Mary Ann Moon

Declines in testosterone regulate decreases in men's muscle mass and strength, declines in estrogen regulate increases in men’s fat mass and abdominal fat, and declines in both hormones regulate decreases in men’s libido and erectile function, according to a report published online Sept. 11 in the New England Journal of Medicine.

These are the key findings from a dose-ranging study designed to tease out the complex roles played by both testosterone and estrogen in so-called androgen deficiency. They indicate that a simple, straightforward decline in testosterone doesn’t account for the myriad changes in body composition, strength, and sexual factors experienced by men with "low T."

This in turn suggests that the current approach to assessing and managing the condition – a one-time measurement of serum testosterone only, an across-the-board designation of a "low" level, and simple replenishment with endogenous testosterone only – should be replaced by more rational, nuanced approaches, said Dr. Joel S. Finkelstein of the endocrine unit and his associates at Massachusetts General Hospital, Boston.

They examined a wide spectrum of testosterone levels, and the adverse effects of different levels, by temporarily suppressing the normal endogenous gonadal steroids of healthy men aged 20-50 years using subcutaneous goserelin. In one cohort, 198 men then were randomly assigned to receive placebo, 1.25 g, 2.5 g, 5 g, or 10 g of a topical testosterone gel daily for 16 weeks. In another cohort, 202 men were randomly assigned to receive these same doses of topical testosterone plus 1 mg daily of anastrozole to block the aromatization of testosterone to estrogen.

All the study subjects, who were blinded to their medication assignments, were assessed every 4 weeks for the duration of the study for gonadal steroid levels, physical function, health status, vitality, and sexual function. Dual-energy x-ray absorptiometry (DXA) was used to measure body fat and lean mass, and CT was used to measure the areas of subcutaneous fat, intra-abdominal fat, and thigh muscle. Thigh-muscle strength was assessed using leg presses.

"By administering a variety of testosterone doses, with and without concomitant aromatase inhibition, we found that changes in lean mass, thigh-muscle area, and leg-press strength were attributable to changes in testosterone levels, whereas changes in fat measures were primarily related to changes in estradiol levels. Both androgens and estrogens contributed to the maintenance of normal libido and erectile function," Dr. Finkelstein and his associates said (N. Engl. J. Med. 2013 Sept. 11 [doi:10.1056/NEJMoa1206168]).

As important, the level of testosterone needed to maintain lean mass, fat mass, strength, and sexual function was found to vary considerably among these study subjects.

Most men showed reduced lean mass, muscle area, and erectile function at a mean serum testosterone level of 200 ng/dL, so testosterone supplementation appears to be justified at this level. However, many men showed impairment in these outcomes at lower or higher testosterone levels. In addition, the testosterone levels at which body fat increased and sexual desire decreased varied widely.

"Thus, each person’s specific clinical scenario should be considered when interpreting the clinical significance of the circulating testosterone level," Dr. Finkelstein and his colleagues said.

Also important was the finding that deficiency of estrogen, not testosterone, "is largely responsible for some of the key consequences of male hypogonadism." This indicates that measuring men’s estradiol levels may help in assessing their risk for sexual dysfunction, bone loss, or fat accumulation, the researchers added.

This study was limited in that the duration was restricted to 16 weeks, so as to avoid inducing clinically significant changes in the healthy men who participated. "Because changes in body composition may progress over time, greater changes might have been seen at higher testosterone and estradiol levels if gonadal steroids had been suppressed over a longer period," the investigators noted.

This study was supported by the National Institutes of Health and Abbott Laboratories. Abbott also supplied the testosterone gel at no cost, and Astra Zeneca provided goserelin and anastrozole at no cost, but neither company played a role in study design, data analysis, data interpretation, or manuscript preparation.

Declines in testosterone regulate decreases in men's muscle mass and strength, declines in estrogen regulate increases in men’s fat mass and abdominal fat, and declines in both hormones regulate decreases in men’s libido and erectile function, according to a report published online Sept. 11 in the New England Journal of Medicine.

These are the key findings from a dose-ranging study designed to tease out the complex roles played by both testosterone and estrogen in so-called androgen deficiency. They indicate that a simple, straightforward decline in testosterone doesn’t account for the myriad changes in body composition, strength, and sexual factors experienced by men with "low T."

This in turn suggests that the current approach to assessing and managing the condition – a one-time measurement of serum testosterone only, an across-the-board designation of a "low" level, and simple replenishment with endogenous testosterone only – should be replaced by more rational, nuanced approaches, said Dr. Joel S. Finkelstein of the endocrine unit and his associates at Massachusetts General Hospital, Boston.

They examined a wide spectrum of testosterone levels, and the adverse effects of different levels, by temporarily suppressing the normal endogenous gonadal steroids of healthy men aged 20-50 years using subcutaneous goserelin. In one cohort, 198 men then were randomly assigned to receive placebo, 1.25 g, 2.5 g, 5 g, or 10 g of a topical testosterone gel daily for 16 weeks. In another cohort, 202 men were randomly assigned to receive these same doses of topical testosterone plus 1 mg daily of anastrozole to block the aromatization of testosterone to estrogen.

All the study subjects, who were blinded to their medication assignments, were assessed every 4 weeks for the duration of the study for gonadal steroid levels, physical function, health status, vitality, and sexual function. Dual-energy x-ray absorptiometry (DXA) was used to measure body fat and lean mass, and CT was used to measure the areas of subcutaneous fat, intra-abdominal fat, and thigh muscle. Thigh-muscle strength was assessed using leg presses.

"By administering a variety of testosterone doses, with and without concomitant aromatase inhibition, we found that changes in lean mass, thigh-muscle area, and leg-press strength were attributable to changes in testosterone levels, whereas changes in fat measures were primarily related to changes in estradiol levels. Both androgens and estrogens contributed to the maintenance of normal libido and erectile function," Dr. Finkelstein and his associates said (N. Engl. J. Med. 2013 Sept. 11 [doi:10.1056/NEJMoa1206168]).

As important, the level of testosterone needed to maintain lean mass, fat mass, strength, and sexual function was found to vary considerably among these study subjects.

Most men showed reduced lean mass, muscle area, and erectile function at a mean serum testosterone level of 200 ng/dL, so testosterone supplementation appears to be justified at this level. However, many men showed impairment in these outcomes at lower or higher testosterone levels. In addition, the testosterone levels at which body fat increased and sexual desire decreased varied widely.

"Thus, each person’s specific clinical scenario should be considered when interpreting the clinical significance of the circulating testosterone level," Dr. Finkelstein and his colleagues said.

Also important was the finding that deficiency of estrogen, not testosterone, "is largely responsible for some of the key consequences of male hypogonadism." This indicates that measuring men’s estradiol levels may help in assessing their risk for sexual dysfunction, bone loss, or fat accumulation, the researchers added.

This study was limited in that the duration was restricted to 16 weeks, so as to avoid inducing clinically significant changes in the healthy men who participated. "Because changes in body composition may progress over time, greater changes might have been seen at higher testosterone and estradiol levels if gonadal steroids had been suppressed over a longer period," the investigators noted.

This study was supported by the National Institutes of Health and Abbott Laboratories. Abbott also supplied the testosterone gel at no cost, and Astra Zeneca provided goserelin and anastrozole at no cost, but neither company played a role in study design, data analysis, data interpretation, or manuscript preparation.

Declines in testosterone regulate decreases in men's muscle mass and strength, declines in estrogen regulate increases in men’s fat mass and abdominal fat, and declines in both hormones regulate decreases in men’s libido and erectile function, according to a report published online Sept. 11 in the New England Journal of Medicine.

These are the key findings from a dose-ranging study designed to tease out the complex roles played by both testosterone and estrogen in so-called androgen deficiency. They indicate that a simple, straightforward decline in testosterone doesn’t account for the myriad changes in body composition, strength, and sexual factors experienced by men with "low T."

This in turn suggests that the current approach to assessing and managing the condition – a one-time measurement of serum testosterone only, an across-the-board designation of a "low" level, and simple replenishment with endogenous testosterone only – should be replaced by more rational, nuanced approaches, said Dr. Joel S. Finkelstein of the endocrine unit and his associates at Massachusetts General Hospital, Boston.

They examined a wide spectrum of testosterone levels, and the adverse effects of different levels, by temporarily suppressing the normal endogenous gonadal steroids of healthy men aged 20-50 years using subcutaneous goserelin. In one cohort, 198 men then were randomly assigned to receive placebo, 1.25 g, 2.5 g, 5 g, or 10 g of a topical testosterone gel daily for 16 weeks. In another cohort, 202 men were randomly assigned to receive these same doses of topical testosterone plus 1 mg daily of anastrozole to block the aromatization of testosterone to estrogen.

All the study subjects, who were blinded to their medication assignments, were assessed every 4 weeks for the duration of the study for gonadal steroid levels, physical function, health status, vitality, and sexual function. Dual-energy x-ray absorptiometry (DXA) was used to measure body fat and lean mass, and CT was used to measure the areas of subcutaneous fat, intra-abdominal fat, and thigh muscle. Thigh-muscle strength was assessed using leg presses.

"By administering a variety of testosterone doses, with and without concomitant aromatase inhibition, we found that changes in lean mass, thigh-muscle area, and leg-press strength were attributable to changes in testosterone levels, whereas changes in fat measures were primarily related to changes in estradiol levels. Both androgens and estrogens contributed to the maintenance of normal libido and erectile function," Dr. Finkelstein and his associates said (N. Engl. J. Med. 2013 Sept. 11 [doi:10.1056/NEJMoa1206168]).

As important, the level of testosterone needed to maintain lean mass, fat mass, strength, and sexual function was found to vary considerably among these study subjects.

Most men showed reduced lean mass, muscle area, and erectile function at a mean serum testosterone level of 200 ng/dL, so testosterone supplementation appears to be justified at this level. However, many men showed impairment in these outcomes at lower or higher testosterone levels. In addition, the testosterone levels at which body fat increased and sexual desire decreased varied widely.

"Thus, each person’s specific clinical scenario should be considered when interpreting the clinical significance of the circulating testosterone level," Dr. Finkelstein and his colleagues said.

Also important was the finding that deficiency of estrogen, not testosterone, "is largely responsible for some of the key consequences of male hypogonadism." This indicates that measuring men’s estradiol levels may help in assessing their risk for sexual dysfunction, bone loss, or fat accumulation, the researchers added.

This study was limited in that the duration was restricted to 16 weeks, so as to avoid inducing clinically significant changes in the healthy men who participated. "Because changes in body composition may progress over time, greater changes might have been seen at higher testosterone and estradiol levels if gonadal steroids had been suppressed over a longer period," the investigators noted.

This study was supported by the National Institutes of Health and Abbott Laboratories. Abbott also supplied the testosterone gel at no cost, and Astra Zeneca provided goserelin and anastrozole at no cost, but neither company played a role in study design, data analysis, data interpretation, or manuscript preparation.

Combined therapy with pentoxifylline and prednisolone failed to improve 6-month survival in patients with severe alcoholic hepatitis, compared with prednisolone alone, according to a report published online Sept. 10 in JAMA.

In the largest and the only double-blind randomized clinical trial of this combination therapy performed to date, overall survival at 6 months was 69.9% for pentoxifylline plus prednisolone, compared with 69.2% for placebo plus prednisolone. "Our study does not support the use of a combination of pentoxifylline and prednisolone for severe alcoholic hepatitis," said Dr. Philippe Mathurin of Hopital Huriez, Lille (France), and his associates in their report (JAMA. 2013;310:1033-41. doi:10.1001/jama.2013.276300).

The two agents are believed to have two different and perhaps complementary mechanisms of action, so it was thought that combining them might have a synergistic therapeutic effect. Pentoxifylline appears to protect against the hepatorenal syndrome without exerting any significant effect on inflammatory cytokines or liver tests, while prednisolone improves liver function, inhibits inflammatory cytokines, and interferes with the activation of polymorphonuclear neutrophils.

Dr. Mathurin and his colleagues compared the combination therapy against prednisolone alone in 270 patients treated at 23 French and 1 Belgian hospital during a 3-year period. The study subjects were heavy drinkers with biopsy-proven alcoholic hepatitis whose disease was judged to be severe based on the recent onset of jaundice and a Maddrey score of at least 32.

The 163 men and 107 women were assigned randomly to receive either 40 mg prednisolone once daily plus 400 mg pentoxifylline three times daily (133 patients) or 40 mg prednisolone once daily plus a placebo three times daily (137 patients), for 28 days. If adverse effects developed, treatment could be reduced or interrupted at the discretion of the treating physician.

The primary endpoint was survival 6 months after initiating treatment.

There was no significant difference in this outcome between the combination-therapy group (69.9%) and the single-therapy group (69.2%) in the intention-to-treat analysis nor in the per-protocol analysis (72.4% and 70%, respectively).

The mean length of time until death also was not significantly different: 49.7 days with combination therapy and 51.4 days with single therapy, the investigators said.

Causes of death also were similar between the two study groups. Complications of liver failure were cited in approximately 82% of the entire study population and gastrointestinal bleeding in the remaining 18%.

Overall, 26% of the study subjects relapsed and began drinking alcohol again during 6-month follow-up. However, survival did not differ between patients who relapsed and those who did not.

Patients deemed to be treatment responders had markedly better 6-month survival (85%) than did nonresponders (46%), but the treatment response rate did not differ between the two study groups. Similarly, in an analysis restricted only to complete responders and null responders, survival did not differ significantly between patients who received the combination therapy and those who received prednisolone alone.

At the beginning of the study, it was thought that the combination of pentoxifylline plus prednisolone would improve survival chiefly by reducing the incidence of hepatorenal syndrome, relative to prednisolone alone. And at the conclusion of the 1-month course of treatment, the risk of hepatorenal syndrome was significantly lower with combination therapy (3.1%) than with prednisolone alone (11.7%). However, this difference disappeared by the end of follow-up.

But it is important to note that this study was only powered to detect a difference in survival, the primary outcome, and was likely underpowered to detect differences in secondary outcomes such as the rate of the hepatorenal syndrome. "Therefore, the difference in the incidence of hepatorenal syndrome in our study should not be interpreted as being null, and a larger study is necessary to evaluate this issue," according to Dr. Mathurin and his associates.

Regarding the adverse effects of treatment, 13 patients in each study group required temporary withdrawal from therapy. And the rate of complete withdrawal due to adverse treatment effects was not significantly different between the two study groups.

Adverse effects included infections, pruritus, diarrhea, and nausea.

The study findings do not support the use of combination therapy for severe alcoholic hepatitis, and suggest that other agents that target different pathways, such as those involved in liver regeneration, should be explored, the researchers said.

This study was supported by a grant from the French Ministry of Health to the Hospital-Based Clinical Research Program. Pentoxifylline and its matching placebo were supplied by Sanofi-Aventis. No financial conflicts of interest were reported.

Combined therapy with pentoxifylline and prednisolone failed to improve 6-month survival in patients with severe alcoholic hepatitis, compared with prednisolone alone, according to a report published online Sept. 10 in JAMA.

In the largest and the only double-blind randomized clinical trial of this combination therapy performed to date, overall survival at 6 months was 69.9% for pentoxifylline plus prednisolone, compared with 69.2% for placebo plus prednisolone. "Our study does not support the use of a combination of pentoxifylline and prednisolone for severe alcoholic hepatitis," said Dr. Philippe Mathurin of Hopital Huriez, Lille (France), and his associates in their report (JAMA. 2013;310:1033-41. doi:10.1001/jama.2013.276300).

The two agents are believed to have two different and perhaps complementary mechanisms of action, so it was thought that combining them might have a synergistic therapeutic effect. Pentoxifylline appears to protect against the hepatorenal syndrome without exerting any significant effect on inflammatory cytokines or liver tests, while prednisolone improves liver function, inhibits inflammatory cytokines, and interferes with the activation of polymorphonuclear neutrophils.

Dr. Mathurin and his colleagues compared the combination therapy against prednisolone alone in 270 patients treated at 23 French and 1 Belgian hospital during a 3-year period. The study subjects were heavy drinkers with biopsy-proven alcoholic hepatitis whose disease was judged to be severe based on the recent onset of jaundice and a Maddrey score of at least 32.

The 163 men and 107 women were assigned randomly to receive either 40 mg prednisolone once daily plus 400 mg pentoxifylline three times daily (133 patients) or 40 mg prednisolone once daily plus a placebo three times daily (137 patients), for 28 days. If adverse effects developed, treatment could be reduced or interrupted at the discretion of the treating physician.

The primary endpoint was survival 6 months after initiating treatment.

There was no significant difference in this outcome between the combination-therapy group (69.9%) and the single-therapy group (69.2%) in the intention-to-treat analysis nor in the per-protocol analysis (72.4% and 70%, respectively).

The mean length of time until death also was not significantly different: 49.7 days with combination therapy and 51.4 days with single therapy, the investigators said.

Causes of death also were similar between the two study groups. Complications of liver failure were cited in approximately 82% of the entire study population and gastrointestinal bleeding in the remaining 18%.

Overall, 26% of the study subjects relapsed and began drinking alcohol again during 6-month follow-up. However, survival did not differ between patients who relapsed and those who did not.

Patients deemed to be treatment responders had markedly better 6-month survival (85%) than did nonresponders (46%), but the treatment response rate did not differ between the two study groups. Similarly, in an analysis restricted only to complete responders and null responders, survival did not differ significantly between patients who received the combination therapy and those who received prednisolone alone.

At the beginning of the study, it was thought that the combination of pentoxifylline plus prednisolone would improve survival chiefly by reducing the incidence of hepatorenal syndrome, relative to prednisolone alone. And at the conclusion of the 1-month course of treatment, the risk of hepatorenal syndrome was significantly lower with combination therapy (3.1%) than with prednisolone alone (11.7%). However, this difference disappeared by the end of follow-up.

But it is important to note that this study was only powered to detect a difference in survival, the primary outcome, and was likely underpowered to detect differences in secondary outcomes such as the rate of the hepatorenal syndrome. "Therefore, the difference in the incidence of hepatorenal syndrome in our study should not be interpreted as being null, and a larger study is necessary to evaluate this issue," according to Dr. Mathurin and his associates.

Regarding the adverse effects of treatment, 13 patients in each study group required temporary withdrawal from therapy. And the rate of complete withdrawal due to adverse treatment effects was not significantly different between the two study groups.

Adverse effects included infections, pruritus, diarrhea, and nausea.

The study findings do not support the use of combination therapy for severe alcoholic hepatitis, and suggest that other agents that target different pathways, such as those involved in liver regeneration, should be explored, the researchers said.

This study was supported by a grant from the French Ministry of Health to the Hospital-Based Clinical Research Program. Pentoxifylline and its matching placebo were supplied by Sanofi-Aventis. No financial conflicts of interest were reported.

Combined therapy with pentoxifylline and prednisolone failed to improve 6-month survival in patients with severe alcoholic hepatitis, compared with prednisolone alone, according to a report published online Sept. 10 in JAMA.

In the largest and the only double-blind randomized clinical trial of this combination therapy performed to date, overall survival at 6 months was 69.9% for pentoxifylline plus prednisolone, compared with 69.2% for placebo plus prednisolone. "Our study does not support the use of a combination of pentoxifylline and prednisolone for severe alcoholic hepatitis," said Dr. Philippe Mathurin of Hopital Huriez, Lille (France), and his associates in their report (JAMA. 2013;310:1033-41. doi:10.1001/jama.2013.276300).

The two agents are believed to have two different and perhaps complementary mechanisms of action, so it was thought that combining them might have a synergistic therapeutic effect. Pentoxifylline appears to protect against the hepatorenal syndrome without exerting any significant effect on inflammatory cytokines or liver tests, while prednisolone improves liver function, inhibits inflammatory cytokines, and interferes with the activation of polymorphonuclear neutrophils.

Dr. Mathurin and his colleagues compared the combination therapy against prednisolone alone in 270 patients treated at 23 French and 1 Belgian hospital during a 3-year period. The study subjects were heavy drinkers with biopsy-proven alcoholic hepatitis whose disease was judged to be severe based on the recent onset of jaundice and a Maddrey score of at least 32.

The 163 men and 107 women were assigned randomly to receive either 40 mg prednisolone once daily plus 400 mg pentoxifylline three times daily (133 patients) or 40 mg prednisolone once daily plus a placebo three times daily (137 patients), for 28 days. If adverse effects developed, treatment could be reduced or interrupted at the discretion of the treating physician.

The primary endpoint was survival 6 months after initiating treatment.

There was no significant difference in this outcome between the combination-therapy group (69.9%) and the single-therapy group (69.2%) in the intention-to-treat analysis nor in the per-protocol analysis (72.4% and 70%, respectively).

The mean length of time until death also was not significantly different: 49.7 days with combination therapy and 51.4 days with single therapy, the investigators said.

Causes of death also were similar between the two study groups. Complications of liver failure were cited in approximately 82% of the entire study population and gastrointestinal bleeding in the remaining 18%.

Overall, 26% of the study subjects relapsed and began drinking alcohol again during 6-month follow-up. However, survival did not differ between patients who relapsed and those who did not.

Patients deemed to be treatment responders had markedly better 6-month survival (85%) than did nonresponders (46%), but the treatment response rate did not differ between the two study groups. Similarly, in an analysis restricted only to complete responders and null responders, survival did not differ significantly between patients who received the combination therapy and those who received prednisolone alone.

At the beginning of the study, it was thought that the combination of pentoxifylline plus prednisolone would improve survival chiefly by reducing the incidence of hepatorenal syndrome, relative to prednisolone alone. And at the conclusion of the 1-month course of treatment, the risk of hepatorenal syndrome was significantly lower with combination therapy (3.1%) than with prednisolone alone (11.7%). However, this difference disappeared by the end of follow-up.

But it is important to note that this study was only powered to detect a difference in survival, the primary outcome, and was likely underpowered to detect differences in secondary outcomes such as the rate of the hepatorenal syndrome. "Therefore, the difference in the incidence of hepatorenal syndrome in our study should not be interpreted as being null, and a larger study is necessary to evaluate this issue," according to Dr. Mathurin and his associates.

Regarding the adverse effects of treatment, 13 patients in each study group required temporary withdrawal from therapy. And the rate of complete withdrawal due to adverse treatment effects was not significantly different between the two study groups.

Adverse effects included infections, pruritus, diarrhea, and nausea.

The study findings do not support the use of combination therapy for severe alcoholic hepatitis, and suggest that other agents that target different pathways, such as those involved in liver regeneration, should be explored, the researchers said.

This study was supported by a grant from the French Ministry of Health to the Hospital-Based Clinical Research Program. Pentoxifylline and its matching placebo were supplied by Sanofi-Aventis. No financial conflicts of interest were reported.

In patients with asymptomatic or minimally symptomatic mitral valve regurgitation as a result of flail mitral leaflets, early surgery yields better survival, lower risk of heart failure, and equivalent rates of atrial fibrillation, compared with watchful waiting, according to a report published online on August 13 in JAMA.

Overall long-term mortality is approximately 40% lower and HF risk approximately 60% lower for early surgery vs. watchful waiting. These benefits persist for up to 20 years and are seen across every important subgroup of patients, said Dr. Rakesh M. Suri of the Mayo Clinic, Rochester, Minn., and his associates.

These are the findings of a series of analyses of data from an international registry of consecutive patients diagnosed in routine clinical practice – the largest study in the world of the comparative effectiveness of early surgery vs. watchful waiting in patients without traditional indications for immediate surgery. The study results "emanate from institutions that together provide a very high rate of mitral valve repair (more than 90%) with low operative mortality, emphasizing that such results might also be achieved in routine practice at many advanced repair centers," the investigators noted.

Despite the safety and efficacy of current surgical correction of flail mitral leaflets, clinicians disagree as to the best approach for patients who have no or minimal HF symptoms, a left ventricular ejection fraction of 60% or more, and a left ventricular end-systolic diameter of 40 mm or more. Those who support watchful waiting consider the consequences of uncorrected mitral regurgitation to be benign, especially when weighed against the potential morbidity and mortality of early surgical intervention. North American guidelines favor early surgery while European guidelines favor watchful waiting.

The Mitral Regurgitation International Database (MIDA) – a registry of patients at two tertiary care centers in France, two in Italy, one in Belgium, and one in the United States – provided an ideal study population to compare the two approaches. For their study, Dr. Suri and his associates examined data for 1,021 of these patients who had been diagnosed in 1980-2004 and followed for up to 25 years (mean follow-up, 10.3 years).

This study included only patients who had no ischemic mitral regurgitation and no significant concomitant aortic valve disease, congenital heart disease, mitral stenosis, or previous valve surgery.

A total of 446 of these patients underwent early surgery (within 30 days of diagnosis) and 575 had watchful waiting at the discretion of their treating physicians. Importantly, 339 (59%) of the watchful-waiting group eventually were advised by their cardiologists to undergo valve repair, at a median of 1.65 years after diagnosis.

Overall, there were 319 deaths during follow-up.

The primary end points of this study were all-cause mortality at 5, 10, and 20 years.

In the initial, unadjusted analysis, survival was 95%, 86%, and 63%, respectively, with early surgery. In contrast, survival was significantly lower with watchful waiting, at 84% at 5 years, 69% at 10 years, and 41% at 20 years, the researchers said (JAMA 2013; 310:609-16).

The large survival benefit with early surgery was confirmed in a multivariable analysis that adjusted for patient age, sex, comorbidities, and the presence of subtle symptoms.

To account for differences between the two study groups in the propensity to undergo surgery, the investigators performed an analysis of the data in a set of 648 patients who were matched for age, comorbidities, and other factors. This analysis also showed a similar and distinct survival advantage with early surgery. Several subgroup analyses also confirmed the results.

Secondary end points were the incidence of heart failure and the onset of new atrial fibrillation during follow-up.

A total of 167 patients had at least one episode of HF. The rates were 7% with early surgery and 23% with watchful waiting at 10 years, and 10% vs. 35% at 20 years, showing a clear advantage for early surgery.

This strong advantage persisted in further analyses of the propensity-matched patients and in all other subgroups examined, at all time points examined.

New-onset AF developed in 227 patients overall. The rate was slightly higher in the early-surgery group during the immediate postoperative period but decreased thereafter and was equivalent between the two study groups at 5, 10, and 20 years.

"Long-term, the results are coherent by all methods used (direct comparison, adjusted comparison, propensity score matching, inverse probability weighing) that early surgical correction of mitral valve regurgitation was associated with a significant survival benefit (total mortality decrement of approximately 40%) and diminished HF risk (reduction of approximately 60%)," Dr. Suri and his associates wrote.

Dr. Suri reported ties to Edwards Lifesciences, Sorin Group, St. Jude Medical, and Abbott.

In patients with asymptomatic or minimally symptomatic mitral valve regurgitation as a result of flail mitral leaflets, early surgery yields better survival, lower risk of heart failure, and equivalent rates of atrial fibrillation, compared with watchful waiting, according to a report published online on August 13 in JAMA.

Overall long-term mortality is approximately 40% lower and HF risk approximately 60% lower for early surgery vs. watchful waiting. These benefits persist for up to 20 years and are seen across every important subgroup of patients, said Dr. Rakesh M. Suri of the Mayo Clinic, Rochester, Minn., and his associates.

These are the findings of a series of analyses of data from an international registry of consecutive patients diagnosed in routine clinical practice – the largest study in the world of the comparative effectiveness of early surgery vs. watchful waiting in patients without traditional indications for immediate surgery. The study results "emanate from institutions that together provide a very high rate of mitral valve repair (more than 90%) with low operative mortality, emphasizing that such results might also be achieved in routine practice at many advanced repair centers," the investigators noted.

Despite the safety and efficacy of current surgical correction of flail mitral leaflets, clinicians disagree as to the best approach for patients who have no or minimal HF symptoms, a left ventricular ejection fraction of 60% or more, and a left ventricular end-systolic diameter of 40 mm or more. Those who support watchful waiting consider the consequences of uncorrected mitral regurgitation to be benign, especially when weighed against the potential morbidity and mortality of early surgical intervention. North American guidelines favor early surgery while European guidelines favor watchful waiting.

The Mitral Regurgitation International Database (MIDA) – a registry of patients at two tertiary care centers in France, two in Italy, one in Belgium, and one in the United States – provided an ideal study population to compare the two approaches. For their study, Dr. Suri and his associates examined data for 1,021 of these patients who had been diagnosed in 1980-2004 and followed for up to 25 years (mean follow-up, 10.3 years).

This study included only patients who had no ischemic mitral regurgitation and no significant concomitant aortic valve disease, congenital heart disease, mitral stenosis, or previous valve surgery.

A total of 446 of these patients underwent early surgery (within 30 days of diagnosis) and 575 had watchful waiting at the discretion of their treating physicians. Importantly, 339 (59%) of the watchful-waiting group eventually were advised by their cardiologists to undergo valve repair, at a median of 1.65 years after diagnosis.

Overall, there were 319 deaths during follow-up.

The primary end points of this study were all-cause mortality at 5, 10, and 20 years.

In the initial, unadjusted analysis, survival was 95%, 86%, and 63%, respectively, with early surgery. In contrast, survival was significantly lower with watchful waiting, at 84% at 5 years, 69% at 10 years, and 41% at 20 years, the researchers said (JAMA 2013; 310:609-16).

The large survival benefit with early surgery was confirmed in a multivariable analysis that adjusted for patient age, sex, comorbidities, and the presence of subtle symptoms.

To account for differences between the two study groups in the propensity to undergo surgery, the investigators performed an analysis of the data in a set of 648 patients who were matched for age, comorbidities, and other factors. This analysis also showed a similar and distinct survival advantage with early surgery. Several subgroup analyses also confirmed the results.

Secondary end points were the incidence of heart failure and the onset of new atrial fibrillation during follow-up.

A total of 167 patients had at least one episode of HF. The rates were 7% with early surgery and 23% with watchful waiting at 10 years, and 10% vs. 35% at 20 years, showing a clear advantage for early surgery.

This strong advantage persisted in further analyses of the propensity-matched patients and in all other subgroups examined, at all time points examined.

New-onset AF developed in 227 patients overall. The rate was slightly higher in the early-surgery group during the immediate postoperative period but decreased thereafter and was equivalent between the two study groups at 5, 10, and 20 years.

"Long-term, the results are coherent by all methods used (direct comparison, adjusted comparison, propensity score matching, inverse probability weighing) that early surgical correction of mitral valve regurgitation was associated with a significant survival benefit (total mortality decrement of approximately 40%) and diminished HF risk (reduction of approximately 60%)," Dr. Suri and his associates wrote.

Dr. Suri reported ties to Edwards Lifesciences, Sorin Group, St. Jude Medical, and Abbott.

In patients with asymptomatic or minimally symptomatic mitral valve regurgitation as a result of flail mitral leaflets, early surgery yields better survival, lower risk of heart failure, and equivalent rates of atrial fibrillation, compared with watchful waiting, according to a report published online on August 13 in JAMA.

Overall long-term mortality is approximately 40% lower and HF risk approximately 60% lower for early surgery vs. watchful waiting. These benefits persist for up to 20 years and are seen across every important subgroup of patients, said Dr. Rakesh M. Suri of the Mayo Clinic, Rochester, Minn., and his associates.

These are the findings of a series of analyses of data from an international registry of consecutive patients diagnosed in routine clinical practice – the largest study in the world of the comparative effectiveness of early surgery vs. watchful waiting in patients without traditional indications for immediate surgery. The study results "emanate from institutions that together provide a very high rate of mitral valve repair (more than 90%) with low operative mortality, emphasizing that such results might also be achieved in routine practice at many advanced repair centers," the investigators noted.

Despite the safety and efficacy of current surgical correction of flail mitral leaflets, clinicians disagree as to the best approach for patients who have no or minimal HF symptoms, a left ventricular ejection fraction of 60% or more, and a left ventricular end-systolic diameter of 40 mm or more. Those who support watchful waiting consider the consequences of uncorrected mitral regurgitation to be benign, especially when weighed against the potential morbidity and mortality of early surgical intervention. North American guidelines favor early surgery while European guidelines favor watchful waiting.

The Mitral Regurgitation International Database (MIDA) – a registry of patients at two tertiary care centers in France, two in Italy, one in Belgium, and one in the United States – provided an ideal study population to compare the two approaches. For their study, Dr. Suri and his associates examined data for 1,021 of these patients who had been diagnosed in 1980-2004 and followed for up to 25 years (mean follow-up, 10.3 years).

This study included only patients who had no ischemic mitral regurgitation and no significant concomitant aortic valve disease, congenital heart disease, mitral stenosis, or previous valve surgery.

A total of 446 of these patients underwent early surgery (within 30 days of diagnosis) and 575 had watchful waiting at the discretion of their treating physicians. Importantly, 339 (59%) of the watchful-waiting group eventually were advised by their cardiologists to undergo valve repair, at a median of 1.65 years after diagnosis.

Overall, there were 319 deaths during follow-up.

The primary end points of this study were all-cause mortality at 5, 10, and 20 years.

In the initial, unadjusted analysis, survival was 95%, 86%, and 63%, respectively, with early surgery. In contrast, survival was significantly lower with watchful waiting, at 84% at 5 years, 69% at 10 years, and 41% at 20 years, the researchers said (JAMA 2013; 310:609-16).

The large survival benefit with early surgery was confirmed in a multivariable analysis that adjusted for patient age, sex, comorbidities, and the presence of subtle symptoms.

To account for differences between the two study groups in the propensity to undergo surgery, the investigators performed an analysis of the data in a set of 648 patients who were matched for age, comorbidities, and other factors. This analysis also showed a similar and distinct survival advantage with early surgery. Several subgroup analyses also confirmed the results.

Secondary end points were the incidence of heart failure and the onset of new atrial fibrillation during follow-up.

A total of 167 patients had at least one episode of HF. The rates were 7% with early surgery and 23% with watchful waiting at 10 years, and 10% vs. 35% at 20 years, showing a clear advantage for early surgery.

This strong advantage persisted in further analyses of the propensity-matched patients and in all other subgroups examined, at all time points examined.

New-onset AF developed in 227 patients overall. The rate was slightly higher in the early-surgery group during the immediate postoperative period but decreased thereafter and was equivalent between the two study groups at 5, 10, and 20 years.

"Long-term, the results are coherent by all methods used (direct comparison, adjusted comparison, propensity score matching, inverse probability weighing) that early surgical correction of mitral valve regurgitation was associated with a significant survival benefit (total mortality decrement of approximately 40%) and diminished HF risk (reduction of approximately 60%)," Dr. Suri and his associates wrote.

Dr. Suri reported ties to Edwards Lifesciences, Sorin Group, St. Jude Medical, and Abbott.

Despite the frequent assertion that survival has improved in recent years for patients who have pulmonary hypertension associated with systemic sclerosis, a meta-analysis that allowed pooling of data from numerous small studies shows otherwise.

In a report published online Aug. 26 in Arthritis & Rheumatism, 3-year survival was only 52% in these patients. This confirms that pulmonary hypertension is a severe complication of, and a leading cause of death in, systemic sclerosis, said Dr. Guillame Lefèvre of Université Lille Nord de France in Lille, and his associates.

Many studies have examined survival in systemic sclerosis–associated pulmonary hypertension (PH) and have asserted that survival has improved of late, but none have clearly demonstrated such a trend because they haven’t fully accounted for confounding factors such as baseline differences in disease severity over time. Dr. Lefèvre and his colleagues assessed survival by pooling the data on 2,244 adult patients who participated in 22 cohort studies between 1960 and 2012 in which detailed information on prognostic factors was included.

Overall, 83% of the patients were women; 79% had limited cutaneous systemic sclerosis, and 18% had diffuse cutaneous disease. The mean patient age was 60 years, and 83% were white.

The pooled survival rates were 81% at 1 year, 64% at 2 years, and 52% at 3 years.

There was no evidence that survival has improved over time. In fact, the evidence indicated instead that because of screening programs and increased awareness of the disease in recent years, contemporary patients are being diagnosed sooner in the course of the disease, and thus have less severe disease at presentation than do their counterparts diagnosed 30 or 40 years ago, the investigators said (Arth. Rheum. 2013;65: 2412-23 [doi:10.1002/art.38029]).

This study could not assess whether newer treatments may have contributed to the impression that survival has improved over time, because of the extreme heterogeneity of therapies across the 22 studies and the numerous instances of missing data on this topic.

However, several factors other than time trends and therapies were found to correlate with improved survival.

Disease severity at baseline, as measured by hemodynamic factors (particularly pulmonary vascular resistance), was strongly correlated with survival. Beyond that, prognostic factors were found to be quite different between pulmonary arterial hypertension (PAH) and PH related to interstitial lung disease (ILD-associated PH).

Three-year survival was deemed "dismal" for ILD-associated PH at 35%, compared with the 56% 3-year-survival for PAH.

In PAH, older age at diagnosis, male gender, worse New York Heart Association functional class, shorter 6-minute walk distance, pericardial effusion, and adverse results on several laboratory tests (diffusing capacity for carbon monoxide, right atrial pressure, mean pulmonary artery pressure (mPAP), cardiac index, and pulmonary vascular resistance) all were significant prognostic factors. In contrast, subtype of systemic sclerosis, the presence or absence of anticentromere antibodies, forced vital capacity, and pulmonary capillary wedge pressure were not significant prognostic factors.

In ILD-associated PH, only pericardial effusion and diffusing capacity for carbon monoxide were found to be prognostic factors.

It was somewhat surprising that 6-minute walk distance proved to be a good predictor of survival in this study, because it has been considered by many researchers to be a poor prognostic tool. Several studies have reported that this test reflects many factors unrelated to pulmonary function, such as musculoskeletal impairment or depression. Yet 6-minute walk distance was clearly predictive in this metaanalysis, Dr. Lefèvre and his associates said.

Similarly, the pooling of data in this study showed that factors such as cardiac index, pulmonary vascular resistance, right atrial pressure, and mPAP were useful for prognosis. Previous studies that argued against the usefulness of these factors probably had sample sizes that were too small to demonstrate a significant association with survival, they added.

Dr. Lefèvre’s associates reported ties to Actelion, Bayer, GlaxoSmithKline, Novartis, Pfizer, and Lilly.

Despite the frequent assertion that survival has improved in recent years for patients who have pulmonary hypertension associated with systemic sclerosis, a meta-analysis that allowed pooling of data from numerous small studies shows otherwise.

In a report published online Aug. 26 in Arthritis & Rheumatism, 3-year survival was only 52% in these patients. This confirms that pulmonary hypertension is a severe complication of, and a leading cause of death in, systemic sclerosis, said Dr. Guillame Lefèvre of Université Lille Nord de France in Lille, and his associates.

Many studies have examined survival in systemic sclerosis–associated pulmonary hypertension (PH) and have asserted that survival has improved of late, but none have clearly demonstrated such a trend because they haven’t fully accounted for confounding factors such as baseline differences in disease severity over time. Dr. Lefèvre and his colleagues assessed survival by pooling the data on 2,244 adult patients who participated in 22 cohort studies between 1960 and 2012 in which detailed information on prognostic factors was included.

Overall, 83% of the patients were women; 79% had limited cutaneous systemic sclerosis, and 18% had diffuse cutaneous disease. The mean patient age was 60 years, and 83% were white.

The pooled survival rates were 81% at 1 year, 64% at 2 years, and 52% at 3 years.

There was no evidence that survival has improved over time. In fact, the evidence indicated instead that because of screening programs and increased awareness of the disease in recent years, contemporary patients are being diagnosed sooner in the course of the disease, and thus have less severe disease at presentation than do their counterparts diagnosed 30 or 40 years ago, the investigators said (Arth. Rheum. 2013;65: 2412-23 [doi:10.1002/art.38029]).

This study could not assess whether newer treatments may have contributed to the impression that survival has improved over time, because of the extreme heterogeneity of therapies across the 22 studies and the numerous instances of missing data on this topic.

However, several factors other than time trends and therapies were found to correlate with improved survival.

Disease severity at baseline, as measured by hemodynamic factors (particularly pulmonary vascular resistance), was strongly correlated with survival. Beyond that, prognostic factors were found to be quite different between pulmonary arterial hypertension (PAH) and PH related to interstitial lung disease (ILD-associated PH).

Three-year survival was deemed "dismal" for ILD-associated PH at 35%, compared with the 56% 3-year-survival for PAH.

In PAH, older age at diagnosis, male gender, worse New York Heart Association functional class, shorter 6-minute walk distance, pericardial effusion, and adverse results on several laboratory tests (diffusing capacity for carbon monoxide, right atrial pressure, mean pulmonary artery pressure (mPAP), cardiac index, and pulmonary vascular resistance) all were significant prognostic factors. In contrast, subtype of systemic sclerosis, the presence or absence of anticentromere antibodies, forced vital capacity, and pulmonary capillary wedge pressure were not significant prognostic factors.

In ILD-associated PH, only pericardial effusion and diffusing capacity for carbon monoxide were found to be prognostic factors.

It was somewhat surprising that 6-minute walk distance proved to be a good predictor of survival in this study, because it has been considered by many researchers to be a poor prognostic tool. Several studies have reported that this test reflects many factors unrelated to pulmonary function, such as musculoskeletal impairment or depression. Yet 6-minute walk distance was clearly predictive in this metaanalysis, Dr. Lefèvre and his associates said.

Similarly, the pooling of data in this study showed that factors such as cardiac index, pulmonary vascular resistance, right atrial pressure, and mPAP were useful for prognosis. Previous studies that argued against the usefulness of these factors probably had sample sizes that were too small to demonstrate a significant association with survival, they added.

Dr. Lefèvre’s associates reported ties to Actelion, Bayer, GlaxoSmithKline, Novartis, Pfizer, and Lilly.

Despite the frequent assertion that survival has improved in recent years for patients who have pulmonary hypertension associated with systemic sclerosis, a meta-analysis that allowed pooling of data from numerous small studies shows otherwise.

In a report published online Aug. 26 in Arthritis & Rheumatism, 3-year survival was only 52% in these patients. This confirms that pulmonary hypertension is a severe complication of, and a leading cause of death in, systemic sclerosis, said Dr. Guillame Lefèvre of Université Lille Nord de France in Lille, and his associates.

Many studies have examined survival in systemic sclerosis–associated pulmonary hypertension (PH) and have asserted that survival has improved of late, but none have clearly demonstrated such a trend because they haven’t fully accounted for confounding factors such as baseline differences in disease severity over time. Dr. Lefèvre and his colleagues assessed survival by pooling the data on 2,244 adult patients who participated in 22 cohort studies between 1960 and 2012 in which detailed information on prognostic factors was included.

Overall, 83% of the patients were women; 79% had limited cutaneous systemic sclerosis, and 18% had diffuse cutaneous disease. The mean patient age was 60 years, and 83% were white.

The pooled survival rates were 81% at 1 year, 64% at 2 years, and 52% at 3 years.

There was no evidence that survival has improved over time. In fact, the evidence indicated instead that because of screening programs and increased awareness of the disease in recent years, contemporary patients are being diagnosed sooner in the course of the disease, and thus have less severe disease at presentation than do their counterparts diagnosed 30 or 40 years ago, the investigators said (Arth. Rheum. 2013;65: 2412-23 [doi:10.1002/art.38029]).

This study could not assess whether newer treatments may have contributed to the impression that survival has improved over time, because of the extreme heterogeneity of therapies across the 22 studies and the numerous instances of missing data on this topic.

However, several factors other than time trends and therapies were found to correlate with improved survival.

Disease severity at baseline, as measured by hemodynamic factors (particularly pulmonary vascular resistance), was strongly correlated with survival. Beyond that, prognostic factors were found to be quite different between pulmonary arterial hypertension (PAH) and PH related to interstitial lung disease (ILD-associated PH).

Three-year survival was deemed "dismal" for ILD-associated PH at 35%, compared with the 56% 3-year-survival for PAH.

In PAH, older age at diagnosis, male gender, worse New York Heart Association functional class, shorter 6-minute walk distance, pericardial effusion, and adverse results on several laboratory tests (diffusing capacity for carbon monoxide, right atrial pressure, mean pulmonary artery pressure (mPAP), cardiac index, and pulmonary vascular resistance) all were significant prognostic factors. In contrast, subtype of systemic sclerosis, the presence or absence of anticentromere antibodies, forced vital capacity, and pulmonary capillary wedge pressure were not significant prognostic factors.

In ILD-associated PH, only pericardial effusion and diffusing capacity for carbon monoxide were found to be prognostic factors.

It was somewhat surprising that 6-minute walk distance proved to be a good predictor of survival in this study, because it has been considered by many researchers to be a poor prognostic tool. Several studies have reported that this test reflects many factors unrelated to pulmonary function, such as musculoskeletal impairment or depression. Yet 6-minute walk distance was clearly predictive in this metaanalysis, Dr. Lefèvre and his associates said.

Similarly, the pooling of data in this study showed that factors such as cardiac index, pulmonary vascular resistance, right atrial pressure, and mPAP were useful for prognosis. Previous studies that argued against the usefulness of these factors probably had sample sizes that were too small to demonstrate a significant association with survival, they added.

Dr. Lefèvre’s associates reported ties to Actelion, Bayer, GlaxoSmithKline, Novartis, Pfizer, and Lilly.

Women who have systemic lupus erythematosus report greater sleep disturbance than did healthy women, with more than 75% of them experiencing poor sleep quality, according to a report published in the Egyptian Rheumatologist.

In a study of 30 Egyptian women with SLE and 30 healthy, age-matched women, the SLE patients had higher scores on the Pittsburgh Sleep Quality Index (PSQI), indicating clinical sleep impairment, said Dr. Hanan A. Kotb of the department of rheumatology and rehabilitation, Cairo University, and associates.

© YinYang/iStockphoto.com

Yet despite the high frequency and clinical severity of their sleep problems, only 30% of the SLE patients reported using any sleep medication. This indicates that clinicians routinely underestimate sleep disturbance in this patient population, the investigators said.

Dr. Kotb and colleagues assessed sleep problems in these 60 study subjects using the PSQI, which measures seven sleep components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The global score on this instrument ranges from 0 to 21 points, and a cutoff score of 6 or higher differentiates clinical sleep impairment with a sensitivity of 89.6% and a specificity of 86.5%.

The investigators assessed pain severity by using the visual analogue scale.

Among the SLE patients in this study, 13 (43%) had mild disease activity and 14 (47%) had moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The remaining three patients (10%) had severe disease activity.

All of the SLE patients were taking corticosteroids.

Compared with the control subjects, the SLE patients had significantly higher PSQI scores, indicating poorer sleep quality. The mean PSQI score was 8.47 among SLE patients, compared with 5.1 among healthy women.

In addition, the proportion of SLE patients who had high global PSQI scores was 77%, compared with only 30% of the control subjects, the researchers said (Egypt. Rheumatologist 2013;35:127-32 [doi: 10.1016/j.ejr.2013.02.003]).

The differences between the two study groups were significant for most of the seven individual sleep components measured. The single most prominent component of sleep disturbance in this study population was daytime dysfunction.

In a data analysis designed to identify which particular disease factors correlated with sleep problems, SLE activity, and duration, the degree of the patient’s functional disability, the severity of organ damage, pain severity, and depressed mood all were significantly associated with sleep disturbance.

However, in further refined analyses, only disease activity and scores on an index of organ damage were significant contributors to sleep disturbance.

In contrast, the use of corticosteroids, subject age, and subject education level showed no association with sleep problems.

These findings indicate that the routine management of SLE should include the assessment and management of sleep problems, Dr. Kotb and associates said.

The exact mechanism by which SLE impairs sleep is not yet known. "In autoimmune diseases, the elevated levels of proinflammatory cytokines may influence daytime sleepiness and disrupt nocturnal sleep. This pathway remains to be explored in SLE," they added.

No funding sources or financial conflicts of interest were reported.

Women who have systemic lupus erythematosus report greater sleep disturbance than did healthy women, with more than 75% of them experiencing poor sleep quality, according to a report published in the Egyptian Rheumatologist.

In a study of 30 Egyptian women with SLE and 30 healthy, age-matched women, the SLE patients had higher scores on the Pittsburgh Sleep Quality Index (PSQI), indicating clinical sleep impairment, said Dr. Hanan A. Kotb of the department of rheumatology and rehabilitation, Cairo University, and associates.

© YinYang/iStockphoto.com

Yet despite the high frequency and clinical severity of their sleep problems, only 30% of the SLE patients reported using any sleep medication. This indicates that clinicians routinely underestimate sleep disturbance in this patient population, the investigators said.

Dr. Kotb and colleagues assessed sleep problems in these 60 study subjects using the PSQI, which measures seven sleep components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The global score on this instrument ranges from 0 to 21 points, and a cutoff score of 6 or higher differentiates clinical sleep impairment with a sensitivity of 89.6% and a specificity of 86.5%.

The investigators assessed pain severity by using the visual analogue scale.

Among the SLE patients in this study, 13 (43%) had mild disease activity and 14 (47%) had moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The remaining three patients (10%) had severe disease activity.

All of the SLE patients were taking corticosteroids.

Compared with the control subjects, the SLE patients had significantly higher PSQI scores, indicating poorer sleep quality. The mean PSQI score was 8.47 among SLE patients, compared with 5.1 among healthy women.

In addition, the proportion of SLE patients who had high global PSQI scores was 77%, compared with only 30% of the control subjects, the researchers said (Egypt. Rheumatologist 2013;35:127-32 [doi: 10.1016/j.ejr.2013.02.003]).

The differences between the two study groups were significant for most of the seven individual sleep components measured. The single most prominent component of sleep disturbance in this study population was daytime dysfunction.

In a data analysis designed to identify which particular disease factors correlated with sleep problems, SLE activity, and duration, the degree of the patient’s functional disability, the severity of organ damage, pain severity, and depressed mood all were significantly associated with sleep disturbance.

However, in further refined analyses, only disease activity and scores on an index of organ damage were significant contributors to sleep disturbance.

In contrast, the use of corticosteroids, subject age, and subject education level showed no association with sleep problems.

These findings indicate that the routine management of SLE should include the assessment and management of sleep problems, Dr. Kotb and associates said.

The exact mechanism by which SLE impairs sleep is not yet known. "In autoimmune diseases, the elevated levels of proinflammatory cytokines may influence daytime sleepiness and disrupt nocturnal sleep. This pathway remains to be explored in SLE," they added.

No funding sources or financial conflicts of interest were reported.

Women who have systemic lupus erythematosus report greater sleep disturbance than did healthy women, with more than 75% of them experiencing poor sleep quality, according to a report published in the Egyptian Rheumatologist.

In a study of 30 Egyptian women with SLE and 30 healthy, age-matched women, the SLE patients had higher scores on the Pittsburgh Sleep Quality Index (PSQI), indicating clinical sleep impairment, said Dr. Hanan A. Kotb of the department of rheumatology and rehabilitation, Cairo University, and associates.

© YinYang/iStockphoto.com

Yet despite the high frequency and clinical severity of their sleep problems, only 30% of the SLE patients reported using any sleep medication. This indicates that clinicians routinely underestimate sleep disturbance in this patient population, the investigators said.

Dr. Kotb and colleagues assessed sleep problems in these 60 study subjects using the PSQI, which measures seven sleep components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The global score on this instrument ranges from 0 to 21 points, and a cutoff score of 6 or higher differentiates clinical sleep impairment with a sensitivity of 89.6% and a specificity of 86.5%.

The investigators assessed pain severity by using the visual analogue scale.

Among the SLE patients in this study, 13 (43%) had mild disease activity and 14 (47%) had moderate disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). The remaining three patients (10%) had severe disease activity.

All of the SLE patients were taking corticosteroids.

Compared with the control subjects, the SLE patients had significantly higher PSQI scores, indicating poorer sleep quality. The mean PSQI score was 8.47 among SLE patients, compared with 5.1 among healthy women.

In addition, the proportion of SLE patients who had high global PSQI scores was 77%, compared with only 30% of the control subjects, the researchers said (Egypt. Rheumatologist 2013;35:127-32 [doi: 10.1016/j.ejr.2013.02.003]).

The differences between the two study groups were significant for most of the seven individual sleep components measured. The single most prominent component of sleep disturbance in this study population was daytime dysfunction.

In a data analysis designed to identify which particular disease factors correlated with sleep problems, SLE activity, and duration, the degree of the patient’s functional disability, the severity of organ damage, pain severity, and depressed mood all were significantly associated with sleep disturbance.

However, in further refined analyses, only disease activity and scores on an index of organ damage were significant contributors to sleep disturbance.

In contrast, the use of corticosteroids, subject age, and subject education level showed no association with sleep problems.

These findings indicate that the routine management of SLE should include the assessment and management of sleep problems, Dr. Kotb and associates said.

The exact mechanism by which SLE impairs sleep is not yet known. "In autoimmune diseases, the elevated levels of proinflammatory cytokines may influence daytime sleepiness and disrupt nocturnal sleep. This pathway remains to be explored in SLE," they added.

No funding sources or financial conflicts of interest were reported.

New statistical models can be used to predict with "excellent" accuracy which lung nodules found on screening low-dose computed tomography scans of high-risk patients are likely to be cancerous, according to a report published online Sept. 4 in the New England Journal of Medicine.

"Our models are coupled with risk calculators, which make possible the rapid and easy calculation of lung-cancer risk given the characteristics of the person and the nodules," said Dr. Annette McWilliams of Vancouver General Hospital and the British Columbia Cancer Agency, and her associates (N. Engl. J. Med. 2013;369:910-9).

Several previous studies have reported that more than 20% of people who participate in low-dose computed tomography (LDCT) screening programs are found to have at least one lung nodule that requires further investigation. Yet only a small percentage of these nodules turn out to be malignant.

In one large screening trial, 25% of the surgical procedures that were prompted by an initial LDCT scan were performed on nodules that proved to be benign. That means that many patients were needlessly exposed to invasive diagnostic procedures, Dr. McWilliams and her colleagues said.

They developed models that would accurately predict the likelihood that such nodules are malignant, so as to guide clinical decision making and thereby reduce the risks and the costs of morbidity and mortality in LDCT screening programs.

The first step was to collect a large amount of detailed data regarding nodules identified on LDCT that were either cancerous when detected or later developed into cancers. To do that, the researchers analyzed data from the multicenter Pan-Canadian Early Detection of Lung Cancer Study, a population-based sample of current and former smokers aged 50-75 years who had no history of lung cancer but had a 3-year risk of at least 2% of developing the disease.

A total of 1,871 of the 2,537 participants in that study (74%) were found to have 7,008 lung nodules on initial scanning. They were followed for a median of 3.1 years using repeat LDCT at 3- to 12-month intervals, depending on the size of the largest nodule.

Lung cancer was diagnosed on the basis of histopathologic assessment of resection specimens or cytopathologic examination of needle-aspiration biopsy samples. A total of 102 nodules (5.5%) were found to be malignant.

Tumor characteristics that strongly correlated with malignancy were larger nodule size, partially solid type (as opposed to nonsolid, fully solid, or perifissural types), location of the nodule in the upper lung lobes, a small number of nodules (rather than numerous nodules), and the presence of spiculation.

Patient characteristics that strongly correlated with malignancy were female sex, older age, family history of lung cancer, and emphysema.

Dr. McWilliams and her associates used these traits to develop prediction models. They then tested the models in a validation cohort: 1,090 current and former smokers aged 50-74 years who underwent LDCT as part of several chemoprevention trials conducted by the British Columbia Cancer Agency over a 10-year period.

Those study subjects were found to have 5,021 lung nodules. Forty of those patients were found to have 42 lung cancers during a median follow-up of 8.6 years.

"Our models showed excellent predictive accuracy," clearly differentiating study subjects who had or developed lung cancer from those who did not. "The models performed well even when applied to nodules 10 mm or smaller, which are the most clinically challenging and most numerous nodules," the investigators noted.

None of the 571 perifissural nodules found on LDCT in those two cohorts proved to be malignant. "When the data from the two studies were pooled, the probability of lung cancer in perifissural nodules was 0," Dr. McWilliams and her associates said.

Such nodules "probably do not require longitudinal follow-up with CT," they added.

Their models are not intended for use in low-risk people for whom LDCT is not currently recommended. The models also "do not apply to persons with hilar or mediastinal lymphadenopathy, for whom further investigations are warranted irrespective of the nodule size," the researchers added.

The Terry Fox Research Institute, the Canadian Partnership Against Cancer, the U.S. Public Health Service, and the National Cancer Institute supported the study. Dr. McWilliams reported no financial conflicts of interest; her associates reported ties to CareFusion, Eli Lilly, GlaxoSmithKline, Med Biogene, Olympus, Pfizer, Roche, Siemens, and Toshiba.

New statistical models can be used to predict with "excellent" accuracy which lung nodules found on screening low-dose computed tomography scans of high-risk patients are likely to be cancerous, according to a report published online Sept. 4 in the New England Journal of Medicine.

"Our models are coupled with risk calculators, which make possible the rapid and easy calculation of lung-cancer risk given the characteristics of the person and the nodules," said Dr. Annette McWilliams of Vancouver General Hospital and the British Columbia Cancer Agency, and her associates (N. Engl. J. Med. 2013;369:910-9).

Several previous studies have reported that more than 20% of people who participate in low-dose computed tomography (LDCT) screening programs are found to have at least one lung nodule that requires further investigation. Yet only a small percentage of these nodules turn out to be malignant.

In one large screening trial, 25% of the surgical procedures that were prompted by an initial LDCT scan were performed on nodules that proved to be benign. That means that many patients were needlessly exposed to invasive diagnostic procedures, Dr. McWilliams and her colleagues said.

They developed models that would accurately predict the likelihood that such nodules are malignant, so as to guide clinical decision making and thereby reduce the risks and the costs of morbidity and mortality in LDCT screening programs.

The first step was to collect a large amount of detailed data regarding nodules identified on LDCT that were either cancerous when detected or later developed into cancers. To do that, the researchers analyzed data from the multicenter Pan-Canadian Early Detection of Lung Cancer Study, a population-based sample of current and former smokers aged 50-75 years who had no history of lung cancer but had a 3-year risk of at least 2% of developing the disease.

A total of 1,871 of the 2,537 participants in that study (74%) were found to have 7,008 lung nodules on initial scanning. They were followed for a median of 3.1 years using repeat LDCT at 3- to 12-month intervals, depending on the size of the largest nodule.

Lung cancer was diagnosed on the basis of histopathologic assessment of resection specimens or cytopathologic examination of needle-aspiration biopsy samples. A total of 102 nodules (5.5%) were found to be malignant.

Tumor characteristics that strongly correlated with malignancy were larger nodule size, partially solid type (as opposed to nonsolid, fully solid, or perifissural types), location of the nodule in the upper lung lobes, a small number of nodules (rather than numerous nodules), and the presence of spiculation.

Patient characteristics that strongly correlated with malignancy were female sex, older age, family history of lung cancer, and emphysema.

Dr. McWilliams and her associates used these traits to develop prediction models. They then tested the models in a validation cohort: 1,090 current and former smokers aged 50-74 years who underwent LDCT as part of several chemoprevention trials conducted by the British Columbia Cancer Agency over a 10-year period.

Those study subjects were found to have 5,021 lung nodules. Forty of those patients were found to have 42 lung cancers during a median follow-up of 8.6 years.

"Our models showed excellent predictive accuracy," clearly differentiating study subjects who had or developed lung cancer from those who did not. "The models performed well even when applied to nodules 10 mm or smaller, which are the most clinically challenging and most numerous nodules," the investigators noted.

None of the 571 perifissural nodules found on LDCT in those two cohorts proved to be malignant. "When the data from the two studies were pooled, the probability of lung cancer in perifissural nodules was 0," Dr. McWilliams and her associates said.

Such nodules "probably do not require longitudinal follow-up with CT," they added.

Their models are not intended for use in low-risk people for whom LDCT is not currently recommended. The models also "do not apply to persons with hilar or mediastinal lymphadenopathy, for whom further investigations are warranted irrespective of the nodule size," the researchers added.

The Terry Fox Research Institute, the Canadian Partnership Against Cancer, the U.S. Public Health Service, and the National Cancer Institute supported the study. Dr. McWilliams reported no financial conflicts of interest; her associates reported ties to CareFusion, Eli Lilly, GlaxoSmithKline, Med Biogene, Olympus, Pfizer, Roche, Siemens, and Toshiba.

New statistical models can be used to predict with "excellent" accuracy which lung nodules found on screening low-dose computed tomography scans of high-risk patients are likely to be cancerous, according to a report published online Sept. 4 in the New England Journal of Medicine.

"Our models are coupled with risk calculators, which make possible the rapid and easy calculation of lung-cancer risk given the characteristics of the person and the nodules," said Dr. Annette McWilliams of Vancouver General Hospital and the British Columbia Cancer Agency, and her associates (N. Engl. J. Med. 2013;369:910-9).

Several previous studies have reported that more than 20% of people who participate in low-dose computed tomography (LDCT) screening programs are found to have at least one lung nodule that requires further investigation. Yet only a small percentage of these nodules turn out to be malignant.

In one large screening trial, 25% of the surgical procedures that were prompted by an initial LDCT scan were performed on nodules that proved to be benign. That means that many patients were needlessly exposed to invasive diagnostic procedures, Dr. McWilliams and her colleagues said.

They developed models that would accurately predict the likelihood that such nodules are malignant, so as to guide clinical decision making and thereby reduce the risks and the costs of morbidity and mortality in LDCT screening programs.

The first step was to collect a large amount of detailed data regarding nodules identified on LDCT that were either cancerous when detected or later developed into cancers. To do that, the researchers analyzed data from the multicenter Pan-Canadian Early Detection of Lung Cancer Study, a population-based sample of current and former smokers aged 50-75 years who had no history of lung cancer but had a 3-year risk of at least 2% of developing the disease.

A total of 1,871 of the 2,537 participants in that study (74%) were found to have 7,008 lung nodules on initial scanning. They were followed for a median of 3.1 years using repeat LDCT at 3- to 12-month intervals, depending on the size of the largest nodule.

Lung cancer was diagnosed on the basis of histopathologic assessment of resection specimens or cytopathologic examination of needle-aspiration biopsy samples. A total of 102 nodules (5.5%) were found to be malignant.

Tumor characteristics that strongly correlated with malignancy were larger nodule size, partially solid type (as opposed to nonsolid, fully solid, or perifissural types), location of the nodule in the upper lung lobes, a small number of nodules (rather than numerous nodules), and the presence of spiculation.

Patient characteristics that strongly correlated with malignancy were female sex, older age, family history of lung cancer, and emphysema.

Dr. McWilliams and her associates used these traits to develop prediction models. They then tested the models in a validation cohort: 1,090 current and former smokers aged 50-74 years who underwent LDCT as part of several chemoprevention trials conducted by the British Columbia Cancer Agency over a 10-year period.

Those study subjects were found to have 5,021 lung nodules. Forty of those patients were found to have 42 lung cancers during a median follow-up of 8.6 years.

"Our models showed excellent predictive accuracy," clearly differentiating study subjects who had or developed lung cancer from those who did not. "The models performed well even when applied to nodules 10 mm or smaller, which are the most clinically challenging and most numerous nodules," the investigators noted.

None of the 571 perifissural nodules found on LDCT in those two cohorts proved to be malignant. "When the data from the two studies were pooled, the probability of lung cancer in perifissural nodules was 0," Dr. McWilliams and her associates said.

Such nodules "probably do not require longitudinal follow-up with CT," they added.

Their models are not intended for use in low-risk people for whom LDCT is not currently recommended. The models also "do not apply to persons with hilar or mediastinal lymphadenopathy, for whom further investigations are warranted irrespective of the nodule size," the researchers added.

The Terry Fox Research Institute, the Canadian Partnership Against Cancer, the U.S. Public Health Service, and the National Cancer Institute supported the study. Dr. McWilliams reported no financial conflicts of interest; her associates reported ties to CareFusion, Eli Lilly, GlaxoSmithKline, Med Biogene, Olympus, Pfizer, Roche, Siemens, and Toshiba.

Low-dose CT screening of adults at high risk for lung cancer was three times better than radiography at detecting early, more treatable malignancies in the National Lung Screening Trial, according to a report published online Sept. 4 in the New England Journal of Medicine.

The initial findings from the NLST showed that low-dose CT (LDCT) lung screening reduced lung-cancer mortality by 20%, relative to radiographic screening. The investigators now report more detailed findings from the first two rounds of screening, which show that this decrease in lung-cancer mortality "was coupled with a shift to detection of earlier-stage non-small-cell lung cancers," which are potentially curable, said Dr. Denise R. Aberle of the department of radiological sciences, University of California, Los Angeles, and her associates.

In the NLST, 53,454 adults at high risk for lung cancer were randomly assigned to undergo three annual screenings using either LDCT or radiography at 33 medical centers across the country. The screening took place between August 2002 and September 2007.

At the first round of screening, the sensitivity of LDCT was 94.4%, the specificity was 72.6%, the positive predictive value was 2.4%, and the negative predictive value was 99.9%. In comparison, the sensitivity of radiography was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8%.

At the second round of screening, LDCT’s sensitivity was 93%, specificity was 83.9%, positive predictive value was 5.2%, and negative predictive value was 99.9%. In comparison, radiography’s sensitivity was 63.9%, specificity was 95.3%, positive predictive value was 6.7%, and negative predictive value was 99.8%.

During the first round of screening, nearly half (47.5%) of the staged cancers detected on LDCT were stage IA, compared with only 23.5% of those detected on radiography. In contrast, only 31.1% of the staged cancers detected on LDCT were advanced stage III or IV cancers, compared with 59.1% of those detected on radiography.

This discrepancy in the distribution of early- vs. late-stage cancers persisted during the second round of screening, Dr. Aberle and her associates reported (N. Engl. J. Med. 2013 Sept. 4 [doi: 10.1056/NEJMoa1208962]).

In the future, "the performance characteristics of LDCT may be enhanced by determining the most appropriate risk cohort, refining both algorithms for interpreting the results of screening and definitions of positive findings, and determining the appropriate duration and timing of screening," they added.

The NLST was funded by the National Cancer Institute. Dr. Aberle reported no potential financial conflicts of interest; one of her associates reported ties to Endocyte, Frontier Science, and other companies.

Low-dose CT screening of adults at high risk for lung cancer was three times better than radiography at detecting early, more treatable malignancies in the National Lung Screening Trial, according to a report published online Sept. 4 in the New England Journal of Medicine.

The initial findings from the NLST showed that low-dose CT (LDCT) lung screening reduced lung-cancer mortality by 20%, relative to radiographic screening. The investigators now report more detailed findings from the first two rounds of screening, which show that this decrease in lung-cancer mortality "was coupled with a shift to detection of earlier-stage non-small-cell lung cancers," which are potentially curable, said Dr. Denise R. Aberle of the department of radiological sciences, University of California, Los Angeles, and her associates.

In the NLST, 53,454 adults at high risk for lung cancer were randomly assigned to undergo three annual screenings using either LDCT or radiography at 33 medical centers across the country. The screening took place between August 2002 and September 2007.

At the first round of screening, the sensitivity of LDCT was 94.4%, the specificity was 72.6%, the positive predictive value was 2.4%, and the negative predictive value was 99.9%. In comparison, the sensitivity of radiography was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8%.

At the second round of screening, LDCT’s sensitivity was 93%, specificity was 83.9%, positive predictive value was 5.2%, and negative predictive value was 99.9%. In comparison, radiography’s sensitivity was 63.9%, specificity was 95.3%, positive predictive value was 6.7%, and negative predictive value was 99.8%.

During the first round of screening, nearly half (47.5%) of the staged cancers detected on LDCT were stage IA, compared with only 23.5% of those detected on radiography. In contrast, only 31.1% of the staged cancers detected on LDCT were advanced stage III or IV cancers, compared with 59.1% of those detected on radiography.

This discrepancy in the distribution of early- vs. late-stage cancers persisted during the second round of screening, Dr. Aberle and her associates reported (N. Engl. J. Med. 2013 Sept. 4 [doi: 10.1056/NEJMoa1208962]).

In the future, "the performance characteristics of LDCT may be enhanced by determining the most appropriate risk cohort, refining both algorithms for interpreting the results of screening and definitions of positive findings, and determining the appropriate duration and timing of screening," they added.

The NLST was funded by the National Cancer Institute. Dr. Aberle reported no potential financial conflicts of interest; one of her associates reported ties to Endocyte, Frontier Science, and other companies.

Low-dose CT screening of adults at high risk for lung cancer was three times better than radiography at detecting early, more treatable malignancies in the National Lung Screening Trial, according to a report published online Sept. 4 in the New England Journal of Medicine.

The initial findings from the NLST showed that low-dose CT (LDCT) lung screening reduced lung-cancer mortality by 20%, relative to radiographic screening. The investigators now report more detailed findings from the first two rounds of screening, which show that this decrease in lung-cancer mortality "was coupled with a shift to detection of earlier-stage non-small-cell lung cancers," which are potentially curable, said Dr. Denise R. Aberle of the department of radiological sciences, University of California, Los Angeles, and her associates.

In the NLST, 53,454 adults at high risk for lung cancer were randomly assigned to undergo three annual screenings using either LDCT or radiography at 33 medical centers across the country. The screening took place between August 2002 and September 2007.

At the first round of screening, the sensitivity of LDCT was 94.4%, the specificity was 72.6%, the positive predictive value was 2.4%, and the negative predictive value was 99.9%. In comparison, the sensitivity of radiography was 59.6%, the specificity was 94.1%, the positive predictive value was 4.4%, and the negative predictive value was 99.8%.

At the second round of screening, LDCT’s sensitivity was 93%, specificity was 83.9%, positive predictive value was 5.2%, and negative predictive value was 99.9%. In comparison, radiography’s sensitivity was 63.9%, specificity was 95.3%, positive predictive value was 6.7%, and negative predictive value was 99.8%.

During the first round of screening, nearly half (47.5%) of the staged cancers detected on LDCT were stage IA, compared with only 23.5% of those detected on radiography. In contrast, only 31.1% of the staged cancers detected on LDCT were advanced stage III or IV cancers, compared with 59.1% of those detected on radiography.

This discrepancy in the distribution of early- vs. late-stage cancers persisted during the second round of screening, Dr. Aberle and her associates reported (N. Engl. J. Med. 2013 Sept. 4 [doi: 10.1056/NEJMoa1208962]).

In the future, "the performance characteristics of LDCT may be enhanced by determining the most appropriate risk cohort, refining both algorithms for interpreting the results of screening and definitions of positive findings, and determining the appropriate duration and timing of screening," they added.

The NLST was funded by the National Cancer Institute. Dr. Aberle reported no potential financial conflicts of interest; one of her associates reported ties to Endocyte, Frontier Science, and other companies.

Bariatric surgery doesn’t reduce long-term health care costs, according to a report in the June issue of JAMA Surgery.

In a 6-year follow-up study comparing nearly 30,000 patients who underwent bariatric surgery against the same number of well-matched patients who did not have the surgery, the surgery group showed decreases in costs for office visits and prescriptions, but these were offset by their significant increases in inpatient costs, said Jonathan P. Weiner, Dr.P.H., of the department of health policy and management, Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates.

Health care costs for the bariatric surgery patients did fall off somewhat during the fourth, fifth, and sixth years following the operation, but not enough to outweigh the expenses incurred during the first 3 postoperative years, the investigators said.

Taken together with the results of two other recent studies of the total health care costs related to bariatric surgery, these findings indicate that "to assess the value of bariatric surgery, future studies should focus on the potential benefit of improved health and well-being of persons undergoing the procedure rather than on cost savings," they noted.

It seems intuitive that bariatric surgery, which produces considerable weight loss and alleviates or eliminates many obesity-related disorders such as hypertension and diabetes, would of course save future health care costs, at least in the long term. But studies of the impact of the procedure on such costs have shown mixed results.

"Many uncertainties remain about whether and when a return on investment can be expected, which type of bariatric surgical procedure produces the greatest cost reduction, and whether cost reductions are sustained over time," Dr. Weiner and his colleagues said.

To clarify the issue, they analyzed health care costs in a large cohort of privately insured people covered by seven Blue Cross Blue Shield plans in seven states, of which 29,820 underwent a variety of bariatric procedures during a 6-year period. Each of these subjects was matched for age, sex, area of residence, and 33 markers of obesity with a control subject who did not have bariatric surgery.

Surgical trends shifted during the course of the study. At the beginning, 72% of the procedures were open gastric bypass operations; by the end, laparoscopic procedures were predominant.

Although laparoscopic operations were associated with lower costs in the short term than other procedures, this advantage lasted only for a brief period. So overall, health care costs were not significantly different by type of bariatric surgery.

In an unadjusted analysis of the data, the surgical group showed an approximately 30% decrease in pharmacy costs during the first 3 years after the procedure. The control group showed no such drop.

However, the surgical group had significantly more hospital admissions for GI-related diagnoses than the control group during all 6 years of follow-up, which were concentrated during the second and third years following the procedure. Most of these admissions likely were for surgery-related complications, the investigators said.

In an analysis that adjusted for multiple possible confounders, inpatient costs remained higher for the surgical group than the control group throughout follow-up, but particularly during year 2 and year 3 following the procedure. Pharmacy and office visit costs were significantly lower for the surgery group but did not offset the excess in inpatient costs, Dr. Weiner and his associates reported (JAMA Surg. 2013;148:555-61).

This study "adds substantially to the existing literature on cost of bariatric surgery" because the study population was the largest to date and was representative of a broad cross section of the commercially insured U.S. population. The study also boasts one of the longest follow-ups of bariatric surgery outcomes in the United States, since previous studies generally had follow-ups of only 6 months to 2 years, the researchers said.

In a Clinical Review & Education piece accompanying this report (JAMA Surg. 2013;310:742-3), Matthew L. Maciejewski, Ph.D., and Dr. David E. Arterburn said that bariatric surgery may still be cost-effective even if it is not cost-saving.

"Does bariatric surgery need to be cost-effective (i.e., more effective but more costly than usual care), or does it need to achieve the higher standard of cost savings (i.e., more effective and less costly than usual care) to justify broader insurance coverage?" they asked.

The procedures are so expensive that they are unlikely to meet the threshold of "cost saving" for most patients. Even if a patient’s total health care costs are cut by half after the surgery, "it may take up to 20 years to achieve cost neutrality," said Dr. Maciejewski of the Center for Health Services Research in Primary Care, Durham (N.C.) VA Medical Center, and Dr. Arterburn of the Group Health Research Institute, Seattle.

This lack of cost savings shouldn’t be surprising, given that Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding are invasive procedures that carry high early complication rates. It is possible that newer procedures such as sleeve gastrectomy might eventually yield cost savings because of relatively low complication rates, but these operations haven’t yet undergone long-term economic evaluation, they added.

This study was supported in part by Ethicon Endo-Surgery (a division of Johnson & Johnson), Pfizer, and GlaxoSmithKline, as well as by the National BlueCross BlueShield Association and the seven local plans that participated. No other financial conflicts of interest were reported.

Bariatric surgery doesn’t reduce long-term health care costs, according to a report in the June issue of JAMA Surgery.

In a 6-year follow-up study comparing nearly 30,000 patients who underwent bariatric surgery against the same number of well-matched patients who did not have the surgery, the surgery group showed decreases in costs for office visits and prescriptions, but these were offset by their significant increases in inpatient costs, said Jonathan P. Weiner, Dr.P.H., of the department of health policy and management, Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates.

Health care costs for the bariatric surgery patients did fall off somewhat during the fourth, fifth, and sixth years following the operation, but not enough to outweigh the expenses incurred during the first 3 postoperative years, the investigators said.

Taken together with the results of two other recent studies of the total health care costs related to bariatric surgery, these findings indicate that "to assess the value of bariatric surgery, future studies should focus on the potential benefit of improved health and well-being of persons undergoing the procedure rather than on cost savings," they noted.

It seems intuitive that bariatric surgery, which produces considerable weight loss and alleviates or eliminates many obesity-related disorders such as hypertension and diabetes, would of course save future health care costs, at least in the long term. But studies of the impact of the procedure on such costs have shown mixed results.

"Many uncertainties remain about whether and when a return on investment can be expected, which type of bariatric surgical procedure produces the greatest cost reduction, and whether cost reductions are sustained over time," Dr. Weiner and his colleagues said.

To clarify the issue, they analyzed health care costs in a large cohort of privately insured people covered by seven Blue Cross Blue Shield plans in seven states, of which 29,820 underwent a variety of bariatric procedures during a 6-year period. Each of these subjects was matched for age, sex, area of residence, and 33 markers of obesity with a control subject who did not have bariatric surgery.

Surgical trends shifted during the course of the study. At the beginning, 72% of the procedures were open gastric bypass operations; by the end, laparoscopic procedures were predominant.

Although laparoscopic operations were associated with lower costs in the short term than other procedures, this advantage lasted only for a brief period. So overall, health care costs were not significantly different by type of bariatric surgery.

In an unadjusted analysis of the data, the surgical group showed an approximately 30% decrease in pharmacy costs during the first 3 years after the procedure. The control group showed no such drop.

However, the surgical group had significantly more hospital admissions for GI-related diagnoses than the control group during all 6 years of follow-up, which were concentrated during the second and third years following the procedure. Most of these admissions likely were for surgery-related complications, the investigators said.

In an analysis that adjusted for multiple possible confounders, inpatient costs remained higher for the surgical group than the control group throughout follow-up, but particularly during year 2 and year 3 following the procedure. Pharmacy and office visit costs were significantly lower for the surgery group but did not offset the excess in inpatient costs, Dr. Weiner and his associates reported (JAMA Surg. 2013;148:555-61).

This study "adds substantially to the existing literature on cost of bariatric surgery" because the study population was the largest to date and was representative of a broad cross section of the commercially insured U.S. population. The study also boasts one of the longest follow-ups of bariatric surgery outcomes in the United States, since previous studies generally had follow-ups of only 6 months to 2 years, the researchers said.

In a Clinical Review & Education piece accompanying this report (JAMA Surg. 2013;310:742-3), Matthew L. Maciejewski, Ph.D., and Dr. David E. Arterburn said that bariatric surgery may still be cost-effective even if it is not cost-saving.

"Does bariatric surgery need to be cost-effective (i.e., more effective but more costly than usual care), or does it need to achieve the higher standard of cost savings (i.e., more effective and less costly than usual care) to justify broader insurance coverage?" they asked.

The procedures are so expensive that they are unlikely to meet the threshold of "cost saving" for most patients. Even if a patient’s total health care costs are cut by half after the surgery, "it may take up to 20 years to achieve cost neutrality," said Dr. Maciejewski of the Center for Health Services Research in Primary Care, Durham (N.C.) VA Medical Center, and Dr. Arterburn of the Group Health Research Institute, Seattle.

This lack of cost savings shouldn’t be surprising, given that Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding are invasive procedures that carry high early complication rates. It is possible that newer procedures such as sleeve gastrectomy might eventually yield cost savings because of relatively low complication rates, but these operations haven’t yet undergone long-term economic evaluation, they added.

This study was supported in part by Ethicon Endo-Surgery (a division of Johnson & Johnson), Pfizer, and GlaxoSmithKline, as well as by the National BlueCross BlueShield Association and the seven local plans that participated. No other financial conflicts of interest were reported.

Bariatric surgery doesn’t reduce long-term health care costs, according to a report in the June issue of JAMA Surgery.

In a 6-year follow-up study comparing nearly 30,000 patients who underwent bariatric surgery against the same number of well-matched patients who did not have the surgery, the surgery group showed decreases in costs for office visits and prescriptions, but these were offset by their significant increases in inpatient costs, said Jonathan P. Weiner, Dr.P.H., of the department of health policy and management, Johns Hopkins Bloomberg School of Public Health, Baltimore, and his associates.

Health care costs for the bariatric surgery patients did fall off somewhat during the fourth, fifth, and sixth years following the operation, but not enough to outweigh the expenses incurred during the first 3 postoperative years, the investigators said.

Taken together with the results of two other recent studies of the total health care costs related to bariatric surgery, these findings indicate that "to assess the value of bariatric surgery, future studies should focus on the potential benefit of improved health and well-being of persons undergoing the procedure rather than on cost savings," they noted.

It seems intuitive that bariatric surgery, which produces considerable weight loss and alleviates or eliminates many obesity-related disorders such as hypertension and diabetes, would of course save future health care costs, at least in the long term. But studies of the impact of the procedure on such costs have shown mixed results.

"Many uncertainties remain about whether and when a return on investment can be expected, which type of bariatric surgical procedure produces the greatest cost reduction, and whether cost reductions are sustained over time," Dr. Weiner and his colleagues said.

To clarify the issue, they analyzed health care costs in a large cohort of privately insured people covered by seven Blue Cross Blue Shield plans in seven states, of which 29,820 underwent a variety of bariatric procedures during a 6-year period. Each of these subjects was matched for age, sex, area of residence, and 33 markers of obesity with a control subject who did not have bariatric surgery.

Surgical trends shifted during the course of the study. At the beginning, 72% of the procedures were open gastric bypass operations; by the end, laparoscopic procedures were predominant.

Although laparoscopic operations were associated with lower costs in the short term than other procedures, this advantage lasted only for a brief period. So overall, health care costs were not significantly different by type of bariatric surgery.

In an unadjusted analysis of the data, the surgical group showed an approximately 30% decrease in pharmacy costs during the first 3 years after the procedure. The control group showed no such drop.

However, the surgical group had significantly more hospital admissions for GI-related diagnoses than the control group during all 6 years of follow-up, which were concentrated during the second and third years following the procedure. Most of these admissions likely were for surgery-related complications, the investigators said.

In an analysis that adjusted for multiple possible confounders, inpatient costs remained higher for the surgical group than the control group throughout follow-up, but particularly during year 2 and year 3 following the procedure. Pharmacy and office visit costs were significantly lower for the surgery group but did not offset the excess in inpatient costs, Dr. Weiner and his associates reported (JAMA Surg. 2013;148:555-61).

This study "adds substantially to the existing literature on cost of bariatric surgery" because the study population was the largest to date and was representative of a broad cross section of the commercially insured U.S. population. The study also boasts one of the longest follow-ups of bariatric surgery outcomes in the United States, since previous studies generally had follow-ups of only 6 months to 2 years, the researchers said.

In a Clinical Review & Education piece accompanying this report (JAMA Surg. 2013;310:742-3), Matthew L. Maciejewski, Ph.D., and Dr. David E. Arterburn said that bariatric surgery may still be cost-effective even if it is not cost-saving.

"Does bariatric surgery need to be cost-effective (i.e., more effective but more costly than usual care), or does it need to achieve the higher standard of cost savings (i.e., more effective and less costly than usual care) to justify broader insurance coverage?" they asked.

The procedures are so expensive that they are unlikely to meet the threshold of "cost saving" for most patients. Even if a patient’s total health care costs are cut by half after the surgery, "it may take up to 20 years to achieve cost neutrality," said Dr. Maciejewski of the Center for Health Services Research in Primary Care, Durham (N.C.) VA Medical Center, and Dr. Arterburn of the Group Health Research Institute, Seattle.

This lack of cost savings shouldn’t be surprising, given that Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding are invasive procedures that carry high early complication rates. It is possible that newer procedures such as sleeve gastrectomy might eventually yield cost savings because of relatively low complication rates, but these operations haven’t yet undergone long-term economic evaluation, they added.

This study was supported in part by Ethicon Endo-Surgery (a division of Johnson & Johnson), Pfizer, and GlaxoSmithKline, as well as by the National BlueCross BlueShield Association and the seven local plans that participated. No other financial conflicts of interest were reported.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

Use of a single "polypill" containing drugs to lower blood pressure, cholesterol, and platelet aggregation markedly improved medication adherence and modestly improved hypertension and hypercholesterolemia, according to a report published online Sept. 3 in JAMA.

The results are from the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) study. UMPIRE is the first randomized trial to assess the long-term use of a fixed-dose combination therapy containing antiplatelet, statin, and BP-lowering drugs among patients who either had established cardiovascular disease or were at high risk – the group in whom 40% of all cardiovascular events occur, said Dr. Simon Thom of the International Centre for Circulatory Health, Imperial College London, and his associates.

The fixed-dose combination therapy, or polypill, has been proposed as a way to simplify complex medication regimens and reduce costs. However, the benefits and risks have not been examined in high-risk CVD patients until now, the study authors noted.

The clinical trial primarily involved patients who were already adherent to a multiple-pill regimen at baseline. However, in the subgroup of 727 patients who were not taking all the recommended medications at baseline, use of the polypill prompted a threefold rise in adherence rates, from 23% to 77%. It also produced larger reductions in blood pressure and LDL cholesterol levels, the investigators noted.

Dr. Thom and his colleagues performed the open-label study among 1,000 patients at 28 clinics across India and 1,004 patients in England, Ireland, and the Netherlands. All the study subjects either had established CVD (1,771 patients) or a 15% or higher estimated 5-year risk of experiencing a CVD event (233 patients).

The study participants were randomly assigned to receive a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol (589 patients), or a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide (413 patients), or usual care (1,002 patients who served as control subjects). They were followed for 12-24 months, with a median follow-up of 15 months.

After 1 month, adherence rates were 97.3% for both polypill groups, compared with 68.3% for the control group.

At the conclusion of the study, rates of adherence were 86.3% for both polypill groups, compared with 64.7% for the control group, a statistically significant absolute difference of 21.6%, the researchers said (JAMA 2013;310:918-29).

The findings were essentially the same in several sensitivity analyses that used slightly altered definitions of adherence.

Blood pressure levels decreased modestly but significantly (2.6 mm Hg lower) in both polypill groups, compared with usual care, as did LDL-cholesterol levels (4.2 mg/dL lower).

The treatment effects were similar and statistically significant across all subgroups of patients studied, including smokers and patients at the highest risk for a CVD event.

The subgroup that benefitted the most from using a polypill was the 36% of patients who were not taking all their recommended medications at baseline. Their adherence rate improved from 23% to 77%; median blood pressure dropped significantly by 4.9 mm Hg, and LDL-cholesterol declined by 6.7 mg/dL.

"Weight, waist circumference, and BMI did not change during follow-up and did not differ between groups at the end of the study," the investigators noted. Self-reported time engaged in vigorous physical activity, participation in exercise programs, attendance at dietetic clinics, and participation in smoking cessation programs were also similar in both groups at the end of follow-up.

Patients taking a polypill showed a significant increase in creatinine and uric acid levels, but no changes in sodium, potassium, alanine transaminase, aspartate aminotransferase, or glucose levels.

Rates of serious adverse events were similar between patients taking the polypills (11.8%) and those under usual care (10.2%), and there were no significant differences between the two groups in any major subcategory of adverse event. A total of 85 study subjects had a CVD event, including 5.0% of the polypill groups and 3.5% in the control group.

Similarly, a comparable number of deaths occurred among the study subjects, with 17 in the polypill groups and 15 in the control group.

Because there were only 85 CVD events, the study was insufficiently powered to detect any meaningful differences between groups specifically for CVD outcomes. However, given the magnitude of benefit in blood pressure and cholesterol outcomes, it would be expected that patients taking the polypill would show a 15% reduction in coronary artery disease and stroke incidence after a few years, Dr. Thom and his associates said.

The European Commission and Dr. Reddy’s Laboratories funded the UMPIRE study. Dr. Thom reported no financial conflicts of interest; his associates reported numerous ties to industry sources.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Earn 0.25 hours AMA PRA Category 1 credit: Read this article, and click the link at the end to take the post-test.

Use of a single "polypill" containing drugs to lower blood pressure, cholesterol, and platelet aggregation markedly improved medication adherence and modestly improved hypertension and hypercholesterolemia, according to a report published online Sept. 3 in JAMA.

The results are from the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) study. UMPIRE is the first randomized trial to assess the long-term use of a fixed-dose combination therapy containing antiplatelet, statin, and BP-lowering drugs among patients who either had established cardiovascular disease or were at high risk – the group in whom 40% of all cardiovascular events occur, said Dr. Simon Thom of the International Centre for Circulatory Health, Imperial College London, and his associates.

The fixed-dose combination therapy, or polypill, has been proposed as a way to simplify complex medication regimens and reduce costs. However, the benefits and risks have not been examined in high-risk CVD patients until now, the study authors noted.

The clinical trial primarily involved patients who were already adherent to a multiple-pill regimen at baseline. However, in the subgroup of 727 patients who were not taking all the recommended medications at baseline, use of the polypill prompted a threefold rise in adherence rates, from 23% to 77%. It also produced larger reductions in blood pressure and LDL cholesterol levels, the investigators noted.

Dr. Thom and his colleagues performed the open-label study among 1,000 patients at 28 clinics across India and 1,004 patients in England, Ireland, and the Netherlands. All the study subjects either had established CVD (1,771 patients) or a 15% or higher estimated 5-year risk of experiencing a CVD event (233 patients).

The study participants were randomly assigned to receive a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol (589 patients), or a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide (413 patients), or usual care (1,002 patients who served as control subjects). They were followed for 12-24 months, with a median follow-up of 15 months.

After 1 month, adherence rates were 97.3% for both polypill groups, compared with 68.3% for the control group.

At the conclusion of the study, rates of adherence were 86.3% for both polypill groups, compared with 64.7% for the control group, a statistically significant absolute difference of 21.6%, the researchers said (JAMA 2013;310:918-29).

The findings were essentially the same in several sensitivity analyses that used slightly altered definitions of adherence.

Blood pressure levels decreased modestly but significantly (2.6 mm Hg lower) in both polypill groups, compared with usual care, as did LDL-cholesterol levels (4.2 mg/dL lower).

The treatment effects were similar and statistically significant across all subgroups of patients studied, including smokers and patients at the highest risk for a CVD event.

The subgroup that benefitted the most from using a polypill was the 36% of patients who were not taking all their recommended medications at baseline. Their adherence rate improved from 23% to 77%; median blood pressure dropped significantly by 4.9 mm Hg, and LDL-cholesterol declined by 6.7 mg/dL.

"Weight, waist circumference, and BMI did not change during follow-up and did not differ between groups at the end of the study," the investigators noted. Self-reported time engaged in vigorous physical activity, participation in exercise programs, attendance at dietetic clinics, and participation in smoking cessation programs were also similar in both groups at the end of follow-up.

Patients taking a polypill showed a significant increase in creatinine and uric acid levels, but no changes in sodium, potassium, alanine transaminase, aspartate aminotransferase, or glucose levels.

Rates of serious adverse events were similar between patients taking the polypills (11.8%) and those under usual care (10.2%), and there were no significant differences between the two groups in any major subcategory of adverse event. A total of 85 study subjects had a CVD event, including 5.0% of the polypill groups and 3.5% in the control group.

Similarly, a comparable number of deaths occurred among the study subjects, with 17 in the polypill groups and 15 in the control group.

Because there were only 85 CVD events, the study was insufficiently powered to detect any meaningful differences between groups specifically for CVD outcomes. However, given the magnitude of benefit in blood pressure and cholesterol outcomes, it would be expected that patients taking the polypill would show a 15% reduction in coronary artery disease and stroke incidence after a few years, Dr. Thom and his associates said.

The European Commission and Dr. Reddy’s Laboratories funded the UMPIRE study. Dr. Thom reported no financial conflicts of interest; his associates reported numerous ties to industry sources.

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Use of a single "polypill" containing drugs to lower blood pressure, cholesterol, and platelet aggregation markedly improved medication adherence and modestly improved hypertension and hypercholesterolemia, according to a report published online Sept. 3 in JAMA.

The results are from the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) study. UMPIRE is the first randomized trial to assess the long-term use of a fixed-dose combination therapy containing antiplatelet, statin, and BP-lowering drugs among patients who either had established cardiovascular disease or were at high risk – the group in whom 40% of all cardiovascular events occur, said Dr. Simon Thom of the International Centre for Circulatory Health, Imperial College London, and his associates.

The fixed-dose combination therapy, or polypill, has been proposed as a way to simplify complex medication regimens and reduce costs. However, the benefits and risks have not been examined in high-risk CVD patients until now, the study authors noted.

The clinical trial primarily involved patients who were already adherent to a multiple-pill regimen at baseline. However, in the subgroup of 727 patients who were not taking all the recommended medications at baseline, use of the polypill prompted a threefold rise in adherence rates, from 23% to 77%. It also produced larger reductions in blood pressure and LDL cholesterol levels, the investigators noted.

Dr. Thom and his colleagues performed the open-label study among 1,000 patients at 28 clinics across India and 1,004 patients in England, Ireland, and the Netherlands. All the study subjects either had established CVD (1,771 patients) or a 15% or higher estimated 5-year risk of experiencing a CVD event (233 patients).

The study participants were randomly assigned to receive a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol (589 patients), or a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide (413 patients), or usual care (1,002 patients who served as control subjects). They were followed for 12-24 months, with a median follow-up of 15 months.

After 1 month, adherence rates were 97.3% for both polypill groups, compared with 68.3% for the control group.

At the conclusion of the study, rates of adherence were 86.3% for both polypill groups, compared with 64.7% for the control group, a statistically significant absolute difference of 21.6%, the researchers said (JAMA 2013;310:918-29).

The findings were essentially the same in several sensitivity analyses that used slightly altered definitions of adherence.

Blood pressure levels decreased modestly but significantly (2.6 mm Hg lower) in both polypill groups, compared with usual care, as did LDL-cholesterol levels (4.2 mg/dL lower).

The treatment effects were similar and statistically significant across all subgroups of patients studied, including smokers and patients at the highest risk for a CVD event.

The subgroup that benefitted the most from using a polypill was the 36% of patients who were not taking all their recommended medications at baseline. Their adherence rate improved from 23% to 77%; median blood pressure dropped significantly by 4.9 mm Hg, and LDL-cholesterol declined by 6.7 mg/dL.

"Weight, waist circumference, and BMI did not change during follow-up and did not differ between groups at the end of the study," the investigators noted. Self-reported time engaged in vigorous physical activity, participation in exercise programs, attendance at dietetic clinics, and participation in smoking cessation programs were also similar in both groups at the end of follow-up.

Patients taking a polypill showed a significant increase in creatinine and uric acid levels, but no changes in sodium, potassium, alanine transaminase, aspartate aminotransferase, or glucose levels.

Rates of serious adverse events were similar between patients taking the polypills (11.8%) and those under usual care (10.2%), and there were no significant differences between the two groups in any major subcategory of adverse event. A total of 85 study subjects had a CVD event, including 5.0% of the polypill groups and 3.5% in the control group.

Similarly, a comparable number of deaths occurred among the study subjects, with 17 in the polypill groups and 15 in the control group.

Because there were only 85 CVD events, the study was insufficiently powered to detect any meaningful differences between groups specifically for CVD outcomes. However, given the magnitude of benefit in blood pressure and cholesterol outcomes, it would be expected that patients taking the polypill would show a 15% reduction in coronary artery disease and stroke incidence after a few years, Dr. Thom and his associates said.

The European Commission and Dr. Reddy’s Laboratories funded the UMPIRE study. Dr. Thom reported no financial conflicts of interest; his associates reported numerous ties to industry sources.

To earn 0.25 hours AMA PRA Category 1 credit after reading this article, take the post-test here.

Use of a single "polypill" containing drugs to lower blood pressure, cholesterol, and platelet aggregation markedly improved medication adherence and modestly improved hypertension and hypercholesterolemia, according to a report published online Sept. 3 in JAMA.

The results are from the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) study. UMPIRE is the first randomized trial to assess the long-term use of a fixed-dose combination therapy containing antiplatelet, statin, and BP-lowering drugs among patients who either had established cardiovascular disease or were at high risk – the group in whom 40% of all cardiovascular events occur, said Dr. Simon Thom of the International Centre for Circulatory Health, Imperial College London, and his associates.

The fixed-dose combination therapy, or polypill, has been proposed as a way to simplify complex medication regimens and reduce costs. However, the benefits and risks have not been examined in high-risk CVD patients until now, the study authors noted.

The clinical trial primarily involved patients who were already adherent to a multiple-pill regimen at baseline. However, in the subgroup of 727 patients who were not taking all the recommended medications at baseline, use of the polypill prompted a threefold rise in adherence rates, from 23% to 77%. It also produced larger reductions in blood pressure and LDL cholesterol levels, the investigators noted.

Dr. Thom and his colleagues performed the open-label study among 1,000 patients at 28 clinics across India and 1,004 patients in England, Ireland, and the Netherlands. All the study subjects either had established CVD (1,771 patients) or a 15% or higher estimated 5-year risk of experiencing a CVD event (233 patients).

The study participants were randomly assigned to receive a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol (589 patients), or a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide (413 patients), or usual care (1,002 patients who served as control subjects). They were followed for 12-24 months, with a median follow-up of 15 months.

After 1 month, adherence rates were 97.3% for both polypill groups, compared with 68.3% for the control group.

At the conclusion of the study, rates of adherence were 86.3% for both polypill groups, compared with 64.7% for the control group, a statistically significant absolute difference of 21.6%, the researchers said (JAMA 2013;310:918-29).

The findings were essentially the same in several sensitivity analyses that used slightly altered definitions of adherence.

Blood pressure levels decreased modestly but significantly (2.6 mm Hg lower) in both polypill groups, compared with usual care, as did LDL-cholesterol levels (4.2 mg/dL lower).

The treatment effects were similar and statistically significant across all subgroups of patients studied, including smokers and patients at the highest risk for a CVD event.

The subgroup that benefitted the most from using a polypill was the 36% of patients who were not taking all their recommended medications at baseline. Their adherence rate improved from 23% to 77%; median blood pressure dropped significantly by 4.9 mm Hg, and LDL-cholesterol declined by 6.7 mg/dL.

"Weight, waist circumference, and BMI did not change during follow-up and did not differ between groups at the end of the study," the investigators noted. Self-reported time engaged in vigorous physical activity, participation in exercise programs, attendance at dietetic clinics, and participation in smoking cessation programs were also similar in both groups at the end of follow-up.

Patients taking a polypill showed a significant increase in creatinine and uric acid levels, but no changes in sodium, potassium, alanine transaminase, aspartate aminotransferase, or glucose levels.

Rates of serious adverse events were similar between patients taking the polypills (11.8%) and those under usual care (10.2%), and there were no significant differences between the two groups in any major subcategory of adverse event. A total of 85 study subjects had a CVD event, including 5.0% of the polypill groups and 3.5% in the control group.

Similarly, a comparable number of deaths occurred among the study subjects, with 17 in the polypill groups and 15 in the control group.

Because there were only 85 CVD events, the study was insufficiently powered to detect any meaningful differences between groups specifically for CVD outcomes. However, given the magnitude of benefit in blood pressure and cholesterol outcomes, it would be expected that patients taking the polypill would show a 15% reduction in coronary artery disease and stroke incidence after a few years, Dr. Thom and his associates said.

The European Commission and Dr. Reddy’s Laboratories funded the UMPIRE study. Dr. Thom reported no financial conflicts of interest; his associates reported numerous ties to industry sources.

Use of a single "polypill" containing drugs to lower blood pressure, cholesterol, and platelet aggregation markedly improved medication adherence and modestly improved hypertension and hypercholesterolemia, according to a report published online Sept. 3 in JAMA.

The results are from the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) study. UMPIRE is the first randomized trial to assess the long-term use of a fixed-dose combination therapy containing antiplatelet, statin, and BP-lowering drugs among patients who either had established cardiovascular disease or were at high risk – the group in whom 40% of all cardiovascular events occur, said Dr. Simon Thom of the International Centre for Circulatory Health, Imperial College London, and his associates.

The fixed-dose combination therapy, or polypill, has been proposed as a way to simplify complex medication regimens and reduce costs. However, the benefits and risks have not been examined in high-risk CVD patients until now, the study authors noted.

The clinical trial primarily involved patients who were already adherent to a multiple-pill regimen at baseline. However, in the subgroup of 727 patients who were not taking all the recommended medications at baseline, use of the polypill prompted a threefold rise in adherence rates, from 23% to 77%. It also produced larger reductions in blood pressure and LDL cholesterol levels, the investigators noted.

Dr. Thom and his colleagues performed the open-label study among 1,000 patients at 28 clinics across India and 1,004 patients in England, Ireland, and the Netherlands. All the study subjects either had established CVD (1,771 patients) or a 15% or higher estimated 5-year risk of experiencing a CVD event (233 patients).

The study participants were randomly assigned to receive a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol (589 patients), or a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide (413 patients), or usual care (1,002 patients who served as control subjects). They were followed for 12-24 months, with a median follow-up of 15 months.

After 1 month, adherence rates were 97.3% for both polypill groups, compared with 68.3% for the control group.

At the conclusion of the study, rates of adherence were 86.3% for both polypill groups, compared with 64.7% for the control group, a statistically significant absolute difference of 21.6%, the researchers said (JAMA 2013;310:918-29).

The findings were essentially the same in several sensitivity analyses that used slightly altered definitions of adherence.

Blood pressure levels decreased modestly but significantly (2.6 mm Hg lower) in both polypill groups, compared with usual care, as did LDL-cholesterol levels (4.2 mg/dL lower).

The treatment effects were similar and statistically significant across all subgroups of patients studied, including smokers and patients at the highest risk for a CVD event.

The subgroup that benefitted the most from using a polypill was the 36% of patients who were not taking all their recommended medications at baseline. Their adherence rate improved from 23% to 77%; median blood pressure dropped significantly by 4.9 mm Hg, and LDL-cholesterol declined by 6.7 mg/dL.

"Weight, waist circumference, and BMI did not change during follow-up and did not differ between groups at the end of the study," the investigators noted. Self-reported time engaged in vigorous physical activity, participation in exercise programs, attendance at dietetic clinics, and participation in smoking cessation programs were also similar in both groups at the end of follow-up.

Patients taking a polypill showed a significant increase in creatinine and uric acid levels, but no changes in sodium, potassium, alanine transaminase, aspartate aminotransferase, or glucose levels.

Rates of serious adverse events were similar between patients taking the polypills (11.8%) and those under usual care (10.2%), and there were no significant differences between the two groups in any major subcategory of adverse event. A total of 85 study subjects had a CVD event, including 5.0% of the polypill groups and 3.5% in the control group.

Similarly, a comparable number of deaths occurred among the study subjects, with 17 in the polypill groups and 15 in the control group.

Because there were only 85 CVD events, the study was insufficiently powered to detect any meaningful differences between groups specifically for CVD outcomes. However, given the magnitude of benefit in blood pressure and cholesterol outcomes, it would be expected that patients taking the polypill would show a 15% reduction in coronary artery disease and stroke incidence after a few years, Dr. Thom and his associates said.

The European Commission and Dr. Reddy’s Laboratories funded the UMPIRE study. Dr. Thom reported no financial conflicts of interest; his associates reported numerous ties to industry sources.

Use of a single "polypill" containing drugs to lower blood pressure, cholesterol, and platelet aggregation markedly improved medication adherence and modestly improved hypertension and hypercholesterolemia, according to a report published online Sept. 3 in JAMA.

The results are from the UMPIRE (Use of a Multidrug Pill in Reducing Cardiovascular Events) study. UMPIRE is the first randomized trial to assess the long-term use of a fixed-dose combination therapy containing antiplatelet, statin, and BP-lowering drugs among patients who either had established cardiovascular disease or were at high risk – the group in whom 40% of all cardiovascular events occur, said Dr. Simon Thom of the International Centre for Circulatory Health, Imperial College London, and his associates.

The fixed-dose combination therapy, or polypill, has been proposed as a way to simplify complex medication regimens and reduce costs. However, the benefits and risks have not been examined in high-risk CVD patients until now, the study authors noted.

The clinical trial primarily involved patients who were already adherent to a multiple-pill regimen at baseline. However, in the subgroup of 727 patients who were not taking all the recommended medications at baseline, use of the polypill prompted a threefold rise in adherence rates, from 23% to 77%. It also produced larger reductions in blood pressure and LDL cholesterol levels, the investigators noted.

Dr. Thom and his colleagues performed the open-label study among 1,000 patients at 28 clinics across India and 1,004 patients in England, Ireland, and the Netherlands. All the study subjects either had established CVD (1,771 patients) or a 15% or higher estimated 5-year risk of experiencing a CVD event (233 patients).

The study participants were randomly assigned to receive a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 50 mg atenolol (589 patients), or a polypill containing 75 mg aspirin, 40 mg simvastatin, 10 mg lisinopril, and 12.5 mg hydrochlorothiazide (413 patients), or usual care (1,002 patients who served as control subjects). They were followed for 12-24 months, with a median follow-up of 15 months.

After 1 month, adherence rates were 97.3% for both polypill groups, compared with 68.3% for the control group.

At the conclusion of the study, rates of adherence were 86.3% for both polypill groups, compared with 64.7% for the control group, a statistically significant absolute difference of 21.6%, the researchers said (JAMA 2013;310:918-29).

The findings were essentially the same in several sensitivity analyses that used slightly altered definitions of adherence.

Blood pressure levels decreased modestly but significantly (2.6 mm Hg lower) in both polypill groups, compared with usual care, as did LDL-cholesterol levels (4.2 mg/dL lower).

The treatment effects were similar and statistically significant across all subgroups of patients studied, including smokers and patients at the highest risk for a CVD event.

The subgroup that benefitted the most from using a polypill was the 36% of patients who were not taking all their recommended medications at baseline. Their adherence rate improved from 23% to 77%; median blood pressure dropped significantly by 4.9 mm Hg, and LDL-cholesterol declined by 6.7 mg/dL.

"Weight, waist circumference, and BMI did not change during follow-up and did not differ between groups at the end of the study," the investigators noted. Self-reported time engaged in vigorous physical activity, participation in exercise programs, attendance at dietetic clinics, and participation in smoking cessation programs were also similar in both groups at the end of follow-up.

Patients taking a polypill showed a significant increase in creatinine and uric acid levels, but no changes in sodium, potassium, alanine transaminase, aspartate aminotransferase, or glucose levels.

Rates of serious adverse events were similar between patients taking the polypills (11.8%) and those under usual care (10.2%), and there were no significant differences between the two groups in any major subcategory of adverse event. A total of 85 study subjects had a CVD event, including 5.0% of the polypill groups and 3.5% in the control group.

Similarly, a comparable number of deaths occurred among the study subjects, with 17 in the polypill groups and 15 in the control group.

Because there were only 85 CVD events, the study was insufficiently powered to detect any meaningful differences between groups specifically for CVD outcomes. However, given the magnitude of benefit in blood pressure and cholesterol outcomes, it would be expected that patients taking the polypill would show a 15% reduction in coronary artery disease and stroke incidence after a few years, Dr. Thom and his associates said.

The European Commission and Dr. Reddy’s Laboratories funded the UMPIRE study. Dr. Thom reported no financial conflicts of interest; his associates reported numerous ties to industry sources.