-64 years who constituted a nationally representative sample of the U.S. population.

A total of 5,474 of these subjects qualified as overweight, with a BMI of 25 kg/m² or greater, including 2,874 who qualified as obese, with a BMI of 30 or greater.

Of the overweight subjects, 45% reported that their physicians had told them they were overweight, as did 66% of the obese subjects. These subjects were much more likely to identify themselves as overweight (94%) or obese (97%) than were overweight subjects whose physicians had not so informed them (63% and 81%, respectively). They also were much more likely to report that they wanted to lose weight and had attempted to lose weight during the preceding year.

However, about 37% of overweight and 19% of obese subjects had not been told they were overweight by their physicians and did not consider themselves to be. In comparison, only 6% of overweight and 3% of obese subjects who had been told by their physicians that they were overweight continued to consider themselves to be of normal weight.

"This speaks strongly to the influence that physicians’ words have on their patients," Dr. Post and his colleagues said (Arch. Intern. Med. 2011;171:316-21).

Extrapolating this finding to the general U.S. adult population, "this equates to more than 74 million overweight individuals, including nearly 23 million obese individuals, who have never been told that they are overweight," they added.

Telling patients that they are overweight was associated with an eightfold increase in the odds that they would accurately see themselves as overweight and a sixfold increase in the odds that they would accurately see themselves as obese. This recognition is essential because being aware of the problem is the first step in changing behavior to overcome it, the investigators noted.

This study could not assess why physicians fail to identify patients as overweight. It is possible that some patients didn’t "hear" this even though their physicians did tell them.

Alternatively, some physicians may not bother to inform patients of weight status because they see patients as lacking in self-control or motivation to change. Some may feel that labeling patients as overweight or obese is simply stating the obvious and won’t make much difference. Still others may cite time constraints, feeling that if they don’t have the time, they should "avoid starting a potentially long conversation" during a patient visit.

The strong association found in this study between physicians’ remarks and patients’ beliefs "should help to change these negative perceptions among physicians and encourage incorporating extra time into visits to discuss weight management with their patients," Dr. Post and his associates said.

No financial conflicts of interest were reported.

When physicians tell patients directly that they are overweight, it raises the odds that the patients will perceive their weight realistically, will want to lose weight, and will try to lose weight, according to a report in the Feb. 28 issue of Archives of Internal Medicine.

However, fewer than half of overweight patients and fewer than two-thirds of obese patients say they have been told by their physicians that they are overweight.

"This is an important intervention point that is being missed by many physicians. Physicians need to tell more overweight and obese patients that they are overweight because this may help encourage them to change their behavior to lose weight and lower their risk for many diseases," said Dr. Robert E. Post of the department of family medicine, Medical University of South Carolina, Charleston, and his associates.

Today’s overweight and obese patients are more likely to consider themselves to be of normal weight than their counterparts of 20 years ago were, in part because the current obesity epidemic has made higher weights and larger sizes seem more normal. Patients who don’t perceive their weight accurately won’t recognize their health risks and won’t work to reduce them, the investigators said.

They analyzed data from the 2005-2008 National Health and Nutrition Examination Survey in a cross-sectional study to assess the effect of physician acknowledgment of weight status on patient behavior. The study included data for 7,790 men and women aged 20-64 years who constituted a nationally representative sample of the U.S. population.

A total of 5,474 of these subjects qualified as overweight, with a BMI of 25 kg/m² or greater, including 2,874 who qualified as obese, with a BMI of 30 or greater.

Of the overweight subjects, 45% reported that their physicians had told them they were overweight, as did 66% of the obese subjects. These subjects were much more likely to identify themselves as overweight (94%) or obese (97%) than were overweight subjects whose physicians had not so informed them (63% and 81%, respectively). They also were much more likely to report that they wanted to lose weight and had attempted to lose weight during the preceding year.

However, about 37% of overweight and 19% of obese subjects had not been told they were overweight by their physicians and did not consider themselves to be. In comparison, only 6% of overweight and 3% of obese subjects who had been told by their physicians that they were overweight continued to consider themselves to be of normal weight.

"This speaks strongly to the influence that physicians’ words have on their patients," Dr. Post and his colleagues said (Arch. Intern. Med. 2011;171:316-21).

Extrapolating this finding to the general U.S. adult population, "this equates to more than 74 million overweight individuals, including nearly 23 million obese individuals, who have never been told that they are overweight," they added.

Telling patients that they are overweight was associated with an eightfold increase in the odds that they would accurately see themselves as overweight and a sixfold increase in the odds that they would accurately see themselves as obese. This recognition is essential because being aware of the problem is the first step in changing behavior to overcome it, the investigators noted.

This study could not assess why physicians fail to identify patients as overweight. It is possible that some patients didn’t "hear" this even though their physicians did tell them.

Alternatively, some physicians may not bother to inform patients of weight status because they see patients as lacking in self-control or motivation to change. Some may feel that labeling patients as overweight or obese is simply stating the obvious and won’t make much difference. Still others may cite time constraints, feeling that if they don’t have the time, they should "avoid starting a potentially long conversation" during a patient visit.

The strong association found in this study between physicians’ remarks and patients’ beliefs "should help to change these negative perceptions among physicians and encourage incorporating extra time into visits to discuss weight management with their patients," Dr. Post and his associates said.

No financial conflicts of interest were reported.

When physicians tell patients directly that they are overweight, it raises the odds that the patients will perceive their weight realistically, will want to lose weight, and will try to lose weight, according to a report in the Feb. 28 issue of Archives of Internal Medicine.

However, fewer than half of overweight patients and fewer than two-thirds of obese patients say they have been told by their physicians that they are overweight.

"This is an important intervention point that is being missed by many physicians. Physicians need to tell more overweight and obese patients that they are overweight because this may help encourage them to change their behavior to lose weight and lower their risk for many diseases," said Dr. Robert E. Post of the department of family medicine, Medical University of South Carolina, Charleston, and his associates.

Today’s overweight and obese patients are more likely to consider themselves to be of normal weight than their counterparts of 20 years ago were, in part because the current obesity epidemic has made higher weights and larger sizes seem more normal. Patients who don’t perceive their weight accurately won’t recognize their health risks and won’t work to reduce them, the investigators said.

They analyzed data from the 2005-2008 National Health and Nutrition Examination Survey in a cross-sectional study to assess the effect of physician acknowledgment of weight status on patient behavior. The study included data for 7,790 men and women aged 20-64 years who constituted a nationally representative sample of the U.S. population.

A total of 5,474 of these subjects qualified as overweight, with a BMI of 25 kg/m² or greater, including 2,874 who qualified as obese, with a BMI of 30 or greater.

Of the overweight subjects, 45% reported that their physicians had told them they were overweight, as did 66% of the obese subjects. These subjects were much more likely to identify themselves as overweight (94%) or obese (97%) than were overweight subjects whose physicians had not so informed them (63% and 81%, respectively). They also were much more likely to report that they wanted to lose weight and had attempted to lose weight during the preceding year.

However, about 37% of overweight and 19% of obese subjects had not been told they were overweight by their physicians and did not consider themselves to be. In comparison, only 6% of overweight and 3% of obese subjects who had been told by their physicians that they were overweight continued to consider themselves to be of normal weight.

"This speaks strongly to the influence that physicians’ words have on their patients," Dr. Post and his colleagues said (Arch. Intern. Med. 2011;171:316-21).

Extrapolating this finding to the general U.S. adult population, "this equates to more than 74 million overweight individuals, including nearly 23 million obese individuals, who have never been told that they are overweight," they added.

Telling patients that they are overweight was associated with an eightfold increase in the odds that they would accurately see themselves as overweight and a sixfold increase in the odds that they would accurately see themselves as obese. This recognition is essential because being aware of the problem is the first step in changing behavior to overcome it, the investigators noted.

This study could not assess why physicians fail to identify patients as overweight. It is possible that some patients didn’t "hear" this even though their physicians did tell them.

Alternatively, some physicians may not bother to inform patients of weight status because they see patients as lacking in self-control or motivation to change. Some may feel that labeling patients as overweight or obese is simply stating the obvious and won’t make much difference. Still others may cite time constraints, feeling that if they don’t have the time, they should "avoid starting a potentially long conversation" during a patient visit.

The strong association found in this study between physicians’ remarks and patients’ beliefs "should help to change these negative perceptions among physicians and encourage incorporating extra time into visits to discuss weight management with their patients," Dr. Post and his associates said.

No financial conflicts of interest were reported.

When physicians tell patients directly that they are overweight, it raises the odds that the patients will perceive their weight realistically, will want to lose weight, and will try to lose weight, according to a report in the Feb. 28 issue of Archives of Internal Medicine.

However, fewer than half of overweight patients and fewer than two-thirds of obese patients say they have been told by their physicians that they are overweight.

"This is an important intervention point that is being missed by many physicians. Physicians need to tell more overweight and obese patients that they are overweight because this may help encourage them to change their behavior to lose weight and lower their risk for many diseases," said Dr. Robert E. Post of the department of family medicine, Medical University of South Carolina, Charleston, and his associates.

Today’s overweight and obese patients are more likely to consider themselves to be of normal weight than their counterparts of 20 years ago were, in part because the current obesity epidemic has made higher weights and larger sizes seem more normal. Patients who don’t perceive their weight accurately won’t recognize their health risks and won’t work to reduce them, the investigators said.

They analyzed data from the 2005-2008 National Health and Nutrition Examination Survey in a cross-sectional study to assess the effect of physician acknowledgment of weight status on patient behavior. The study included data for 7,790 men and women aged 20-64 years who constituted a nationally representative sample of the U.S. population.

A total of 5,474 of these subjects qualified as overweight, with a BMI of 25 kg/m² or greater, including 2,874 who qualified as obese, with a BMI of 30 or greater.

Of the overweight subjects, 45% reported that their physicians had told them they were overweight, as did 66% of the obese subjects. These subjects were much more likely to identify themselves as overweight (94%) or obese (97%) than were overweight subjects whose physicians had not so informed them (63% and 81%, respectively). They also were much more likely to report that they wanted to lose weight and had attempted to lose weight during the preceding year.

However, about 37% of overweight and 19% of obese subjects had not been told they were overweight by their physicians and did not consider themselves to be. In comparison, only 6% of overweight and 3% of obese subjects who had been told by their physicians that they were overweight continued to consider themselves to be of normal weight.

"This speaks strongly to the influence that physicians’ words have on their patients," Dr. Post and his colleagues said (Arch. Intern. Med. 2011;171:316-21).

Extrapolating this finding to the general U.S. adult population, "this equates to more than 74 million overweight individuals, including nearly 23 million obese individuals, who have never been told that they are overweight," they added.

Telling patients that they are overweight was associated with an eightfold increase in the odds that they would accurately see themselves as overweight and a sixfold increase in the odds that they would accurately see themselves as obese. This recognition is essential because being aware of the problem is the first step in changing behavior to overcome it, the investigators noted.

This study could not assess why physicians fail to identify patients as overweight. It is possible that some patients didn’t "hear" this even though their physicians did tell them.

Alternatively, some physicians may not bother to inform patients of weight status because they see patients as lacking in self-control or motivation to change. Some may feel that labeling patients as overweight or obese is simply stating the obvious and won’t make much difference. Still others may cite time constraints, feeling that if they don’t have the time, they should "avoid starting a potentially long conversation" during a patient visit.

The strong association found in this study between physicians’ remarks and patients’ beliefs "should help to change these negative perceptions among physicians and encourage incorporating extra time into visits to discuss weight management with their patients," Dr. Post and his associates said.

No financial conflicts of interest were reported.

When physicians tell patients directly that they are overweight, it raises the odds that the patients will perceive their weight realistically, will want to lose weight, and will try to lose weight, according to a report in the Feb. 28 issue of Archives of Internal Medicine.

However, fewer than half of overweight patients and fewer than two-thirds of obese patients say they have been told by their physicians that they are overweight.

"This is an important intervention point that is being missed by many physicians. Physicians need to tell more overweight and obese patients that they are overweight because this may help encourage them to change their behavior to lose weight and lower their risk for many diseases," said Dr. Robert E. Post of the department of family medicine, Medical University of South Carolina, Charleston, and his associates.

Today’s overweight and obese patients are more likely to consider themselves to be of normal weight than their counterparts of 20 years ago were, in part because the current obesity epidemic has made higher weights and larger sizes seem more normal. Patients who don’t perceive their weight accurately won’t recognize their health risks and won’t work to reduce them, the investigators said.

They analyzed data from the 2005-2008 National Health and Nutrition Examination Survey in a cross-sectional study to assess the effect of physician acknowledgment of weight status on patient behavior. The study included data for 7,790 men and women aged 20-64 years who constituted a nationally representative sample of the U.S. population.

A total of 5,474 of these subjects qualified as overweight, with a BMI of 25 kg/m² or greater, including 2,874 who qualified as obese, with a BMI of 30 or greater.

Of the overweight subjects, 45% reported that their physicians had told them they were overweight, as did 66% of the obese subjects. These subjects were much more likely to identify themselves as overweight (94%) or obese (97%) than were overweight subjects whose physicians had not so informed them (63% and 81%, respectively). They also were much more likely to report that they wanted to lose weight and had attempted to lose weight during the preceding year.

However, about 37% of overweight and 19% of obese subjects had not been told they were overweight by their physicians and did not consider themselves to be. In comparison, only 6% of overweight and 3% of obese subjects who had been told by their physicians that they were overweight continued to consider themselves to be of normal weight.

"This speaks strongly to the influence that physicians’ words have on their patients," Dr. Post and his colleagues said (Arch. Intern. Med. 2011;171:316-21).

Extrapolating this finding to the general U.S. adult population, "this equates to more than 74 million overweight individuals, including nearly 23 million obese individuals, who have never been told that they are overweight," they added.

Telling patients that they are overweight was associated with an eightfold increase in the odds that they would accurately see themselves as overweight and a sixfold increase in the odds that they would accurately see themselves as obese. This recognition is essential because being aware of the problem is the first step in changing behavior to overcome it, the investigators noted.

This study could not assess why physicians fail to identify patients as overweight. It is possible that some patients didn’t "hear" this even though their physicians did tell them.

Alternatively, some physicians may not bother to inform patients of weight status because they see patients as lacking in self-control or motivation to change. Some may feel that labeling patients as overweight or obese is simply stating the obvious and won’t make much difference. Still others may cite time constraints, feeling that if they don’t have the time, they should "avoid starting a potentially long conversation" during a patient visit.

The strong association found in this study between physicians’ remarks and patients’ beliefs "should help to change these negative perceptions among physicians and encourage incorporating extra time into visits to discuss weight management with their patients," Dr. Post and his associates said.

No financial conflicts of interest were reported.

A sustained virologic response to antiviral therapy signals a favorable prognosis in patients with decompensated cirrhosis due to chronic hepatitis C, reported Dr. Angelo Iacobellis and his colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Mean survival was 20 months longer in patients who achieved a sustained virologic response (SVR) with antiviral therapy than in patients who did not achieve SVR (73 vs. 53 months; P = .004). Thus, antiviral therapy "might represent a life-sparing intervention" for patients who have progressed to the stage of liver decompensation and who aren’t eligible for liver transplant, said Dr. Iacobellis and his associates at Casa Sollievo della Sofferenza in San Giovanni Rotondo, Italy.

The authors previously reported on the short-term benefits of pegylated interferon alfa-2b plus ribavirin in patients whose cirrhosis had caused at least one episode of decompensation, as evidenced by esophageal bleeding, ascites, or hepatic encephalopathy. However, "for cirrhotic patients with advanced disease, achieving a sustained virologic response might be only a cosmetic goal of low clinical relevance if it does not guarantee a positive impact on their poor prognosis."

Therefore, Dr. Iacobellis and his colleagues studied the survival rates after 5-year follow-up in 75 patients (mean follow-up, 51 months; range, 3-78 months). A total of 24 patients achieved an SVR with either standard dosing (13 patients) or a low-dose regimen (11 patients).

"The main finding of our study was the improved survival of patients who attained a sustained virologic response." Mean survival was 73 months in patients who achieved an SVR, compared with 53 months in those who did not (Clin. Gastroenterol. Hepatol. 2011 March [doi:10.1016/j.cgh.2010.10.036]).

In all, 25 patients died during follow-up. Only two patients (8%) who had achieved SVR died, both of them from liver disease. In contrast, 23 of the 51 patients (43%) who had not achieved a sustained virologic response died – all but one of them from liver disease.

During follow-up, only 8 of the 24 treatment responders (33%) experienced further decompensation events such as bleeding, ascites, sepsis, or development of hepatocellular carcinoma. In contrast, 49 of the 51 treatment nonresponders (96%) experienced further decompensation events; this was a highly significant difference (P less than .0001).

There were 20 adverse events requiring hospitalization among the treatment responders, compared with 137 in treatment nonresponders. Readmission rates were eight times higher among nonresponders: 56 per 1,000 person-months, compared with 7 per 1,000 person-months for responders.

However, the achievement of SVR did not appear to affect the development of hepatocellular carcinoma. The malignancy developed in 21% of patients who had achieved an SVR and 22% of those who had not. The incidence rates were 3.7 per 1,000 person-months and 4.5 per 1,000 person-months, respectively, which was not a significant difference.

"This finding reinforces the concept that decompensated cirrhosis is a unique step of liver disease, in which derangement of liver architecture assumes a negative prognostic role on the probability of developing hepatocellular carcinoma," the investigators said.

"It is also worth noting that only 1 patient who attained a sustained virologic response was transplanted for hepatocellular cancer development, without a reinfection of the liver graft. In contrast, of the 7 patients without a sustained virologic response [who were approved for a liver transplant], 6 died while on the waiting list and 1 grafted patient had immediate [HCV] reinfection of the graft," they added.

This study received no industry support. Dr. Iacobellis and his associates reported no financial conflicts of interest.

A sustained virologic response to antiviral therapy signals a favorable prognosis in patients with decompensated cirrhosis due to chronic hepatitis C, reported Dr. Angelo Iacobellis and his colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Mean survival was 20 months longer in patients who achieved a sustained virologic response (SVR) with antiviral therapy than in patients who did not achieve SVR (73 vs. 53 months; P = .004). Thus, antiviral therapy "might represent a life-sparing intervention" for patients who have progressed to the stage of liver decompensation and who aren’t eligible for liver transplant, said Dr. Iacobellis and his associates at Casa Sollievo della Sofferenza in San Giovanni Rotondo, Italy.

The authors previously reported on the short-term benefits of pegylated interferon alfa-2b plus ribavirin in patients whose cirrhosis had caused at least one episode of decompensation, as evidenced by esophageal bleeding, ascites, or hepatic encephalopathy. However, "for cirrhotic patients with advanced disease, achieving a sustained virologic response might be only a cosmetic goal of low clinical relevance if it does not guarantee a positive impact on their poor prognosis."

Therefore, Dr. Iacobellis and his colleagues studied the survival rates after 5-year follow-up in 75 patients (mean follow-up, 51 months; range, 3-78 months). A total of 24 patients achieved an SVR with either standard dosing (13 patients) or a low-dose regimen (11 patients).

"The main finding of our study was the improved survival of patients who attained a sustained virologic response." Mean survival was 73 months in patients who achieved an SVR, compared with 53 months in those who did not (Clin. Gastroenterol. Hepatol. 2011 March [doi:10.1016/j.cgh.2010.10.036]).

In all, 25 patients died during follow-up. Only two patients (8%) who had achieved SVR died, both of them from liver disease. In contrast, 23 of the 51 patients (43%) who had not achieved a sustained virologic response died – all but one of them from liver disease.

During follow-up, only 8 of the 24 treatment responders (33%) experienced further decompensation events such as bleeding, ascites, sepsis, or development of hepatocellular carcinoma. In contrast, 49 of the 51 treatment nonresponders (96%) experienced further decompensation events; this was a highly significant difference (P less than .0001).

There were 20 adverse events requiring hospitalization among the treatment responders, compared with 137 in treatment nonresponders. Readmission rates were eight times higher among nonresponders: 56 per 1,000 person-months, compared with 7 per 1,000 person-months for responders.

However, the achievement of SVR did not appear to affect the development of hepatocellular carcinoma. The malignancy developed in 21% of patients who had achieved an SVR and 22% of those who had not. The incidence rates were 3.7 per 1,000 person-months and 4.5 per 1,000 person-months, respectively, which was not a significant difference.

"This finding reinforces the concept that decompensated cirrhosis is a unique step of liver disease, in which derangement of liver architecture assumes a negative prognostic role on the probability of developing hepatocellular carcinoma," the investigators said.

"It is also worth noting that only 1 patient who attained a sustained virologic response was transplanted for hepatocellular cancer development, without a reinfection of the liver graft. In contrast, of the 7 patients without a sustained virologic response [who were approved for a liver transplant], 6 died while on the waiting list and 1 grafted patient had immediate [HCV] reinfection of the graft," they added.

This study received no industry support. Dr. Iacobellis and his associates reported no financial conflicts of interest.

A sustained virologic response to antiviral therapy signals a favorable prognosis in patients with decompensated cirrhosis due to chronic hepatitis C, reported Dr. Angelo Iacobellis and his colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Mean survival was 20 months longer in patients who achieved a sustained virologic response (SVR) with antiviral therapy than in patients who did not achieve SVR (73 vs. 53 months; P = .004). Thus, antiviral therapy "might represent a life-sparing intervention" for patients who have progressed to the stage of liver decompensation and who aren’t eligible for liver transplant, said Dr. Iacobellis and his associates at Casa Sollievo della Sofferenza in San Giovanni Rotondo, Italy.

The authors previously reported on the short-term benefits of pegylated interferon alfa-2b plus ribavirin in patients whose cirrhosis had caused at least one episode of decompensation, as evidenced by esophageal bleeding, ascites, or hepatic encephalopathy. However, "for cirrhotic patients with advanced disease, achieving a sustained virologic response might be only a cosmetic goal of low clinical relevance if it does not guarantee a positive impact on their poor prognosis."

Therefore, Dr. Iacobellis and his colleagues studied the survival rates after 5-year follow-up in 75 patients (mean follow-up, 51 months; range, 3-78 months). A total of 24 patients achieved an SVR with either standard dosing (13 patients) or a low-dose regimen (11 patients).

"The main finding of our study was the improved survival of patients who attained a sustained virologic response." Mean survival was 73 months in patients who achieved an SVR, compared with 53 months in those who did not (Clin. Gastroenterol. Hepatol. 2011 March [doi:10.1016/j.cgh.2010.10.036]).

In all, 25 patients died during follow-up. Only two patients (8%) who had achieved SVR died, both of them from liver disease. In contrast, 23 of the 51 patients (43%) who had not achieved a sustained virologic response died – all but one of them from liver disease.

During follow-up, only 8 of the 24 treatment responders (33%) experienced further decompensation events such as bleeding, ascites, sepsis, or development of hepatocellular carcinoma. In contrast, 49 of the 51 treatment nonresponders (96%) experienced further decompensation events; this was a highly significant difference (P less than .0001).

There were 20 adverse events requiring hospitalization among the treatment responders, compared with 137 in treatment nonresponders. Readmission rates were eight times higher among nonresponders: 56 per 1,000 person-months, compared with 7 per 1,000 person-months for responders.

However, the achievement of SVR did not appear to affect the development of hepatocellular carcinoma. The malignancy developed in 21% of patients who had achieved an SVR and 22% of those who had not. The incidence rates were 3.7 per 1,000 person-months and 4.5 per 1,000 person-months, respectively, which was not a significant difference.

"This finding reinforces the concept that decompensated cirrhosis is a unique step of liver disease, in which derangement of liver architecture assumes a negative prognostic role on the probability of developing hepatocellular carcinoma," the investigators said.

"It is also worth noting that only 1 patient who attained a sustained virologic response was transplanted for hepatocellular cancer development, without a reinfection of the liver graft. In contrast, of the 7 patients without a sustained virologic response [who were approved for a liver transplant], 6 died while on the waiting list and 1 grafted patient had immediate [HCV] reinfection of the graft," they added.

This study received no industry support. Dr. Iacobellis and his associates reported no financial conflicts of interest.

A sustained virologic response to antiviral therapy signals a favorable prognosis in patients with decompensated cirrhosis due to chronic hepatitis C, reported Dr. Angelo Iacobellis and his colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Mean survival was 20 months longer in patients who achieved a sustained virologic response (SVR) with antiviral therapy than in patients who did not achieve SVR (73 vs. 53 months; P = .004). Thus, antiviral therapy "might represent a life-sparing intervention" for patients who have progressed to the stage of liver decompensation and who aren’t eligible for liver transplant, said Dr. Iacobellis and his associates at Casa Sollievo della Sofferenza in San Giovanni Rotondo, Italy.

The authors previously reported on the short-term benefits of pegylated interferon alfa-2b plus ribavirin in patients whose cirrhosis had caused at least one episode of decompensation, as evidenced by esophageal bleeding, ascites, or hepatic encephalopathy. However, "for cirrhotic patients with advanced disease, achieving a sustained virologic response might be only a cosmetic goal of low clinical relevance if it does not guarantee a positive impact on their poor prognosis."

Therefore, Dr. Iacobellis and his colleagues studied the survival rates after 5-year follow-up in 75 patients (mean follow-up, 51 months; range, 3-78 months). A total of 24 patients achieved an SVR with either standard dosing (13 patients) or a low-dose regimen (11 patients).

"The main finding of our study was the improved survival of patients who attained a sustained virologic response." Mean survival was 73 months in patients who achieved an SVR, compared with 53 months in those who did not (Clin. Gastroenterol. Hepatol. 2011 March [doi:10.1016/j.cgh.2010.10.036]).

In all, 25 patients died during follow-up. Only two patients (8%) who had achieved SVR died, both of them from liver disease. In contrast, 23 of the 51 patients (43%) who had not achieved a sustained virologic response died – all but one of them from liver disease.

During follow-up, only 8 of the 24 treatment responders (33%) experienced further decompensation events such as bleeding, ascites, sepsis, or development of hepatocellular carcinoma. In contrast, 49 of the 51 treatment nonresponders (96%) experienced further decompensation events; this was a highly significant difference (P less than .0001).

There were 20 adverse events requiring hospitalization among the treatment responders, compared with 137 in treatment nonresponders. Readmission rates were eight times higher among nonresponders: 56 per 1,000 person-months, compared with 7 per 1,000 person-months for responders.

However, the achievement of SVR did not appear to affect the development of hepatocellular carcinoma. The malignancy developed in 21% of patients who had achieved an SVR and 22% of those who had not. The incidence rates were 3.7 per 1,000 person-months and 4.5 per 1,000 person-months, respectively, which was not a significant difference.

"This finding reinforces the concept that decompensated cirrhosis is a unique step of liver disease, in which derangement of liver architecture assumes a negative prognostic role on the probability of developing hepatocellular carcinoma," the investigators said.

"It is also worth noting that only 1 patient who attained a sustained virologic response was transplanted for hepatocellular cancer development, without a reinfection of the liver graft. In contrast, of the 7 patients without a sustained virologic response [who were approved for a liver transplant], 6 died while on the waiting list and 1 grafted patient had immediate [HCV] reinfection of the graft," they added.

This study received no industry support. Dr. Iacobellis and his associates reported no financial conflicts of interest.

A sustained virologic response to antiviral therapy signals a favorable prognosis in patients with decompensated cirrhosis due to chronic hepatitis C, reported Dr. Angelo Iacobellis and his colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Mean survival was 20 months longer in patients who achieved a sustained virologic response (SVR) with antiviral therapy than in patients who did not achieve SVR (73 vs. 53 months; P = .004). Thus, antiviral therapy "might represent a life-sparing intervention" for patients who have progressed to the stage of liver decompensation and who aren’t eligible for liver transplant, said Dr. Iacobellis and his associates at Casa Sollievo della Sofferenza in San Giovanni Rotondo, Italy.

The authors previously reported on the short-term benefits of pegylated interferon alfa-2b plus ribavirin in patients whose cirrhosis had caused at least one episode of decompensation, as evidenced by esophageal bleeding, ascites, or hepatic encephalopathy. However, "for cirrhotic patients with advanced disease, achieving a sustained virologic response might be only a cosmetic goal of low clinical relevance if it does not guarantee a positive impact on their poor prognosis."

Therefore, Dr. Iacobellis and his colleagues studied the survival rates after 5-year follow-up in 75 patients (mean follow-up, 51 months; range, 3-78 months). A total of 24 patients achieved an SVR with either standard dosing (13 patients) or a low-dose regimen (11 patients).

"The main finding of our study was the improved survival of patients who attained a sustained virologic response." Mean survival was 73 months in patients who achieved an SVR, compared with 53 months in those who did not (Clin. Gastroenterol. Hepatol. 2011 March [doi:10.1016/j.cgh.2010.10.036]).

In all, 25 patients died during follow-up. Only two patients (8%) who had achieved SVR died, both of them from liver disease. In contrast, 23 of the 51 patients (43%) who had not achieved a sustained virologic response died – all but one of them from liver disease.

During follow-up, only 8 of the 24 treatment responders (33%) experienced further decompensation events such as bleeding, ascites, sepsis, or development of hepatocellular carcinoma. In contrast, 49 of the 51 treatment nonresponders (96%) experienced further decompensation events; this was a highly significant difference (P less than .0001).

There were 20 adverse events requiring hospitalization among the treatment responders, compared with 137 in treatment nonresponders. Readmission rates were eight times higher among nonresponders: 56 per 1,000 person-months, compared with 7 per 1,000 person-months for responders.

However, the achievement of SVR did not appear to affect the development of hepatocellular carcinoma. The malignancy developed in 21% of patients who had achieved an SVR and 22% of those who had not. The incidence rates were 3.7 per 1,000 person-months and 4.5 per 1,000 person-months, respectively, which was not a significant difference.

"This finding reinforces the concept that decompensated cirrhosis is a unique step of liver disease, in which derangement of liver architecture assumes a negative prognostic role on the probability of developing hepatocellular carcinoma," the investigators said.

"It is also worth noting that only 1 patient who attained a sustained virologic response was transplanted for hepatocellular cancer development, without a reinfection of the liver graft. In contrast, of the 7 patients without a sustained virologic response [who were approved for a liver transplant], 6 died while on the waiting list and 1 grafted patient had immediate [HCV] reinfection of the graft," they added.

This study received no industry support. Dr. Iacobellis and his associates reported no financial conflicts of interest.

A sustained virologic response to antiviral therapy signals a favorable prognosis in patients with decompensated cirrhosis due to chronic hepatitis C, reported Dr. Angelo Iacobellis and his colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Mean survival was 20 months longer in patients who achieved a sustained virologic response (SVR) with antiviral therapy than in patients who did not achieve SVR (73 vs. 53 months; P = .004). Thus, antiviral therapy "might represent a life-sparing intervention" for patients who have progressed to the stage of liver decompensation and who aren’t eligible for liver transplant, said Dr. Iacobellis and his associates at Casa Sollievo della Sofferenza in San Giovanni Rotondo, Italy.

The authors previously reported on the short-term benefits of pegylated interferon alfa-2b plus ribavirin in patients whose cirrhosis had caused at least one episode of decompensation, as evidenced by esophageal bleeding, ascites, or hepatic encephalopathy. However, "for cirrhotic patients with advanced disease, achieving a sustained virologic response might be only a cosmetic goal of low clinical relevance if it does not guarantee a positive impact on their poor prognosis."

Therefore, Dr. Iacobellis and his colleagues studied the survival rates after 5-year follow-up in 75 patients (mean follow-up, 51 months; range, 3-78 months). A total of 24 patients achieved an SVR with either standard dosing (13 patients) or a low-dose regimen (11 patients).

"The main finding of our study was the improved survival of patients who attained a sustained virologic response." Mean survival was 73 months in patients who achieved an SVR, compared with 53 months in those who did not (Clin. Gastroenterol. Hepatol. 2011 March [doi:10.1016/j.cgh.2010.10.036]).

In all, 25 patients died during follow-up. Only two patients (8%) who had achieved SVR died, both of them from liver disease. In contrast, 23 of the 51 patients (43%) who had not achieved a sustained virologic response died – all but one of them from liver disease.

During follow-up, only 8 of the 24 treatment responders (33%) experienced further decompensation events such as bleeding, ascites, sepsis, or development of hepatocellular carcinoma. In contrast, 49 of the 51 treatment nonresponders (96%) experienced further decompensation events; this was a highly significant difference (P less than .0001).

There were 20 adverse events requiring hospitalization among the treatment responders, compared with 137 in treatment nonresponders. Readmission rates were eight times higher among nonresponders: 56 per 1,000 person-months, compared with 7 per 1,000 person-months for responders.

However, the achievement of SVR did not appear to affect the development of hepatocellular carcinoma. The malignancy developed in 21% of patients who had achieved an SVR and 22% of those who had not. The incidence rates were 3.7 per 1,000 person-months and 4.5 per 1,000 person-months, respectively, which was not a significant difference.

"This finding reinforces the concept that decompensated cirrhosis is a unique step of liver disease, in which derangement of liver architecture assumes a negative prognostic role on the probability of developing hepatocellular carcinoma," the investigators said.

"It is also worth noting that only 1 patient who attained a sustained virologic response was transplanted for hepatocellular cancer development, without a reinfection of the liver graft. In contrast, of the 7 patients without a sustained virologic response [who were approved for a liver transplant], 6 died while on the waiting list and 1 grafted patient had immediate [HCV] reinfection of the graft," they added.

This study received no industry support. Dr. Iacobellis and his associates reported no financial conflicts of interest.

A sustained virologic response to antiviral therapy signals a favorable prognosis in patients with decompensated cirrhosis due to chronic hepatitis C, reported Dr. Angelo Iacobellis and his colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Mean survival was 20 months longer in patients who achieved a sustained virologic response (SVR) with antiviral therapy than in patients who did not achieve SVR (73 vs. 53 months; P = .004). Thus, antiviral therapy "might represent a life-sparing intervention" for patients who have progressed to the stage of liver decompensation and who aren’t eligible for liver transplant, said Dr. Iacobellis and his associates at Casa Sollievo della Sofferenza in San Giovanni Rotondo, Italy.

The authors previously reported on the short-term benefits of pegylated interferon alfa-2b plus ribavirin in patients whose cirrhosis had caused at least one episode of decompensation, as evidenced by esophageal bleeding, ascites, or hepatic encephalopathy. However, "for cirrhotic patients with advanced disease, achieving a sustained virologic response might be only a cosmetic goal of low clinical relevance if it does not guarantee a positive impact on their poor prognosis."

Therefore, Dr. Iacobellis and his colleagues studied the survival rates after 5-year follow-up in 75 patients (mean follow-up, 51 months; range, 3-78 months). A total of 24 patients achieved an SVR with either standard dosing (13 patients) or a low-dose regimen (11 patients).

"The main finding of our study was the improved survival of patients who attained a sustained virologic response." Mean survival was 73 months in patients who achieved an SVR, compared with 53 months in those who did not (Clin. Gastroenterol. Hepatol. 2011 March [doi:10.1016/j.cgh.2010.10.036]).

In all, 25 patients died during follow-up. Only two patients (8%) who had achieved SVR died, both of them from liver disease. In contrast, 23 of the 51 patients (43%) who had not achieved a sustained virologic response died – all but one of them from liver disease.

During follow-up, only 8 of the 24 treatment responders (33%) experienced further decompensation events such as bleeding, ascites, sepsis, or development of hepatocellular carcinoma. In contrast, 49 of the 51 treatment nonresponders (96%) experienced further decompensation events; this was a highly significant difference (P less than .0001).

There were 20 adverse events requiring hospitalization among the treatment responders, compared with 137 in treatment nonresponders. Readmission rates were eight times higher among nonresponders: 56 per 1,000 person-months, compared with 7 per 1,000 person-months for responders.

However, the achievement of SVR did not appear to affect the development of hepatocellular carcinoma. The malignancy developed in 21% of patients who had achieved an SVR and 22% of those who had not. The incidence rates were 3.7 per 1,000 person-months and 4.5 per 1,000 person-months, respectively, which was not a significant difference.

"This finding reinforces the concept that decompensated cirrhosis is a unique step of liver disease, in which derangement of liver architecture assumes a negative prognostic role on the probability of developing hepatocellular carcinoma," the investigators said.

"It is also worth noting that only 1 patient who attained a sustained virologic response was transplanted for hepatocellular cancer development, without a reinfection of the liver graft. In contrast, of the 7 patients without a sustained virologic response [who were approved for a liver transplant], 6 died while on the waiting list and 1 grafted patient had immediate [HCV] reinfection of the graft," they added.

This study received no industry support. Dr. Iacobellis and his associates reported no financial conflicts of interest.

A sustained virologic response to antiviral therapy signals a favorable prognosis in patients with decompensated cirrhosis due to chronic hepatitis C, reported Dr. Angelo Iacobellis and his colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Mean survival was 20 months longer in patients who achieved a sustained virologic response (SVR) with antiviral therapy than in patients who did not achieve SVR (73 vs. 53 months; P = .004). Thus, antiviral therapy "might represent a life-sparing intervention" for patients who have progressed to the stage of liver decompensation and who aren’t eligible for liver transplant, said Dr. Iacobellis and his associates at Casa Sollievo della Sofferenza in San Giovanni Rotondo, Italy.

The authors previously reported on the short-term benefits of pegylated interferon alfa-2b plus ribavirin in patients whose cirrhosis had caused at least one episode of decompensation, as evidenced by esophageal bleeding, ascites, or hepatic encephalopathy. However, "for cirrhotic patients with advanced disease, achieving a sustained virologic response might be only a cosmetic goal of low clinical relevance if it does not guarantee a positive impact on their poor prognosis."

Therefore, Dr. Iacobellis and his colleagues studied the survival rates after 5-year follow-up in 75 patients (mean follow-up, 51 months; range, 3-78 months). A total of 24 patients achieved an SVR with either standard dosing (13 patients) or a low-dose regimen (11 patients).

"The main finding of our study was the improved survival of patients who attained a sustained virologic response." Mean survival was 73 months in patients who achieved an SVR, compared with 53 months in those who did not (Clin. Gastroenterol. Hepatol. 2011 March [doi:10.1016/j.cgh.2010.10.036]).

In all, 25 patients died during follow-up. Only two patients (8%) who had achieved SVR died, both of them from liver disease. In contrast, 23 of the 51 patients (43%) who had not achieved a sustained virologic response died – all but one of them from liver disease.

During follow-up, only 8 of the 24 treatment responders (33%) experienced further decompensation events such as bleeding, ascites, sepsis, or development of hepatocellular carcinoma. In contrast, 49 of the 51 treatment nonresponders (96%) experienced further decompensation events; this was a highly significant difference (P less than .0001).

There were 20 adverse events requiring hospitalization among the treatment responders, compared with 137 in treatment nonresponders. Readmission rates were eight times higher among nonresponders: 56 per 1,000 person-months, compared with 7 per 1,000 person-months for responders.

However, the achievement of SVR did not appear to affect the development of hepatocellular carcinoma. The malignancy developed in 21% of patients who had achieved an SVR and 22% of those who had not. The incidence rates were 3.7 per 1,000 person-months and 4.5 per 1,000 person-months, respectively, which was not a significant difference.

"This finding reinforces the concept that decompensated cirrhosis is a unique step of liver disease, in which derangement of liver architecture assumes a negative prognostic role on the probability of developing hepatocellular carcinoma," the investigators said.

"It is also worth noting that only 1 patient who attained a sustained virologic response was transplanted for hepatocellular cancer development, without a reinfection of the liver graft. In contrast, of the 7 patients without a sustained virologic response [who were approved for a liver transplant], 6 died while on the waiting list and 1 grafted patient had immediate [HCV] reinfection of the graft," they added.

This study received no industry support. Dr. Iacobellis and his associates reported no financial conflicts of interest.

A sustained virologic response to antiviral therapy signals a favorable prognosis in patients with decompensated cirrhosis due to chronic hepatitis C, reported Dr. Angelo Iacobellis and his colleagues in the March issue of Clinical Gastroenterology and Hepatology.

Mean survival was 20 months longer in patients who achieved a sustained virologic response (SVR) with antiviral therapy than in patients who did not achieve SVR (73 vs. 53 months; P = .004). Thus, antiviral therapy "might represent a life-sparing intervention" for patients who have progressed to the stage of liver decompensation and who aren’t eligible for liver transplant, said Dr. Iacobellis and his associates at Casa Sollievo della Sofferenza in San Giovanni Rotondo, Italy.

The authors previously reported on the short-term benefits of pegylated interferon alfa-2b plus ribavirin in patients whose cirrhosis had caused at least one episode of decompensation, as evidenced by esophageal bleeding, ascites, or hepatic encephalopathy. However, "for cirrhotic patients with advanced disease, achieving a sustained virologic response might be only a cosmetic goal of low clinical relevance if it does not guarantee a positive impact on their poor prognosis."

Therefore, Dr. Iacobellis and his colleagues studied the survival rates after 5-year follow-up in 75 patients (mean follow-up, 51 months; range, 3-78 months). A total of 24 patients achieved an SVR with either standard dosing (13 patients) or a low-dose regimen (11 patients).

"The main finding of our study was the improved survival of patients who attained a sustained virologic response." Mean survival was 73 months in patients who achieved an SVR, compared with 53 months in those who did not (Clin. Gastroenterol. Hepatol. 2011 March [doi:10.1016/j.cgh.2010.10.036]).

In all, 25 patients died during follow-up. Only two patients (8%) who had achieved SVR died, both of them from liver disease. In contrast, 23 of the 51 patients (43%) who had not achieved a sustained virologic response died – all but one of them from liver disease.

During follow-up, only 8 of the 24 treatment responders (33%) experienced further decompensation events such as bleeding, ascites, sepsis, or development of hepatocellular carcinoma. In contrast, 49 of the 51 treatment nonresponders (96%) experienced further decompensation events; this was a highly significant difference (P less than .0001).

There were 20 adverse events requiring hospitalization among the treatment responders, compared with 137 in treatment nonresponders. Readmission rates were eight times higher among nonresponders: 56 per 1,000 person-months, compared with 7 per 1,000 person-months for responders.

However, the achievement of SVR did not appear to affect the development of hepatocellular carcinoma. The malignancy developed in 21% of patients who had achieved an SVR and 22% of those who had not. The incidence rates were 3.7 per 1,000 person-months and 4.5 per 1,000 person-months, respectively, which was not a significant difference.

"This finding reinforces the concept that decompensated cirrhosis is a unique step of liver disease, in which derangement of liver architecture assumes a negative prognostic role on the probability of developing hepatocellular carcinoma," the investigators said.

"It is also worth noting that only 1 patient who attained a sustained virologic response was transplanted for hepatocellular cancer development, without a reinfection of the liver graft. In contrast, of the 7 patients without a sustained virologic response [who were approved for a liver transplant], 6 died while on the waiting list and 1 grafted patient had immediate [HCV] reinfection of the graft," they added.

This study received no industry support. Dr. Iacobellis and his associates reported no financial conflicts of interest.

A subtype of hemoglobin H disease distinguished by life-threatening anemia during infectious illnesses should be recognized as a clinical entity distinct from other thalassemias, all of which are becoming more common in the United States, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Hemoglobin H Constant Spring (hemoglobin HCS) causes significant growth delay, causes repeated plunges in hemoglobin levels requiring urgent blood transfusions as early as infancy, and can lead to iron overload in early childhood, with its attendant sequelae. Most important, patients with HCS show acute, life-threatening worsening of anemia during common illnesses caused by viral or bacterial infections such as strep throat.

In contrast, other hemoglobin H disease does not cause growth deficits or iron overload during childhood, and it rarely causes severe anemia, said Dr. Ashutosh Lal of the department of hematology/oncology at Children’s Hospital and Research Center Oakland (Calif.), and his associates.

The investigators were able to characterize the natural history of hemoglobin H disease and the subtype hemoglobin HCS among children in the United States for the first time largely because of newborn screening for the disorders, which has been done in California since 1998. They identified and followed 86 cases of hemoglobin H disease.

In the past, hemoglobin H disease has been prevalent in Asian and Mediterranean populations but rare in others. Now, however, it appears to be making inroads into the United States. In this study, many patients were of mixed ethnic backgrounds, including African Americans, who historically have a very low rate of alpha-thalassemias.

This finding supports the usefulness of universal newborn screening for hemoglobin H syndromes. "Life-threatening anemia may develop in infants before the diagnosis can be made through conventional means in the absence of newborn screening," Dr. Lal and his colleagues noted (N. Engl. J. Med. 2011;364:710-8).

Among the 86 cases, 60 patients (70%) had hemoglobin H, 23 (27%) had the more severe HCS, and 3 (3.5%) had other, nondeletional hemoglobin H illness.

All of the episodes of acute worsening of anemia requiring blood transfusions occurred in the HCS group, while the children with hemoglobin H disease "had a predictably benign course." In HCS, the probability of requiring at least one transfusion before 1 year of age was 13%; this increased to 39% by the age of 5 years, 75% by the age of 10 years, and 80% by the age of 20 years. Thirty-seven transfusions (82%) were precipitated by infections.

Growth was significantly delayed in children with HCS but not in the other children. "This finding suggests that close attention to growth is required and that nutritional and hematologic associations with growth delay should be evaluated," the investigators said.

Ferritin levels were elevated in young children with HCS and continued to increase over time, whereas they were lower and did not increase significantly before adulthood in children with hemoglobin H disease.

Patients with HCS required nearly twice as many clinic visits each year and nearly four times as many hospital admissions. In addition, "substantial fatigue was observed in a subgroup of older patients with HCS, a finding that raises concern that the quality of life of patients may deteriorate with age," Dr. Lal and his associates said.

Five patients with HCS underwent splenectomy between the ages of 3.9 and 13 years because of their need for frequent blood transfusions, while no children with hemoglobin H disease did. Splenectomy reduced or eliminated acute hemolytic episodes in four of the five children.

"We suggest that HCS be recognized as a thalassemia syndrome that is distinct from hemoglobin H disease, so that the appropriate treatment approach can be devised for each group," they noted.

This study was supported in part by the Maternal and Child Health Bureau of the U.S. Department of Health and Human Services. The authors reported no relevant financial disclosures.

A subtype of hemoglobin H disease distinguished by life-threatening anemia during infectious illnesses should be recognized as a clinical entity distinct from other thalassemias, all of which are becoming more common in the United States, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Hemoglobin H Constant Spring (hemoglobin HCS) causes significant growth delay, causes repeated plunges in hemoglobin levels requiring urgent blood transfusions as early as infancy, and can lead to iron overload in early childhood, with its attendant sequelae. Most important, patients with HCS show acute, life-threatening worsening of anemia during common illnesses caused by viral or bacterial infections such as strep throat.

In contrast, other hemoglobin H disease does not cause growth deficits or iron overload during childhood, and it rarely causes severe anemia, said Dr. Ashutosh Lal of the department of hematology/oncology at Children’s Hospital and Research Center Oakland (Calif.), and his associates.

The investigators were able to characterize the natural history of hemoglobin H disease and the subtype hemoglobin HCS among children in the United States for the first time largely because of newborn screening for the disorders, which has been done in California since 1998. They identified and followed 86 cases of hemoglobin H disease.

In the past, hemoglobin H disease has been prevalent in Asian and Mediterranean populations but rare in others. Now, however, it appears to be making inroads into the United States. In this study, many patients were of mixed ethnic backgrounds, including African Americans, who historically have a very low rate of alpha-thalassemias.

This finding supports the usefulness of universal newborn screening for hemoglobin H syndromes. "Life-threatening anemia may develop in infants before the diagnosis can be made through conventional means in the absence of newborn screening," Dr. Lal and his colleagues noted (N. Engl. J. Med. 2011;364:710-8).

Among the 86 cases, 60 patients (70%) had hemoglobin H, 23 (27%) had the more severe HCS, and 3 (3.5%) had other, nondeletional hemoglobin H illness.

All of the episodes of acute worsening of anemia requiring blood transfusions occurred in the HCS group, while the children with hemoglobin H disease "had a predictably benign course." In HCS, the probability of requiring at least one transfusion before 1 year of age was 13%; this increased to 39% by the age of 5 years, 75% by the age of 10 years, and 80% by the age of 20 years. Thirty-seven transfusions (82%) were precipitated by infections.

Growth was significantly delayed in children with HCS but not in the other children. "This finding suggests that close attention to growth is required and that nutritional and hematologic associations with growth delay should be evaluated," the investigators said.

Ferritin levels were elevated in young children with HCS and continued to increase over time, whereas they were lower and did not increase significantly before adulthood in children with hemoglobin H disease.

Patients with HCS required nearly twice as many clinic visits each year and nearly four times as many hospital admissions. In addition, "substantial fatigue was observed in a subgroup of older patients with HCS, a finding that raises concern that the quality of life of patients may deteriorate with age," Dr. Lal and his associates said.

Five patients with HCS underwent splenectomy between the ages of 3.9 and 13 years because of their need for frequent blood transfusions, while no children with hemoglobin H disease did. Splenectomy reduced or eliminated acute hemolytic episodes in four of the five children.

"We suggest that HCS be recognized as a thalassemia syndrome that is distinct from hemoglobin H disease, so that the appropriate treatment approach can be devised for each group," they noted.

This study was supported in part by the Maternal and Child Health Bureau of the U.S. Department of Health and Human Services. The authors reported no relevant financial disclosures.

A subtype of hemoglobin H disease distinguished by life-threatening anemia during infectious illnesses should be recognized as a clinical entity distinct from other thalassemias, all of which are becoming more common in the United States, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Hemoglobin H Constant Spring (hemoglobin HCS) causes significant growth delay, causes repeated plunges in hemoglobin levels requiring urgent blood transfusions as early as infancy, and can lead to iron overload in early childhood, with its attendant sequelae. Most important, patients with HCS show acute, life-threatening worsening of anemia during common illnesses caused by viral or bacterial infections such as strep throat.

In contrast, other hemoglobin H disease does not cause growth deficits or iron overload during childhood, and it rarely causes severe anemia, said Dr. Ashutosh Lal of the department of hematology/oncology at Children’s Hospital and Research Center Oakland (Calif.), and his associates.

The investigators were able to characterize the natural history of hemoglobin H disease and the subtype hemoglobin HCS among children in the United States for the first time largely because of newborn screening for the disorders, which has been done in California since 1998. They identified and followed 86 cases of hemoglobin H disease.

In the past, hemoglobin H disease has been prevalent in Asian and Mediterranean populations but rare in others. Now, however, it appears to be making inroads into the United States. In this study, many patients were of mixed ethnic backgrounds, including African Americans, who historically have a very low rate of alpha-thalassemias.

This finding supports the usefulness of universal newborn screening for hemoglobin H syndromes. "Life-threatening anemia may develop in infants before the diagnosis can be made through conventional means in the absence of newborn screening," Dr. Lal and his colleagues noted (N. Engl. J. Med. 2011;364:710-8).

Among the 86 cases, 60 patients (70%) had hemoglobin H, 23 (27%) had the more severe HCS, and 3 (3.5%) had other, nondeletional hemoglobin H illness.

All of the episodes of acute worsening of anemia requiring blood transfusions occurred in the HCS group, while the children with hemoglobin H disease "had a predictably benign course." In HCS, the probability of requiring at least one transfusion before 1 year of age was 13%; this increased to 39% by the age of 5 years, 75% by the age of 10 years, and 80% by the age of 20 years. Thirty-seven transfusions (82%) were precipitated by infections.

Growth was significantly delayed in children with HCS but not in the other children. "This finding suggests that close attention to growth is required and that nutritional and hematologic associations with growth delay should be evaluated," the investigators said.

Ferritin levels were elevated in young children with HCS and continued to increase over time, whereas they were lower and did not increase significantly before adulthood in children with hemoglobin H disease.

Patients with HCS required nearly twice as many clinic visits each year and nearly four times as many hospital admissions. In addition, "substantial fatigue was observed in a subgroup of older patients with HCS, a finding that raises concern that the quality of life of patients may deteriorate with age," Dr. Lal and his associates said.

Five patients with HCS underwent splenectomy between the ages of 3.9 and 13 years because of their need for frequent blood transfusions, while no children with hemoglobin H disease did. Splenectomy reduced or eliminated acute hemolytic episodes in four of the five children.

"We suggest that HCS be recognized as a thalassemia syndrome that is distinct from hemoglobin H disease, so that the appropriate treatment approach can be devised for each group," they noted.

This study was supported in part by the Maternal and Child Health Bureau of the U.S. Department of Health and Human Services. The authors reported no relevant financial disclosures.

Children living on farms have a lower prevalence of asthma, likely due to a protective effect of their early exposure to a greater variety of environmental bacteria and fungi compared with what other children are exposed to, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Photo credit: © LindaYolanda/istock.com

In an epidemiologic analysis of data from two large observational studies of school-aged children in rural areas of central Europe, environmental samples from farmhouses showed a greater diversity of microbes than those from other homes. "The central finding of this analysis was the inverse association of the diversity scores with asthma [prevalence], which was not confounded by living on a farm," said Dr. Markus J. Ege of University Children’s Hospital, Munich, and his associates.

The analysis included data from a cross-sectional survey of 6,963 school children (aged 6-13 years), approximately half of whom lived on farms and the other half of whom lived in rural and suburban areas of Bavaria. Dust samples were collected from the mattresses of a randomly selected subgroup of 489 of the participants. Data also were obtained on the children’s respiratory and allergic symptoms, medical diagnoses, and potential confounders.

Children living on farms had a lower prevalence of asthma than did other children, with an adjusted odds ratio of 0.49. The percentage of dust samples that were positive for bacteria was significantly higher among farm dwellers, and the risk of asthma decreased significantly with an increasing number of detectable bands of bacterial DNA.

The analysis also included data from a second cross-sectional study involving 9,668 children attending elementary schools in rural areas of southern Germany, Switzerland, and Austria. Airborne dust samples were collected from the children’s bedrooms.

Again, children living on farms had a lower prevalence of asthma than did other children, with an odds ratio of 0.76. All bacterial and fungal taxa cultured from the dust samples were more prevalent among children living on farms than among other children, and the risk of asthma decreased significantly with an increasing number of fungal taxa, Dr. Ege and his colleagues said (N. Engl. J. Med. 2011;364:701-9).

In both studies, the diversity of microbes explained a substantial portion of the protective effect of the farming environment on asthma risk.

"Our methods do not allow us to identify specific microbes that may confer protection, but they have allowed us to identify broad families of species within microbial taxa that could be responsible for the effect of the farming environment.

"The challenge will be to identify these species with the precision needed to allow specific tests of the relationship between microbial exposure and protection against asthma," the investigators noted.

The analysis also could not determine the mechanism underlying this protective effect – how the diversity of microbial stimuli protects against asthma – but the researchers agreed with the prevailing view that perhaps micro-organisms trigger the innate immune system, which then bolsters resistance to asthma.

An alternative explanation may be that exposure to a broad rather than a narrow range of micro-organisms may prevent colonization of the lower airways with harmful bacteria. "Balanced colonization of the airways may parallel the beneficial effects of a diverse microbiome at other surfaces, such as the gut and skin," they added.

This study was funded by the Deutsche Forschungsgemeinschaft and the European Commission. Dr. Ege reported having a planned patent on asthma-protective bacteria. His associates reported ties to GlaxoSmithKline, Novartis, Protectimum, and ALK.

Children living on farms have a lower prevalence of asthma, likely due to a protective effect of their early exposure to a greater variety of environmental bacteria and fungi compared with what other children are exposed to, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Photo credit: © LindaYolanda/istock.com

In an epidemiologic analysis of data from two large observational studies of school-aged children in rural areas of central Europe, environmental samples from farmhouses showed a greater diversity of microbes than those from other homes. "The central finding of this analysis was the inverse association of the diversity scores with asthma [prevalence], which was not confounded by living on a farm," said Dr. Markus J. Ege of University Children’s Hospital, Munich, and his associates.

The analysis included data from a cross-sectional survey of 6,963 school children (aged 6-13 years), approximately half of whom lived on farms and the other half of whom lived in rural and suburban areas of Bavaria. Dust samples were collected from the mattresses of a randomly selected subgroup of 489 of the participants. Data also were obtained on the children’s respiratory and allergic symptoms, medical diagnoses, and potential confounders.

Children living on farms had a lower prevalence of asthma than did other children, with an adjusted odds ratio of 0.49. The percentage of dust samples that were positive for bacteria was significantly higher among farm dwellers, and the risk of asthma decreased significantly with an increasing number of detectable bands of bacterial DNA.

The analysis also included data from a second cross-sectional study involving 9,668 children attending elementary schools in rural areas of southern Germany, Switzerland, and Austria. Airborne dust samples were collected from the children’s bedrooms.

Again, children living on farms had a lower prevalence of asthma than did other children, with an odds ratio of 0.76. All bacterial and fungal taxa cultured from the dust samples were more prevalent among children living on farms than among other children, and the risk of asthma decreased significantly with an increasing number of fungal taxa, Dr. Ege and his colleagues said (N. Engl. J. Med. 2011;364:701-9).

In both studies, the diversity of microbes explained a substantial portion of the protective effect of the farming environment on asthma risk.

"Our methods do not allow us to identify specific microbes that may confer protection, but they have allowed us to identify broad families of species within microbial taxa that could be responsible for the effect of the farming environment.

"The challenge will be to identify these species with the precision needed to allow specific tests of the relationship between microbial exposure and protection against asthma," the investigators noted.

The analysis also could not determine the mechanism underlying this protective effect – how the diversity of microbial stimuli protects against asthma – but the researchers agreed with the prevailing view that perhaps micro-organisms trigger the innate immune system, which then bolsters resistance to asthma.

An alternative explanation may be that exposure to a broad rather than a narrow range of micro-organisms may prevent colonization of the lower airways with harmful bacteria. "Balanced colonization of the airways may parallel the beneficial effects of a diverse microbiome at other surfaces, such as the gut and skin," they added.

This study was funded by the Deutsche Forschungsgemeinschaft and the European Commission. Dr. Ege reported having a planned patent on asthma-protective bacteria. His associates reported ties to GlaxoSmithKline, Novartis, Protectimum, and ALK.

Children living on farms have a lower prevalence of asthma, likely due to a protective effect of their early exposure to a greater variety of environmental bacteria and fungi compared with what other children are exposed to, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Photo credit: © LindaYolanda/istock.com

In an epidemiologic analysis of data from two large observational studies of school-aged children in rural areas of central Europe, environmental samples from farmhouses showed a greater diversity of microbes than those from other homes. "The central finding of this analysis was the inverse association of the diversity scores with asthma [prevalence], which was not confounded by living on a farm," said Dr. Markus J. Ege of University Children’s Hospital, Munich, and his associates.

The analysis included data from a cross-sectional survey of 6,963 school children (aged 6-13 years), approximately half of whom lived on farms and the other half of whom lived in rural and suburban areas of Bavaria. Dust samples were collected from the mattresses of a randomly selected subgroup of 489 of the participants. Data also were obtained on the children’s respiratory and allergic symptoms, medical diagnoses, and potential confounders.

Children living on farms had a lower prevalence of asthma than did other children, with an adjusted odds ratio of 0.49. The percentage of dust samples that were positive for bacteria was significantly higher among farm dwellers, and the risk of asthma decreased significantly with an increasing number of detectable bands of bacterial DNA.

The analysis also included data from a second cross-sectional study involving 9,668 children attending elementary schools in rural areas of southern Germany, Switzerland, and Austria. Airborne dust samples were collected from the children’s bedrooms.

Again, children living on farms had a lower prevalence of asthma than did other children, with an odds ratio of 0.76. All bacterial and fungal taxa cultured from the dust samples were more prevalent among children living on farms than among other children, and the risk of asthma decreased significantly with an increasing number of fungal taxa, Dr. Ege and his colleagues said (N. Engl. J. Med. 2011;364:701-9).

In both studies, the diversity of microbes explained a substantial portion of the protective effect of the farming environment on asthma risk.

"Our methods do not allow us to identify specific microbes that may confer protection, but they have allowed us to identify broad families of species within microbial taxa that could be responsible for the effect of the farming environment.

"The challenge will be to identify these species with the precision needed to allow specific tests of the relationship between microbial exposure and protection against asthma," the investigators noted.

The analysis also could not determine the mechanism underlying this protective effect – how the diversity of microbial stimuli protects against asthma – but the researchers agreed with the prevailing view that perhaps micro-organisms trigger the innate immune system, which then bolsters resistance to asthma.

An alternative explanation may be that exposure to a broad rather than a narrow range of micro-organisms may prevent colonization of the lower airways with harmful bacteria. "Balanced colonization of the airways may parallel the beneficial effects of a diverse microbiome at other surfaces, such as the gut and skin," they added.

This study was funded by the Deutsche Forschungsgemeinschaft and the European Commission. Dr. Ege reported having a planned patent on asthma-protective bacteria. His associates reported ties to GlaxoSmithKline, Novartis, Protectimum, and ALK.

A subtype of hemoglobin H disease distinguished by life-threatening anemia during infectious illnesses should be recognized as a clinical entity distinct from other thalassemias, all of which are becoming more common in the United States, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Hemoglobin H Constant Spring (hemoglobin HCS) causes significant growth delay, causes repeated plunges in hemoglobin levels requiring urgent blood transfusions as early as infancy, and can lead to iron overload in early childhood, with its attendant sequelae. Most important, patients with HCS show acute, life-threatening worsening of anemia during common illnesses caused by viral or bacterial infections such as strep throat.

In contrast, other hemoglobin H disease does not cause growth deficits or iron overload during childhood, and it rarely causes severe anemia, said Dr. Ashutosh Lal of the department of hematology/oncology at Children’s Hospital and Research Center Oakland (Calif.), and his associates.

The investigators were able to characterize the natural history of hemoglobin H disease and the subtype hemoglobin HCS among children in the United States for the first time largely because of newborn screening for the disorders, which has been done in California since 1998. They identified and followed 86 cases of hemoglobin H disease.

In the past, hemoglobin H disease has been prevalent in Asian and Mediterranean populations but rare in others. Now, however, it appears to be making inroads into the United States. In this study, many patients were of mixed ethnic backgrounds, including African Americans, who historically have a very low rate of alpha-thalassemias.

This finding supports the usefulness of universal newborn screening for hemoglobin H syndromes. "Life-threatening anemia may develop in infants before the diagnosis can be made through conventional means in the absence of newborn screening," Dr. Lal and his colleagues noted (N. Engl. J. Med. 2011;364:710-8).

Among the 86 cases, 60 patients (70%) had hemoglobin H, 23 (27%) had the more severe HCS, and 3 (3.5%) had other, nondeletional hemoglobin H illness.

All of the episodes of acute worsening of anemia requiring blood transfusions occurred in the HCS group, while the children with hemoglobin H disease "had a predictably benign course." In HCS, the probability of requiring at least one transfusion before 1 year of age was 13%; this increased to 39% by the age of 5 years, 75% by the age of 10 years, and 80% by the age of 20 years. Thirty-seven transfusions (82%) were precipitated by infections.

Growth was significantly delayed in children with HCS but not in the other children. "This finding suggests that close attention to growth is required and that nutritional and hematologic associations with growth delay should be evaluated," the investigators said.

Ferritin levels were elevated in young children with HCS and continued to increase over time, whereas they were lower and did not increase significantly before adulthood in children with hemoglobin H disease.

Patients with HCS required nearly twice as many clinic visits each year and nearly four times as many hospital admissions. In addition, "substantial fatigue was observed in a subgroup of older patients with HCS, a finding that raises concern that the quality of life of patients may deteriorate with age," Dr. Lal and his associates said.

Five patients with HCS underwent splenectomy between the ages of 3.9 and 13 years because of their need for frequent blood transfusions, while no children with hemoglobin H disease did. Splenectomy reduced or eliminated acute hemolytic episodes in four of the five children.

"We suggest that HCS be recognized as a thalassemia syndrome that is distinct from hemoglobin H disease, so that the appropriate treatment approach can be devised for each group," they noted.

This study was supported in part by the Maternal and Child Health Bureau of the U.S. Department of Health and Human Services. The authors reported no relevant financial disclosures.

A subtype of hemoglobin H disease distinguished by life-threatening anemia during infectious illnesses should be recognized as a clinical entity distinct from other thalassemias, all of which are becoming more common in the United States, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Hemoglobin H Constant Spring (hemoglobin HCS) causes significant growth delay, causes repeated plunges in hemoglobin levels requiring urgent blood transfusions as early as infancy, and can lead to iron overload in early childhood, with its attendant sequelae. Most important, patients with HCS show acute, life-threatening worsening of anemia during common illnesses caused by viral or bacterial infections such as strep throat.

In contrast, other hemoglobin H disease does not cause growth deficits or iron overload during childhood, and it rarely causes severe anemia, said Dr. Ashutosh Lal of the department of hematology/oncology at Children’s Hospital and Research Center Oakland (Calif.), and his associates.

The investigators were able to characterize the natural history of hemoglobin H disease and the subtype hemoglobin HCS among children in the United States for the first time largely because of newborn screening for the disorders, which has been done in California since 1998. They identified and followed 86 cases of hemoglobin H disease.

In the past, hemoglobin H disease has been prevalent in Asian and Mediterranean populations but rare in others. Now, however, it appears to be making inroads into the United States. In this study, many patients were of mixed ethnic backgrounds, including African Americans, who historically have a very low rate of alpha-thalassemias.

This finding supports the usefulness of universal newborn screening for hemoglobin H syndromes. "Life-threatening anemia may develop in infants before the diagnosis can be made through conventional means in the absence of newborn screening," Dr. Lal and his colleagues noted (N. Engl. J. Med. 2011;364:710-8).

Among the 86 cases, 60 patients (70%) had hemoglobin H, 23 (27%) had the more severe HCS, and 3 (3.5%) had other, nondeletional hemoglobin H illness.

All of the episodes of acute worsening of anemia requiring blood transfusions occurred in the HCS group, while the children with hemoglobin H disease "had a predictably benign course." In HCS, the probability of requiring at least one transfusion before 1 year of age was 13%; this increased to 39% by the age of 5 years, 75% by the age of 10 years, and 80% by the age of 20 years. Thirty-seven transfusions (82%) were precipitated by infections.

Growth was significantly delayed in children with HCS but not in the other children. "This finding suggests that close attention to growth is required and that nutritional and hematologic associations with growth delay should be evaluated," the investigators said.

Ferritin levels were elevated in young children with HCS and continued to increase over time, whereas they were lower and did not increase significantly before adulthood in children with hemoglobin H disease.

Patients with HCS required nearly twice as many clinic visits each year and nearly four times as many hospital admissions. In addition, "substantial fatigue was observed in a subgroup of older patients with HCS, a finding that raises concern that the quality of life of patients may deteriorate with age," Dr. Lal and his associates said.

Five patients with HCS underwent splenectomy between the ages of 3.9 and 13 years because of their need for frequent blood transfusions, while no children with hemoglobin H disease did. Splenectomy reduced or eliminated acute hemolytic episodes in four of the five children.

"We suggest that HCS be recognized as a thalassemia syndrome that is distinct from hemoglobin H disease, so that the appropriate treatment approach can be devised for each group," they noted.

This study was supported in part by the Maternal and Child Health Bureau of the U.S. Department of Health and Human Services. The authors reported no relevant financial disclosures.

A subtype of hemoglobin H disease distinguished by life-threatening anemia during infectious illnesses should be recognized as a clinical entity distinct from other thalassemias, all of which are becoming more common in the United States, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Hemoglobin H Constant Spring (hemoglobin HCS) causes significant growth delay, causes repeated plunges in hemoglobin levels requiring urgent blood transfusions as early as infancy, and can lead to iron overload in early childhood, with its attendant sequelae. Most important, patients with HCS show acute, life-threatening worsening of anemia during common illnesses caused by viral or bacterial infections such as strep throat.

In contrast, other hemoglobin H disease does not cause growth deficits or iron overload during childhood, and it rarely causes severe anemia, said Dr. Ashutosh Lal of the department of hematology/oncology at Children’s Hospital and Research Center Oakland (Calif.), and his associates.

The investigators were able to characterize the natural history of hemoglobin H disease and the subtype hemoglobin HCS among children in the United States for the first time largely because of newborn screening for the disorders, which has been done in California since 1998. They identified and followed 86 cases of hemoglobin H disease.

In the past, hemoglobin H disease has been prevalent in Asian and Mediterranean populations but rare in others. Now, however, it appears to be making inroads into the United States. In this study, many patients were of mixed ethnic backgrounds, including African Americans, who historically have a very low rate of alpha-thalassemias.

This finding supports the usefulness of universal newborn screening for hemoglobin H syndromes. "Life-threatening anemia may develop in infants before the diagnosis can be made through conventional means in the absence of newborn screening," Dr. Lal and his colleagues noted (N. Engl. J. Med. 2011;364:710-8).

Among the 86 cases, 60 patients (70%) had hemoglobin H, 23 (27%) had the more severe HCS, and 3 (3.5%) had other, nondeletional hemoglobin H illness.

All of the episodes of acute worsening of anemia requiring blood transfusions occurred in the HCS group, while the children with hemoglobin H disease "had a predictably benign course." In HCS, the probability of requiring at least one transfusion before 1 year of age was 13%; this increased to 39% by the age of 5 years, 75% by the age of 10 years, and 80% by the age of 20 years. Thirty-seven transfusions (82%) were precipitated by infections.

Growth was significantly delayed in children with HCS but not in the other children. "This finding suggests that close attention to growth is required and that nutritional and hematologic associations with growth delay should be evaluated," the investigators said.

Ferritin levels were elevated in young children with HCS and continued to increase over time, whereas they were lower and did not increase significantly before adulthood in children with hemoglobin H disease.

Patients with HCS required nearly twice as many clinic visits each year and nearly four times as many hospital admissions. In addition, "substantial fatigue was observed in a subgroup of older patients with HCS, a finding that raises concern that the quality of life of patients may deteriorate with age," Dr. Lal and his associates said.

Five patients with HCS underwent splenectomy between the ages of 3.9 and 13 years because of their need for frequent blood transfusions, while no children with hemoglobin H disease did. Splenectomy reduced or eliminated acute hemolytic episodes in four of the five children.

"We suggest that HCS be recognized as a thalassemia syndrome that is distinct from hemoglobin H disease, so that the appropriate treatment approach can be devised for each group," they noted.

This study was supported in part by the Maternal and Child Health Bureau of the U.S. Department of Health and Human Services. The authors reported no relevant financial disclosures.

Children living on farms have a lower prevalence of asthma, likely due to a protective effect of their early exposure to a greater variety of environmental bacteria and fungi compared with what other children are exposed to, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Photo credit: © LindaYolanda/istock.com

In an epidemiologic analysis of data from two large observational studies of school-aged children in rural areas of central Europe, environmental samples from farmhouses showed a greater diversity of microbes than those from other homes. "The central finding of this analysis was the inverse association of the diversity scores with asthma [prevalence], which was not confounded by living on a farm," said Dr. Markus J. Ege of University Children’s Hospital, Munich, and his associates.

The analysis included data from a cross-sectional survey of 6,963 school children (aged 6-13 years), approximately half of whom lived on farms and the other half of whom lived in rural and suburban areas of Bavaria. Dust samples were collected from the mattresses of a randomly selected subgroup of 489 of the participants. Data also were obtained on the children’s respiratory and allergic symptoms, medical diagnoses, and potential confounders.

Children living on farms had a lower prevalence of asthma than did other children, with an adjusted odds ratio of 0.49. The percentage of dust samples that were positive for bacteria was significantly higher among farm dwellers, and the risk of asthma decreased significantly with an increasing number of detectable bands of bacterial DNA.

The analysis also included data from a second cross-sectional study involving 9,668 children attending elementary schools in rural areas of southern Germany, Switzerland, and Austria. Airborne dust samples were collected from the children’s bedrooms.

Again, children living on farms had a lower prevalence of asthma than did other children, with an odds ratio of 0.76. All bacterial and fungal taxa cultured from the dust samples were more prevalent among children living on farms than among other children, and the risk of asthma decreased significantly with an increasing number of fungal taxa, Dr. Ege and his colleagues said (N. Engl. J. Med. 2011;364:701-9).

In both studies, the diversity of microbes explained a substantial portion of the protective effect of the farming environment on asthma risk.

"Our methods do not allow us to identify specific microbes that may confer protection, but they have allowed us to identify broad families of species within microbial taxa that could be responsible for the effect of the farming environment.

"The challenge will be to identify these species with the precision needed to allow specific tests of the relationship between microbial exposure and protection against asthma," the investigators noted.

The analysis also could not determine the mechanism underlying this protective effect – how the diversity of microbial stimuli protects against asthma – but the researchers agreed with the prevailing view that perhaps micro-organisms trigger the innate immune system, which then bolsters resistance to asthma.

An alternative explanation may be that exposure to a broad rather than a narrow range of micro-organisms may prevent colonization of the lower airways with harmful bacteria. "Balanced colonization of the airways may parallel the beneficial effects of a diverse microbiome at other surfaces, such as the gut and skin," they added.

This study was funded by the Deutsche Forschungsgemeinschaft and the European Commission. Dr. Ege reported having a planned patent on asthma-protective bacteria. His associates reported ties to GlaxoSmithKline, Novartis, Protectimum, and ALK.

Children living on farms have a lower prevalence of asthma, likely due to a protective effect of their early exposure to a greater variety of environmental bacteria and fungi compared with what other children are exposed to, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Photo credit: © LindaYolanda/istock.com

In an epidemiologic analysis of data from two large observational studies of school-aged children in rural areas of central Europe, environmental samples from farmhouses showed a greater diversity of microbes than those from other homes. "The central finding of this analysis was the inverse association of the diversity scores with asthma [prevalence], which was not confounded by living on a farm," said Dr. Markus J. Ege of University Children’s Hospital, Munich, and his associates.

The analysis included data from a cross-sectional survey of 6,963 school children (aged 6-13 years), approximately half of whom lived on farms and the other half of whom lived in rural and suburban areas of Bavaria. Dust samples were collected from the mattresses of a randomly selected subgroup of 489 of the participants. Data also were obtained on the children’s respiratory and allergic symptoms, medical diagnoses, and potential confounders.

Children living on farms had a lower prevalence of asthma than did other children, with an adjusted odds ratio of 0.49. The percentage of dust samples that were positive for bacteria was significantly higher among farm dwellers, and the risk of asthma decreased significantly with an increasing number of detectable bands of bacterial DNA.

The analysis also included data from a second cross-sectional study involving 9,668 children attending elementary schools in rural areas of southern Germany, Switzerland, and Austria. Airborne dust samples were collected from the children’s bedrooms.

Again, children living on farms had a lower prevalence of asthma than did other children, with an odds ratio of 0.76. All bacterial and fungal taxa cultured from the dust samples were more prevalent among children living on farms than among other children, and the risk of asthma decreased significantly with an increasing number of fungal taxa, Dr. Ege and his colleagues said (N. Engl. J. Med. 2011;364:701-9).

In both studies, the diversity of microbes explained a substantial portion of the protective effect of the farming environment on asthma risk.

"Our methods do not allow us to identify specific microbes that may confer protection, but they have allowed us to identify broad families of species within microbial taxa that could be responsible for the effect of the farming environment.

"The challenge will be to identify these species with the precision needed to allow specific tests of the relationship between microbial exposure and protection against asthma," the investigators noted.

The analysis also could not determine the mechanism underlying this protective effect – how the diversity of microbial stimuli protects against asthma – but the researchers agreed with the prevailing view that perhaps micro-organisms trigger the innate immune system, which then bolsters resistance to asthma.

An alternative explanation may be that exposure to a broad rather than a narrow range of micro-organisms may prevent colonization of the lower airways with harmful bacteria. "Balanced colonization of the airways may parallel the beneficial effects of a diverse microbiome at other surfaces, such as the gut and skin," they added.

This study was funded by the Deutsche Forschungsgemeinschaft and the European Commission. Dr. Ege reported having a planned patent on asthma-protective bacteria. His associates reported ties to GlaxoSmithKline, Novartis, Protectimum, and ALK.

Children living on farms have a lower prevalence of asthma, likely due to a protective effect of their early exposure to a greater variety of environmental bacteria and fungi compared with what other children are exposed to, according to a report in the Feb. 24 issue of the New England Journal of Medicine.

Photo credit: © LindaYolanda/istock.com

In an epidemiologic analysis of data from two large observational studies of school-aged children in rural areas of central Europe, environmental samples from farmhouses showed a greater diversity of microbes than those from other homes. "The central finding of this analysis was the inverse association of the diversity scores with asthma [prevalence], which was not confounded by living on a farm," said Dr. Markus J. Ege of University Children’s Hospital, Munich, and his associates.

The analysis included data from a cross-sectional survey of 6,963 school children (aged 6-13 years), approximately half of whom lived on farms and the other half of whom lived in rural and suburban areas of Bavaria. Dust samples were collected from the mattresses of a randomly selected subgroup of 489 of the participants. Data also were obtained on the children’s respiratory and allergic symptoms, medical diagnoses, and potential confounders.

Children living on farms had a lower prevalence of asthma than did other children, with an adjusted odds ratio of 0.49. The percentage of dust samples that were positive for bacteria was significantly higher among farm dwellers, and the risk of asthma decreased significantly with an increasing number of detectable bands of bacterial DNA.

The analysis also included data from a second cross-sectional study involving 9,668 children attending elementary schools in rural areas of southern Germany, Switzerland, and Austria. Airborne dust samples were collected from the children’s bedrooms.

Again, children living on farms had a lower prevalence of asthma than did other children, with an odds ratio of 0.76. All bacterial and fungal taxa cultured from the dust samples were more prevalent among children living on farms than among other children, and the risk of asthma decreased significantly with an increasing number of fungal taxa, Dr. Ege and his colleagues said (N. Engl. J. Med. 2011;364:701-9).

In both studies, the diversity of microbes explained a substantial portion of the protective effect of the farming environment on asthma risk.

"Our methods do not allow us to identify specific microbes that may confer protection, but they have allowed us to identify broad families of species within microbial taxa that could be responsible for the effect of the farming environment.

"The challenge will be to identify these species with the precision needed to allow specific tests of the relationship between microbial exposure and protection against asthma," the investigators noted.

The analysis also could not determine the mechanism underlying this protective effect – how the diversity of microbial stimuli protects against asthma – but the researchers agreed with the prevailing view that perhaps micro-organisms trigger the innate immune system, which then bolsters resistance to asthma.

An alternative explanation may be that exposure to a broad rather than a narrow range of micro-organisms may prevent colonization of the lower airways with harmful bacteria. "Balanced colonization of the airways may parallel the beneficial effects of a diverse microbiome at other surfaces, such as the gut and skin," they added.

This study was funded by the Deutsche Forschungsgemeinschaft and the European Commission. Dr. Ege reported having a planned patent on asthma-protective bacteria. His associates reported ties to GlaxoSmithKline, Novartis, Protectimum, and ALK.

Topical nitroglycerin ointment raises bone mineral density, cuts resorption, and alters bone structure so that bone strength is increased, according to results of a double-blind trial in 243 women reported in the Feb. 23 issue of JAMA.

The magnitude of improvement equals or exceeds that observed with other therapies, including teriparatide. "Together, these findings suggest that nitroglycerin may significantly decrease the risk of fractures, including fractures in long bones such as the hip, legs, and upper arm, which are largely composed of cortical bone," wrote Dr. Sophie A. Jamal of the University of Toronto and her associates.

In a single-center double-blind clinical trial, they assessed the efficacy of daily application of 2% nitroglycerin ointment over the course of 2 years in increasing bone mineral density (BMD). The study was not large enough to directly determine the drug’s effects on fracture risk.

The study subjects were randomly assigned to apply active 15 mg/d nitroglycerin or a matching placebo ointment to a piece of onion skin that was taped to the upper outer arm overnight, every night. The study subjects were women aged 50 years or older (mean age, 62 years) who were at least 1 year past menopause. None had osteoporosis, but all had BMD T scores of 0 to –2.0 at the lumbar spine and higher than –2.0 at the total hip.

A total of 400 women were enrolled, but only 243 remained in the study long enough to be included in the analysis; 126 in the nitroglycerin group and 117 in the placebo group. A total of 106 subjects dropped out because of headache, nausea, or allergic reaction, and another 51 "lost interest" or became ineligible.

After randomization, another 30 subjects in the nitroglycerin group (24%) and 15 in the placebo group (13%) discontinued treatment or were lost to follow-up, including 26 who cited adverse reactions including headache.

The primary end point was change in lumbar spine areal BMD after 2 years of treatment. Compared with women in the placebo group, those who received active nitroglycerin showed a significant increase of approximately 7% in areal BMD at the lumbar spine.

They also showed comparable increases in areal BMD at the total hip (6%) and femoral neck (7%). Compared with placebo users, the nitroglycerin group also showed increases in volumetric trabecular BMD of 12% at the radius and 8.5% at the tibia; increases in cortical thickness of 14% at the radius and 25% at the tibia; and increases in periosteal circumference of 7% at the radius and 3% at the tibia. The latter finding has not been reported with any other agent, the investigators said (JAMA 2011;305:800-07).

Nitroglycerin therapy also was associated with increases in measures of bone strength, with rises of 11% and 10% in polar section modulus and of 7% and 14.5% in polar moment of inertia at the radius and tibia, respectively. These findings indicate significant improvement in bone bending and twisting strength, which in previous research has correlated with fewer fractures.

Compared with placebo, nitroglycerin treatment was associated with significant increases in bone-specific alkaline phosphatase, a marker of bone formation. This rose 14% at 3 months, 21% at 12 months, and 35% at 24 months. At the same time, urinary N-telopeptide level, a marker of bone resorption, decreased by 20% at 3 months, 33% at 12 months, and 54% at 24 months.

This concomitant change indicates that nitroglycerin uncouples bone formation from bone resorption. Moreover, "the differential effects of nitroglycerin on formation and resorption appear to widen with time, suggesting that its efficacy continues or even increases during 24 months of use. In contrast, the effects of other antiresorptives and teriparatide either plateau or wane with time," Dr. Jamal and her colleagues wrote.

The incidence of serious adverse effects did not differ between the two groups, at 4% in both. However, headaches were much more common with active nitroglycerin, and often led to discontinuation of therapy. The number of headaches markedly declined with time, and no subjects dropped out of the second year of the study because of headache.

"The possibility that different preparations, doses, or schedules of administration would reduce the frequency of headaches without diminishing the effects on bone should be explored in future studies," the researchers said.

In addition, two fractures occurred in both the nitroglycerin and placebo groups, and there was one death from stroke in the nitroglycerin group.

Given the benefits of topical nitroglycerin in this study, together with its wide availability, easy administration, and low cost, "the efficacy of nitrates for reducing risk of fracture should be tested in a larger randomized clinical trial," they said.

This study was supported by the Canadian Institutes of Health Research and Physicians’ Services Inc. Dr. Jamal reported receiving support from Novartis, Amgen, Warner-Chilcott, Genzyme, and Shire, and her associates reported ties to numerous drug, device, and technology companies.

Topical nitroglycerin ointment raises bone mineral density, cuts resorption, and alters bone structure so that bone strength is increased, according to results of a double-blind trial in 243 women reported in the Feb. 23 issue of JAMA.

The magnitude of improvement equals or exceeds that observed with other therapies, including teriparatide. "Together, these findings suggest that nitroglycerin may significantly decrease the risk of fractures, including fractures in long bones such as the hip, legs, and upper arm, which are largely composed of cortical bone," wrote Dr. Sophie A. Jamal of the University of Toronto and her associates.

In a single-center double-blind clinical trial, they assessed the efficacy of daily application of 2% nitroglycerin ointment over the course of 2 years in increasing bone mineral density (BMD). The study was not large enough to directly determine the drug’s effects on fracture risk.

The study subjects were randomly assigned to apply active 15 mg/d nitroglycerin or a matching placebo ointment to a piece of onion skin that was taped to the upper outer arm overnight, every night. The study subjects were women aged 50 years or older (mean age, 62 years) who were at least 1 year past menopause. None had osteoporosis, but all had BMD T scores of 0 to –2.0 at the lumbar spine and higher than –2.0 at the total hip.

A total of 400 women were enrolled, but only 243 remained in the study long enough to be included in the analysis; 126 in the nitroglycerin group and 117 in the placebo group. A total of 106 subjects dropped out because of headache, nausea, or allergic reaction, and another 51 "lost interest" or became ineligible.

After randomization, another 30 subjects in the nitroglycerin group (24%) and 15 in the placebo group (13%) discontinued treatment or were lost to follow-up, including 26 who cited adverse reactions including headache.

The primary end point was change in lumbar spine areal BMD after 2 years of treatment. Compared with women in the placebo group, those who received active nitroglycerin showed a significant increase of approximately 7% in areal BMD at the lumbar spine.

They also showed comparable increases in areal BMD at the total hip (6%) and femoral neck (7%). Compared with placebo users, the nitroglycerin group also showed increases in volumetric trabecular BMD of 12% at the radius and 8.5% at the tibia; increases in cortical thickness of 14% at the radius and 25% at the tibia; and increases in periosteal circumference of 7% at the radius and 3% at the tibia. The latter finding has not been reported with any other agent, the investigators said (JAMA 2011;305:800-07).

Nitroglycerin therapy also was associated with increases in measures of bone strength, with rises of 11% and 10% in polar section modulus and of 7% and 14.5% in polar moment of inertia at the radius and tibia, respectively. These findings indicate significant improvement in bone bending and twisting strength, which in previous research has correlated with fewer fractures.

Compared with placebo, nitroglycerin treatment was associated with significant increases in bone-specific alkaline phosphatase, a marker of bone formation. This rose 14% at 3 months, 21% at 12 months, and 35% at 24 months. At the same time, urinary N-telopeptide level, a marker of bone resorption, decreased by 20% at 3 months, 33% at 12 months, and 54% at 24 months.

This concomitant change indicates that nitroglycerin uncouples bone formation from bone resorption. Moreover, "the differential effects of nitroglycerin on formation and resorption appear to widen with time, suggesting that its efficacy continues or even increases during 24 months of use. In contrast, the effects of other antiresorptives and teriparatide either plateau or wane with time," Dr. Jamal and her colleagues wrote.

The incidence of serious adverse effects did not differ between the two groups, at 4% in both. However, headaches were much more common with active nitroglycerin, and often led to discontinuation of therapy. The number of headaches markedly declined with time, and no subjects dropped out of the second year of the study because of headache.

"The possibility that different preparations, doses, or schedules of administration would reduce the frequency of headaches without diminishing the effects on bone should be explored in future studies," the researchers said.

In addition, two fractures occurred in both the nitroglycerin and placebo groups, and there was one death from stroke in the nitroglycerin group.

Given the benefits of topical nitroglycerin in this study, together with its wide availability, easy administration, and low cost, "the efficacy of nitrates for reducing risk of fracture should be tested in a larger randomized clinical trial," they said.

This study was supported by the Canadian Institutes of Health Research and Physicians’ Services Inc. Dr. Jamal reported receiving support from Novartis, Amgen, Warner-Chilcott, Genzyme, and Shire, and her associates reported ties to numerous drug, device, and technology companies.

Topical nitroglycerin ointment raises bone mineral density, cuts resorption, and alters bone structure so that bone strength is increased, according to results of a double-blind trial in 243 women reported in the Feb. 23 issue of JAMA.

The magnitude of improvement equals or exceeds that observed with other therapies, including teriparatide. "Together, these findings suggest that nitroglycerin may significantly decrease the risk of fractures, including fractures in long bones such as the hip, legs, and upper arm, which are largely composed of cortical bone," wrote Dr. Sophie A. Jamal of the University of Toronto and her associates.

In a single-center double-blind clinical trial, they assessed the efficacy of daily application of 2% nitroglycerin ointment over the course of 2 years in increasing bone mineral density (BMD). The study was not large enough to directly determine the drug’s effects on fracture risk.

The study subjects were randomly assigned to apply active 15 mg/d nitroglycerin or a matching placebo ointment to a piece of onion skin that was taped to the upper outer arm overnight, every night. The study subjects were women aged 50 years or older (mean age, 62 years) who were at least 1 year past menopause. None had osteoporosis, but all had BMD T scores of 0 to –2.0 at the lumbar spine and higher than –2.0 at the total hip.

A total of 400 women were enrolled, but only 243 remained in the study long enough to be included in the analysis; 126 in the nitroglycerin group and 117 in the placebo group. A total of 106 subjects dropped out because of headache, nausea, or allergic reaction, and another 51 "lost interest" or became ineligible.

After randomization, another 30 subjects in the nitroglycerin group (24%) and 15 in the placebo group (13%) discontinued treatment or were lost to follow-up, including 26 who cited adverse reactions including headache.

The primary end point was change in lumbar spine areal BMD after 2 years of treatment. Compared with women in the placebo group, those who received active nitroglycerin showed a significant increase of approximately 7% in areal BMD at the lumbar spine.

They also showed comparable increases in areal BMD at the total hip (6%) and femoral neck (7%). Compared with placebo users, the nitroglycerin group also showed increases in volumetric trabecular BMD of 12% at the radius and 8.5% at the tibia; increases in cortical thickness of 14% at the radius and 25% at the tibia; and increases in periosteal circumference of 7% at the radius and 3% at the tibia. The latter finding has not been reported with any other agent, the investigators said (JAMA 2011;305:800-07).

Nitroglycerin therapy also was associated with increases in measures of bone strength, with rises of 11% and 10% in polar section modulus and of 7% and 14.5% in polar moment of inertia at the radius and tibia, respectively. These findings indicate significant improvement in bone bending and twisting strength, which in previous research has correlated with fewer fractures.

Compared with placebo, nitroglycerin treatment was associated with significant increases in bone-specific alkaline phosphatase, a marker of bone formation. This rose 14% at 3 months, 21% at 12 months, and 35% at 24 months. At the same time, urinary N-telopeptide level, a marker of bone resorption, decreased by 20% at 3 months, 33% at 12 months, and 54% at 24 months.

This concomitant change indicates that nitroglycerin uncouples bone formation from bone resorption. Moreover, "the differential effects of nitroglycerin on formation and resorption appear to widen with time, suggesting that its efficacy continues or even increases during 24 months of use. In contrast, the effects of other antiresorptives and teriparatide either plateau or wane with time," Dr. Jamal and her colleagues wrote.

The incidence of serious adverse effects did not differ between the two groups, at 4% in both. However, headaches were much more common with active nitroglycerin, and often led to discontinuation of therapy. The number of headaches markedly declined with time, and no subjects dropped out of the second year of the study because of headache.

"The possibility that different preparations, doses, or schedules of administration would reduce the frequency of headaches without diminishing the effects on bone should be explored in future studies," the researchers said.

In addition, two fractures occurred in both the nitroglycerin and placebo groups, and there was one death from stroke in the nitroglycerin group.

Given the benefits of topical nitroglycerin in this study, together with its wide availability, easy administration, and low cost, "the efficacy of nitrates for reducing risk of fracture should be tested in a larger randomized clinical trial," they said.

This study was supported by the Canadian Institutes of Health Research and Physicians’ Services Inc. Dr. Jamal reported receiving support from Novartis, Amgen, Warner-Chilcott, Genzyme, and Shire, and her associates reported ties to numerous drug, device, and technology companies.