Mary Ann Moon

Live birth rates achieved with assisted reproductive technologies can approach the natural fecundity rate in the general population, as long as patient and embryo characteristics are favorable "and there are no barriers to treatment continuation," according to a report in the June 28 issue of the New England Journal of Medicine.

However, when such barriers arise – when women terminate treatment because of financial constraints, stress, lack of treatment success on the first two or three tries, or other reasons – live birth rates associated with ART decline considerably, said Barbara Luke, Sc.D., of the departments of ob.gyn. and reproductive biology, Michigan State University, East Lansing, and her associates.

Discontinuation rates are high even when insurance covers the cost of ART, ranging from 17% to 65% in several studies. "Our results suggest a substantive potential benefit of additional cycles of treatment in many cases, unless physiologically contraindicated," the investigators noted.

To quantify live-birth rates achieved with ART, Dr. Luke and her colleagues analyzed detailed deidentified information in the Society for Assisted Reproductive Technology’s reporting system database, which covers more than 90% of all clinics that provide ART in the United States. They assessed outcomes for 246,740 women who underwent 471,208 treatment cycles over a 5-year period and delivered 140,859 live infants.

Approximately 47% of these women were younger than age 35 years, and 15% were older than age 40.

Overall, live births occurred in 30% of the treatment cycles. A total of 57% of the women had a live birth.

Under optimal conditions, by the third treatment cycle the live birth rate was 65% for transfer of cleavage embryos and 81% for transfer of blastocyst embryos from fresh autologous oocytes.

"The estimated natural fecundity rate of the general population is about 20% per month, and estimated rates of conceiving naturally are 45%, 65%, and 85% after 3, 6, and 12 months, respectively.

"Our optimal estimates – representing the likelihood of a live birth when there are no barriers to treatment continuation – support the hypothesis that similar rates can be achieved by means of ART, in the context of favorable patient characteristics, embryo quality, and treatment method," Dr. Luke and her associates said (N. Engl. J. Med. 2012;366:2483-91).

As an example, the overall cumulative live-birth rate after two treatment cycles was higher than 70% in most women, depending on numerous patient, embryo, and treatment factors.

"Currently, many U.S. states have laws requiring insurance coverage for infertility treatment," but the number of covered cycles "is typically limited to two or three. Our findings show that when autologous oocytes are used, the success rates continue to rise beyond these limits," the researchers noted.

Among the study’s other findings:

• Cycles using donor oocytes were consistently associated with higher rates of live birth than were cycles with autologous oocytes.

• Live-birth rates declined as maternal age increased when autologous oocytes were used, but not when donor oocytes were used. With donor oocytes, live-birth rates were 60%-80% for women of all ages.

• Cycles in which "extra" embryos were cryopreserved – "an imperfect proxy measure of embryo quality" – produced more live births than cycles without cryopreservation.

• Transferring an embryo at the blastocyst stage yielded higher live-birth rates than did transferring at an earlier stage. "This may be an indirect measure of embryo quality or favorable patient characteristics," the investigators said.

• For both autologous and frozen donor oocytes, live-birth rates were highest when two embryos, rather than one or three, were transferred. However, transfer of two embryos also increased the likelihood of multiple gestations.

• For cycles using donor oocytes, the live-birth rate was higher for fresh than for thawed embryos.

This study was supported by the National Cancer Institute, the National Institutes of Health, and the Society for Assisted Reproductive Technologies. Dr. Luke reported no potential financial conflicts of interest, and one of her associates reported ties to Ferring, EMD Serono, MSP Organon, and Theralogix.

Live birth rates achieved with assisted reproductive technologies can approach the natural fecundity rate in the general population, as long as patient and embryo characteristics are favorable "and there are no barriers to treatment continuation," according to a report in the June 28 issue of the New England Journal of Medicine.

However, when such barriers arise – when women terminate treatment because of financial constraints, stress, lack of treatment success on the first two or three tries, or other reasons – live birth rates associated with ART decline considerably, said Barbara Luke, Sc.D., of the departments of ob.gyn. and reproductive biology, Michigan State University, East Lansing, and her associates.

Discontinuation rates are high even when insurance covers the cost of ART, ranging from 17% to 65% in several studies. "Our results suggest a substantive potential benefit of additional cycles of treatment in many cases, unless physiologically contraindicated," the investigators noted.

To quantify live-birth rates achieved with ART, Dr. Luke and her colleagues analyzed detailed deidentified information in the Society for Assisted Reproductive Technology’s reporting system database, which covers more than 90% of all clinics that provide ART in the United States. They assessed outcomes for 246,740 women who underwent 471,208 treatment cycles over a 5-year period and delivered 140,859 live infants.

Approximately 47% of these women were younger than age 35 years, and 15% were older than age 40.

Overall, live births occurred in 30% of the treatment cycles. A total of 57% of the women had a live birth.

Under optimal conditions, by the third treatment cycle the live birth rate was 65% for transfer of cleavage embryos and 81% for transfer of blastocyst embryos from fresh autologous oocytes.

"The estimated natural fecundity rate of the general population is about 20% per month, and estimated rates of conceiving naturally are 45%, 65%, and 85% after 3, 6, and 12 months, respectively.

"Our optimal estimates – representing the likelihood of a live birth when there are no barriers to treatment continuation – support the hypothesis that similar rates can be achieved by means of ART, in the context of favorable patient characteristics, embryo quality, and treatment method," Dr. Luke and her associates said (N. Engl. J. Med. 2012;366:2483-91).

As an example, the overall cumulative live-birth rate after two treatment cycles was higher than 70% in most women, depending on numerous patient, embryo, and treatment factors.

"Currently, many U.S. states have laws requiring insurance coverage for infertility treatment," but the number of covered cycles "is typically limited to two or three. Our findings show that when autologous oocytes are used, the success rates continue to rise beyond these limits," the researchers noted.

Among the study’s other findings:

• Cycles using donor oocytes were consistently associated with higher rates of live birth than were cycles with autologous oocytes.

• Live-birth rates declined as maternal age increased when autologous oocytes were used, but not when donor oocytes were used. With donor oocytes, live-birth rates were 60%-80% for women of all ages.

• Cycles in which "extra" embryos were cryopreserved – "an imperfect proxy measure of embryo quality" – produced more live births than cycles without cryopreservation.

• Transferring an embryo at the blastocyst stage yielded higher live-birth rates than did transferring at an earlier stage. "This may be an indirect measure of embryo quality or favorable patient characteristics," the investigators said.

• For both autologous and frozen donor oocytes, live-birth rates were highest when two embryos, rather than one or three, were transferred. However, transfer of two embryos also increased the likelihood of multiple gestations.

• For cycles using donor oocytes, the live-birth rate was higher for fresh than for thawed embryos.

This study was supported by the National Cancer Institute, the National Institutes of Health, and the Society for Assisted Reproductive Technologies. Dr. Luke reported no potential financial conflicts of interest, and one of her associates reported ties to Ferring, EMD Serono, MSP Organon, and Theralogix.

Live birth rates achieved with assisted reproductive technologies can approach the natural fecundity rate in the general population, as long as patient and embryo characteristics are favorable "and there are no barriers to treatment continuation," according to a report in the June 28 issue of the New England Journal of Medicine.

However, when such barriers arise – when women terminate treatment because of financial constraints, stress, lack of treatment success on the first two or three tries, or other reasons – live birth rates associated with ART decline considerably, said Barbara Luke, Sc.D., of the departments of ob.gyn. and reproductive biology, Michigan State University, East Lansing, and her associates.

Discontinuation rates are high even when insurance covers the cost of ART, ranging from 17% to 65% in several studies. "Our results suggest a substantive potential benefit of additional cycles of treatment in many cases, unless physiologically contraindicated," the investigators noted.

To quantify live-birth rates achieved with ART, Dr. Luke and her colleagues analyzed detailed deidentified information in the Society for Assisted Reproductive Technology’s reporting system database, which covers more than 90% of all clinics that provide ART in the United States. They assessed outcomes for 246,740 women who underwent 471,208 treatment cycles over a 5-year period and delivered 140,859 live infants.

Approximately 47% of these women were younger than age 35 years, and 15% were older than age 40.

Overall, live births occurred in 30% of the treatment cycles. A total of 57% of the women had a live birth.

Under optimal conditions, by the third treatment cycle the live birth rate was 65% for transfer of cleavage embryos and 81% for transfer of blastocyst embryos from fresh autologous oocytes.

"The estimated natural fecundity rate of the general population is about 20% per month, and estimated rates of conceiving naturally are 45%, 65%, and 85% after 3, 6, and 12 months, respectively.

"Our optimal estimates – representing the likelihood of a live birth when there are no barriers to treatment continuation – support the hypothesis that similar rates can be achieved by means of ART, in the context of favorable patient characteristics, embryo quality, and treatment method," Dr. Luke and her associates said (N. Engl. J. Med. 2012;366:2483-91).

As an example, the overall cumulative live-birth rate after two treatment cycles was higher than 70% in most women, depending on numerous patient, embryo, and treatment factors.

"Currently, many U.S. states have laws requiring insurance coverage for infertility treatment," but the number of covered cycles "is typically limited to two or three. Our findings show that when autologous oocytes are used, the success rates continue to rise beyond these limits," the researchers noted.

Among the study’s other findings:

• Cycles using donor oocytes were consistently associated with higher rates of live birth than were cycles with autologous oocytes.

• Live-birth rates declined as maternal age increased when autologous oocytes were used, but not when donor oocytes were used. With donor oocytes, live-birth rates were 60%-80% for women of all ages.

• Cycles in which "extra" embryos were cryopreserved – "an imperfect proxy measure of embryo quality" – produced more live births than cycles without cryopreservation.

• Transferring an embryo at the blastocyst stage yielded higher live-birth rates than did transferring at an earlier stage. "This may be an indirect measure of embryo quality or favorable patient characteristics," the investigators said.

• For both autologous and frozen donor oocytes, live-birth rates were highest when two embryos, rather than one or three, were transferred. However, transfer of two embryos also increased the likelihood of multiple gestations.

• For cycles using donor oocytes, the live-birth rate was higher for fresh than for thawed embryos.

This study was supported by the National Cancer Institute, the National Institutes of Health, and the Society for Assisted Reproductive Technologies. Dr. Luke reported no potential financial conflicts of interest, and one of her associates reported ties to Ferring, EMD Serono, MSP Organon, and Theralogix.

Hydroxyethyl starch 130/0.4, widely used for fluid resuscitation in hypovolemia due to severe sepsis, raises the risk of death within 90 days, compared with Ringer’s acetate, according to a report published online June 27 in the New England Journal of Medicine.

The low-molecular-weight hydroxyethyl starch (HES) is a colloid solution thought to afford more rapid and lasting circulatory stabilization, compared with standard IV fluids such as Ringer’s acetate. HES 130/0.4 has been widely adopted in ICUs around the world, even though data about its effectiveness are limited and several trials have raised concerns about its safety, said Dr. Anders Perner of the department of intensive care, Copenhagen University Hospital, and his associates.

Their Scandinavian Starch for Severe Sepsis/Septic Shock study was an international trial to compare the effects of HES 130/0.4 against Ringer’s acetate on the composite outcome of death or end-stage kidney failure within 90 days of treatment. The study population comprised 800 septic shock patients treated at 13 university-affiliated ICUs and 13 nonacademic general ICUs in Denmark, Norway, Finland, and Iceland between December 2009 and November 2011.

When their physicians decided that volume expansion was required, the study participants were randomly assigned in equal numbers to receive fluid resuscitation with either HES 130/0.4 or Ringer’s acetate in a manner that concealed treatment assignment from patients, clinicians, research staff, and study committee members.

The median cumulative volume of fluid administered was 3,000 mL.

The primary outcome measure (a composite of death or dependence on dialysis), occurred in 51% of patients who received the starch, compared with 43% of those who received Ringer’s solution. When the two outcomes were analyzed separately, this difference was found to be entirely due to an increased risk of death in the starch group, the investigators said (N. Engl. J. Med. 2012 July 27 [doi:10.1056/NEJMoa1204242]).

In multiple further analyses of the data, including logistic regression and per-protocol analyses, these results persisted. The separation of the survival curves indicated that HES 130/0.4 tends to induce death late in the course of hospitalization, Dr. Perner and his colleagues said.

In addition, more patients in the starch group than in the Ringer’s group required renal replacement therapy (61% vs. 44%) or developed bleeding complications (10% vs. 6%).

Previous studies suggested that a high proportion of HES "is taken up and deposited in tissues, where it cannot be metabolized and it acts as a foreign body. Long-term toxic effects of HES deposition have been described in the kidney, liver, and bone marrow.

"Together, all these negative effects of HES may have caused the late deaths observed in our trial" and in previous studies, the researchers noted.

This study also raises the question of whether HES 130/0.4 is actually more potent than crystalloids in patients with severe sepsis. "We did not observe significant differences in trial fluid volumes between the study groups," a result that has been reported in a previous study, they added.

The study findings should be generalizable to other populations because this trial had broad inclusion criteria and very few exclusion criteria. It even included patients who had acute kidney injury at baseline, the authors said.

This study was supported by the Danish Research Council, the Rigshospitalet Research Council, and the Scandinavian Society of Anesthesiology and Intensive Care Medicine. Dr. Perner reported receiving grant support from Fresenius Kabi.

Hydroxyethyl starch 130/0.4, widely used for fluid resuscitation in hypovolemia due to severe sepsis, raises the risk of death within 90 days, compared with Ringer’s acetate, according to a report published online June 27 in the New England Journal of Medicine.

The low-molecular-weight hydroxyethyl starch (HES) is a colloid solution thought to afford more rapid and lasting circulatory stabilization, compared with standard IV fluids such as Ringer’s acetate. HES 130/0.4 has been widely adopted in ICUs around the world, even though data about its effectiveness are limited and several trials have raised concerns about its safety, said Dr. Anders Perner of the department of intensive care, Copenhagen University Hospital, and his associates.

Their Scandinavian Starch for Severe Sepsis/Septic Shock study was an international trial to compare the effects of HES 130/0.4 against Ringer’s acetate on the composite outcome of death or end-stage kidney failure within 90 days of treatment. The study population comprised 800 septic shock patients treated at 13 university-affiliated ICUs and 13 nonacademic general ICUs in Denmark, Norway, Finland, and Iceland between December 2009 and November 2011.

When their physicians decided that volume expansion was required, the study participants were randomly assigned in equal numbers to receive fluid resuscitation with either HES 130/0.4 or Ringer’s acetate in a manner that concealed treatment assignment from patients, clinicians, research staff, and study committee members.

The median cumulative volume of fluid administered was 3,000 mL.

The primary outcome measure (a composite of death or dependence on dialysis), occurred in 51% of patients who received the starch, compared with 43% of those who received Ringer’s solution. When the two outcomes were analyzed separately, this difference was found to be entirely due to an increased risk of death in the starch group, the investigators said (N. Engl. J. Med. 2012 July 27 [doi:10.1056/NEJMoa1204242]).

In multiple further analyses of the data, including logistic regression and per-protocol analyses, these results persisted. The separation of the survival curves indicated that HES 130/0.4 tends to induce death late in the course of hospitalization, Dr. Perner and his colleagues said.

In addition, more patients in the starch group than in the Ringer’s group required renal replacement therapy (61% vs. 44%) or developed bleeding complications (10% vs. 6%).

Previous studies suggested that a high proportion of HES "is taken up and deposited in tissues, where it cannot be metabolized and it acts as a foreign body. Long-term toxic effects of HES deposition have been described in the kidney, liver, and bone marrow.

"Together, all these negative effects of HES may have caused the late deaths observed in our trial" and in previous studies, the researchers noted.

This study also raises the question of whether HES 130/0.4 is actually more potent than crystalloids in patients with severe sepsis. "We did not observe significant differences in trial fluid volumes between the study groups," a result that has been reported in a previous study, they added.

The study findings should be generalizable to other populations because this trial had broad inclusion criteria and very few exclusion criteria. It even included patients who had acute kidney injury at baseline, the authors said.

This study was supported by the Danish Research Council, the Rigshospitalet Research Council, and the Scandinavian Society of Anesthesiology and Intensive Care Medicine. Dr. Perner reported receiving grant support from Fresenius Kabi.

Hydroxyethyl starch 130/0.4, widely used for fluid resuscitation in hypovolemia due to severe sepsis, raises the risk of death within 90 days, compared with Ringer’s acetate, according to a report published online June 27 in the New England Journal of Medicine.

The low-molecular-weight hydroxyethyl starch (HES) is a colloid solution thought to afford more rapid and lasting circulatory stabilization, compared with standard IV fluids such as Ringer’s acetate. HES 130/0.4 has been widely adopted in ICUs around the world, even though data about its effectiveness are limited and several trials have raised concerns about its safety, said Dr. Anders Perner of the department of intensive care, Copenhagen University Hospital, and his associates.

Their Scandinavian Starch for Severe Sepsis/Septic Shock study was an international trial to compare the effects of HES 130/0.4 against Ringer’s acetate on the composite outcome of death or end-stage kidney failure within 90 days of treatment. The study population comprised 800 septic shock patients treated at 13 university-affiliated ICUs and 13 nonacademic general ICUs in Denmark, Norway, Finland, and Iceland between December 2009 and November 2011.

When their physicians decided that volume expansion was required, the study participants were randomly assigned in equal numbers to receive fluid resuscitation with either HES 130/0.4 or Ringer’s acetate in a manner that concealed treatment assignment from patients, clinicians, research staff, and study committee members.

The median cumulative volume of fluid administered was 3,000 mL.

The primary outcome measure (a composite of death or dependence on dialysis), occurred in 51% of patients who received the starch, compared with 43% of those who received Ringer’s solution. When the two outcomes were analyzed separately, this difference was found to be entirely due to an increased risk of death in the starch group, the investigators said (N. Engl. J. Med. 2012 July 27 [doi:10.1056/NEJMoa1204242]).

In multiple further analyses of the data, including logistic regression and per-protocol analyses, these results persisted. The separation of the survival curves indicated that HES 130/0.4 tends to induce death late in the course of hospitalization, Dr. Perner and his colleagues said.

In addition, more patients in the starch group than in the Ringer’s group required renal replacement therapy (61% vs. 44%) or developed bleeding complications (10% vs. 6%).

Previous studies suggested that a high proportion of HES "is taken up and deposited in tissues, where it cannot be metabolized and it acts as a foreign body. Long-term toxic effects of HES deposition have been described in the kidney, liver, and bone marrow.

"Together, all these negative effects of HES may have caused the late deaths observed in our trial" and in previous studies, the researchers noted.

This study also raises the question of whether HES 130/0.4 is actually more potent than crystalloids in patients with severe sepsis. "We did not observe significant differences in trial fluid volumes between the study groups," a result that has been reported in a previous study, they added.

The study findings should be generalizable to other populations because this trial had broad inclusion criteria and very few exclusion criteria. It even included patients who had acute kidney injury at baseline, the authors said.

This study was supported by the Danish Research Council, the Rigshospitalet Research Council, and the Scandinavian Society of Anesthesiology and Intensive Care Medicine. Dr. Perner reported receiving grant support from Fresenius Kabi.

A stepped-care intervention for weight loss was nearly as effective as a standard behavioral diet-and-exercise approach but only cost about half as much, in a study of 363 overweight adults reported in the June 27 JAMA.

The overall weight loss during the 18-month intervention was greater with the standard approach. But, at the conclusion of the study, when both groups of subjects had regained some of their lost weight, the 1.3-kg difference between the two was not significant.

Moreover, the cost of the stepped-care program was estimated to be $785/person, compared with a $1,357/person price tag for the standard approach, according to John M. Jakicic, Ph.D., of the University of Pittsburgh, and his associates.

The stepped-care approach involves low-intensity intervention at first, which is escalated only if subjects fail to achieve their weight-loss milestones according to a fixed schedule. Stepped care has proved effective in the treatment of other conditions such as eating disorders, substance abuse, and anxiety disorders, the investigators noted.

In this study, performed at two clinical sites, adults aged 18-55 years with a body mass index between 25 kg/m² and 40 kg/m² were randomly assigned to a traditional diet-and-exercise program (165 subjects) or to the stepped-care program (198 subjects). All participants were free of cardiovascular disease as well as metabolic or medical conditions that might affect weight or physical activity.

The two groups received identical recommendations for diet and physical activity, aimed at reducing energy intake as well as fat consumption. They were offered sample meal plans and prescribed exercise that increased to 300 minutes/wk of moderate to vigorous activity by week 24.

For the standard intervention, subjects attended group sessions throughout the 18-month intervention, starting with weekly sessions for 6 weeks, decreasing to bimonthly sessions through 12 months, and further decreasing to monthly sessions for the final 6 months. These sessions focused on adopting and maintaining healthy eating and exercise behaviors, as well as learning strategies to facilitate long-term behavioral change.

For the stepped-care intervention, the content was the same but the "contact frequency, contact type, and other weight-loss strategies were modified, depending on the achievement of specific weight goals at 3-month intervals." In step 1, the subjects were offered one monthly group session and three mailings. If they failed to reach a weight-loss goal, step 2 added a 10-minute phone contact each month. If that also failed, step 3 added a second 10-minute phone call per month.

Step 4 added one individual, in-person session per month. Step 5 added replacement shakes and bars to take the place of one meal and one snack per day. Step 6 replaced one of the telephone contacts with a second individual, in-person session per month.

A total of 260 participants (72%) completed the 18-month intervention.

The pattern of weight loss was different between the two groups. Subjects in the standard-care group lost more weight overall and lost weight more quickly than did those in the stepped-care group.

With the standard intervention, subjects averaged a loss of 9.6 kg at 6 months, compared with a 7.6-kg loss in the stepped-care group. The percentage loss of weight from baseline to 6 months was 10.4% with the standard approach, compared with 8.2% with the stepped-care approach.

At 18 months, weight loss averaged 7.6 kg with the standard intervention and 6.2 kg with stepped care, a nonsignificant difference. The percentage loss of weight from baseline to 18 months was 8.1% and 6.9%, respectively. "The effect size for the difference in absolute weight at 18 months between the groups was 6.3%, and the effect size for the weight loss at 18 months between the groups was 18%," the investigators said.

Viewed another way, similar numbers of subjects in the two groups achieved weight losses of 5% or more, 7% or more, and 10% or more, so the stepped-care approach "may be a viable alternative to traditional [care]," the researchers concluded (JAMA 2012;307:2617-26).

Subjects’ resting heart rate, systolic blood pressure, and diastolic blood pressure decreased significantly in both groups, and there was no significant difference between the two groups. Similarly, subjects’ fitness level, defined as the time to achieve 85% of age-predicted maximal heart rate, improved to the same degree in both groups.

The cost of the standard approach was significantly higher mainly because of the reduced reliance on in-person meetings with stepped care. The incremental cost-effectiveness ratio for stepped care was $127/kg of weight lost, compared with $409/kg for standard care.

"Comparisons with the literature suggest these results are likely to compare favorably with other pharmacologic and behavioral weight loss interventions," Dr. Jakicic and his associates said.

They added that it has not yet been shown whether this weight loss will actually improve health-related outcomes.

This study was supported by the National Institutes of Health and the National Heart, Lung, and Blood Institute. Dr. Jakicic reported ties to Alere Wellbeing, Jenny Craig, Nestle Nutrition Institute, Beverage Institute for Health and Wellness, and Body Media. His associate reported ties to Allergan.

A stepped-care intervention for weight loss was nearly as effective as a standard behavioral diet-and-exercise approach but only cost about half as much, in a study of 363 overweight adults reported in the June 27 JAMA.

The overall weight loss during the 18-month intervention was greater with the standard approach. But, at the conclusion of the study, when both groups of subjects had regained some of their lost weight, the 1.3-kg difference between the two was not significant.

Moreover, the cost of the stepped-care program was estimated to be $785/person, compared with a $1,357/person price tag for the standard approach, according to John M. Jakicic, Ph.D., of the University of Pittsburgh, and his associates.

The stepped-care approach involves low-intensity intervention at first, which is escalated only if subjects fail to achieve their weight-loss milestones according to a fixed schedule. Stepped care has proved effective in the treatment of other conditions such as eating disorders, substance abuse, and anxiety disorders, the investigators noted.

In this study, performed at two clinical sites, adults aged 18-55 years with a body mass index between 25 kg/m² and 40 kg/m² were randomly assigned to a traditional diet-and-exercise program (165 subjects) or to the stepped-care program (198 subjects). All participants were free of cardiovascular disease as well as metabolic or medical conditions that might affect weight or physical activity.

The two groups received identical recommendations for diet and physical activity, aimed at reducing energy intake as well as fat consumption. They were offered sample meal plans and prescribed exercise that increased to 300 minutes/wk of moderate to vigorous activity by week 24.

For the standard intervention, subjects attended group sessions throughout the 18-month intervention, starting with weekly sessions for 6 weeks, decreasing to bimonthly sessions through 12 months, and further decreasing to monthly sessions for the final 6 months. These sessions focused on adopting and maintaining healthy eating and exercise behaviors, as well as learning strategies to facilitate long-term behavioral change.

For the stepped-care intervention, the content was the same but the "contact frequency, contact type, and other weight-loss strategies were modified, depending on the achievement of specific weight goals at 3-month intervals." In step 1, the subjects were offered one monthly group session and three mailings. If they failed to reach a weight-loss goal, step 2 added a 10-minute phone contact each month. If that also failed, step 3 added a second 10-minute phone call per month.

Step 4 added one individual, in-person session per month. Step 5 added replacement shakes and bars to take the place of one meal and one snack per day. Step 6 replaced one of the telephone contacts with a second individual, in-person session per month.

A total of 260 participants (72%) completed the 18-month intervention.

The pattern of weight loss was different between the two groups. Subjects in the standard-care group lost more weight overall and lost weight more quickly than did those in the stepped-care group.

With the standard intervention, subjects averaged a loss of 9.6 kg at 6 months, compared with a 7.6-kg loss in the stepped-care group. The percentage loss of weight from baseline to 6 months was 10.4% with the standard approach, compared with 8.2% with the stepped-care approach.

At 18 months, weight loss averaged 7.6 kg with the standard intervention and 6.2 kg with stepped care, a nonsignificant difference. The percentage loss of weight from baseline to 18 months was 8.1% and 6.9%, respectively. "The effect size for the difference in absolute weight at 18 months between the groups was 6.3%, and the effect size for the weight loss at 18 months between the groups was 18%," the investigators said.

Viewed another way, similar numbers of subjects in the two groups achieved weight losses of 5% or more, 7% or more, and 10% or more, so the stepped-care approach "may be a viable alternative to traditional [care]," the researchers concluded (JAMA 2012;307:2617-26).

Subjects’ resting heart rate, systolic blood pressure, and diastolic blood pressure decreased significantly in both groups, and there was no significant difference between the two groups. Similarly, subjects’ fitness level, defined as the time to achieve 85% of age-predicted maximal heart rate, improved to the same degree in both groups.

The cost of the standard approach was significantly higher mainly because of the reduced reliance on in-person meetings with stepped care. The incremental cost-effectiveness ratio for stepped care was $127/kg of weight lost, compared with $409/kg for standard care.

"Comparisons with the literature suggest these results are likely to compare favorably with other pharmacologic and behavioral weight loss interventions," Dr. Jakicic and his associates said.

They added that it has not yet been shown whether this weight loss will actually improve health-related outcomes.

This study was supported by the National Institutes of Health and the National Heart, Lung, and Blood Institute. Dr. Jakicic reported ties to Alere Wellbeing, Jenny Craig, Nestle Nutrition Institute, Beverage Institute for Health and Wellness, and Body Media. His associate reported ties to Allergan.

A stepped-care intervention for weight loss was nearly as effective as a standard behavioral diet-and-exercise approach but only cost about half as much, in a study of 363 overweight adults reported in the June 27 JAMA.

The overall weight loss during the 18-month intervention was greater with the standard approach. But, at the conclusion of the study, when both groups of subjects had regained some of their lost weight, the 1.3-kg difference between the two was not significant.

Moreover, the cost of the stepped-care program was estimated to be $785/person, compared with a $1,357/person price tag for the standard approach, according to John M. Jakicic, Ph.D., of the University of Pittsburgh, and his associates.

The stepped-care approach involves low-intensity intervention at first, which is escalated only if subjects fail to achieve their weight-loss milestones according to a fixed schedule. Stepped care has proved effective in the treatment of other conditions such as eating disorders, substance abuse, and anxiety disorders, the investigators noted.

In this study, performed at two clinical sites, adults aged 18-55 years with a body mass index between 25 kg/m² and 40 kg/m² were randomly assigned to a traditional diet-and-exercise program (165 subjects) or to the stepped-care program (198 subjects). All participants were free of cardiovascular disease as well as metabolic or medical conditions that might affect weight or physical activity.

The two groups received identical recommendations for diet and physical activity, aimed at reducing energy intake as well as fat consumption. They were offered sample meal plans and prescribed exercise that increased to 300 minutes/wk of moderate to vigorous activity by week 24.

For the standard intervention, subjects attended group sessions throughout the 18-month intervention, starting with weekly sessions for 6 weeks, decreasing to bimonthly sessions through 12 months, and further decreasing to monthly sessions for the final 6 months. These sessions focused on adopting and maintaining healthy eating and exercise behaviors, as well as learning strategies to facilitate long-term behavioral change.

For the stepped-care intervention, the content was the same but the "contact frequency, contact type, and other weight-loss strategies were modified, depending on the achievement of specific weight goals at 3-month intervals." In step 1, the subjects were offered one monthly group session and three mailings. If they failed to reach a weight-loss goal, step 2 added a 10-minute phone contact each month. If that also failed, step 3 added a second 10-minute phone call per month.

Step 4 added one individual, in-person session per month. Step 5 added replacement shakes and bars to take the place of one meal and one snack per day. Step 6 replaced one of the telephone contacts with a second individual, in-person session per month.

A total of 260 participants (72%) completed the 18-month intervention.

The pattern of weight loss was different between the two groups. Subjects in the standard-care group lost more weight overall and lost weight more quickly than did those in the stepped-care group.

With the standard intervention, subjects averaged a loss of 9.6 kg at 6 months, compared with a 7.6-kg loss in the stepped-care group. The percentage loss of weight from baseline to 6 months was 10.4% with the standard approach, compared with 8.2% with the stepped-care approach.

At 18 months, weight loss averaged 7.6 kg with the standard intervention and 6.2 kg with stepped care, a nonsignificant difference. The percentage loss of weight from baseline to 18 months was 8.1% and 6.9%, respectively. "The effect size for the difference in absolute weight at 18 months between the groups was 6.3%, and the effect size for the weight loss at 18 months between the groups was 18%," the investigators said.

Viewed another way, similar numbers of subjects in the two groups achieved weight losses of 5% or more, 7% or more, and 10% or more, so the stepped-care approach "may be a viable alternative to traditional [care]," the researchers concluded (JAMA 2012;307:2617-26).

Subjects’ resting heart rate, systolic blood pressure, and diastolic blood pressure decreased significantly in both groups, and there was no significant difference between the two groups. Similarly, subjects’ fitness level, defined as the time to achieve 85% of age-predicted maximal heart rate, improved to the same degree in both groups.

The cost of the standard approach was significantly higher mainly because of the reduced reliance on in-person meetings with stepped care. The incremental cost-effectiveness ratio for stepped care was $127/kg of weight lost, compared with $409/kg for standard care.

"Comparisons with the literature suggest these results are likely to compare favorably with other pharmacologic and behavioral weight loss interventions," Dr. Jakicic and his associates said.

They added that it has not yet been shown whether this weight loss will actually improve health-related outcomes.

This study was supported by the National Institutes of Health and the National Heart, Lung, and Blood Institute. Dr. Jakicic reported ties to Alere Wellbeing, Jenny Craig, Nestle Nutrition Institute, Beverage Institute for Health and Wellness, and Body Media. His associate reported ties to Allergan.

Three different diets designed to maintain a recent weight loss were found to exert markedly different metabolic effects independently of their energy content in obese and overweight young adults, according to a report in the June 27 issue of JAMA.

"The results of our study challenge the notion that a calorie is a calorie from a metabolic perspective," said Cara B. Ebbeling, Ph.D., of the New Balance Foundation Obesity Prevention Center, Children’s Hospital Boston, and her associates.

©Marc Dietrich/Fotolia.com

The researchers performed a controlled feeding study to compare the effects of three weight-loss-maintenance diets on energy expenditure, hormones, and components of the metabolic syndrome. Their first step was to screen 681 men and women aged 18-40 years with a BMI of 27 or higher for participation in the study. Of these, only 32 potential subjects (17 men and 15 women) met entry criteria and agreed to the rigorous dietary restrictions of the study. Of these 32 subjects, 21 completed the study and were included in the data analysis.

During the run-in phase of the study, subjects followed a standard low-calorie diet that restricted energy intake to achieve a 12.5% decrease in body weight. Detailed assessments also were done to establish each subject’s energy requirements for stabilizing their weight at this reduced level.

After the subjects achieved a 10%-15% weight reduction, they each consumed one of the three isocaloric diets for 4 weeks, then switched to another of the diets for another 4 weeks, then to the third diet for a final 4 weeks in a three-way crossover design.

The three diets were the following: a low-fat diet with a high glycemic load and 20% of energy from protein, which reflected conventional recommendations to reduce fat, increase whole grain products, and include a variety of vegetables and fruits; a low-glycemic-index diet with moderate glycemic load and 20% of energy from protein, which replaced some grain products and starchy vegetables with other vegetables, legumes, and fruits; and a very-low-carbohydrate diet with a low glycemic load and 30% of energy from protein, which was modeled on the Atkins diet.

Body weight did not differ significantly among the three maintenance diets, nor did total physical activity or time spent performing moderate to vigorous-intensity activity. Subjects’ ratings of subjective hunger and well-being did not differ significantly among the diets, and blood pressure levels also did not differ.

Both resting energy expenditure and total energy expenditure decreased with all the diets, but the decrease was significantly greater with the low-fat diet. In addition, serum leptin levels were highest with the low-fat diet. These two findings suggest that people following the low-fat diet would be more likely to regain weight than those following the other diets, Dr. Ebbeling and her colleagues said (JAMA 2012;307:2627-34).

Moreover, the low-fat diet also had the most unfavorable effects on peripheral and hepatic insulin sensitivity, serum HDL cholesterol, triglycerides, and plasminogen activator inhibitor 1.

In contrast, the very-low-carbohydrate diet had the most favorable effects on these components of the metabolic syndrome and on energy expenditure.

The very-low-carbohydrate diet, however, produced higher C-reactive protein levels and higher cortisol excretion levels than the other diets, both of which signal physiological stress and chronic inflammation. In addition, "higher cortisol levels may promote adiposity, insulin resistance, and cardiovascular disease," the investigators wrote.

"These findings suggest that a strategy to reduce glycemic load rather than dietary fat may be advantageous for weight-loss maintenance and CVD prevention," they noted.

The chief limitation of this study is "the difficulty extrapolating findings from a feeding study to a more natural setting, in which individuals consume self-selected diets. In particular, the very-low-carbohydrate diet involved more severe carbohydrate restriction than would be feasible for many individuals over the long term," Dr. Ebbeling and her associates said.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Research Resources, and the New Balance Foundation. No other financial conflicts of interest were reported.

Three different diets designed to maintain a recent weight loss were found to exert markedly different metabolic effects independently of their energy content in obese and overweight young adults, according to a report in the June 27 issue of JAMA.

"The results of our study challenge the notion that a calorie is a calorie from a metabolic perspective," said Cara B. Ebbeling, Ph.D., of the New Balance Foundation Obesity Prevention Center, Children’s Hospital Boston, and her associates.

©Marc Dietrich/Fotolia.com

The researchers performed a controlled feeding study to compare the effects of three weight-loss-maintenance diets on energy expenditure, hormones, and components of the metabolic syndrome. Their first step was to screen 681 men and women aged 18-40 years with a BMI of 27 or higher for participation in the study. Of these, only 32 potential subjects (17 men and 15 women) met entry criteria and agreed to the rigorous dietary restrictions of the study. Of these 32 subjects, 21 completed the study and were included in the data analysis.

During the run-in phase of the study, subjects followed a standard low-calorie diet that restricted energy intake to achieve a 12.5% decrease in body weight. Detailed assessments also were done to establish each subject’s energy requirements for stabilizing their weight at this reduced level.

After the subjects achieved a 10%-15% weight reduction, they each consumed one of the three isocaloric diets for 4 weeks, then switched to another of the diets for another 4 weeks, then to the third diet for a final 4 weeks in a three-way crossover design.

The three diets were the following: a low-fat diet with a high glycemic load and 20% of energy from protein, which reflected conventional recommendations to reduce fat, increase whole grain products, and include a variety of vegetables and fruits; a low-glycemic-index diet with moderate glycemic load and 20% of energy from protein, which replaced some grain products and starchy vegetables with other vegetables, legumes, and fruits; and a very-low-carbohydrate diet with a low glycemic load and 30% of energy from protein, which was modeled on the Atkins diet.

Body weight did not differ significantly among the three maintenance diets, nor did total physical activity or time spent performing moderate to vigorous-intensity activity. Subjects’ ratings of subjective hunger and well-being did not differ significantly among the diets, and blood pressure levels also did not differ.

Both resting energy expenditure and total energy expenditure decreased with all the diets, but the decrease was significantly greater with the low-fat diet. In addition, serum leptin levels were highest with the low-fat diet. These two findings suggest that people following the low-fat diet would be more likely to regain weight than those following the other diets, Dr. Ebbeling and her colleagues said (JAMA 2012;307:2627-34).

Moreover, the low-fat diet also had the most unfavorable effects on peripheral and hepatic insulin sensitivity, serum HDL cholesterol, triglycerides, and plasminogen activator inhibitor 1.

In contrast, the very-low-carbohydrate diet had the most favorable effects on these components of the metabolic syndrome and on energy expenditure.

The very-low-carbohydrate diet, however, produced higher C-reactive protein levels and higher cortisol excretion levels than the other diets, both of which signal physiological stress and chronic inflammation. In addition, "higher cortisol levels may promote adiposity, insulin resistance, and cardiovascular disease," the investigators wrote.

"These findings suggest that a strategy to reduce glycemic load rather than dietary fat may be advantageous for weight-loss maintenance and CVD prevention," they noted.

The chief limitation of this study is "the difficulty extrapolating findings from a feeding study to a more natural setting, in which individuals consume self-selected diets. In particular, the very-low-carbohydrate diet involved more severe carbohydrate restriction than would be feasible for many individuals over the long term," Dr. Ebbeling and her associates said.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Research Resources, and the New Balance Foundation. No other financial conflicts of interest were reported.

Three different diets designed to maintain a recent weight loss were found to exert markedly different metabolic effects independently of their energy content in obese and overweight young adults, according to a report in the June 27 issue of JAMA.

"The results of our study challenge the notion that a calorie is a calorie from a metabolic perspective," said Cara B. Ebbeling, Ph.D., of the New Balance Foundation Obesity Prevention Center, Children’s Hospital Boston, and her associates.

©Marc Dietrich/Fotolia.com

The researchers performed a controlled feeding study to compare the effects of three weight-loss-maintenance diets on energy expenditure, hormones, and components of the metabolic syndrome. Their first step was to screen 681 men and women aged 18-40 years with a BMI of 27 or higher for participation in the study. Of these, only 32 potential subjects (17 men and 15 women) met entry criteria and agreed to the rigorous dietary restrictions of the study. Of these 32 subjects, 21 completed the study and were included in the data analysis.

During the run-in phase of the study, subjects followed a standard low-calorie diet that restricted energy intake to achieve a 12.5% decrease in body weight. Detailed assessments also were done to establish each subject’s energy requirements for stabilizing their weight at this reduced level.

After the subjects achieved a 10%-15% weight reduction, they each consumed one of the three isocaloric diets for 4 weeks, then switched to another of the diets for another 4 weeks, then to the third diet for a final 4 weeks in a three-way crossover design.

The three diets were the following: a low-fat diet with a high glycemic load and 20% of energy from protein, which reflected conventional recommendations to reduce fat, increase whole grain products, and include a variety of vegetables and fruits; a low-glycemic-index diet with moderate glycemic load and 20% of energy from protein, which replaced some grain products and starchy vegetables with other vegetables, legumes, and fruits; and a very-low-carbohydrate diet with a low glycemic load and 30% of energy from protein, which was modeled on the Atkins diet.

Body weight did not differ significantly among the three maintenance diets, nor did total physical activity or time spent performing moderate to vigorous-intensity activity. Subjects’ ratings of subjective hunger and well-being did not differ significantly among the diets, and blood pressure levels also did not differ.

Both resting energy expenditure and total energy expenditure decreased with all the diets, but the decrease was significantly greater with the low-fat diet. In addition, serum leptin levels were highest with the low-fat diet. These two findings suggest that people following the low-fat diet would be more likely to regain weight than those following the other diets, Dr. Ebbeling and her colleagues said (JAMA 2012;307:2627-34).

Moreover, the low-fat diet also had the most unfavorable effects on peripheral and hepatic insulin sensitivity, serum HDL cholesterol, triglycerides, and plasminogen activator inhibitor 1.

In contrast, the very-low-carbohydrate diet had the most favorable effects on these components of the metabolic syndrome and on energy expenditure.

The very-low-carbohydrate diet, however, produced higher C-reactive protein levels and higher cortisol excretion levels than the other diets, both of which signal physiological stress and chronic inflammation. In addition, "higher cortisol levels may promote adiposity, insulin resistance, and cardiovascular disease," the investigators wrote.

"These findings suggest that a strategy to reduce glycemic load rather than dietary fat may be advantageous for weight-loss maintenance and CVD prevention," they noted.

The chief limitation of this study is "the difficulty extrapolating findings from a feeding study to a more natural setting, in which individuals consume self-selected diets. In particular, the very-low-carbohydrate diet involved more severe carbohydrate restriction than would be feasible for many individuals over the long term," Dr. Ebbeling and her associates said.

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the National Center for Research Resources, and the New Balance Foundation. No other financial conflicts of interest were reported.

Statins are beneficial in women for the secondary prevention of some cardiovascular events, but they don’t appear to be any better than placebo at preventing stroke or all-cause mortality, according to a meta-analysis reported in the June 25 issue of Archives of Internal Medicine.

These findings, from a study of 11 randomized, placebo-controlled clinical trials, underscore the differences between men and women in the benefits conferred by statin therapy, said Dr. Jose Gutierrez of the Neurological Institute, Columbia University, New York, and his associates.

Clinical trials have yielded conflicting results concerning the benefit of statins in women known to have cardiovascular disease, compared with those in men. Dr. Gutierrez and his colleagues hoped to clarify the question by restricting their meta-analysis to clinical trials that used randomization and double-blinding; compared statin therapy with placebo rather than usual care or other treatments; included samples of at least 100 subjects; and had follow-up of at least 16 weeks.

The 11 studies they reviewed had a pooled sample size of 43,191 subjects. Even so, only 20% of the subjects were women.

The drugs that were studied included lovastatin, simvastatin, pravastatin, fluvastatin, and atorvastatin.

In the overall study population, statins were effective at preventing any cardiovascular event, all-cause mortality, coronary death, any myocardial infarction, cardiac intervention, and any type of stroke. When the data were stratified by sex, all of these benefits remained significant for men taking statins compared with men taking placebo.

However, women taking statins did not have significantly lower risk than women taking placebo for all-cause mortality or stroke. They did have significantly lower risk for coronary death, any MI, and coronary interventions, the investigators said (Arch. Intern. Med. 2012;172:909-19).

These results did not change in several sensitivity analyses, such as when the analysis was restricted to subjects with the shortest follow-up, the oldest subjects, or subjects taking only hydrophilic statins as opposed to lipophilic statins.

The reason for this discrepancy between men and women is uncertain. "One possibility is that the small sample size of women" – which they characterized as "a major limitation" of their meta-analysis – limited the power of the study to detect significant differences in women, the researchers noted.

"In addition, it is possible that the worse cardiovascular profile of women enrolled in studies, as well as the lower proportion of antiplatelet agent use, could account for some of these differences," they wrote. Biological differences between the sexes likely play a role as well, as do sex-specific disparities in health care and in biomedical research, they added.

Overall, the study findings support the use of statins in women as in men for the secondary prevention of some cardiovascular events, Dr. Gutierrez and his associates said.

No conflicts of interest were reported.

Statins are beneficial in women for the secondary prevention of some cardiovascular events, but they don’t appear to be any better than placebo at preventing stroke or all-cause mortality, according to a meta-analysis reported in the June 25 issue of Archives of Internal Medicine.

These findings, from a study of 11 randomized, placebo-controlled clinical trials, underscore the differences between men and women in the benefits conferred by statin therapy, said Dr. Jose Gutierrez of the Neurological Institute, Columbia University, New York, and his associates.

Clinical trials have yielded conflicting results concerning the benefit of statins in women known to have cardiovascular disease, compared with those in men. Dr. Gutierrez and his colleagues hoped to clarify the question by restricting their meta-analysis to clinical trials that used randomization and double-blinding; compared statin therapy with placebo rather than usual care or other treatments; included samples of at least 100 subjects; and had follow-up of at least 16 weeks.

The 11 studies they reviewed had a pooled sample size of 43,191 subjects. Even so, only 20% of the subjects were women.

The drugs that were studied included lovastatin, simvastatin, pravastatin, fluvastatin, and atorvastatin.

In the overall study population, statins were effective at preventing any cardiovascular event, all-cause mortality, coronary death, any myocardial infarction, cardiac intervention, and any type of stroke. When the data were stratified by sex, all of these benefits remained significant for men taking statins compared with men taking placebo.

However, women taking statins did not have significantly lower risk than women taking placebo for all-cause mortality or stroke. They did have significantly lower risk for coronary death, any MI, and coronary interventions, the investigators said (Arch. Intern. Med. 2012;172:909-19).

These results did not change in several sensitivity analyses, such as when the analysis was restricted to subjects with the shortest follow-up, the oldest subjects, or subjects taking only hydrophilic statins as opposed to lipophilic statins.

The reason for this discrepancy between men and women is uncertain. "One possibility is that the small sample size of women" – which they characterized as "a major limitation" of their meta-analysis – limited the power of the study to detect significant differences in women, the researchers noted.

"In addition, it is possible that the worse cardiovascular profile of women enrolled in studies, as well as the lower proportion of antiplatelet agent use, could account for some of these differences," they wrote. Biological differences between the sexes likely play a role as well, as do sex-specific disparities in health care and in biomedical research, they added.

Overall, the study findings support the use of statins in women as in men for the secondary prevention of some cardiovascular events, Dr. Gutierrez and his associates said.

No conflicts of interest were reported.

Statins are beneficial in women for the secondary prevention of some cardiovascular events, but they don’t appear to be any better than placebo at preventing stroke or all-cause mortality, according to a meta-analysis reported in the June 25 issue of Archives of Internal Medicine.

These findings, from a study of 11 randomized, placebo-controlled clinical trials, underscore the differences between men and women in the benefits conferred by statin therapy, said Dr. Jose Gutierrez of the Neurological Institute, Columbia University, New York, and his associates.

Clinical trials have yielded conflicting results concerning the benefit of statins in women known to have cardiovascular disease, compared with those in men. Dr. Gutierrez and his colleagues hoped to clarify the question by restricting their meta-analysis to clinical trials that used randomization and double-blinding; compared statin therapy with placebo rather than usual care or other treatments; included samples of at least 100 subjects; and had follow-up of at least 16 weeks.

The 11 studies they reviewed had a pooled sample size of 43,191 subjects. Even so, only 20% of the subjects were women.

The drugs that were studied included lovastatin, simvastatin, pravastatin, fluvastatin, and atorvastatin.

In the overall study population, statins were effective at preventing any cardiovascular event, all-cause mortality, coronary death, any myocardial infarction, cardiac intervention, and any type of stroke. When the data were stratified by sex, all of these benefits remained significant for men taking statins compared with men taking placebo.

However, women taking statins did not have significantly lower risk than women taking placebo for all-cause mortality or stroke. They did have significantly lower risk for coronary death, any MI, and coronary interventions, the investigators said (Arch. Intern. Med. 2012;172:909-19).

These results did not change in several sensitivity analyses, such as when the analysis was restricted to subjects with the shortest follow-up, the oldest subjects, or subjects taking only hydrophilic statins as opposed to lipophilic statins.

The reason for this discrepancy between men and women is uncertain. "One possibility is that the small sample size of women" – which they characterized as "a major limitation" of their meta-analysis – limited the power of the study to detect significant differences in women, the researchers noted.

"In addition, it is possible that the worse cardiovascular profile of women enrolled in studies, as well as the lower proportion of antiplatelet agent use, could account for some of these differences," they wrote. Biological differences between the sexes likely play a role as well, as do sex-specific disparities in health care and in biomedical research, they added.

Overall, the study findings support the use of statins in women as in men for the secondary prevention of some cardiovascular events, Dr. Gutierrez and his associates said.

No conflicts of interest were reported.

Using newer lipid markers to either replace or supplement conventional cholesterol measurements doesn’t improve cardiovascular risk prediction, according to a report from the Emerging Risk Factors Collaboration in the June 20 issue of JAMA.

Some experts have advocated simplifying and perhaps improving cardiovascular disease risk prediction by replacing the currently accepted measurements of total and HDL cholesterol with other measurements (such as the ratio of total:HDL cholesterol, or the difference of total minus HDL cholesterol) because these are believed to better reflect the underlying atherosclerotic process. Others have proposed adding measures of apolipoprotein B, apolipoprotein A-I, lipoprotein (a), or lipoprotein-associated phospholipase A₂ to the current risk prediction formulas to improve risk prediction.

To examine whether any of these alternative methods of risk prediction would improve on the currently accepted method, researchers in the Emerging Risk Factors Collaboration reviewed the literature from 1968 through 2007 for prospective cohort studies that obtained numerous lipid measures and reported CVD outcomes, said Dr. Emanuele Di Angelantonio, head of the collaboration’s writing group, and his colleagues.

To assess the accuracy of each method of risk prediction, the researchers selected 37 studies involving 165,544 subjects in 15 countries who had no CVD at baseline and were followed for a median of 10 years. There were 15,126 incident fatal and nonfatal cardiovascular events, including 10,132 coronary heart disease and 4,994 stroke events.

Replacing total and HDL cholesterol measures with any other lipid markers did not improve CVD risk prediction in the study population as a whole, or in clinically relevant subgroups such as diabetes patients or people with elevated triglycerides. In fact, using apolipoprotein B and A-I measures instead of total and HDL cholesterol measures significantly worsened risk discrimination, said Dr. Di Angelantonio of the department of public health and primary care at the University of Cambridge (England), and his associates.

Adding information on various "emerging" lipid markers to existing risk assessments only improved prediction slightly. And none of the newer lipid markers significantly changed classification of subjects "across the clinical risk cutoff levels that are currently used to inform treatment decisions," the investigators said (JAMA 2012;307:2499-506).

The researchers then created a statistical model that assessed various lipid markers specifically in 13,622 patients who were judged to be at intermediate risk after screening by conventional risk factors alone. Such patients would not be recommended for statin therapy according to Adult Treatment Panel III guidelines.

Using lipoprotein (a) measures would reclassify only 555 of these subjects (4.1%) to a higher-risk group, using lipoprotein-associated phospholipase A₂ would reclassify only 365 subjects (2.7%) to a higher-risk group, and using a combination of apolipoprotein B and A-I would reclassify only 154 subjects (1.1%) to a higher-risk group. "In other words, such targeted assessment of [and initiation of statin therapy in] individuals at intermediate CVD risk could help prevent [one] extra CVD outcome over 10 years for every 801 assessed for lipoprotein (a), every 973 assessed for lipoprotein-associated phospholipase A₂, and every 4,541 assessed for the combination of apolipoprotein B and A-I," Dr. Di Angelantonio and his associates said.

This study was funded by the British Heart Foundation, the U.K. Medical Research Council, and the U.K. National Institute of Health Research, Cambridge Biomedical Research Centre. Dr. Di Angelantonio reported ties to Merck Sharp and Dohme, John Wiley & Sons, and Pfizer, and his associates reported ties to numerous industry sources.

Using newer lipid markers to either replace or supplement conventional cholesterol measurements doesn’t improve cardiovascular risk prediction, according to a report from the Emerging Risk Factors Collaboration in the June 20 issue of JAMA.

Some experts have advocated simplifying and perhaps improving cardiovascular disease risk prediction by replacing the currently accepted measurements of total and HDL cholesterol with other measurements (such as the ratio of total:HDL cholesterol, or the difference of total minus HDL cholesterol) because these are believed to better reflect the underlying atherosclerotic process. Others have proposed adding measures of apolipoprotein B, apolipoprotein A-I, lipoprotein (a), or lipoprotein-associated phospholipase A₂ to the current risk prediction formulas to improve risk prediction.

To examine whether any of these alternative methods of risk prediction would improve on the currently accepted method, researchers in the Emerging Risk Factors Collaboration reviewed the literature from 1968 through 2007 for prospective cohort studies that obtained numerous lipid measures and reported CVD outcomes, said Dr. Emanuele Di Angelantonio, head of the collaboration’s writing group, and his colleagues.

To assess the accuracy of each method of risk prediction, the researchers selected 37 studies involving 165,544 subjects in 15 countries who had no CVD at baseline and were followed for a median of 10 years. There were 15,126 incident fatal and nonfatal cardiovascular events, including 10,132 coronary heart disease and 4,994 stroke events.

Replacing total and HDL cholesterol measures with any other lipid markers did not improve CVD risk prediction in the study population as a whole, or in clinically relevant subgroups such as diabetes patients or people with elevated triglycerides. In fact, using apolipoprotein B and A-I measures instead of total and HDL cholesterol measures significantly worsened risk discrimination, said Dr. Di Angelantonio of the department of public health and primary care at the University of Cambridge (England), and his associates.

Adding information on various "emerging" lipid markers to existing risk assessments only improved prediction slightly. And none of the newer lipid markers significantly changed classification of subjects "across the clinical risk cutoff levels that are currently used to inform treatment decisions," the investigators said (JAMA 2012;307:2499-506).

The researchers then created a statistical model that assessed various lipid markers specifically in 13,622 patients who were judged to be at intermediate risk after screening by conventional risk factors alone. Such patients would not be recommended for statin therapy according to Adult Treatment Panel III guidelines.

Using lipoprotein (a) measures would reclassify only 555 of these subjects (4.1%) to a higher-risk group, using lipoprotein-associated phospholipase A₂ would reclassify only 365 subjects (2.7%) to a higher-risk group, and using a combination of apolipoprotein B and A-I would reclassify only 154 subjects (1.1%) to a higher-risk group. "In other words, such targeted assessment of [and initiation of statin therapy in] individuals at intermediate CVD risk could help prevent [one] extra CVD outcome over 10 years for every 801 assessed for lipoprotein (a), every 973 assessed for lipoprotein-associated phospholipase A₂, and every 4,541 assessed for the combination of apolipoprotein B and A-I," Dr. Di Angelantonio and his associates said.

This study was funded by the British Heart Foundation, the U.K. Medical Research Council, and the U.K. National Institute of Health Research, Cambridge Biomedical Research Centre. Dr. Di Angelantonio reported ties to Merck Sharp and Dohme, John Wiley & Sons, and Pfizer, and his associates reported ties to numerous industry sources.

Using newer lipid markers to either replace or supplement conventional cholesterol measurements doesn’t improve cardiovascular risk prediction, according to a report from the Emerging Risk Factors Collaboration in the June 20 issue of JAMA.

Some experts have advocated simplifying and perhaps improving cardiovascular disease risk prediction by replacing the currently accepted measurements of total and HDL cholesterol with other measurements (such as the ratio of total:HDL cholesterol, or the difference of total minus HDL cholesterol) because these are believed to better reflect the underlying atherosclerotic process. Others have proposed adding measures of apolipoprotein B, apolipoprotein A-I, lipoprotein (a), or lipoprotein-associated phospholipase A₂ to the current risk prediction formulas to improve risk prediction.

To examine whether any of these alternative methods of risk prediction would improve on the currently accepted method, researchers in the Emerging Risk Factors Collaboration reviewed the literature from 1968 through 2007 for prospective cohort studies that obtained numerous lipid measures and reported CVD outcomes, said Dr. Emanuele Di Angelantonio, head of the collaboration’s writing group, and his colleagues.

To assess the accuracy of each method of risk prediction, the researchers selected 37 studies involving 165,544 subjects in 15 countries who had no CVD at baseline and were followed for a median of 10 years. There were 15,126 incident fatal and nonfatal cardiovascular events, including 10,132 coronary heart disease and 4,994 stroke events.

Replacing total and HDL cholesterol measures with any other lipid markers did not improve CVD risk prediction in the study population as a whole, or in clinically relevant subgroups such as diabetes patients or people with elevated triglycerides. In fact, using apolipoprotein B and A-I measures instead of total and HDL cholesterol measures significantly worsened risk discrimination, said Dr. Di Angelantonio of the department of public health and primary care at the University of Cambridge (England), and his associates.

Adding information on various "emerging" lipid markers to existing risk assessments only improved prediction slightly. And none of the newer lipid markers significantly changed classification of subjects "across the clinical risk cutoff levels that are currently used to inform treatment decisions," the investigators said (JAMA 2012;307:2499-506).

The researchers then created a statistical model that assessed various lipid markers specifically in 13,622 patients who were judged to be at intermediate risk after screening by conventional risk factors alone. Such patients would not be recommended for statin therapy according to Adult Treatment Panel III guidelines.

Using lipoprotein (a) measures would reclassify only 555 of these subjects (4.1%) to a higher-risk group, using lipoprotein-associated phospholipase A₂ would reclassify only 365 subjects (2.7%) to a higher-risk group, and using a combination of apolipoprotein B and A-I would reclassify only 154 subjects (1.1%) to a higher-risk group. "In other words, such targeted assessment of [and initiation of statin therapy in] individuals at intermediate CVD risk could help prevent [one] extra CVD outcome over 10 years for every 801 assessed for lipoprotein (a), every 973 assessed for lipoprotein-associated phospholipase A₂, and every 4,541 assessed for the combination of apolipoprotein B and A-I," Dr. Di Angelantonio and his associates said.

This study was funded by the British Heart Foundation, the U.K. Medical Research Council, and the U.K. National Institute of Health Research, Cambridge Biomedical Research Centre. Dr. Di Angelantonio reported ties to Merck Sharp and Dohme, John Wiley & Sons, and Pfizer, and his associates reported ties to numerous industry sources.

Monitoring of rates of surgical site infection, as well as reporting of those rates to the public, vary dramatically from state to state, according to a study published online in the Journal for Healthcare Quality.

Monitoring and publicly reporting data on surgical site infections (SSIs) has been demonstrated to markedly improve patient outcomes, and the Centers for Medicare and Medicaid Services recently announced that hospitals must report such data (for certain procedures) and meet benchmarks to avoid financial penalties. Yet currently there is no standardized system for collecting or reporting SSI data, with each state addressing the issue through its own individual laws, regulations, or "plans," said Dr. Martin A. Makary, a laparoscopic and pancreatic surgeon at Johns Hopkins University, Baltimore, and his associates.

"It is critical to standardize the reporting process before SSIs are incorporated into the Medicare payment scheme," they noted.

Dr. Makary and his colleagues reviewed the legislation on SSI monitoring and reporting for all 50 states and the District of Columbia, then assessed each state’s actual reporting of such data for a single month – September 2010.

They found that only 21 states mandate the monitoring of SSI rates and only 20 require public reporting; the remaining states had no such laws. And despite these legal mandates, only 8 of the 21 states had SSI data available in an easily accessible manner.

These states were South Carolina, Missouri, Colorado, Massachusetts, New York, Ohio, Vermont, and Oregon.

Among these eight states, SSI reporting still varied widely, with each state tracking different procedures. Seven states reported on CABG, six on hip or knee replacements, four on hysterectomies, and two each on colon surgeries or herniorrphaphies. One state reported on breast surgeries, one on gallbladder procedures, one on cesarean sections, and one on spinal fusions.

"Interestingly, colon surgery, which has the highest rate of SSIs nationally, was only reported by two states. And gallbladder surgery, which is among the most common surgical procedures ... was only reported by one state," the investigators said (J. Healthc. Qual. 2012 [doi: 10.1111/j.1945-1474.2011.00176.x]).).

The data collection itself varied greatly by state. For example, some states monitored only in-hospital SSIs for colorectal surgery, while others monitored 30-day SSIs for the same procedure. This resulted in a nearly 40% discrepancy in colorectal SSIs between these states, since many of these infections don’t develop until after hospital discharge, the researchers said.

The lag time between collection of the information and its publication tended to be long, with some states failing to post their SSI data until 11 months after it was obtained.

"Without the same quality and type of data, it is difficult for consumers, payers, or regulators to compare infections within or across states, potentially making inaccurate inferences about the quality of care," Dr. Makary and his associates said.

"Our study highlights the need for the federal government to set the rules for how hospitals define, monitor, and report SSIs," they added.

No conflicts of interest were reported.

Monitoring of rates of surgical site infection, as well as reporting of those rates to the public, vary dramatically from state to state, according to a study published online in the Journal for Healthcare Quality.

Monitoring and publicly reporting data on surgical site infections (SSIs) has been demonstrated to markedly improve patient outcomes, and the Centers for Medicare and Medicaid Services recently announced that hospitals must report such data (for certain procedures) and meet benchmarks to avoid financial penalties. Yet currently there is no standardized system for collecting or reporting SSI data, with each state addressing the issue through its own individual laws, regulations, or "plans," said Dr. Martin A. Makary, a laparoscopic and pancreatic surgeon at Johns Hopkins University, Baltimore, and his associates.

"It is critical to standardize the reporting process before SSIs are incorporated into the Medicare payment scheme," they noted.

Dr. Makary and his colleagues reviewed the legislation on SSI monitoring and reporting for all 50 states and the District of Columbia, then assessed each state’s actual reporting of such data for a single month – September 2010.

They found that only 21 states mandate the monitoring of SSI rates and only 20 require public reporting; the remaining states had no such laws. And despite these legal mandates, only 8 of the 21 states had SSI data available in an easily accessible manner.

These states were South Carolina, Missouri, Colorado, Massachusetts, New York, Ohio, Vermont, and Oregon.

Among these eight states, SSI reporting still varied widely, with each state tracking different procedures. Seven states reported on CABG, six on hip or knee replacements, four on hysterectomies, and two each on colon surgeries or herniorrphaphies. One state reported on breast surgeries, one on gallbladder procedures, one on cesarean sections, and one on spinal fusions.

"Interestingly, colon surgery, which has the highest rate of SSIs nationally, was only reported by two states. And gallbladder surgery, which is among the most common surgical procedures ... was only reported by one state," the investigators said (J. Healthc. Qual. 2012 [doi: 10.1111/j.1945-1474.2011.00176.x]).).

The data collection itself varied greatly by state. For example, some states monitored only in-hospital SSIs for colorectal surgery, while others monitored 30-day SSIs for the same procedure. This resulted in a nearly 40% discrepancy in colorectal SSIs between these states, since many of these infections don’t develop until after hospital discharge, the researchers said.

The lag time between collection of the information and its publication tended to be long, with some states failing to post their SSI data until 11 months after it was obtained.

"Without the same quality and type of data, it is difficult for consumers, payers, or regulators to compare infections within or across states, potentially making inaccurate inferences about the quality of care," Dr. Makary and his associates said.

"Our study highlights the need for the federal government to set the rules for how hospitals define, monitor, and report SSIs," they added.

No conflicts of interest were reported.

Monitoring of rates of surgical site infection, as well as reporting of those rates to the public, vary dramatically from state to state, according to a study published online in the Journal for Healthcare Quality.

Monitoring and publicly reporting data on surgical site infections (SSIs) has been demonstrated to markedly improve patient outcomes, and the Centers for Medicare and Medicaid Services recently announced that hospitals must report such data (for certain procedures) and meet benchmarks to avoid financial penalties. Yet currently there is no standardized system for collecting or reporting SSI data, with each state addressing the issue through its own individual laws, regulations, or "plans," said Dr. Martin A. Makary, a laparoscopic and pancreatic surgeon at Johns Hopkins University, Baltimore, and his associates.

"It is critical to standardize the reporting process before SSIs are incorporated into the Medicare payment scheme," they noted.

Dr. Makary and his colleagues reviewed the legislation on SSI monitoring and reporting for all 50 states and the District of Columbia, then assessed each state’s actual reporting of such data for a single month – September 2010.

They found that only 21 states mandate the monitoring of SSI rates and only 20 require public reporting; the remaining states had no such laws. And despite these legal mandates, only 8 of the 21 states had SSI data available in an easily accessible manner.

These states were South Carolina, Missouri, Colorado, Massachusetts, New York, Ohio, Vermont, and Oregon.

Among these eight states, SSI reporting still varied widely, with each state tracking different procedures. Seven states reported on CABG, six on hip or knee replacements, four on hysterectomies, and two each on colon surgeries or herniorrphaphies. One state reported on breast surgeries, one on gallbladder procedures, one on cesarean sections, and one on spinal fusions.

"Interestingly, colon surgery, which has the highest rate of SSIs nationally, was only reported by two states. And gallbladder surgery, which is among the most common surgical procedures ... was only reported by one state," the investigators said (J. Healthc. Qual. 2012 [doi: 10.1111/j.1945-1474.2011.00176.x]).).

The data collection itself varied greatly by state. For example, some states monitored only in-hospital SSIs for colorectal surgery, while others monitored 30-day SSIs for the same procedure. This resulted in a nearly 40% discrepancy in colorectal SSIs between these states, since many of these infections don’t develop until after hospital discharge, the researchers said.

The lag time between collection of the information and its publication tended to be long, with some states failing to post their SSI data until 11 months after it was obtained.

"Without the same quality and type of data, it is difficult for consumers, payers, or regulators to compare infections within or across states, potentially making inaccurate inferences about the quality of care," Dr. Makary and his associates said.

"Our study highlights the need for the federal government to set the rules for how hospitals define, monitor, and report SSIs," they added.

No conflicts of interest were reported.

Higher spending intensity was associated with substantially better hospital care in Ontario, which has a universal health care system, according to a report in JAMA.

Patients with acute illness treated at hospitals with higher spending intensity had lower mortality, lower readmission rates, and fewer adverse events than did those treated at hospitals with lower spending intensity, said Therese A. Stukel, Ph.D., of the Institute for Clinical Evaluative Sciences, Toronto, and her associates.

However, it would be "facile" to conclude that more spending necessarily leads to better patient outcomes, and that providing more money to lower-spending facilities would necessarily improve their patient outcomes. "Higher-spending hospitals differed in many ways, such as greater use of evidence-based care, skilled nursing and critical care staff, more intensive inpatient specialist services, and high technology, all of which are more expensive," the investigators noted.

Many studies have examined whether higher health care spending produces better patient outcomes, but until now, none have assessed the issue in an area with universal access to health care but a lower supply of specialists and of medical technology than in the United States. "Our objective was to assess whether acute care patients admitted to Canadian hospitals that treat patients more intensively (and at higher cost) have lower mortality and readmissions and higher quality of care," Dr. Stukel and her colleagues said.

They analyzed the medical records of adults with an index admission to one of 129 acute care hospitals in Ontario in 1998-2008 for any of four common conditions for which treatment follows relatively standard protocols: acute myocardial infarction (179,139 patients), heart failure (92,377 patients), hip fracture (90,046 patients), or surgical resection of colon cancer (26,195 patients). The study subjects were followed for 1 year after the index admission.

Several quality-of-care measures were assessed: whether patients received preoperative visits from a surgeon and an anesthetist, whether surgery took place within 2 days of admission, whether patients received in-hospital rehabilitation, whether MI patients underwent same-day percutaneous coronary intervention, and the number of visits from medical specialists during the hospital stay.

Higher-spending hospitals tended to be high-volume centers in urban areas. They tended to be affiliated with regional cancer centers and to have on-site CT, MRI, cardiac catheterization, and cardiac surgery capabilities. They also tended to employ critical care response teams, as well as attending physicians who were specialists. And they provided 30% more inpatient nursing hours per patient-day and per bed than did lower-spending hospitals.

At higher-spending hospitals, 30-day mortality was 12.7% (vs 12.8%) for acute MI, 10.2% (vs. 12.4%) for CHF, 7.7% (vs. 9.7%) for hip fracture, and 3.3% (vs 3.9%) for colon cancer. The 30-day major cardiac event rate was 17.4% (vs.18.7%) for acute MI and 15.0% (vs. 17.6%) for CHF. And the 30-day readmission rate was 23.1% (vs. 25.8%) for hip fracture and 10.3% (vs 13.1%) for colon cancer.

After the data were adjusted fully to account for patient age, sex, illness severity, and other variables, mortality and readmission rates remained significantly lower in high-spending hospitals for every study subgroup, Dr. Stukel and her colleagues said (JAMA 2012;307:1037-45).

Compared with patients at lower-spending hospitals, those at higher-spending hospitals were more likely to see a medical specialist during their stay. Cardiac patients at higher-spending hospitals were more likely to receive the indicated cardiac interventions and evidence-based medications, to attend ambulatory care within 1 month, and to visit a cardiologist within 1 year.

CHF patients at higher-spending hospitals were less likely than were those at lower-spending hospitals to receive contraindicated medications. Those with hip fracture were more likely to begin rehabilitation during their inpatient stay. And those with colon cancer were more likely to have a preoperative consultation with a surgeon and an anesthetist, and to undergo CT for preoperative staging, compared with colon cancer patients at lower-spending hospitals.

The study findings "suggest that it is critical to understand not simply how much money is spent but whether it is spent on effective procedures and services," the researchers noted.

This study was supported by the Canadian Institute of Health Research, the U.S. National Institute on Aging, the Institute for Clinical Evaluative Sciences, and the Ontario Ministry of Health and Long-Term Care. No relevant financial conflicts of interest were reported.

"The notion that payments to hospitals can be reduced while maintaining or improving the quality of care delivered at these hospitals has become so ingrained in policy circles as to be a given," said Dr. Karen E. Joynt and Dr. Ashish K. Jha in remarks were taken from their editorial accompanying Dr. Stukel’s report (JAMA 2012;307:1082-3).

"Although paying hospitals less may appear to be a good strategy to save money, the findings reported by Stukel et al. serve as a timely reminder that this approach is likely to have negative consequences for patients," they noted.

So-called "expensive" hospitals are likely spending that money directly on nurses, specialists, and technology – in other words, on care that improves the outcomes of acutely ill patients, Dr. Joynt and Dr. Jha said.

Dr. Joynt and Dr. Jha are in the department of health policy and management at Harvard School of Public Health, Boston. Dr. Joynt is also in the cardiovascular division and Dr. Jha is in the division of general internal medicine at Brigham and Women’s Hospital, Boston. They reported no relevant financial conflicts of interest.

Higher spending intensity was associated with substantially better hospital care in Ontario, which has a universal health care system, according to a report in JAMA.

Patients with acute illness treated at hospitals with higher spending intensity had lower mortality, lower readmission rates, and fewer adverse events than did those treated at hospitals with lower spending intensity, said Therese A. Stukel, Ph.D., of the Institute for Clinical Evaluative Sciences, Toronto, and her associates.

However, it would be "facile" to conclude that more spending necessarily leads to better patient outcomes, and that providing more money to lower-spending facilities would necessarily improve their patient outcomes. "Higher-spending hospitals differed in many ways, such as greater use of evidence-based care, skilled nursing and critical care staff, more intensive inpatient specialist services, and high technology, all of which are more expensive," the investigators noted.

Many studies have examined whether higher health care spending produces better patient outcomes, but until now, none have assessed the issue in an area with universal access to health care but a lower supply of specialists and of medical technology than in the United States. "Our objective was to assess whether acute care patients admitted to Canadian hospitals that treat patients more intensively (and at higher cost) have lower mortality and readmissions and higher quality of care," Dr. Stukel and her colleagues said.

They analyzed the medical records of adults with an index admission to one of 129 acute care hospitals in Ontario in 1998-2008 for any of four common conditions for which treatment follows relatively standard protocols: acute myocardial infarction (179,139 patients), heart failure (92,377 patients), hip fracture (90,046 patients), or surgical resection of colon cancer (26,195 patients). The study subjects were followed for 1 year after the index admission.

Several quality-of-care measures were assessed: whether patients received preoperative visits from a surgeon and an anesthetist, whether surgery took place within 2 days of admission, whether patients received in-hospital rehabilitation, whether MI patients underwent same-day percutaneous coronary intervention, and the number of visits from medical specialists during the hospital stay.

Higher-spending hospitals tended to be high-volume centers in urban areas. They tended to be affiliated with regional cancer centers and to have on-site CT, MRI, cardiac catheterization, and cardiac surgery capabilities. They also tended to employ critical care response teams, as well as attending physicians who were specialists. And they provided 30% more inpatient nursing hours per patient-day and per bed than did lower-spending hospitals.

At higher-spending hospitals, 30-day mortality was 12.7% (vs 12.8%) for acute MI, 10.2% (vs. 12.4%) for CHF, 7.7% (vs. 9.7%) for hip fracture, and 3.3% (vs 3.9%) for colon cancer. The 30-day major cardiac event rate was 17.4% (vs.18.7%) for acute MI and 15.0% (vs. 17.6%) for CHF. And the 30-day readmission rate was 23.1% (vs. 25.8%) for hip fracture and 10.3% (vs 13.1%) for colon cancer.

After the data were adjusted fully to account for patient age, sex, illness severity, and other variables, mortality and readmission rates remained significantly lower in high-spending hospitals for every study subgroup, Dr. Stukel and her colleagues said (JAMA 2012;307:1037-45).

Compared with patients at lower-spending hospitals, those at higher-spending hospitals were more likely to see a medical specialist during their stay. Cardiac patients at higher-spending hospitals were more likely to receive the indicated cardiac interventions and evidence-based medications, to attend ambulatory care within 1 month, and to visit a cardiologist within 1 year.

CHF patients at higher-spending hospitals were less likely than were those at lower-spending hospitals to receive contraindicated medications. Those with hip fracture were more likely to begin rehabilitation during their inpatient stay. And those with colon cancer were more likely to have a preoperative consultation with a surgeon and an anesthetist, and to undergo CT for preoperative staging, compared with colon cancer patients at lower-spending hospitals.

The study findings "suggest that it is critical to understand not simply how much money is spent but whether it is spent on effective procedures and services," the researchers noted.

This study was supported by the Canadian Institute of Health Research, the U.S. National Institute on Aging, the Institute for Clinical Evaluative Sciences, and the Ontario Ministry of Health and Long-Term Care. No relevant financial conflicts of interest were reported.

"The notion that payments to hospitals can be reduced while maintaining or improving the quality of care delivered at these hospitals has become so ingrained in policy circles as to be a given," said Dr. Karen E. Joynt and Dr. Ashish K. Jha in remarks were taken from their editorial accompanying Dr. Stukel’s report (JAMA 2012;307:1082-3).

"Although paying hospitals less may appear to be a good strategy to save money, the findings reported by Stukel et al. serve as a timely reminder that this approach is likely to have negative consequences for patients," they noted.

So-called "expensive" hospitals are likely spending that money directly on nurses, specialists, and technology – in other words, on care that improves the outcomes of acutely ill patients, Dr. Joynt and Dr. Jha said.

Dr. Joynt and Dr. Jha are in the department of health policy and management at Harvard School of Public Health, Boston. Dr. Joynt is also in the cardiovascular division and Dr. Jha is in the division of general internal medicine at Brigham and Women’s Hospital, Boston. They reported no relevant financial conflicts of interest.

Higher spending intensity was associated with substantially better hospital care in Ontario, which has a universal health care system, according to a report in JAMA.

Patients with acute illness treated at hospitals with higher spending intensity had lower mortality, lower readmission rates, and fewer adverse events than did those treated at hospitals with lower spending intensity, said Therese A. Stukel, Ph.D., of the Institute for Clinical Evaluative Sciences, Toronto, and her associates.

However, it would be "facile" to conclude that more spending necessarily leads to better patient outcomes, and that providing more money to lower-spending facilities would necessarily improve their patient outcomes. "Higher-spending hospitals differed in many ways, such as greater use of evidence-based care, skilled nursing and critical care staff, more intensive inpatient specialist services, and high technology, all of which are more expensive," the investigators noted.

Many studies have examined whether higher health care spending produces better patient outcomes, but until now, none have assessed the issue in an area with universal access to health care but a lower supply of specialists and of medical technology than in the United States. "Our objective was to assess whether acute care patients admitted to Canadian hospitals that treat patients more intensively (and at higher cost) have lower mortality and readmissions and higher quality of care," Dr. Stukel and her colleagues said.

They analyzed the medical records of adults with an index admission to one of 129 acute care hospitals in Ontario in 1998-2008 for any of four common conditions for which treatment follows relatively standard protocols: acute myocardial infarction (179,139 patients), heart failure (92,377 patients), hip fracture (90,046 patients), or surgical resection of colon cancer (26,195 patients). The study subjects were followed for 1 year after the index admission.

Several quality-of-care measures were assessed: whether patients received preoperative visits from a surgeon and an anesthetist, whether surgery took place within 2 days of admission, whether patients received in-hospital rehabilitation, whether MI patients underwent same-day percutaneous coronary intervention, and the number of visits from medical specialists during the hospital stay.

Higher-spending hospitals tended to be high-volume centers in urban areas. They tended to be affiliated with regional cancer centers and to have on-site CT, MRI, cardiac catheterization, and cardiac surgery capabilities. They also tended to employ critical care response teams, as well as attending physicians who were specialists. And they provided 30% more inpatient nursing hours per patient-day and per bed than did lower-spending hospitals.

At higher-spending hospitals, 30-day mortality was 12.7% (vs 12.8%) for acute MI, 10.2% (vs. 12.4%) for CHF, 7.7% (vs. 9.7%) for hip fracture, and 3.3% (vs 3.9%) for colon cancer. The 30-day major cardiac event rate was 17.4% (vs.18.7%) for acute MI and 15.0% (vs. 17.6%) for CHF. And the 30-day readmission rate was 23.1% (vs. 25.8%) for hip fracture and 10.3% (vs 13.1%) for colon cancer.

After the data were adjusted fully to account for patient age, sex, illness severity, and other variables, mortality and readmission rates remained significantly lower in high-spending hospitals for every study subgroup, Dr. Stukel and her colleagues said (JAMA 2012;307:1037-45).

Compared with patients at lower-spending hospitals, those at higher-spending hospitals were more likely to see a medical specialist during their stay. Cardiac patients at higher-spending hospitals were more likely to receive the indicated cardiac interventions and evidence-based medications, to attend ambulatory care within 1 month, and to visit a cardiologist within 1 year.

CHF patients at higher-spending hospitals were less likely than were those at lower-spending hospitals to receive contraindicated medications. Those with hip fracture were more likely to begin rehabilitation during their inpatient stay. And those with colon cancer were more likely to have a preoperative consultation with a surgeon and an anesthetist, and to undergo CT for preoperative staging, compared with colon cancer patients at lower-spending hospitals.

The study findings "suggest that it is critical to understand not simply how much money is spent but whether it is spent on effective procedures and services," the researchers noted.

This study was supported by the Canadian Institute of Health Research, the U.S. National Institute on Aging, the Institute for Clinical Evaluative Sciences, and the Ontario Ministry of Health and Long-Term Care. No relevant financial conflicts of interest were reported.

"The notion that payments to hospitals can be reduced while maintaining or improving the quality of care delivered at these hospitals has become so ingrained in policy circles as to be a given," said Dr. Karen E. Joynt and Dr. Ashish K. Jha in remarks were taken from their editorial accompanying Dr. Stukel’s report (JAMA 2012;307:1082-3).

"Although paying hospitals less may appear to be a good strategy to save money, the findings reported by Stukel et al. serve as a timely reminder that this approach is likely to have negative consequences for patients," they noted.

So-called "expensive" hospitals are likely spending that money directly on nurses, specialists, and technology – in other words, on care that improves the outcomes of acutely ill patients, Dr. Joynt and Dr. Jha said.

Dr. Joynt and Dr. Jha are in the department of health policy and management at Harvard School of Public Health, Boston. Dr. Joynt is also in the cardiovascular division and Dr. Jha is in the division of general internal medicine at Brigham and Women’s Hospital, Boston. They reported no relevant financial conflicts of interest.

The risk of myocardial infarction is just as high in patients who have chronic kidney disease as in those who have diabetes, and their subsequent mortality is even higher, according to a report published online June 19 in the Lancet.

"Our research suggests that there is a strong case for considering CKD to be a coronary heart disease risk equivalent," as is the case with diabetes. This means that people with CKD, like diabetes patients, "are at a comparable risk of coronary events to those who have previously had a heart attack," Dr. Marcello Tonelli of the departments of medicine and public health sciences at the University of Alberta, Edmonton, said in a press statement accompanying the release of the report.

Dr. Tonelli and his associates used information from two large, population-based cohorts – the Alberta Kidney Disease Network and the National Health and Nutrition Examination Survey (NHANES) 2003-2006 – to compare the risks of hospitalization for MI among adults with previous MI, adults with diabetes mellitus but no kidney disease, and adults with CKD but no diabetes. The 1,268,029 study subjects were followed for a median of 4 years, during which time 1% (11,340) were admitted for MI.

Compared with healthy adults, the unadjusted rate of MI during follow-up was highest in people with a history of MI (18.5 per 1,000 person-years) but was also significantly elevated in those with diabetes (5.4 per 1,000 person-years) or CKD (6.9 per 1,000 person-years).

In addition, the proportion of patients who died within 30 days of admission for MI was highest for patients with CKD (14%) but also was significantly elevated for patients with diabetes (8%) and those with a history of MI (10%).

These findings suggest that "arguments supporting inclusion of diabetes in the highest risk category for CHD seem also to apply to people with CKD," the investigators said (Lancet 2012 June 19 [doi:10.1016/S0140-6736(12)60572-8]).

In exploratory analyses in which the data were adjusted to account for patient age, socioeconomic status, and comorbidities, the MI rate decreased in those with CKD but not in those with diabetes. This suggests that demographic and clinical characteristics – most notably, old age – are responsible for much of the cardiovascular risk associated with CKD, they noted.

The study findings also imply that patients with CKD, like those with diabetes, would benefit from lipid-lowering treatment.

This study was supported by the Alberta Heritage Foundation for Medical Research, Alberta Health and Wellness, the University of Alberta, and the University of Calgary. Dr. Tonelli reported ties to Pfizer and Merck, and one of his associates reported ties to Amgen.

The risk of myocardial infarction is just as high in patients who have chronic kidney disease as in those who have diabetes, and their subsequent mortality is even higher, according to a report published online June 19 in the Lancet.

"Our research suggests that there is a strong case for considering CKD to be a coronary heart disease risk equivalent," as is the case with diabetes. This means that people with CKD, like diabetes patients, "are at a comparable risk of coronary events to those who have previously had a heart attack," Dr. Marcello Tonelli of the departments of medicine and public health sciences at the University of Alberta, Edmonton, said in a press statement accompanying the release of the report.

Dr. Tonelli and his associates used information from two large, population-based cohorts – the Alberta Kidney Disease Network and the National Health and Nutrition Examination Survey (NHANES) 2003-2006 – to compare the risks of hospitalization for MI among adults with previous MI, adults with diabetes mellitus but no kidney disease, and adults with CKD but no diabetes. The 1,268,029 study subjects were followed for a median of 4 years, during which time 1% (11,340) were admitted for MI.

Compared with healthy adults, the unadjusted rate of MI during follow-up was highest in people with a history of MI (18.5 per 1,000 person-years) but was also significantly elevated in those with diabetes (5.4 per 1,000 person-years) or CKD (6.9 per 1,000 person-years).

In addition, the proportion of patients who died within 30 days of admission for MI was highest for patients with CKD (14%) but also was significantly elevated for patients with diabetes (8%) and those with a history of MI (10%).

These findings suggest that "arguments supporting inclusion of diabetes in the highest risk category for CHD seem also to apply to people with CKD," the investigators said (Lancet 2012 June 19 [doi:10.1016/S0140-6736(12)60572-8]).

In exploratory analyses in which the data were adjusted to account for patient age, socioeconomic status, and comorbidities, the MI rate decreased in those with CKD but not in those with diabetes. This suggests that demographic and clinical characteristics – most notably, old age – are responsible for much of the cardiovascular risk associated with CKD, they noted.

The study findings also imply that patients with CKD, like those with diabetes, would benefit from lipid-lowering treatment.

This study was supported by the Alberta Heritage Foundation for Medical Research, Alberta Health and Wellness, the University of Alberta, and the University of Calgary. Dr. Tonelli reported ties to Pfizer and Merck, and one of his associates reported ties to Amgen.

The risk of myocardial infarction is just as high in patients who have chronic kidney disease as in those who have diabetes, and their subsequent mortality is even higher, according to a report published online June 19 in the Lancet.

"Our research suggests that there is a strong case for considering CKD to be a coronary heart disease risk equivalent," as is the case with diabetes. This means that people with CKD, like diabetes patients, "are at a comparable risk of coronary events to those who have previously had a heart attack," Dr. Marcello Tonelli of the departments of medicine and public health sciences at the University of Alberta, Edmonton, said in a press statement accompanying the release of the report.

Dr. Tonelli and his associates used information from two large, population-based cohorts – the Alberta Kidney Disease Network and the National Health and Nutrition Examination Survey (NHANES) 2003-2006 – to compare the risks of hospitalization for MI among adults with previous MI, adults with diabetes mellitus but no kidney disease, and adults with CKD but no diabetes. The 1,268,029 study subjects were followed for a median of 4 years, during which time 1% (11,340) were admitted for MI.

Compared with healthy adults, the unadjusted rate of MI during follow-up was highest in people with a history of MI (18.5 per 1,000 person-years) but was also significantly elevated in those with diabetes (5.4 per 1,000 person-years) or CKD (6.9 per 1,000 person-years).

In addition, the proportion of patients who died within 30 days of admission for MI was highest for patients with CKD (14%) but also was significantly elevated for patients with diabetes (8%) and those with a history of MI (10%).

These findings suggest that "arguments supporting inclusion of diabetes in the highest risk category for CHD seem also to apply to people with CKD," the investigators said (Lancet 2012 June 19 [doi:10.1016/S0140-6736(12)60572-8]).

In exploratory analyses in which the data were adjusted to account for patient age, socioeconomic status, and comorbidities, the MI rate decreased in those with CKD but not in those with diabetes. This suggests that demographic and clinical characteristics – most notably, old age – are responsible for much of the cardiovascular risk associated with CKD, they noted.

The study findings also imply that patients with CKD, like those with diabetes, would benefit from lipid-lowering treatment.

This study was supported by the Alberta Heritage Foundation for Medical Research, Alberta Health and Wellness, the University of Alberta, and the University of Calgary. Dr. Tonelli reported ties to Pfizer and Merck, and one of his associates reported ties to Amgen.

The use of prescription drugs among pediatric outpatients declined significantly between 2002 and 2010, by an average of 2.4 million prescriptions per year, according to a report published online June 18 in Pediatrics.

This trend was driven in part by a sharp decrease in the use of antibiotics, which account for approximately one-fourth of all prescriptions dispensed to the pediatric population, said Grace Chai, Pharm.D., of the office of surveillance and epidemiology at the center for drug evaluation and research, Food and Drug Administration, and her associates.

Notably, this trend is the opposite of that reported among adult outpatients during the same interval, which showed a dramatic increase of 86 million prescriptions per year, the investigators said.

Until now, few data have been available regarding nationwide drug utilization among children. Studies to date have relied on parental reports rather than more objective data and have been restricted to commercially insured patients; particular age groups; or certain types of medications, such as those for chronic conditions only.

Dr. Chai and her colleagues used two large prescription claims databases from retail pharmacies to examine national trends in drug use among patients aged 0-17 years whose medications were paid for by cash, Medicaid, or commercial insurance. Their study covered information on two-thirds of the approximately 59,000 retail pharmacies nationwide, which accounted for approximately half of all retail prescriptions dispensed in 2002-2010.

The data were deidentified, and patients were categorized into three age groups: infants (aged 0-23 months), children (aged 2-11 years), and adolescents (aged 12-17 years). Neonatal patients could not be distinguished from older babies using the available data.

This study did not include data on over-the-counter medications, herbal preparations, supplements, or mail order prescriptions, they noted (Pediatrics 2012;130:23-31 [doi:10.1542/peds.2011-2879]).

Among the study findings:

• Approximately 263 million prescriptions were dispensed to children in 2010, which is 7% fewer than the number dispensed in 2002. (In contrast, it has been reported that 3.3 billion prescriptions were dispensed to adults in 2010, a 22% increase over the number dispensed in 2002.)

• The use of systemic antibiotics, which accounted for 24%-27% of all pediatric prescriptions during the study period, steeply declined. This suggests that efforts to reduce the inappropriate use of antibiotics may be working, the researchers said.

• Allergy medications were the category of drugs that showed the single largest decline. However, several antihistamines, including loratadine and cetirizine, converted from prescription to OTC status during the study period. So even though the number of prescriptions for allergy medications may have decreased, pediatric use of the drugs may not have decreased.

• The use of prescription cough and cold products without expectorants also decreased significantly, an indication that recent critiques of the safety and efficacy of these agents in children may have been effective.

• The number of contraceptive prescriptions rose 93% during the study period, and prescriptions for norgestimate–ethinyl estradiol ranked among the top 10 prescriptions for adolescents in 2010. However, Centers for Disease Control and Prevention reports during the same interval have noted only a slight increase in the percentage of young women taking OCs. It may be that the large increase noted in this study reflects in part the use of OCs for indications other than contraception, such as for treating acne or for regulating menses, or an increase in the duration of use.

Dr. Chai and her associates also paid particular attention to two classes of prescription medicines that have come under scrutiny recently in the pediatric population: attention-deficit/hyperactivity disorder (ADHD) medications and proton pump inhibitors.

The use of ADHD agents increased markedly overall during the study period. Two drugs, methylphenidate and amphetamine/dextroamphetamine, accounted for the largest portion of ADHD agents prescribed, but their use remained relatively stable throughout the study interval. Instead, the increase in use occurred with newer agents such as lisdexamfetamine, dexmethylphenidate, and guanfacine. The use of atomoxetine initially increased after it was approved in 2002 but declined in 2005, after a boxed warning was added to the label regarding the risk of suicide in children and adolescents taking the drug.

Regarding proton pump inhibitors, 358,000 prescriptions for lansoprazole were dispensed to infants in 2010, even though the label states that the drug is not effective for gastroesophageal reflux in patients aged 1-12 months. Off-label lansoprazole use in the pediatric population is of interest as its safety is explored, the researchers said.

This study was sponsored by the FDA and included commercial proprietary drug utilization data obtained by the FDA under contract. Dr. Chai and her associates said they had no relevant financial disclosures.

The use of prescription drugs among pediatric outpatients declined significantly between 2002 and 2010, by an average of 2.4 million prescriptions per year, according to a report published online June 18 in Pediatrics.

This trend was driven in part by a sharp decrease in the use of antibiotics, which account for approximately one-fourth of all prescriptions dispensed to the pediatric population, said Grace Chai, Pharm.D., of the office of surveillance and epidemiology at the center for drug evaluation and research, Food and Drug Administration, and her associates.

Notably, this trend is the opposite of that reported among adult outpatients during the same interval, which showed a dramatic increase of 86 million prescriptions per year, the investigators said.

Until now, few data have been available regarding nationwide drug utilization among children. Studies to date have relied on parental reports rather than more objective data and have been restricted to commercially insured patients; particular age groups; or certain types of medications, such as those for chronic conditions only.

Dr. Chai and her colleagues used two large prescription claims databases from retail pharmacies to examine national trends in drug use among patients aged 0-17 years whose medications were paid for by cash, Medicaid, or commercial insurance. Their study covered information on two-thirds of the approximately 59,000 retail pharmacies nationwide, which accounted for approximately half of all retail prescriptions dispensed in 2002-2010.

The data were deidentified, and patients were categorized into three age groups: infants (aged 0-23 months), children (aged 2-11 years), and adolescents (aged 12-17 years). Neonatal patients could not be distinguished from older babies using the available data.

This study did not include data on over-the-counter medications, herbal preparations, supplements, or mail order prescriptions, they noted (Pediatrics 2012;130:23-31 [doi:10.1542/peds.2011-2879]).

Among the study findings:

• Approximately 263 million prescriptions were dispensed to children in 2010, which is 7% fewer than the number dispensed in 2002. (In contrast, it has been reported that 3.3 billion prescriptions were dispensed to adults in 2010, a 22% increase over the number dispensed in 2002.)

• The use of systemic antibiotics, which accounted for 24%-27% of all pediatric prescriptions during the study period, steeply declined. This suggests that efforts to reduce the inappropriate use of antibiotics may be working, the researchers said.

• Allergy medications were the category of drugs that showed the single largest decline. However, several antihistamines, including loratadine and cetirizine, converted from prescription to OTC status during the study period. So even though the number of prescriptions for allergy medications may have decreased, pediatric use of the drugs may not have decreased.

• The use of prescription cough and cold products without expectorants also decreased significantly, an indication that recent critiques of the safety and efficacy of these agents in children may have been effective.

• The number of contraceptive prescriptions rose 93% during the study period, and prescriptions for norgestimate–ethinyl estradiol ranked among the top 10 prescriptions for adolescents in 2010. However, Centers for Disease Control and Prevention reports during the same interval have noted only a slight increase in the percentage of young women taking OCs. It may be that the large increase noted in this study reflects in part the use of OCs for indications other than contraception, such as for treating acne or for regulating menses, or an increase in the duration of use.

Dr. Chai and her associates also paid particular attention to two classes of prescription medicines that have come under scrutiny recently in the pediatric population: attention-deficit/hyperactivity disorder (ADHD) medications and proton pump inhibitors.

The use of ADHD agents increased markedly overall during the study period. Two drugs, methylphenidate and amphetamine/dextroamphetamine, accounted for the largest portion of ADHD agents prescribed, but their use remained relatively stable throughout the study interval. Instead, the increase in use occurred with newer agents such as lisdexamfetamine, dexmethylphenidate, and guanfacine. The use of atomoxetine initially increased after it was approved in 2002 but declined in 2005, after a boxed warning was added to the label regarding the risk of suicide in children and adolescents taking the drug.

Regarding proton pump inhibitors, 358,000 prescriptions for lansoprazole were dispensed to infants in 2010, even though the label states that the drug is not effective for gastroesophageal reflux in patients aged 1-12 months. Off-label lansoprazole use in the pediatric population is of interest as its safety is explored, the researchers said.

This study was sponsored by the FDA and included commercial proprietary drug utilization data obtained by the FDA under contract. Dr. Chai and her associates said they had no relevant financial disclosures.

The use of prescription drugs among pediatric outpatients declined significantly between 2002 and 2010, by an average of 2.4 million prescriptions per year, according to a report published online June 18 in Pediatrics.

This trend was driven in part by a sharp decrease in the use of antibiotics, which account for approximately one-fourth of all prescriptions dispensed to the pediatric population, said Grace Chai, Pharm.D., of the office of surveillance and epidemiology at the center for drug evaluation and research, Food and Drug Administration, and her associates.

Notably, this trend is the opposite of that reported among adult outpatients during the same interval, which showed a dramatic increase of 86 million prescriptions per year, the investigators said.

Until now, few data have been available regarding nationwide drug utilization among children. Studies to date have relied on parental reports rather than more objective data and have been restricted to commercially insured patients; particular age groups; or certain types of medications, such as those for chronic conditions only.

Dr. Chai and her colleagues used two large prescription claims databases from retail pharmacies to examine national trends in drug use among patients aged 0-17 years whose medications were paid for by cash, Medicaid, or commercial insurance. Their study covered information on two-thirds of the approximately 59,000 retail pharmacies nationwide, which accounted for approximately half of all retail prescriptions dispensed in 2002-2010.

The data were deidentified, and patients were categorized into three age groups: infants (aged 0-23 months), children (aged 2-11 years), and adolescents (aged 12-17 years). Neonatal patients could not be distinguished from older babies using the available data.

This study did not include data on over-the-counter medications, herbal preparations, supplements, or mail order prescriptions, they noted (Pediatrics 2012;130:23-31 [doi:10.1542/peds.2011-2879]).

Among the study findings:

• Approximately 263 million prescriptions were dispensed to children in 2010, which is 7% fewer than the number dispensed in 2002. (In contrast, it has been reported that 3.3 billion prescriptions were dispensed to adults in 2010, a 22% increase over the number dispensed in 2002.)

• The use of systemic antibiotics, which accounted for 24%-27% of all pediatric prescriptions during the study period, steeply declined. This suggests that efforts to reduce the inappropriate use of antibiotics may be working, the researchers said.

• Allergy medications were the category of drugs that showed the single largest decline. However, several antihistamines, including loratadine and cetirizine, converted from prescription to OTC status during the study period. So even though the number of prescriptions for allergy medications may have decreased, pediatric use of the drugs may not have decreased.

• The use of prescription cough and cold products without expectorants also decreased significantly, an indication that recent critiques of the safety and efficacy of these agents in children may have been effective.

• The number of contraceptive prescriptions rose 93% during the study period, and prescriptions for norgestimate–ethinyl estradiol ranked among the top 10 prescriptions for adolescents in 2010. However, Centers for Disease Control and Prevention reports during the same interval have noted only a slight increase in the percentage of young women taking OCs. It may be that the large increase noted in this study reflects in part the use of OCs for indications other than contraception, such as for treating acne or for regulating menses, or an increase in the duration of use.

Dr. Chai and her associates also paid particular attention to two classes of prescription medicines that have come under scrutiny recently in the pediatric population: attention-deficit/hyperactivity disorder (ADHD) medications and proton pump inhibitors.

The use of ADHD agents increased markedly overall during the study period. Two drugs, methylphenidate and amphetamine/dextroamphetamine, accounted for the largest portion of ADHD agents prescribed, but their use remained relatively stable throughout the study interval. Instead, the increase in use occurred with newer agents such as lisdexamfetamine, dexmethylphenidate, and guanfacine. The use of atomoxetine initially increased after it was approved in 2002 but declined in 2005, after a boxed warning was added to the label regarding the risk of suicide in children and adolescents taking the drug.

Regarding proton pump inhibitors, 358,000 prescriptions for lansoprazole were dispensed to infants in 2010, even though the label states that the drug is not effective for gastroesophageal reflux in patients aged 1-12 months. Off-label lansoprazole use in the pediatric population is of interest as its safety is explored, the researchers said.

This study was sponsored by the FDA and included commercial proprietary drug utilization data obtained by the FDA under contract. Dr. Chai and her associates said they had no relevant financial disclosures.