Sarah Pressman Lovinger

New recommendations from the American Heart Association call for more targeted screening and treatment of lipid disorders in children, according to a statement released in March.

Though the guidelines currently used for managing lipid disorders in children were released by the National Cholesterol Expert Program (NCEP) in 1992 and focused on children with a family history of lipid disorders, the current statement suggests that other at-risk children should also be screened for lipid disorders and that treatment with statins is appropriate if lifestyle management is not adequate. The statement reflects research showing that the pathogenesis of cardiovascular disease begins many years before it is manifested in adulthood.

“It has become clear that atherosclerotic cardiovascular disease begins in childhood and is progressive,” stated Dr. Brian W. McCrindle, of the Hospital for Sick Children in Toronto, and his colleagues (Circulation. 2007; 115: DOI: 10.1161/CIRCULATIONAHA.107.181946).

The AHA panel recommends more widespread lipid testing in children, testing for other parameters of the metabolic syndrome in overweight and obese children with lipid abnormalities, and a major change in recommended drug therapy for children with lipid disorders (Circulation 2007 April 10 [Epub doi:10.1161/CIRCULATIONAHA.107.181946]).

Guidelines released by the NCEP in 1992 recommended that healthy children older than age 2 years follow a low-fat diet and eat a variety of foods to promote good cardiovascular health. They also stated that only children from high-risk families required lipid screening, and that children with lipid abnormalities should be placed on a low-fat diet and encouraged to exercise for 6–12 months. After this period, if repeat screening revealed elevated LDL cholesterol levels, children should be treated, with LDL cholesterol cutoffs similar to those in adults, the NCEP said.

The current guidelines target mostly children with a family history of hyperlipidemia, and researchers are concerned that inadequate numbers of children are being screened.

The AHA panel recommends that children with a strong family history as well as overweight and obese children should undergo testing for lipid abnormalities. Overweight and obese children with lipid disorders should also be screened for hypertension, diabetes, and other metabolic abnormalities, such as central adiposity.

Given the increasing complexity of caring for children with certain chronic diseases, the statement also expounded on certain situations in which treating physicians should consider screening and close monitoring of children with lipid disorders.

The panelists recommended that early screening should be considered in male children, those with hypertension, obesity, and those with chronic conditions such as lupus, HIV, and a history of organ transplantation that can increase their risk for atherosclerotic disease. The LDL cholesterol goal of 190 mg/dL or less for children with no additional cardiovascular disease risk factors remains the same. But the new statement emphasizes that the LDL cholesterol goal of 160 mg/dL or less should be considered in children with additional risk factors.

The AHA statement also recommends changes in the treatment of lipid disorders in children. Past guidelines recommended that children with lipid disorders be treated with bile-acid-binding resins. But the statement released today says that statins should be the first-line therapy in these children.

“Bile-acid-binding resins are associated with very poor compliance in kids, and are incompletely effective,” Dr. McCrindle said in an interview. He added that studies show that statins have similar safety and efficacy in the treatment of lipid disorders in children as in adults.

Despite the modifications that the panel recommended, the emphasis will remain on lifestyle modification rather than drug therapy. Dr. McCrindle pointed out that lipid abnormalities in most children result from obesity, and not from familial hypercholesterolemia. Physicians caring for overweight and obese children who have lipid disorders should emphasize the importance of diet and exercise rather than drug therapy for most of their patients.

New recommendations from the American Heart Association call for more targeted screening and treatment of lipid disorders in children, according to a statement released in March.

Though the guidelines currently used for managing lipid disorders in children were released by the National Cholesterol Expert Program (NCEP) in 1992 and focused on children with a family history of lipid disorders, the current statement suggests that other at-risk children should also be screened for lipid disorders and that treatment with statins is appropriate if lifestyle management is not adequate. The statement reflects research showing that the pathogenesis of cardiovascular disease begins many years before it is manifested in adulthood.

“It has become clear that atherosclerotic cardiovascular disease begins in childhood and is progressive,” stated Dr. Brian W. McCrindle, of the Hospital for Sick Children in Toronto, and his colleagues (Circulation. 2007; 115: DOI: 10.1161/CIRCULATIONAHA.107.181946).

The AHA panel recommends more widespread lipid testing in children, testing for other parameters of the metabolic syndrome in overweight and obese children with lipid abnormalities, and a major change in recommended drug therapy for children with lipid disorders (Circulation 2007 April 10 [Epub doi:10.1161/CIRCULATIONAHA.107.181946]).

Guidelines released by the NCEP in 1992 recommended that healthy children older than age 2 years follow a low-fat diet and eat a variety of foods to promote good cardiovascular health. They also stated that only children from high-risk families required lipid screening, and that children with lipid abnormalities should be placed on a low-fat diet and encouraged to exercise for 6–12 months. After this period, if repeat screening revealed elevated LDL cholesterol levels, children should be treated, with LDL cholesterol cutoffs similar to those in adults, the NCEP said.

The current guidelines target mostly children with a family history of hyperlipidemia, and researchers are concerned that inadequate numbers of children are being screened.

The AHA panel recommends that children with a strong family history as well as overweight and obese children should undergo testing for lipid abnormalities. Overweight and obese children with lipid disorders should also be screened for hypertension, diabetes, and other metabolic abnormalities, such as central adiposity.

Given the increasing complexity of caring for children with certain chronic diseases, the statement also expounded on certain situations in which treating physicians should consider screening and close monitoring of children with lipid disorders.

The panelists recommended that early screening should be considered in male children, those with hypertension, obesity, and those with chronic conditions such as lupus, HIV, and a history of organ transplantation that can increase their risk for atherosclerotic disease. The LDL cholesterol goal of 190 mg/dL or less for children with no additional cardiovascular disease risk factors remains the same. But the new statement emphasizes that the LDL cholesterol goal of 160 mg/dL or less should be considered in children with additional risk factors.

The AHA statement also recommends changes in the treatment of lipid disorders in children. Past guidelines recommended that children with lipid disorders be treated with bile-acid-binding resins. But the statement released today says that statins should be the first-line therapy in these children.

“Bile-acid-binding resins are associated with very poor compliance in kids, and are incompletely effective,” Dr. McCrindle said in an interview. He added that studies show that statins have similar safety and efficacy in the treatment of lipid disorders in children as in adults.

Despite the modifications that the panel recommended, the emphasis will remain on lifestyle modification rather than drug therapy. Dr. McCrindle pointed out that lipid abnormalities in most children result from obesity, and not from familial hypercholesterolemia. Physicians caring for overweight and obese children who have lipid disorders should emphasize the importance of diet and exercise rather than drug therapy for most of their patients.

New recommendations from the American Heart Association call for more targeted screening and treatment of lipid disorders in children, according to a statement released in March.

Though the guidelines currently used for managing lipid disorders in children were released by the National Cholesterol Expert Program (NCEP) in 1992 and focused on children with a family history of lipid disorders, the current statement suggests that other at-risk children should also be screened for lipid disorders and that treatment with statins is appropriate if lifestyle management is not adequate. The statement reflects research showing that the pathogenesis of cardiovascular disease begins many years before it is manifested in adulthood.

“It has become clear that atherosclerotic cardiovascular disease begins in childhood and is progressive,” stated Dr. Brian W. McCrindle, of the Hospital for Sick Children in Toronto, and his colleagues (Circulation. 2007; 115: DOI: 10.1161/CIRCULATIONAHA.107.181946).

The AHA panel recommends more widespread lipid testing in children, testing for other parameters of the metabolic syndrome in overweight and obese children with lipid abnormalities, and a major change in recommended drug therapy for children with lipid disorders (Circulation 2007 April 10 [Epub doi:10.1161/CIRCULATIONAHA.107.181946]).

Guidelines released by the NCEP in 1992 recommended that healthy children older than age 2 years follow a low-fat diet and eat a variety of foods to promote good cardiovascular health. They also stated that only children from high-risk families required lipid screening, and that children with lipid abnormalities should be placed on a low-fat diet and encouraged to exercise for 6–12 months. After this period, if repeat screening revealed elevated LDL cholesterol levels, children should be treated, with LDL cholesterol cutoffs similar to those in adults, the NCEP said.

The current guidelines target mostly children with a family history of hyperlipidemia, and researchers are concerned that inadequate numbers of children are being screened.

The AHA panel recommends that children with a strong family history as well as overweight and obese children should undergo testing for lipid abnormalities. Overweight and obese children with lipid disorders should also be screened for hypertension, diabetes, and other metabolic abnormalities, such as central adiposity.

Given the increasing complexity of caring for children with certain chronic diseases, the statement also expounded on certain situations in which treating physicians should consider screening and close monitoring of children with lipid disorders.

The panelists recommended that early screening should be considered in male children, those with hypertension, obesity, and those with chronic conditions such as lupus, HIV, and a history of organ transplantation that can increase their risk for atherosclerotic disease. The LDL cholesterol goal of 190 mg/dL or less for children with no additional cardiovascular disease risk factors remains the same. But the new statement emphasizes that the LDL cholesterol goal of 160 mg/dL or less should be considered in children with additional risk factors.

The AHA statement also recommends changes in the treatment of lipid disorders in children. Past guidelines recommended that children with lipid disorders be treated with bile-acid-binding resins. But the statement released today says that statins should be the first-line therapy in these children.

“Bile-acid-binding resins are associated with very poor compliance in kids, and are incompletely effective,” Dr. McCrindle said in an interview. He added that studies show that statins have similar safety and efficacy in the treatment of lipid disorders in children as in adults.

Despite the modifications that the panel recommended, the emphasis will remain on lifestyle modification rather than drug therapy. Dr. McCrindle pointed out that lipid abnormalities in most children result from obesity, and not from familial hypercholesterolemia. Physicians caring for overweight and obese children who have lipid disorders should emphasize the importance of diet and exercise rather than drug therapy for most of their patients.

CHICAGO — As the prevalence of thyroid nodules diagnosed on ultrasound increases, clinicians trying to decide whether to biopsy a particular nodule should consider adding a serum TSH test to their work-up, Dr. R. Brooke Jeffrey Jr. said at the annual meeting of the Radiological Society of North America.

At the moment, “what is driving our approach to thyroid diagnosis is money and patient hysteria,” said Dr. Jeffrey of the department of radiology at Stanford (Calif.) University. In addition, the lack of clinical findings that indicate with certainty which nodules are more likely to be malignant contributes to a high biopsy rate.

Deciding which patients to biopsy is “a very contentious issue,” he added, noting that different medical societies have issued conflicting guidelines. Though thyroid nodules are commonly detected, few thyroid cancers are diagnosed. But clinicians do not want to miss a cancer diagnosis, and thyroid biopsies can be lucrative.

A recent review indicated that thyroid cancer mortality has not changed in 30 years, despite the increased incidence of thyroid cancer, a result Dr. Jeffrey attributed to overdiagnosis (JAMA 2006;295:2164–7).

He also concluded that ultrasound, which has become much more widely available in the past 30 years, has not contributed to a decrease in mortality. Ultrasound gives information about many features of thyroid cancer, such as whether a mass is solid, hypoechoic, taller than it is wide, and whether it has microcalcifications and irregular margins. But because no single feature has a high sensitivity and specificity, clinicians cannot rely on ultrasound to rule out cancer, so they order biopsies.

However, recent data indicated that patients with clinically detected goiters and high normal TSH values had a higher incidence of thyroid cancer (J. Clin. Endocrinol. Metab. 2006;91:4295–301). By “combining ultrasound features and laboratory values, we might be able to come up with an algorithm,” Dr. Jeffrey said.

Even if TSH levels prove useful, clinicians will still confront difficult issues when deciding whether to biopsy thyroid nodules: how long to track the nodules before biopsy and what sort of interval growth might indicate a benign or a worrisome condition.

CHICAGO — As the prevalence of thyroid nodules diagnosed on ultrasound increases, clinicians trying to decide whether to biopsy a particular nodule should consider adding a serum TSH test to their work-up, Dr. R. Brooke Jeffrey Jr. said at the annual meeting of the Radiological Society of North America.

At the moment, “what is driving our approach to thyroid diagnosis is money and patient hysteria,” said Dr. Jeffrey of the department of radiology at Stanford (Calif.) University. In addition, the lack of clinical findings that indicate with certainty which nodules are more likely to be malignant contributes to a high biopsy rate.

Deciding which patients to biopsy is “a very contentious issue,” he added, noting that different medical societies have issued conflicting guidelines. Though thyroid nodules are commonly detected, few thyroid cancers are diagnosed. But clinicians do not want to miss a cancer diagnosis, and thyroid biopsies can be lucrative.

A recent review indicated that thyroid cancer mortality has not changed in 30 years, despite the increased incidence of thyroid cancer, a result Dr. Jeffrey attributed to overdiagnosis (JAMA 2006;295:2164–7).

He also concluded that ultrasound, which has become much more widely available in the past 30 years, has not contributed to a decrease in mortality. Ultrasound gives information about many features of thyroid cancer, such as whether a mass is solid, hypoechoic, taller than it is wide, and whether it has microcalcifications and irregular margins. But because no single feature has a high sensitivity and specificity, clinicians cannot rely on ultrasound to rule out cancer, so they order biopsies.

However, recent data indicated that patients with clinically detected goiters and high normal TSH values had a higher incidence of thyroid cancer (J. Clin. Endocrinol. Metab. 2006;91:4295–301). By “combining ultrasound features and laboratory values, we might be able to come up with an algorithm,” Dr. Jeffrey said.

Even if TSH levels prove useful, clinicians will still confront difficult issues when deciding whether to biopsy thyroid nodules: how long to track the nodules before biopsy and what sort of interval growth might indicate a benign or a worrisome condition.

CHICAGO — As the prevalence of thyroid nodules diagnosed on ultrasound increases, clinicians trying to decide whether to biopsy a particular nodule should consider adding a serum TSH test to their work-up, Dr. R. Brooke Jeffrey Jr. said at the annual meeting of the Radiological Society of North America.

At the moment, “what is driving our approach to thyroid diagnosis is money and patient hysteria,” said Dr. Jeffrey of the department of radiology at Stanford (Calif.) University. In addition, the lack of clinical findings that indicate with certainty which nodules are more likely to be malignant contributes to a high biopsy rate.

Deciding which patients to biopsy is “a very contentious issue,” he added, noting that different medical societies have issued conflicting guidelines. Though thyroid nodules are commonly detected, few thyroid cancers are diagnosed. But clinicians do not want to miss a cancer diagnosis, and thyroid biopsies can be lucrative.

A recent review indicated that thyroid cancer mortality has not changed in 30 years, despite the increased incidence of thyroid cancer, a result Dr. Jeffrey attributed to overdiagnosis (JAMA 2006;295:2164–7).

He also concluded that ultrasound, which has become much more widely available in the past 30 years, has not contributed to a decrease in mortality. Ultrasound gives information about many features of thyroid cancer, such as whether a mass is solid, hypoechoic, taller than it is wide, and whether it has microcalcifications and irregular margins. But because no single feature has a high sensitivity and specificity, clinicians cannot rely on ultrasound to rule out cancer, so they order biopsies.

However, recent data indicated that patients with clinically detected goiters and high normal TSH values had a higher incidence of thyroid cancer (J. Clin. Endocrinol. Metab. 2006;91:4295–301). By “combining ultrasound features and laboratory values, we might be able to come up with an algorithm,” Dr. Jeffrey said.

Even if TSH levels prove useful, clinicians will still confront difficult issues when deciding whether to biopsy thyroid nodules: how long to track the nodules before biopsy and what sort of interval growth might indicate a benign or a worrisome condition.

Impaired maternal glucose tolerance can lead to poor pregnancy outcomes, and clinicians should use a lower threshold to diagnose and treat gestational diabetes, according to M. Kwik of the University of Sydney in Australia.

“Untreated glucose intolerance in pregnancy is associated with larger babies, more shoulder dystocia, and higher rates of preeclampsia,” reported M. Kwik and colleagues in Diabetes Research and Clinical Practice (2007 [Epub doi: 10.1016/j.daibres.2006.12.004]).

The researchers conducted a retrospective study of women with a singleton pregnancy who received prenatal care at their hospital between February 2000 and May 2005. They excluded women who gave birth before 34 weeks' gestation. The researchers identified 512 women with a 2-hour glucose level of at least 7.8 mmol/L and a fasting glucose at or below 5.5 mmol/L following a 75-g glucose tolerance test (GTT). They obtained information on pregnancy outcomes for 478 (93%) of these women. The treated group comprised 265 women who had 2-hour glucose levels of more than 7.8 mmol/L and were diagnosed with gestational diabetes mellitus (GDM); these patients were managed according to guidelines. Another 213 women had 2-hour glucose levels of more than 7.8 mmol/L, but did not meet criteria for GDM. They constituted the untreated group. The researchers also evaluated 197 women with GTT values of 7.8 mmol/L or less who did not receive GDM management, and these participants were the comparison group. There were no significant differences in maternal age, body mass index, or proportion of primiparous women in the three groups.

The results showed a significant increase in mean birth weight, macrosomia, and shoulder dystocia in the untreated group, vs. the comparison group (5.2% vs. 1.0%). There was also a statistically significant increase in induction of labor rates in the untreated group, vs. the comparison group (27.7 % vs. 19.3 %). Additionally, the results showed a significantly higher preeclampsia rate in the untreated group vs. the comparison group (11.7% vs. 5.1%). The two groups' cesarean rates were similar.

Impaired maternal glucose tolerance can lead to poor pregnancy outcomes, and clinicians should use a lower threshold to diagnose and treat gestational diabetes, according to M. Kwik of the University of Sydney in Australia.

“Untreated glucose intolerance in pregnancy is associated with larger babies, more shoulder dystocia, and higher rates of preeclampsia,” reported M. Kwik and colleagues in Diabetes Research and Clinical Practice (2007 [Epub doi: 10.1016/j.daibres.2006.12.004]).

The researchers conducted a retrospective study of women with a singleton pregnancy who received prenatal care at their hospital between February 2000 and May 2005. They excluded women who gave birth before 34 weeks' gestation. The researchers identified 512 women with a 2-hour glucose level of at least 7.8 mmol/L and a fasting glucose at or below 5.5 mmol/L following a 75-g glucose tolerance test (GTT). They obtained information on pregnancy outcomes for 478 (93%) of these women. The treated group comprised 265 women who had 2-hour glucose levels of more than 7.8 mmol/L and were diagnosed with gestational diabetes mellitus (GDM); these patients were managed according to guidelines. Another 213 women had 2-hour glucose levels of more than 7.8 mmol/L, but did not meet criteria for GDM. They constituted the untreated group. The researchers also evaluated 197 women with GTT values of 7.8 mmol/L or less who did not receive GDM management, and these participants were the comparison group. There were no significant differences in maternal age, body mass index, or proportion of primiparous women in the three groups.

The results showed a significant increase in mean birth weight, macrosomia, and shoulder dystocia in the untreated group, vs. the comparison group (5.2% vs. 1.0%). There was also a statistically significant increase in induction of labor rates in the untreated group, vs. the comparison group (27.7 % vs. 19.3 %). Additionally, the results showed a significantly higher preeclampsia rate in the untreated group vs. the comparison group (11.7% vs. 5.1%). The two groups' cesarean rates were similar.

Impaired maternal glucose tolerance can lead to poor pregnancy outcomes, and clinicians should use a lower threshold to diagnose and treat gestational diabetes, according to M. Kwik of the University of Sydney in Australia.

“Untreated glucose intolerance in pregnancy is associated with larger babies, more shoulder dystocia, and higher rates of preeclampsia,” reported M. Kwik and colleagues in Diabetes Research and Clinical Practice (2007 [Epub doi: 10.1016/j.daibres.2006.12.004]).

The researchers conducted a retrospective study of women with a singleton pregnancy who received prenatal care at their hospital between February 2000 and May 2005. They excluded women who gave birth before 34 weeks' gestation. The researchers identified 512 women with a 2-hour glucose level of at least 7.8 mmol/L and a fasting glucose at or below 5.5 mmol/L following a 75-g glucose tolerance test (GTT). They obtained information on pregnancy outcomes for 478 (93%) of these women. The treated group comprised 265 women who had 2-hour glucose levels of more than 7.8 mmol/L and were diagnosed with gestational diabetes mellitus (GDM); these patients were managed according to guidelines. Another 213 women had 2-hour glucose levels of more than 7.8 mmol/L, but did not meet criteria for GDM. They constituted the untreated group. The researchers also evaluated 197 women with GTT values of 7.8 mmol/L or less who did not receive GDM management, and these participants were the comparison group. There were no significant differences in maternal age, body mass index, or proportion of primiparous women in the three groups.

The results showed a significant increase in mean birth weight, macrosomia, and shoulder dystocia in the untreated group, vs. the comparison group (5.2% vs. 1.0%). There was also a statistically significant increase in induction of labor rates in the untreated group, vs. the comparison group (27.7 % vs. 19.3 %). Additionally, the results showed a significantly higher preeclampsia rate in the untreated group vs. the comparison group (11.7% vs. 5.1%). The two groups' cesarean rates were similar.

CHICAGO – Treatment outcomes for obese patients with binge-eating disorder differ by disease severity and negative affect, a large study of patients with this disorder shows.

“We are trying to identify a particular subset of the population [that responds to a particular treatment],” Denise E. Wilfley, Ph.D., director of the Weight Management and Eating Disorders Program at Washington University in St. Louis, said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

The study evaluated three treatments for binge-eating disorder (BED): interpersonal therapy (IPT), behavioral weight loss (BWL), and guided self-help (GSH). “This is the first study to compare three different treatments for binge-eating disorder,” Dr. Wilfley said. Participants were also stratified by high versus low negative affect and by severity of bingeing.

According to the DSM-IV, people with BED eat a large amount of food with loss of control on at least 2 days a week for at least 6 months; they do not regularly engage in compensatory behaviors.

Dr. Wilfley said people with this disorder tend to have low self-esteem and very high rates of health care use, traits similar to people with anorexia and bulimia nervosa. But unlike people with those conditions, people with BED are more likely to be male and less likely to be white. Given the large amount of food they consume, people with BED are associated with overweight or obesity. “They're not just obese individuals,” said Dr. Wilfley, also professor of psychiatry at the university. “They are obese individuals with an eating disorder.”

The trial involved 205 participants and was conducted at three sites: Stanford (Calif.) University (data coordinating center), Washington University (clinical site), and Rutgers University (clinical site) in Piscataway, N.J. Participants were at least 18 years old, met the DSM-IV criteria for BED, and had a body mass index (BMI) between 27 and 45 kg/m

In terms of race, 82% were white, 13% were black, 4% were Hispanic, and 1% was Native American. Slightly more than half of the participants were college educated, and the average BMI among the participants was 36.4.

The participants were randomized to one of the three treatments. Participants in both the interpersonal therapy and the behavioral weight loss groups had 20 60-minute therapy sessions over a 24-week period. Those in the guided self-help group used bibliotherapy. They were asked to read “Overcoming Binge Eating,” by Dr. Christopher G. Fairburn (New York: the Guilford Press, 1995), a book aimed at teaching behavior change. This group also had one 55-minute and nine 25-minute therapy sessions over 24 weeks. The IPT group included 75 patients, the BWL group had 64 patients, and the GSH group had 66 patients. There were no significant differences in patient characteristics among the three groups.

The researchers used the Beck Depression Inventory to stratify the participants according to high negative affect (HNA) and low negative affect (LNA). Although they were apt to stay with interpersonal therapy, patients with HNA were significantly more likely to drop out of the behavioral weight loss treatment group than those with LNA. Those with LNA were much more likely to drop out of guided self-help.

Overall, treatment retention rates were significantly better among those treated with interpersonal therapy (93%) than with behavioral weight loss (72%) and guided self-help (70%). Patients in BWL had a significantly better short-term weight loss than those in the other two groups, but this advantage disappeared by the 1-year follow-up.

The primary outcome measures in the trial were binge frequency and remission rates, defined as no binge eating in 28 days. The results showed that all three treatments had similar outcomes in treating binge eating disorder, associated eating disorders, and general psychopathology after 24 weeks.

The researchers followed the patients for 24 months and have analyzed the results for the first 12 months. The posttreatment data showed that interpersonal therapy was superior to the two other treatment options in those patients with severe binge eating. In addition, HNA participants were more likely to do poorly on binge eating outcomes when the behavioral weight loss approach was used, compared with the IPT or guided self-help approach, over the course of the 1-year follow-up period.

CHICAGO – Treatment outcomes for obese patients with binge-eating disorder differ by disease severity and negative affect, a large study of patients with this disorder shows.

“We are trying to identify a particular subset of the population [that responds to a particular treatment],” Denise E. Wilfley, Ph.D., director of the Weight Management and Eating Disorders Program at Washington University in St. Louis, said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

The study evaluated three treatments for binge-eating disorder (BED): interpersonal therapy (IPT), behavioral weight loss (BWL), and guided self-help (GSH). “This is the first study to compare three different treatments for binge-eating disorder,” Dr. Wilfley said. Participants were also stratified by high versus low negative affect and by severity of bingeing.

According to the DSM-IV, people with BED eat a large amount of food with loss of control on at least 2 days a week for at least 6 months; they do not regularly engage in compensatory behaviors.

Dr. Wilfley said people with this disorder tend to have low self-esteem and very high rates of health care use, traits similar to people with anorexia and bulimia nervosa. But unlike people with those conditions, people with BED are more likely to be male and less likely to be white. Given the large amount of food they consume, people with BED are associated with overweight or obesity. “They're not just obese individuals,” said Dr. Wilfley, also professor of psychiatry at the university. “They are obese individuals with an eating disorder.”

The trial involved 205 participants and was conducted at three sites: Stanford (Calif.) University (data coordinating center), Washington University (clinical site), and Rutgers University (clinical site) in Piscataway, N.J. Participants were at least 18 years old, met the DSM-IV criteria for BED, and had a body mass index (BMI) between 27 and 45 kg/m

In terms of race, 82% were white, 13% were black, 4% were Hispanic, and 1% was Native American. Slightly more than half of the participants were college educated, and the average BMI among the participants was 36.4.

The participants were randomized to one of the three treatments. Participants in both the interpersonal therapy and the behavioral weight loss groups had 20 60-minute therapy sessions over a 24-week period. Those in the guided self-help group used bibliotherapy. They were asked to read “Overcoming Binge Eating,” by Dr. Christopher G. Fairburn (New York: the Guilford Press, 1995), a book aimed at teaching behavior change. This group also had one 55-minute and nine 25-minute therapy sessions over 24 weeks. The IPT group included 75 patients, the BWL group had 64 patients, and the GSH group had 66 patients. There were no significant differences in patient characteristics among the three groups.

The researchers used the Beck Depression Inventory to stratify the participants according to high negative affect (HNA) and low negative affect (LNA). Although they were apt to stay with interpersonal therapy, patients with HNA were significantly more likely to drop out of the behavioral weight loss treatment group than those with LNA. Those with LNA were much more likely to drop out of guided self-help.

Overall, treatment retention rates were significantly better among those treated with interpersonal therapy (93%) than with behavioral weight loss (72%) and guided self-help (70%). Patients in BWL had a significantly better short-term weight loss than those in the other two groups, but this advantage disappeared by the 1-year follow-up.

The primary outcome measures in the trial were binge frequency and remission rates, defined as no binge eating in 28 days. The results showed that all three treatments had similar outcomes in treating binge eating disorder, associated eating disorders, and general psychopathology after 24 weeks.

The researchers followed the patients for 24 months and have analyzed the results for the first 12 months. The posttreatment data showed that interpersonal therapy was superior to the two other treatment options in those patients with severe binge eating. In addition, HNA participants were more likely to do poorly on binge eating outcomes when the behavioral weight loss approach was used, compared with the IPT or guided self-help approach, over the course of the 1-year follow-up period.

CHICAGO – Treatment outcomes for obese patients with binge-eating disorder differ by disease severity and negative affect, a large study of patients with this disorder shows.

“We are trying to identify a particular subset of the population [that responds to a particular treatment],” Denise E. Wilfley, Ph.D., director of the Weight Management and Eating Disorders Program at Washington University in St. Louis, said at the annual meeting of the Association for Behavioral and Cognitive Therapies.

The study evaluated three treatments for binge-eating disorder (BED): interpersonal therapy (IPT), behavioral weight loss (BWL), and guided self-help (GSH). “This is the first study to compare three different treatments for binge-eating disorder,” Dr. Wilfley said. Participants were also stratified by high versus low negative affect and by severity of bingeing.

According to the DSM-IV, people with BED eat a large amount of food with loss of control on at least 2 days a week for at least 6 months; they do not regularly engage in compensatory behaviors.

Dr. Wilfley said people with this disorder tend to have low self-esteem and very high rates of health care use, traits similar to people with anorexia and bulimia nervosa. But unlike people with those conditions, people with BED are more likely to be male and less likely to be white. Given the large amount of food they consume, people with BED are associated with overweight or obesity. “They're not just obese individuals,” said Dr. Wilfley, also professor of psychiatry at the university. “They are obese individuals with an eating disorder.”

The trial involved 205 participants and was conducted at three sites: Stanford (Calif.) University (data coordinating center), Washington University (clinical site), and Rutgers University (clinical site) in Piscataway, N.J. Participants were at least 18 years old, met the DSM-IV criteria for BED, and had a body mass index (BMI) between 27 and 45 kg/m

In terms of race, 82% were white, 13% were black, 4% were Hispanic, and 1% was Native American. Slightly more than half of the participants were college educated, and the average BMI among the participants was 36.4.

The participants were randomized to one of the three treatments. Participants in both the interpersonal therapy and the behavioral weight loss groups had 20 60-minute therapy sessions over a 24-week period. Those in the guided self-help group used bibliotherapy. They were asked to read “Overcoming Binge Eating,” by Dr. Christopher G. Fairburn (New York: the Guilford Press, 1995), a book aimed at teaching behavior change. This group also had one 55-minute and nine 25-minute therapy sessions over 24 weeks. The IPT group included 75 patients, the BWL group had 64 patients, and the GSH group had 66 patients. There were no significant differences in patient characteristics among the three groups.

The researchers used the Beck Depression Inventory to stratify the participants according to high negative affect (HNA) and low negative affect (LNA). Although they were apt to stay with interpersonal therapy, patients with HNA were significantly more likely to drop out of the behavioral weight loss treatment group than those with LNA. Those with LNA were much more likely to drop out of guided self-help.

Overall, treatment retention rates were significantly better among those treated with interpersonal therapy (93%) than with behavioral weight loss (72%) and guided self-help (70%). Patients in BWL had a significantly better short-term weight loss than those in the other two groups, but this advantage disappeared by the 1-year follow-up.

The primary outcome measures in the trial were binge frequency and remission rates, defined as no binge eating in 28 days. The results showed that all three treatments had similar outcomes in treating binge eating disorder, associated eating disorders, and general psychopathology after 24 weeks.

The researchers followed the patients for 24 months and have analyzed the results for the first 12 months. The posttreatment data showed that interpersonal therapy was superior to the two other treatment options in those patients with severe binge eating. In addition, HNA participants were more likely to do poorly on binge eating outcomes when the behavioral weight loss approach was used, compared with the IPT or guided self-help approach, over the course of the 1-year follow-up period.

CHICAGO — Treatment outcomes for obese patients with binge-eating disorder differ by disease severity and negative affect, data from a large study of patients with this disorder show.

“We are trying to identify a particular subset of the population [that responds to a particular treatment],” Denise E. Wilfley, Ph.D., director of the Weight Management and Eating Disorders Program at Washington University in St. Louis, reported at the annual meeting of the Association for Behavioral and Cognitive Therapies.

The study evaluated three treatments for binge-eating disorder (BED): interpersonal therapy (IPT), behavioral weight loss (BWL), and guided self-help (GSH). “This is the first study to compare three different treatments for binge-eating disorder,” said Dr. Wilfley. Participants were also stratified by high versus low negative affect and by severity of bingeing.

According to the DSM-IV, people with BED eat a large amount of food with loss of control on at least 2 days a week for at least 6 months; they do not regularly engage in compensatory behaviors.

Dr. Wilfley said that people with this disorder tend to have low self-esteem and very high rates of health care use, traits similar to people with anorexia and bulimia nervosa. But unlike people with those conditions, people who have BED are more likely to be male and less likely to be white.

Given the large amount of food they consume, people with BED are more likley to be overweight or obese. “They're not just obese individuals,” said Dr. Wilfley, also professor of psychiatry at the university. “They are obese individuals with an eating disorder.”

The trial involved 205 participants and was conducted at three sites: Stanford (Calif.) University (data coordinating center), Washington University (clinical site), and Rutgers University (clinical site) in Piscataway, N.J. Participants were at least 18 years old, met the DSM-IV criteria for BED, and had a body mass index (BMI) between 27 and 45 kg/m

Patients who had a psychiatric or physical impairment that would preclude full participation, such as active suicidality, were excluded. Of the participants, 85% were female, and the average age was 49 years.

In terms of race, 82% were white; 13% were black, 4% were Hispanic, and 1% was Native American. Slightly more than half of the participants were college educated, and the average BMI among the participants was 36.

The participants were randomized to one of the three treatments. Participants in both the interpersonal therapy and the behavioral weight loss groups had 20 60-minute therapy sessions over a 24-week period.

The participants who were in the guided self-help group used bibliotherapy. They were asked to read “Overcoming Binge Eating,” by Dr. Christopher G. Fairburn (New York: the Guilford Press, 1995), a book that is aimed at teaching behavior change. This group also had one 55-minute and nine 25-minute therapy sessions over 24 weeks. The IPT group included 75 patients, the BWL group had 64 patients, and the GSH group had 66 patients.

There were no significant differences in patient characteristics among the three groups.

The researchers used the Beck Depression Inventory to stratify the participants according to high negative affect (HNA) and low negative affect (LNA).

Although they were apt to stay with interpersonal therapy, patients with HNA were significantly more likely to drop out of the behavioral weight loss treatment group than those with LNA. Those with LNA were much more likely to drop out of guided self-help.

Overall, treatment retention rates were significantly better among those treated with interpersonal therapy (93%) than with behavioral weight loss (72%) and guided self-help (70%).

The patients who were in the BWL group had a significantly better short-term weight loss than those in the other two groups, but this advantage disappeared by the 1-year follow-up.

The primary outcome measures in the trial were binge frequency and remission rates, defined as no binge eating in 28 days. The results showed that all three treatments had similar outcomes in treating binge eating disorder, associated eating disorders, and general psychopathology after 24 weeks.

The researchers followed the patients for 24 months and have analyzed the results for the first 12 months. The posttreatment data showed that interpersonal therapy was superior to the two other treatment options in those patients with severe binge eating.

In addition, HNA participants were more likely to do poorly on binge eating outcomes when the behavioral weight loss approach was used, compared with the IPT or guided self-help approach, over the course of the 1-year follow-up period.

When data for the 24-month follow-up period become available, clinicians treating BED may have even more valuable insights into the treatment of this disorder, the researchers said.

CHICAGO — Treatment outcomes for obese patients with binge-eating disorder differ by disease severity and negative affect, data from a large study of patients with this disorder show.

“We are trying to identify a particular subset of the population [that responds to a particular treatment],” Denise E. Wilfley, Ph.D., director of the Weight Management and Eating Disorders Program at Washington University in St. Louis, reported at the annual meeting of the Association for Behavioral and Cognitive Therapies.

The study evaluated three treatments for binge-eating disorder (BED): interpersonal therapy (IPT), behavioral weight loss (BWL), and guided self-help (GSH). “This is the first study to compare three different treatments for binge-eating disorder,” said Dr. Wilfley. Participants were also stratified by high versus low negative affect and by severity of bingeing.

According to the DSM-IV, people with BED eat a large amount of food with loss of control on at least 2 days a week for at least 6 months; they do not regularly engage in compensatory behaviors.

Dr. Wilfley said that people with this disorder tend to have low self-esteem and very high rates of health care use, traits similar to people with anorexia and bulimia nervosa. But unlike people with those conditions, people who have BED are more likely to be male and less likely to be white.

Given the large amount of food they consume, people with BED are more likley to be overweight or obese. “They're not just obese individuals,” said Dr. Wilfley, also professor of psychiatry at the university. “They are obese individuals with an eating disorder.”

The trial involved 205 participants and was conducted at three sites: Stanford (Calif.) University (data coordinating center), Washington University (clinical site), and Rutgers University (clinical site) in Piscataway, N.J. Participants were at least 18 years old, met the DSM-IV criteria for BED, and had a body mass index (BMI) between 27 and 45 kg/m

Patients who had a psychiatric or physical impairment that would preclude full participation, such as active suicidality, were excluded. Of the participants, 85% were female, and the average age was 49 years.

In terms of race, 82% were white; 13% were black, 4% were Hispanic, and 1% was Native American. Slightly more than half of the participants were college educated, and the average BMI among the participants was 36.

The participants were randomized to one of the three treatments. Participants in both the interpersonal therapy and the behavioral weight loss groups had 20 60-minute therapy sessions over a 24-week period.

The participants who were in the guided self-help group used bibliotherapy. They were asked to read “Overcoming Binge Eating,” by Dr. Christopher G. Fairburn (New York: the Guilford Press, 1995), a book that is aimed at teaching behavior change. This group also had one 55-minute and nine 25-minute therapy sessions over 24 weeks. The IPT group included 75 patients, the BWL group had 64 patients, and the GSH group had 66 patients.

There were no significant differences in patient characteristics among the three groups.

The researchers used the Beck Depression Inventory to stratify the participants according to high negative affect (HNA) and low negative affect (LNA).

Although they were apt to stay with interpersonal therapy, patients with HNA were significantly more likely to drop out of the behavioral weight loss treatment group than those with LNA. Those with LNA were much more likely to drop out of guided self-help.

Overall, treatment retention rates were significantly better among those treated with interpersonal therapy (93%) than with behavioral weight loss (72%) and guided self-help (70%).

The patients who were in the BWL group had a significantly better short-term weight loss than those in the other two groups, but this advantage disappeared by the 1-year follow-up.

The primary outcome measures in the trial were binge frequency and remission rates, defined as no binge eating in 28 days. The results showed that all three treatments had similar outcomes in treating binge eating disorder, associated eating disorders, and general psychopathology after 24 weeks.

The researchers followed the patients for 24 months and have analyzed the results for the first 12 months. The posttreatment data showed that interpersonal therapy was superior to the two other treatment options in those patients with severe binge eating.

In addition, HNA participants were more likely to do poorly on binge eating outcomes when the behavioral weight loss approach was used, compared with the IPT or guided self-help approach, over the course of the 1-year follow-up period.

When data for the 24-month follow-up period become available, clinicians treating BED may have even more valuable insights into the treatment of this disorder, the researchers said.

CHICAGO — Treatment outcomes for obese patients with binge-eating disorder differ by disease severity and negative affect, data from a large study of patients with this disorder show.

“We are trying to identify a particular subset of the population [that responds to a particular treatment],” Denise E. Wilfley, Ph.D., director of the Weight Management and Eating Disorders Program at Washington University in St. Louis, reported at the annual meeting of the Association for Behavioral and Cognitive Therapies.

The study evaluated three treatments for binge-eating disorder (BED): interpersonal therapy (IPT), behavioral weight loss (BWL), and guided self-help (GSH). “This is the first study to compare three different treatments for binge-eating disorder,” said Dr. Wilfley. Participants were also stratified by high versus low negative affect and by severity of bingeing.

According to the DSM-IV, people with BED eat a large amount of food with loss of control on at least 2 days a week for at least 6 months; they do not regularly engage in compensatory behaviors.

Dr. Wilfley said that people with this disorder tend to have low self-esteem and very high rates of health care use, traits similar to people with anorexia and bulimia nervosa. But unlike people with those conditions, people who have BED are more likely to be male and less likely to be white.

Given the large amount of food they consume, people with BED are more likley to be overweight or obese. “They're not just obese individuals,” said Dr. Wilfley, also professor of psychiatry at the university. “They are obese individuals with an eating disorder.”

The trial involved 205 participants and was conducted at three sites: Stanford (Calif.) University (data coordinating center), Washington University (clinical site), and Rutgers University (clinical site) in Piscataway, N.J. Participants were at least 18 years old, met the DSM-IV criteria for BED, and had a body mass index (BMI) between 27 and 45 kg/m

Patients who had a psychiatric or physical impairment that would preclude full participation, such as active suicidality, were excluded. Of the participants, 85% were female, and the average age was 49 years.

In terms of race, 82% were white; 13% were black, 4% were Hispanic, and 1% was Native American. Slightly more than half of the participants were college educated, and the average BMI among the participants was 36.

The participants were randomized to one of the three treatments. Participants in both the interpersonal therapy and the behavioral weight loss groups had 20 60-minute therapy sessions over a 24-week period.

The participants who were in the guided self-help group used bibliotherapy. They were asked to read “Overcoming Binge Eating,” by Dr. Christopher G. Fairburn (New York: the Guilford Press, 1995), a book that is aimed at teaching behavior change. This group also had one 55-minute and nine 25-minute therapy sessions over 24 weeks. The IPT group included 75 patients, the BWL group had 64 patients, and the GSH group had 66 patients.

There were no significant differences in patient characteristics among the three groups.

The researchers used the Beck Depression Inventory to stratify the participants according to high negative affect (HNA) and low negative affect (LNA).

Although they were apt to stay with interpersonal therapy, patients with HNA were significantly more likely to drop out of the behavioral weight loss treatment group than those with LNA. Those with LNA were much more likely to drop out of guided self-help.

Overall, treatment retention rates were significantly better among those treated with interpersonal therapy (93%) than with behavioral weight loss (72%) and guided self-help (70%).

The patients who were in the BWL group had a significantly better short-term weight loss than those in the other two groups, but this advantage disappeared by the 1-year follow-up.

The primary outcome measures in the trial were binge frequency and remission rates, defined as no binge eating in 28 days. The results showed that all three treatments had similar outcomes in treating binge eating disorder, associated eating disorders, and general psychopathology after 24 weeks.

The researchers followed the patients for 24 months and have analyzed the results for the first 12 months. The posttreatment data showed that interpersonal therapy was superior to the two other treatment options in those patients with severe binge eating.

In addition, HNA participants were more likely to do poorly on binge eating outcomes when the behavioral weight loss approach was used, compared with the IPT or guided self-help approach, over the course of the 1-year follow-up period.

When data for the 24-month follow-up period become available, clinicians treating BED may have even more valuable insights into the treatment of this disorder, the researchers said.

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among physicians, as well as among patients who take these frequently prescribed drugs.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University, Chicago, said while the study indicates that PPIs increase the risk of hip fracture, physicians and patients should avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine2 receptor antagonist (H2RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H2RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not. Cases and matched controls (up to 10 controls for each case) were similar in terms of sex, age, and both the calendar period and duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls (at least 1 control per case).

In addition to an increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy, 1.41 for 2 years, 1.54 for 3 years, and 1.59 for 4 years, with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy. Until guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly.

Dr. Howden cautioned against taking an alarmist approach to this study. “I think the absolute risk is quite small, but it's not zero,” he said.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agreed that the study shows only a small excess risk of hip fracture in the group taking PPIs. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture, he said.

“The findings are not surprising,” commented Dr. Steven Petak, president of the American Association of Clinical Endocrinologists. “Vitamin D and calcium insufficiency are very common in the population and it is likely [that] using a PPI only adds to an already significant problem.”

He recommends that patients consume 1,200–1,400 mg of calcium and 600–1,000 IU of vitamin D3 (cholecalciferol) daily; supplements should be taken in divided doses with food to help absorption.

“If PPI drugs are needed, then certainly they should be used, but with additional evaluation of the bone and calcium status,” Dr. Petak said.

ELSEVIER GLOBAL MEDICAL NEWS

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among physicians, as well as among patients who take these frequently prescribed drugs.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University, Chicago, said while the study indicates that PPIs increase the risk of hip fracture, physicians and patients should avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine2 receptor antagonist (H2RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H2RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not. Cases and matched controls (up to 10 controls for each case) were similar in terms of sex, age, and both the calendar period and duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls (at least 1 control per case).

In addition to an increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy, 1.41 for 2 years, 1.54 for 3 years, and 1.59 for 4 years, with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy. Until guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly.

Dr. Howden cautioned against taking an alarmist approach to this study. “I think the absolute risk is quite small, but it's not zero,” he said.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agreed that the study shows only a small excess risk of hip fracture in the group taking PPIs. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture, he said.

“The findings are not surprising,” commented Dr. Steven Petak, president of the American Association of Clinical Endocrinologists. “Vitamin D and calcium insufficiency are very common in the population and it is likely [that] using a PPI only adds to an already significant problem.”

He recommends that patients consume 1,200–1,400 mg of calcium and 600–1,000 IU of vitamin D3 (cholecalciferol) daily; supplements should be taken in divided doses with food to help absorption.

“If PPI drugs are needed, then certainly they should be used, but with additional evaluation of the bone and calcium status,” Dr. Petak said.

ELSEVIER GLOBAL MEDICAL NEWS

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among physicians, as well as among patients who take these frequently prescribed drugs.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University, Chicago, said while the study indicates that PPIs increase the risk of hip fracture, physicians and patients should avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine2 receptor antagonist (H2RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H2RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not. Cases and matched controls (up to 10 controls for each case) were similar in terms of sex, age, and both the calendar period and duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls (at least 1 control per case).

In addition to an increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy, 1.41 for 2 years, 1.54 for 3 years, and 1.59 for 4 years, with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy. Until guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly.

Dr. Howden cautioned against taking an alarmist approach to this study. “I think the absolute risk is quite small, but it's not zero,” he said.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agreed that the study shows only a small excess risk of hip fracture in the group taking PPIs. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture, he said.

“The findings are not surprising,” commented Dr. Steven Petak, president of the American Association of Clinical Endocrinologists. “Vitamin D and calcium insufficiency are very common in the population and it is likely [that] using a PPI only adds to an already significant problem.”

He recommends that patients consume 1,200–1,400 mg of calcium and 600–1,000 IU of vitamin D3 (cholecalciferol) daily; supplements should be taken in divided doses with food to help absorption.

“If PPI drugs are needed, then certainly they should be used, but with additional evaluation of the bone and calcium status,” Dr. Petak said.

ELSEVIER GLOBAL MEDICAL NEWS

Treatment with duloxetine for diabetic peripheral neuropathy has only a “modest” impact on glycemic control, Dr. Thomas Hardy of Eli Lilly & Co. and colleagues reported using data from three randomized controlled trials.

The researchers noted, however, that the studies they used to look at duloxetine's impact on glycemic control were not specifically designed to answer that question. “The current study does not allow definitive conclusion about the metabolic effects of duloxetine or other medications utilized in these studies,” they wrote (Diabetes Care 2007:30;21–6).

The authors pooled data from three randomized, controlled trials of adults with diabetes and diabetic peripheral neuropathic pain (DPNP). In the acute phase of the study, 1,024 participants were randomized to 60 mg duloxetine once a day or twice a day or to placebo for 12 weeks. In the study's extension phase, a subset of 867 participants was rerandomized to duloxetine or usual care in an open-label mode for another 52 weeks.

Patients with HbA1c values greater than 12% and those with major depressive disorder were excluded from the study. The authors looked at data on fasting plasma glucose (FPG), HbA1c, lipid levels, weight, and pain severity in both the acute and extension phases of the study.

The results showed that in the acute-phase studies, duloxetine-treated patients experienced an average increase in fasting glucose of 0.50 mmol/L, compared with a decrease of 0.11 mmol/L in the placebo group. In the extension studies, FPG again increased in the duloxetine-treated group, compared with the routine care group (0.67 mmol/L vs. −0.64 mmol/L).

HbA1c levels dropped slightly more in the duloxetine-treated group, compared with the placebo group during the acute phase, but the difference was not statistically significant. The longer-term studies showed an increase in HbA1c in both the duloxetine group and the group receiving routine care, with the duloxetine-treated group having a significantly larger increase (0.52 % vs. 0.19%).

This study was supported by Eli Lilly, manufacturer of Cymbalta.

Treatment with duloxetine for diabetic peripheral neuropathy has only a “modest” impact on glycemic control, Dr. Thomas Hardy of Eli Lilly & Co. and colleagues reported using data from three randomized controlled trials.

The researchers noted, however, that the studies they used to look at duloxetine's impact on glycemic control were not specifically designed to answer that question. “The current study does not allow definitive conclusion about the metabolic effects of duloxetine or other medications utilized in these studies,” they wrote (Diabetes Care 2007:30;21–6).

The authors pooled data from three randomized, controlled trials of adults with diabetes and diabetic peripheral neuropathic pain (DPNP). In the acute phase of the study, 1,024 participants were randomized to 60 mg duloxetine once a day or twice a day or to placebo for 12 weeks. In the study's extension phase, a subset of 867 participants was rerandomized to duloxetine or usual care in an open-label mode for another 52 weeks.

Patients with HbA1c values greater than 12% and those with major depressive disorder were excluded from the study. The authors looked at data on fasting plasma glucose (FPG), HbA1c, lipid levels, weight, and pain severity in both the acute and extension phases of the study.

The results showed that in the acute-phase studies, duloxetine-treated patients experienced an average increase in fasting glucose of 0.50 mmol/L, compared with a decrease of 0.11 mmol/L in the placebo group. In the extension studies, FPG again increased in the duloxetine-treated group, compared with the routine care group (0.67 mmol/L vs. −0.64 mmol/L).

HbA1c levels dropped slightly more in the duloxetine-treated group, compared with the placebo group during the acute phase, but the difference was not statistically significant. The longer-term studies showed an increase in HbA1c in both the duloxetine group and the group receiving routine care, with the duloxetine-treated group having a significantly larger increase (0.52 % vs. 0.19%).

This study was supported by Eli Lilly, manufacturer of Cymbalta.

Treatment with duloxetine for diabetic peripheral neuropathy has only a “modest” impact on glycemic control, Dr. Thomas Hardy of Eli Lilly & Co. and colleagues reported using data from three randomized controlled trials.

The researchers noted, however, that the studies they used to look at duloxetine's impact on glycemic control were not specifically designed to answer that question. “The current study does not allow definitive conclusion about the metabolic effects of duloxetine or other medications utilized in these studies,” they wrote (Diabetes Care 2007:30;21–6).

The authors pooled data from three randomized, controlled trials of adults with diabetes and diabetic peripheral neuropathic pain (DPNP). In the acute phase of the study, 1,024 participants were randomized to 60 mg duloxetine once a day or twice a day or to placebo for 12 weeks. In the study's extension phase, a subset of 867 participants was rerandomized to duloxetine or usual care in an open-label mode for another 52 weeks.

Patients with HbA1c values greater than 12% and those with major depressive disorder were excluded from the study. The authors looked at data on fasting plasma glucose (FPG), HbA1c, lipid levels, weight, and pain severity in both the acute and extension phases of the study.

The results showed that in the acute-phase studies, duloxetine-treated patients experienced an average increase in fasting glucose of 0.50 mmol/L, compared with a decrease of 0.11 mmol/L in the placebo group. In the extension studies, FPG again increased in the duloxetine-treated group, compared with the routine care group (0.67 mmol/L vs. −0.64 mmol/L).

HbA1c levels dropped slightly more in the duloxetine-treated group, compared with the placebo group during the acute phase, but the difference was not statistically significant. The longer-term studies showed an increase in HbA1c in both the duloxetine group and the group receiving routine care, with the duloxetine-treated group having a significantly larger increase (0.52 % vs. 0.19%).

This study was supported by Eli Lilly, manufacturer of Cymbalta.

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among both patients who take these frequently prescribed drugs and physicians.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University in Chicago, said the study does indicate that PPIs increase the risk of hip fracture, but he urged physicians and patients to avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine₂ receptor antagonist (H₂RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H₂RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not have a hip fracture. Cases and matched controls were similar in terms of sex, year of birth, and both the calendar period and the duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid-suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls.

In addition to the increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data also showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy (95% CI, 1.15–1.30), 1.41 for 2 years (95% CI, 1.28–1.56), 1.54 for 3 years (95% CI, 1.37–1.73), and 1.59 for 4 years (95% CI, 1.39–1.80), with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may also reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy or for initiating drug therapy to counteract osteoporosis in this patient population.

Until specific guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly. Dr. Howden cautions against taking an alarmist approach to this study.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agrees that the study shows only a small excess risk of hip fracture. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture. “I think if [doctors] have concerns, they can always tell their patients to take extra calcium,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among both patients who take these frequently prescribed drugs and physicians.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University in Chicago, said the study does indicate that PPIs increase the risk of hip fracture, but he urged physicians and patients to avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine₂ receptor antagonist (H₂RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H₂RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not have a hip fracture. Cases and matched controls were similar in terms of sex, year of birth, and both the calendar period and the duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid-suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls.

In addition to the increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data also showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy (95% CI, 1.15–1.30), 1.41 for 2 years (95% CI, 1.28–1.56), 1.54 for 3 years (95% CI, 1.37–1.73), and 1.59 for 4 years (95% CI, 1.39–1.80), with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may also reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy or for initiating drug therapy to counteract osteoporosis in this patient population.

Until specific guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly. Dr. Howden cautions against taking an alarmist approach to this study.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agrees that the study shows only a small excess risk of hip fracture. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture. “I think if [doctors] have concerns, they can always tell their patients to take extra calcium,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among both patients who take these frequently prescribed drugs and physicians.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University in Chicago, said the study does indicate that PPIs increase the risk of hip fracture, but he urged physicians and patients to avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine₂ receptor antagonist (H₂RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H₂RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not have a hip fracture. Cases and matched controls were similar in terms of sex, year of birth, and both the calendar period and the duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid-suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls.

In addition to the increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data also showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy (95% CI, 1.15–1.30), 1.41 for 2 years (95% CI, 1.28–1.56), 1.54 for 3 years (95% CI, 1.37–1.73), and 1.59 for 4 years (95% CI, 1.39–1.80), with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may also reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy or for initiating drug therapy to counteract osteoporosis in this patient population.

Until specific guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly. Dr. Howden cautions against taking an alarmist approach to this study.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agrees that the study shows only a small excess risk of hip fracture. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture. “I think if [doctors] have concerns, they can always tell their patients to take extra calcium,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

A mutation of the gene for cartilage-associated protein may lead to a recessive and lethal form of osteogenesis imperfecta, according to Dr. Joan C. Marini of the National Institute of Child Health and Human Development in Bethesda, Md.

“We identified a recessive form of lethal osteogenesis imperfecta, caused by null mutations in [cartilage-associated protein] CRTAP, a gene that encodes a protein that is essential for one of the posttranslational modifications of types I and II collagen,” Dr. Marini and her colleagues reported.

While mutations in type I collagen lead to most cases of osteogenesis imperfecta (OI), researchers in the field had sought a recessive form of the disease. The authors screened dermal fibroblasts from 10 children with lethal (type II), or very severe (type III) OI who had type I collagen with excess posttranslational modification of the alpha chain helical region but a normal primary structure, using a fibroblast cell line from newborn foreskin as a control. They also evaluated 11 patients who had severe OI without the excess modification described above and without a collagen defect, 6 normal control subjects, and 1 control patient with classic (type III) OI. The authors used polymerase-chain-reaction (PCR) assays to amplify DNA sequences in the subjects' genomes. They used reverse-transcriptase PCR assays to determine CRTAP mRNA levels.

After sampling mRNA from the fibroblasts of 10 children with type II or III OI who had excess posttranslational modification but lacked a collagen mutation, they determined that 3 infants had CRTAP mRNA levels that were 0%–25% of the normal range. In addition to low levels of CRTAP mRNA, the infants had defects in both CRTAP alleles, they lacked CRTAP protein, and they had minimal hydroxylation of type I collagen. All of these infants died within the first year of life. Fibroblasts from the parents of two of these three infants (one set of parents did not participate in the analysis) had normal CRTAP mRNA levels, a finding that suggests that the infants had more than one defective allele. As in all children with lethal OI, those with the recessive form of the disease have severely undermineralized bones that result in multiple prenatal fractures. Those children with the recessive mutation also have a small head circumference, proptosis, and white or light blue sclerae (N. Engl. J. Med. 2006;355:2757–64).

Defects in the CRTAP gene are likely to cause 2%–3% of all cases of lethal OI.

A mutation of the gene for cartilage-associated protein may lead to a recessive and lethal form of osteogenesis imperfecta, according to Dr. Joan C. Marini of the National Institute of Child Health and Human Development in Bethesda, Md.

“We identified a recessive form of lethal osteogenesis imperfecta, caused by null mutations in [cartilage-associated protein] CRTAP, a gene that encodes a protein that is essential for one of the posttranslational modifications of types I and II collagen,” Dr. Marini and her colleagues reported.

While mutations in type I collagen lead to most cases of osteogenesis imperfecta (OI), researchers in the field had sought a recessive form of the disease. The authors screened dermal fibroblasts from 10 children with lethal (type II), or very severe (type III) OI who had type I collagen with excess posttranslational modification of the alpha chain helical region but a normal primary structure, using a fibroblast cell line from newborn foreskin as a control. They also evaluated 11 patients who had severe OI without the excess modification described above and without a collagen defect, 6 normal control subjects, and 1 control patient with classic (type III) OI. The authors used polymerase-chain-reaction (PCR) assays to amplify DNA sequences in the subjects' genomes. They used reverse-transcriptase PCR assays to determine CRTAP mRNA levels.

After sampling mRNA from the fibroblasts of 10 children with type II or III OI who had excess posttranslational modification but lacked a collagen mutation, they determined that 3 infants had CRTAP mRNA levels that were 0%–25% of the normal range. In addition to low levels of CRTAP mRNA, the infants had defects in both CRTAP alleles, they lacked CRTAP protein, and they had minimal hydroxylation of type I collagen. All of these infants died within the first year of life. Fibroblasts from the parents of two of these three infants (one set of parents did not participate in the analysis) had normal CRTAP mRNA levels, a finding that suggests that the infants had more than one defective allele. As in all children with lethal OI, those with the recessive form of the disease have severely undermineralized bones that result in multiple prenatal fractures. Those children with the recessive mutation also have a small head circumference, proptosis, and white or light blue sclerae (N. Engl. J. Med. 2006;355:2757–64).

Defects in the CRTAP gene are likely to cause 2%–3% of all cases of lethal OI.

A mutation of the gene for cartilage-associated protein may lead to a recessive and lethal form of osteogenesis imperfecta, according to Dr. Joan C. Marini of the National Institute of Child Health and Human Development in Bethesda, Md.

“We identified a recessive form of lethal osteogenesis imperfecta, caused by null mutations in [cartilage-associated protein] CRTAP, a gene that encodes a protein that is essential for one of the posttranslational modifications of types I and II collagen,” Dr. Marini and her colleagues reported.

While mutations in type I collagen lead to most cases of osteogenesis imperfecta (OI), researchers in the field had sought a recessive form of the disease. The authors screened dermal fibroblasts from 10 children with lethal (type II), or very severe (type III) OI who had type I collagen with excess posttranslational modification of the alpha chain helical region but a normal primary structure, using a fibroblast cell line from newborn foreskin as a control. They also evaluated 11 patients who had severe OI without the excess modification described above and without a collagen defect, 6 normal control subjects, and 1 control patient with classic (type III) OI. The authors used polymerase-chain-reaction (PCR) assays to amplify DNA sequences in the subjects' genomes. They used reverse-transcriptase PCR assays to determine CRTAP mRNA levels.

After sampling mRNA from the fibroblasts of 10 children with type II or III OI who had excess posttranslational modification but lacked a collagen mutation, they determined that 3 infants had CRTAP mRNA levels that were 0%–25% of the normal range. In addition to low levels of CRTAP mRNA, the infants had defects in both CRTAP alleles, they lacked CRTAP protein, and they had minimal hydroxylation of type I collagen. All of these infants died within the first year of life. Fibroblasts from the parents of two of these three infants (one set of parents did not participate in the analysis) had normal CRTAP mRNA levels, a finding that suggests that the infants had more than one defective allele. As in all children with lethal OI, those with the recessive form of the disease have severely undermineralized bones that result in multiple prenatal fractures. Those children with the recessive mutation also have a small head circumference, proptosis, and white or light blue sclerae (N. Engl. J. Med. 2006;355:2757–64).

Defects in the CRTAP gene are likely to cause 2%–3% of all cases of lethal OI.

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among both gastroenterologists and patients who take these frequently prescribed drugs.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University in Chicago, said the study does indicate that PPIs increase the risk of hip fracture, but he urged physicians and patients to avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine2 receptor antagonist (H₂RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H₂RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not have a hip fracture. Cases and matched controls (up to 10 controls for each case) were similar in terms of sex, year of birth, and both the calendar period and the duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls (at least one control per case).

In addition to the increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data also showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy (95% CI, 1.15–1.30), 1.41 for 2 years (95% CI, 1.28–1.56), 1.54 for 3 years (95% CI, 1.37–1.73), and 1.59 for 4 years (95% CI, 1.39–1.80), with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said.

Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may also reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients who are taking long-term PPI therapy or for initiating drug therapy to counteract osteoporosis in this patient population.

Until specific guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly. Dr. Howden cautions against taking an alarmist approach to this study.

“I think the absolute risk is quite small, but it's not zero,” he said.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agrees that the study shows only a small excess risk of hip fracture in the group taking PPIs. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture. “I think if [doctors] have concerns, they can always tell their patients to take extra calcium,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among both gastroenterologists and patients who take these frequently prescribed drugs.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University in Chicago, said the study does indicate that PPIs increase the risk of hip fracture, but he urged physicians and patients to avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine2 receptor antagonist (H₂RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H₂RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not have a hip fracture. Cases and matched controls (up to 10 controls for each case) were similar in terms of sex, year of birth, and both the calendar period and the duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls (at least one control per case).

In addition to the increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data also showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy (95% CI, 1.15–1.30), 1.41 for 2 years (95% CI, 1.28–1.56), 1.54 for 3 years (95% CI, 1.37–1.73), and 1.59 for 4 years (95% CI, 1.39–1.80), with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said.

Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may also reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients who are taking long-term PPI therapy or for initiating drug therapy to counteract osteoporosis in this patient population.

Until specific guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly. Dr. Howden cautions against taking an alarmist approach to this study.

“I think the absolute risk is quite small, but it's not zero,” he said.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agrees that the study shows only a small excess risk of hip fracture in the group taking PPIs. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture. “I think if [doctors] have concerns, they can always tell their patients to take extra calcium,” he said.

ELSEVIER GLOBAL MEDICAL NEWS

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among both gastroenterologists and patients who take these frequently prescribed drugs.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University in Chicago, said the study does indicate that PPIs increase the risk of hip fracture, but he urged physicians and patients to avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine2 receptor antagonist (H₂RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H₂RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not have a hip fracture. Cases and matched controls (up to 10 controls for each case) were similar in terms of sex, year of birth, and both the calendar period and the duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls (at least one control per case).

In addition to the increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data also showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy (95% CI, 1.15–1.30), 1.41 for 2 years (95% CI, 1.28–1.56), 1.54 for 3 years (95% CI, 1.37–1.73), and 1.59 for 4 years (95% CI, 1.39–1.80), with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said.

Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may also reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients who are taking long-term PPI therapy or for initiating drug therapy to counteract osteoporosis in this patient population.

Until specific guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly. Dr. Howden cautions against taking an alarmist approach to this study.

“I think the absolute risk is quite small, but it's not zero,” he said.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agrees that the study shows only a small excess risk of hip fracture in the group taking PPIs. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture. “I think if [doctors] have concerns, they can always tell their patients to take extra calcium,” he said.

ELSEVIER GLOBAL MEDICAL NEWS