Mary Ann Moon

For women who carry the BRCA1 or BRCA2 genetic mutations, adding MRI screening to mammography screening for breast cancer can be cost effective even though MRI is so expensive, according to Sylvia K. Plevritis, Ph.D., of Stanford (Calif.) University and her associates.

Breast MRI screening is “at least 10 times more expensive than mammographic screening.”

It also produces more false-positive results, which generate further costs for unneeded diagnostic workups.

“Because cost may be the greatest barrier to broader evaluation and dissemination of breast MRI screening, its cost-effectiveness is a critical consideration,” the investigators noted.

Currently there are no randomized clinical trials examining the cost-effectiveness of MRI screening for women at high risk of breast cancer.

And even if such a trial were initiated today, “mortality outcomes would not be available for at least 15 years,” Dr. Plevritis and her associates noted (J. Am. Med. Assoc. 2006;295:2374–84).

They estimated the cost-effectiveness of adding breast MRI screening to mammographic screening in women carrying BRCA1 and BRCA2 mutations using a computer simulation model that incorporated health benefits as well as expenses.

The model projected the long-term effects on clinical and economic outcomes of no breast cancer screening, annual mammography alone for women aged 25–69 years, and annual mammography plus MRI for specific age groups.

The model used a simulated cohort of women carrying the BRCA mutations who were aged 25 in 2005.

MRI screening was found to reduce breast cancer mortality by 23% over that obtained by mammography alone in women carrying either the BRCA1 or BRCA2 mutations.

For women with the BRCA1 mutation, “adding MRI increases the sensitivity of annual screening from 35% to 85%, the proportion of axillary lymph-node-negative cancers from 57% to 81%, the mean lead time from approximately 1.5 to 3 years, and the false-positive rate from approximately 5% to 25%.” Outcomes for women with the BRCA2 mutation were similar.

“With MRI, life expectancy increases from 71.2 to 73.3 years for BRCA1 mutation carriers and from 78.2 to 79.6 years for BRCA2 mutation carriers,” Dr. Plevritis and her associates wrote in their article.

Adding MRI to mammography was found to be cost effective for women aged 35–54 years.

It was not cost effective for the younger women in the simulation model (those aged 25–34 years) because of their lower incidence of the disease, and added MRIwas not cost effective for the older women (those aged 55 and older) because of the competing risk of death from other causes.

For women who carry the BRCA1 or BRCA2 genetic mutations, adding MRI screening to mammography screening for breast cancer can be cost effective even though MRI is so expensive, according to Sylvia K. Plevritis, Ph.D., of Stanford (Calif.) University and her associates.

Breast MRI screening is “at least 10 times more expensive than mammographic screening.”

It also produces more false-positive results, which generate further costs for unneeded diagnostic workups.

“Because cost may be the greatest barrier to broader evaluation and dissemination of breast MRI screening, its cost-effectiveness is a critical consideration,” the investigators noted.

Currently there are no randomized clinical trials examining the cost-effectiveness of MRI screening for women at high risk of breast cancer.

And even if such a trial were initiated today, “mortality outcomes would not be available for at least 15 years,” Dr. Plevritis and her associates noted (J. Am. Med. Assoc. 2006;295:2374–84).

They estimated the cost-effectiveness of adding breast MRI screening to mammographic screening in women carrying BRCA1 and BRCA2 mutations using a computer simulation model that incorporated health benefits as well as expenses.

The model projected the long-term effects on clinical and economic outcomes of no breast cancer screening, annual mammography alone for women aged 25–69 years, and annual mammography plus MRI for specific age groups.

The model used a simulated cohort of women carrying the BRCA mutations who were aged 25 in 2005.

MRI screening was found to reduce breast cancer mortality by 23% over that obtained by mammography alone in women carrying either the BRCA1 or BRCA2 mutations.

For women with the BRCA1 mutation, “adding MRI increases the sensitivity of annual screening from 35% to 85%, the proportion of axillary lymph-node-negative cancers from 57% to 81%, the mean lead time from approximately 1.5 to 3 years, and the false-positive rate from approximately 5% to 25%.” Outcomes for women with the BRCA2 mutation were similar.

“With MRI, life expectancy increases from 71.2 to 73.3 years for BRCA1 mutation carriers and from 78.2 to 79.6 years for BRCA2 mutation carriers,” Dr. Plevritis and her associates wrote in their article.

Adding MRI to mammography was found to be cost effective for women aged 35–54 years.

It was not cost effective for the younger women in the simulation model (those aged 25–34 years) because of their lower incidence of the disease, and added MRIwas not cost effective for the older women (those aged 55 and older) because of the competing risk of death from other causes.

For women who carry the BRCA1 or BRCA2 genetic mutations, adding MRI screening to mammography screening for breast cancer can be cost effective even though MRI is so expensive, according to Sylvia K. Plevritis, Ph.D., of Stanford (Calif.) University and her associates.

Breast MRI screening is “at least 10 times more expensive than mammographic screening.”

It also produces more false-positive results, which generate further costs for unneeded diagnostic workups.

“Because cost may be the greatest barrier to broader evaluation and dissemination of breast MRI screening, its cost-effectiveness is a critical consideration,” the investigators noted.

Currently there are no randomized clinical trials examining the cost-effectiveness of MRI screening for women at high risk of breast cancer.

And even if such a trial were initiated today, “mortality outcomes would not be available for at least 15 years,” Dr. Plevritis and her associates noted (J. Am. Med. Assoc. 2006;295:2374–84).

They estimated the cost-effectiveness of adding breast MRI screening to mammographic screening in women carrying BRCA1 and BRCA2 mutations using a computer simulation model that incorporated health benefits as well as expenses.

The model projected the long-term effects on clinical and economic outcomes of no breast cancer screening, annual mammography alone for women aged 25–69 years, and annual mammography plus MRI for specific age groups.

The model used a simulated cohort of women carrying the BRCA mutations who were aged 25 in 2005.

MRI screening was found to reduce breast cancer mortality by 23% over that obtained by mammography alone in women carrying either the BRCA1 or BRCA2 mutations.

For women with the BRCA1 mutation, “adding MRI increases the sensitivity of annual screening from 35% to 85%, the proportion of axillary lymph-node-negative cancers from 57% to 81%, the mean lead time from approximately 1.5 to 3 years, and the false-positive rate from approximately 5% to 25%.” Outcomes for women with the BRCA2 mutation were similar.

“With MRI, life expectancy increases from 71.2 to 73.3 years for BRCA1 mutation carriers and from 78.2 to 79.6 years for BRCA2 mutation carriers,” Dr. Plevritis and her associates wrote in their article.

Adding MRI to mammography was found to be cost effective for women aged 35–54 years.

It was not cost effective for the younger women in the simulation model (those aged 25–34 years) because of their lower incidence of the disease, and added MRIwas not cost effective for the older women (those aged 55 and older) because of the competing risk of death from other causes.

A relatively simple screening tool helps determine whether patients who present with adult-onset diabetes have type 2 disease or latent autoimmune diabetes, according to Dr. Spiros Fourlanos and his associates at the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria (Australia).

Latent autoimmune diabetes, which is believed to signal slowly progressive autoimmune β-cell destruction, is a form of type 1 disease characterized by adult onset; circulating islet cell antibodies and glutamic acid decarboxylase antibodies; and no initial need for insulin therapy. However, patients typically show dramatic loss of β-cell function within 3 years of diagnosis, which quickly leads to insulin dependence.

“We believe that physicians need to be aware that patients with [latent autoimmune diabetes] are prone to insulin deficiency and often require rapid escalation of oral hypoglycemic treatment or commencement of insulin earlier than islet antibody-negative patients,” Dr. Fourlanos and his associates said (Diabetes Care 2006;29:970–5).

Despite the frequency of the disorder and the difficulty in distinguishing it from type 2 diabetes, “there are no universal recommendations regarding testing for islet antibodies in adult-onset diabetes. Currently, many physicians test for islet antibodies only if they suspect [latent autoimmune diabetes],” the researchers said. Because most physicians also mistakenly assume that this disorder affects only normal-weight individuals, overweight adults who are diagnosed as having diabetes are presumed to have type 2 disease and are not tested.

The investigators conducted a retrospective study of 102 patients with latent autoimmune diabetes and 111 with type 2 diabetes to determine which clinical features distinguished the two groups so that they could develop a simple screening tool for physicians in clinical practice.

The subjects with latent autoimmune diabetes were significantly younger at diagnosis (median age 46 years vs. 61 years). Most (67%) had acute symptoms, such as polydipsia, polyuria, or unintentional weight loss, whereas only a minority of patients with type 2 diabetes (28%) were symptomatic. The median body mass index (BMI) was lower in the subjects with latent autoimmune diabetes, but a majority of them still qualified as overweight or obese. Finally, most also had a personal or family history of autoimmune disease, whereas subjects with type 2 diabetes did not.

Dr. Fourlanos and his associates used these five clinical traits to fashion a screening tool, and validated its usefulness in a prospective study of 130 subjects aged 30–75 years with recently diagnosed diabetes that didn't require insulin therapy. Subjects who had at least two of the five clinical features—age of onset older than 50 years, acute symptoms, BMI (kg/m

If these patients are not tested and identified, “our experience is that suboptimal glycemia in such patients is frequently prolonged because it is not attributed to autoimmune diabetes and insulin deficiency,” they noted.

The screening also proved highly reliable at excluding a diagnosis of latent autoimmune diabetes in patients who had none or one of these features, with a negative predictive value of 99%. A score of 0 or 1 on this screen will exclude the autoimmune disorder and thus the need for antibody testing in approximately two-thirds of adults with diabetes, they added.

“This clinical screening method is superior to the current popular clinical practice of only screening patients with [a low] BMI … because a majority of subjects with [latent autoimmune diabetes] are overweight or obese,” the investigators said.

A relatively simple screening tool helps determine whether patients who present with adult-onset diabetes have type 2 disease or latent autoimmune diabetes, according to Dr. Spiros Fourlanos and his associates at the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria (Australia).

Latent autoimmune diabetes, which is believed to signal slowly progressive autoimmune β-cell destruction, is a form of type 1 disease characterized by adult onset; circulating islet cell antibodies and glutamic acid decarboxylase antibodies; and no initial need for insulin therapy. However, patients typically show dramatic loss of β-cell function within 3 years of diagnosis, which quickly leads to insulin dependence.

“We believe that physicians need to be aware that patients with [latent autoimmune diabetes] are prone to insulin deficiency and often require rapid escalation of oral hypoglycemic treatment or commencement of insulin earlier than islet antibody-negative patients,” Dr. Fourlanos and his associates said (Diabetes Care 2006;29:970–5).

Despite the frequency of the disorder and the difficulty in distinguishing it from type 2 diabetes, “there are no universal recommendations regarding testing for islet antibodies in adult-onset diabetes. Currently, many physicians test for islet antibodies only if they suspect [latent autoimmune diabetes],” the researchers said. Because most physicians also mistakenly assume that this disorder affects only normal-weight individuals, overweight adults who are diagnosed as having diabetes are presumed to have type 2 disease and are not tested.

The investigators conducted a retrospective study of 102 patients with latent autoimmune diabetes and 111 with type 2 diabetes to determine which clinical features distinguished the two groups so that they could develop a simple screening tool for physicians in clinical practice.

The subjects with latent autoimmune diabetes were significantly younger at diagnosis (median age 46 years vs. 61 years). Most (67%) had acute symptoms, such as polydipsia, polyuria, or unintentional weight loss, whereas only a minority of patients with type 2 diabetes (28%) were symptomatic. The median body mass index (BMI) was lower in the subjects with latent autoimmune diabetes, but a majority of them still qualified as overweight or obese. Finally, most also had a personal or family history of autoimmune disease, whereas subjects with type 2 diabetes did not.

Dr. Fourlanos and his associates used these five clinical traits to fashion a screening tool, and validated its usefulness in a prospective study of 130 subjects aged 30–75 years with recently diagnosed diabetes that didn't require insulin therapy. Subjects who had at least two of the five clinical features—age of onset older than 50 years, acute symptoms, BMI (kg/m

If these patients are not tested and identified, “our experience is that suboptimal glycemia in such patients is frequently prolonged because it is not attributed to autoimmune diabetes and insulin deficiency,” they noted.

The screening also proved highly reliable at excluding a diagnosis of latent autoimmune diabetes in patients who had none or one of these features, with a negative predictive value of 99%. A score of 0 or 1 on this screen will exclude the autoimmune disorder and thus the need for antibody testing in approximately two-thirds of adults with diabetes, they added.

“This clinical screening method is superior to the current popular clinical practice of only screening patients with [a low] BMI … because a majority of subjects with [latent autoimmune diabetes] are overweight or obese,” the investigators said.

A relatively simple screening tool helps determine whether patients who present with adult-onset diabetes have type 2 disease or latent autoimmune diabetes, according to Dr. Spiros Fourlanos and his associates at the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria (Australia).

Latent autoimmune diabetes, which is believed to signal slowly progressive autoimmune β-cell destruction, is a form of type 1 disease characterized by adult onset; circulating islet cell antibodies and glutamic acid decarboxylase antibodies; and no initial need for insulin therapy. However, patients typically show dramatic loss of β-cell function within 3 years of diagnosis, which quickly leads to insulin dependence.

“We believe that physicians need to be aware that patients with [latent autoimmune diabetes] are prone to insulin deficiency and often require rapid escalation of oral hypoglycemic treatment or commencement of insulin earlier than islet antibody-negative patients,” Dr. Fourlanos and his associates said (Diabetes Care 2006;29:970–5).

Despite the frequency of the disorder and the difficulty in distinguishing it from type 2 diabetes, “there are no universal recommendations regarding testing for islet antibodies in adult-onset diabetes. Currently, many physicians test for islet antibodies only if they suspect [latent autoimmune diabetes],” the researchers said. Because most physicians also mistakenly assume that this disorder affects only normal-weight individuals, overweight adults who are diagnosed as having diabetes are presumed to have type 2 disease and are not tested.

The investigators conducted a retrospective study of 102 patients with latent autoimmune diabetes and 111 with type 2 diabetes to determine which clinical features distinguished the two groups so that they could develop a simple screening tool for physicians in clinical practice.

The subjects with latent autoimmune diabetes were significantly younger at diagnosis (median age 46 years vs. 61 years). Most (67%) had acute symptoms, such as polydipsia, polyuria, or unintentional weight loss, whereas only a minority of patients with type 2 diabetes (28%) were symptomatic. The median body mass index (BMI) was lower in the subjects with latent autoimmune diabetes, but a majority of them still qualified as overweight or obese. Finally, most also had a personal or family history of autoimmune disease, whereas subjects with type 2 diabetes did not.

Dr. Fourlanos and his associates used these five clinical traits to fashion a screening tool, and validated its usefulness in a prospective study of 130 subjects aged 30–75 years with recently diagnosed diabetes that didn't require insulin therapy. Subjects who had at least two of the five clinical features—age of onset older than 50 years, acute symptoms, BMI (kg/m

If these patients are not tested and identified, “our experience is that suboptimal glycemia in such patients is frequently prolonged because it is not attributed to autoimmune diabetes and insulin deficiency,” they noted.

The screening also proved highly reliable at excluding a diagnosis of latent autoimmune diabetes in patients who had none or one of these features, with a negative predictive value of 99%. A score of 0 or 1 on this screen will exclude the autoimmune disorder and thus the need for antibody testing in approximately two-thirds of adults with diabetes, they added.

“This clinical screening method is superior to the current popular clinical practice of only screening patients with [a low] BMI … because a majority of subjects with [latent autoimmune diabetes] are overweight or obese,” the investigators said.

Clinical trials in the field of cardiovascular medicine that are funded by for-profit groups like drug companies and device manufacturers are more likely to report positive findings than are those funded by not-for-profit groups.

The research community discovered that this was true of clinical trials published between 1990 and 2000, and it instituted some changes to address the issue. To determine whether more recent clinical trials are still affected by this apparent bias, two investigators surveyed the reported outcomes of 349 consecutive cardiovascular randomized clinical trials published in 2000–2005 in the Journal of the American Medical Association, The Lancet, and the New England Journal of Medicine.

“By focusing on manuscripts published in these three journals, we were able to limit our analysis to trials considered to be of high quality on the basis of prior rigorous peer and editorial review,” explained Dr. Paul M. Ridker and Jose Torres of Harvard Medical School, Boston.

A total of 109 (31%) of these trials were financed exclusively by not-for-profit groups such as the federal government, state governments, or foundations. Another 153 (44%) were financed exclusively by for-profit groups such as drug or device manufacturers. And 66 (19%) were funded jointly by both types of organizations. No source of funding was noted for the remaining 21 trials (6%).

Among the not-for-profit trials, approximately half found that newer treatments were no better than or not as good as the standard of care. In contrast, more than 67% of the for-profit trials found that newer treatments were superior to the standard of care, the investigators said (JAMA 2006;295:2270–4).

The proportion of jointly funded trials that favored new treatments was midway between these two points, at 56%.

A similar pattern was observed for the subset of 202 randomized clinical trials that evaluated cardiovascular drugs. The proportions that favored newer pharmaceuticals over the standard of care were 39% of the not-for-profit trials, 54% of the jointly funded trials, and 65% of the for-profit trials.

For the 38 trials that assessed cardiovascular devices, half of the not-for-profit trials favored new devices over the standard of care, compared with 69% of the jointly funded trials and 82% of the for-profit trials.

“These contemporary data appear to show that incentives surrounding for-profit organizations have the potential to influence clinical trial outcomes,” Dr. Ridker and Mr. Torres noted.

In addition, the researchers found there was “minimal” evidence of publication bias. “Contrary to the often-voiced concern that major journals do not report null studies, we found that a substantial proportion of the cardiovascular trials published in JAMA, The Lancet, and the New England Journal of Medicine between 2000 and 2005 reported either no significant differences between therapies (34.6%) or a significant difference favoring the standard of care over newer treatments (6.8%),” they said.

Incentives surrounding for-profits have the potential to influence clinical trial outcomes. DR. RIDKER

ELSEVIER GLOBAL MEDICAL NEWS

Clinical trials in the field of cardiovascular medicine that are funded by for-profit groups like drug companies and device manufacturers are more likely to report positive findings than are those funded by not-for-profit groups.

The research community discovered that this was true of clinical trials published between 1990 and 2000, and it instituted some changes to address the issue. To determine whether more recent clinical trials are still affected by this apparent bias, two investigators surveyed the reported outcomes of 349 consecutive cardiovascular randomized clinical trials published in 2000–2005 in the Journal of the American Medical Association, The Lancet, and the New England Journal of Medicine.

“By focusing on manuscripts published in these three journals, we were able to limit our analysis to trials considered to be of high quality on the basis of prior rigorous peer and editorial review,” explained Dr. Paul M. Ridker and Jose Torres of Harvard Medical School, Boston.

A total of 109 (31%) of these trials were financed exclusively by not-for-profit groups such as the federal government, state governments, or foundations. Another 153 (44%) were financed exclusively by for-profit groups such as drug or device manufacturers. And 66 (19%) were funded jointly by both types of organizations. No source of funding was noted for the remaining 21 trials (6%).

Among the not-for-profit trials, approximately half found that newer treatments were no better than or not as good as the standard of care. In contrast, more than 67% of the for-profit trials found that newer treatments were superior to the standard of care, the investigators said (JAMA 2006;295:2270–4).

The proportion of jointly funded trials that favored new treatments was midway between these two points, at 56%.

A similar pattern was observed for the subset of 202 randomized clinical trials that evaluated cardiovascular drugs. The proportions that favored newer pharmaceuticals over the standard of care were 39% of the not-for-profit trials, 54% of the jointly funded trials, and 65% of the for-profit trials.

For the 38 trials that assessed cardiovascular devices, half of the not-for-profit trials favored new devices over the standard of care, compared with 69% of the jointly funded trials and 82% of the for-profit trials.

“These contemporary data appear to show that incentives surrounding for-profit organizations have the potential to influence clinical trial outcomes,” Dr. Ridker and Mr. Torres noted.

In addition, the researchers found there was “minimal” evidence of publication bias. “Contrary to the often-voiced concern that major journals do not report null studies, we found that a substantial proportion of the cardiovascular trials published in JAMA, The Lancet, and the New England Journal of Medicine between 2000 and 2005 reported either no significant differences between therapies (34.6%) or a significant difference favoring the standard of care over newer treatments (6.8%),” they said.

Incentives surrounding for-profits have the potential to influence clinical trial outcomes. DR. RIDKER

ELSEVIER GLOBAL MEDICAL NEWS

Clinical trials in the field of cardiovascular medicine that are funded by for-profit groups like drug companies and device manufacturers are more likely to report positive findings than are those funded by not-for-profit groups.

The research community discovered that this was true of clinical trials published between 1990 and 2000, and it instituted some changes to address the issue. To determine whether more recent clinical trials are still affected by this apparent bias, two investigators surveyed the reported outcomes of 349 consecutive cardiovascular randomized clinical trials published in 2000–2005 in the Journal of the American Medical Association, The Lancet, and the New England Journal of Medicine.

“By focusing on manuscripts published in these three journals, we were able to limit our analysis to trials considered to be of high quality on the basis of prior rigorous peer and editorial review,” explained Dr. Paul M. Ridker and Jose Torres of Harvard Medical School, Boston.

A total of 109 (31%) of these trials were financed exclusively by not-for-profit groups such as the federal government, state governments, or foundations. Another 153 (44%) were financed exclusively by for-profit groups such as drug or device manufacturers. And 66 (19%) were funded jointly by both types of organizations. No source of funding was noted for the remaining 21 trials (6%).

Among the not-for-profit trials, approximately half found that newer treatments were no better than or not as good as the standard of care. In contrast, more than 67% of the for-profit trials found that newer treatments were superior to the standard of care, the investigators said (JAMA 2006;295:2270–4).

The proportion of jointly funded trials that favored new treatments was midway between these two points, at 56%.

A similar pattern was observed for the subset of 202 randomized clinical trials that evaluated cardiovascular drugs. The proportions that favored newer pharmaceuticals over the standard of care were 39% of the not-for-profit trials, 54% of the jointly funded trials, and 65% of the for-profit trials.

For the 38 trials that assessed cardiovascular devices, half of the not-for-profit trials favored new devices over the standard of care, compared with 69% of the jointly funded trials and 82% of the for-profit trials.

“These contemporary data appear to show that incentives surrounding for-profit organizations have the potential to influence clinical trial outcomes,” Dr. Ridker and Mr. Torres noted.

In addition, the researchers found there was “minimal” evidence of publication bias. “Contrary to the often-voiced concern that major journals do not report null studies, we found that a substantial proportion of the cardiovascular trials published in JAMA, The Lancet, and the New England Journal of Medicine between 2000 and 2005 reported either no significant differences between therapies (34.6%) or a significant difference favoring the standard of care over newer treatments (6.8%),” they said.

Incentives surrounding for-profits have the potential to influence clinical trial outcomes. DR. RIDKER

ELSEVIER GLOBAL MEDICAL NEWS

Adding ezetimibe to simvastatin was found to be safe in a pilot study of patients with chronic kidney disease, and the combined regimen decreased LDL cholesterol by approximately 40%, according to Martin Landray, Ph.D., of the University of Oxford (England) and his associates.

The 6-month study involved 203 patients treated for chronic kidney disease at eight British medical centers. One-fourth of the patients required dialysis. The mean age was 60 years. A total of 102 were randomly assigned to receive 20 mg simvastatin plus 10 mg ezetimibe daily, and the rest received simvastatin plus a placebo.

Both treatments significantly lowered LDL cholesterol levels at 1-, 3-, and 6-month follow-ups, but the addition of ezetimibe cut these levels a further 27% (21 mg/dL). The addition of ezetimibe also decreased total cholesterol levels by a further 16% and apolipoprotein B levels by a further 15% (Am. J. Kidney Dis. 2006;47:385–95).

These beneficial effects were noted in patients who required dialysis and in those who did not, although the study had limited power to assess possible differences between the two groups because of relatively small numbers of subjects, the investigators said.

Compliance with the combined therapy was similar to that with simvastatin monotherapy and approached 90% at 6 months. No serious adverse events were attributed to either treatment. There was no elevation of creatine kinase levels, and the drugs did not appear to affect blood calcium, phosphate, or retinol concentrations.

There was no excess risk with the combined therapy for gastrointestinal symptoms, although more patients taking ezetimibe reported having diarrhea. There also were no reports of myopathy. However, “the size and duration of this pilot study are insufficient to detect a moderate excess risk for serious myopathy or other safety outcomes reliably or [to] assess possible effects on major clinical events,” Dr. Landray and his associates noted.

These results suggest that combined therapy with simvastatin plus ezetimibe “is a potent yet well-tolerated cholesterol-lowering regimen,” they said. The researchers are now conducting a large-scale randomized trial examining the effects of lowering cholesterol on cardiovascular outcomes in patients with chronic kidney disease.

Adding ezetimibe to simvastatin was found to be safe in a pilot study of patients with chronic kidney disease, and the combined regimen decreased LDL cholesterol by approximately 40%, according to Martin Landray, Ph.D., of the University of Oxford (England) and his associates.

The 6-month study involved 203 patients treated for chronic kidney disease at eight British medical centers. One-fourth of the patients required dialysis. The mean age was 60 years. A total of 102 were randomly assigned to receive 20 mg simvastatin plus 10 mg ezetimibe daily, and the rest received simvastatin plus a placebo.

Both treatments significantly lowered LDL cholesterol levels at 1-, 3-, and 6-month follow-ups, but the addition of ezetimibe cut these levels a further 27% (21 mg/dL). The addition of ezetimibe also decreased total cholesterol levels by a further 16% and apolipoprotein B levels by a further 15% (Am. J. Kidney Dis. 2006;47:385–95).

These beneficial effects were noted in patients who required dialysis and in those who did not, although the study had limited power to assess possible differences between the two groups because of relatively small numbers of subjects, the investigators said.

Compliance with the combined therapy was similar to that with simvastatin monotherapy and approached 90% at 6 months. No serious adverse events were attributed to either treatment. There was no elevation of creatine kinase levels, and the drugs did not appear to affect blood calcium, phosphate, or retinol concentrations.

There was no excess risk with the combined therapy for gastrointestinal symptoms, although more patients taking ezetimibe reported having diarrhea. There also were no reports of myopathy. However, “the size and duration of this pilot study are insufficient to detect a moderate excess risk for serious myopathy or other safety outcomes reliably or [to] assess possible effects on major clinical events,” Dr. Landray and his associates noted.

These results suggest that combined therapy with simvastatin plus ezetimibe “is a potent yet well-tolerated cholesterol-lowering regimen,” they said. The researchers are now conducting a large-scale randomized trial examining the effects of lowering cholesterol on cardiovascular outcomes in patients with chronic kidney disease.

Adding ezetimibe to simvastatin was found to be safe in a pilot study of patients with chronic kidney disease, and the combined regimen decreased LDL cholesterol by approximately 40%, according to Martin Landray, Ph.D., of the University of Oxford (England) and his associates.

The 6-month study involved 203 patients treated for chronic kidney disease at eight British medical centers. One-fourth of the patients required dialysis. The mean age was 60 years. A total of 102 were randomly assigned to receive 20 mg simvastatin plus 10 mg ezetimibe daily, and the rest received simvastatin plus a placebo.

Both treatments significantly lowered LDL cholesterol levels at 1-, 3-, and 6-month follow-ups, but the addition of ezetimibe cut these levels a further 27% (21 mg/dL). The addition of ezetimibe also decreased total cholesterol levels by a further 16% and apolipoprotein B levels by a further 15% (Am. J. Kidney Dis. 2006;47:385–95).

These beneficial effects were noted in patients who required dialysis and in those who did not, although the study had limited power to assess possible differences between the two groups because of relatively small numbers of subjects, the investigators said.

Compliance with the combined therapy was similar to that with simvastatin monotherapy and approached 90% at 6 months. No serious adverse events were attributed to either treatment. There was no elevation of creatine kinase levels, and the drugs did not appear to affect blood calcium, phosphate, or retinol concentrations.

There was no excess risk with the combined therapy for gastrointestinal symptoms, although more patients taking ezetimibe reported having diarrhea. There also were no reports of myopathy. However, “the size and duration of this pilot study are insufficient to detect a moderate excess risk for serious myopathy or other safety outcomes reliably or [to] assess possible effects on major clinical events,” Dr. Landray and his associates noted.

These results suggest that combined therapy with simvastatin plus ezetimibe “is a potent yet well-tolerated cholesterol-lowering regimen,” they said. The researchers are now conducting a large-scale randomized trial examining the effects of lowering cholesterol on cardiovascular outcomes in patients with chronic kidney disease.

Despite the avid interest in finding nonhormonal therapies for menopausal hot flashes, most alternative treatments have demonstrated only limited efficacy, and their safety remains in question, according to a systematic review of the literature.

Dr. Heidi D. Nelson and her associates at Oregon Health and Science University, Portland, identified all randomized, placebo-controlled trials of nonhormonal treatments for hot flashes in the English literature and compared the efficacy and adverse effects of agents other than estrogens, progestins, progesterone, or androgens.

From an initial screening of 4,249 abstracts, they narrowed their focus to 43 trials with adequate study designs. However, even these trials were often flawed by high dropout rates, small study samples, short follow-up periods, and methodologic failings, they noted (JAMA 2006;295:2057–71).

The selected studies included 10 that assessed antidepressants, 10 assessing clonidine, 6 assessing other prescription drugs, and 17 assessing isoflavone extracts.

Eleven of the trials included women with breast cancer, many of whom were receiving tamoxifen. This is a population in whom hot flashes are particularly common and for whom estrogen therapy is contraindicated, the researchers said.

A metaanalysis was conducted using 24 of the 43 studies.

Overall, there was some evidence that selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, clonidine, and gabapentin reduce the severity and frequency of hot flashes. However, none of these agents approached the effectiveness of hormone therapy.

“Although these therapies may be most useful for highly symptomatic women who cannot take estrogen, they are not optimal choices for most women.” Their safety as treatments for hot flashes has not been adequately studied, and the adverse effects they cause as well as their cost will make their use prohibitive for many women, Dr. Nelson and her associates said.

The evidence for soy isoflavone extracts was contradictory, “even among the largest and highest quality trials,” they noted. There was no evidence to support the efficacy of red clover isoflavone extracts.

Despite the avid interest in finding nonhormonal therapies for menopausal hot flashes, most alternative treatments have demonstrated only limited efficacy, and their safety remains in question, according to a systematic review of the literature.

Dr. Heidi D. Nelson and her associates at Oregon Health and Science University, Portland, identified all randomized, placebo-controlled trials of nonhormonal treatments for hot flashes in the English literature and compared the efficacy and adverse effects of agents other than estrogens, progestins, progesterone, or androgens.

From an initial screening of 4,249 abstracts, they narrowed their focus to 43 trials with adequate study designs. However, even these trials were often flawed by high dropout rates, small study samples, short follow-up periods, and methodologic failings, they noted (JAMA 2006;295:2057–71).

The selected studies included 10 that assessed antidepressants, 10 assessing clonidine, 6 assessing other prescription drugs, and 17 assessing isoflavone extracts.

Eleven of the trials included women with breast cancer, many of whom were receiving tamoxifen. This is a population in whom hot flashes are particularly common and for whom estrogen therapy is contraindicated, the researchers said.

A metaanalysis was conducted using 24 of the 43 studies.

Overall, there was some evidence that selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, clonidine, and gabapentin reduce the severity and frequency of hot flashes. However, none of these agents approached the effectiveness of hormone therapy.

“Although these therapies may be most useful for highly symptomatic women who cannot take estrogen, they are not optimal choices for most women.” Their safety as treatments for hot flashes has not been adequately studied, and the adverse effects they cause as well as their cost will make their use prohibitive for many women, Dr. Nelson and her associates said.

The evidence for soy isoflavone extracts was contradictory, “even among the largest and highest quality trials,” they noted. There was no evidence to support the efficacy of red clover isoflavone extracts.

Despite the avid interest in finding nonhormonal therapies for menopausal hot flashes, most alternative treatments have demonstrated only limited efficacy, and their safety remains in question, according to a systematic review of the literature.

Dr. Heidi D. Nelson and her associates at Oregon Health and Science University, Portland, identified all randomized, placebo-controlled trials of nonhormonal treatments for hot flashes in the English literature and compared the efficacy and adverse effects of agents other than estrogens, progestins, progesterone, or androgens.

From an initial screening of 4,249 abstracts, they narrowed their focus to 43 trials with adequate study designs. However, even these trials were often flawed by high dropout rates, small study samples, short follow-up periods, and methodologic failings, they noted (JAMA 2006;295:2057–71).

The selected studies included 10 that assessed antidepressants, 10 assessing clonidine, 6 assessing other prescription drugs, and 17 assessing isoflavone extracts.

Eleven of the trials included women with breast cancer, many of whom were receiving tamoxifen. This is a population in whom hot flashes are particularly common and for whom estrogen therapy is contraindicated, the researchers said.

A metaanalysis was conducted using 24 of the 43 studies.

Overall, there was some evidence that selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, clonidine, and gabapentin reduce the severity and frequency of hot flashes. However, none of these agents approached the effectiveness of hormone therapy.

“Although these therapies may be most useful for highly symptomatic women who cannot take estrogen, they are not optimal choices for most women.” Their safety as treatments for hot flashes has not been adequately studied, and the adverse effects they cause as well as their cost will make their use prohibitive for many women, Dr. Nelson and her associates said.

The evidence for soy isoflavone extracts was contradictory, “even among the largest and highest quality trials,” they noted. There was no evidence to support the efficacy of red clover isoflavone extracts.

For patients with coronary artery disease who develop diabetes, pioglitazone improves endothelial dysfunction independently of its beneficial effects on insulin resistance and glycemia, reported Dr. Harald Sourij and his associates at the Medical University of Graz, Austria.

This added benefit is important because “better endothelial function is associated with improved cardiovascular outcome in patients with manifest CAD,” the investigators noted.

Preliminary research indicated glitazones, “a new class of antidiabetic drugs that primarily act via amelioration of insulin resistance,” might also influence endothelial function. The researchers assessed endothelial function in 42 patients with stable CAD and newly diagnosed type 2 diabetes. Their mean age was 60 years.

All participants had profoundly impaired endothelial function when they entered the study. They were randomly assigned to treatment with 30 mg pioglitazone or a placebo once daily for 12 weeks.

Only pioglitazone significantly improved endothelial function. Although the drug also improved insulin resistance and β-cell function, its effects on endothelial function were independent of those metabolic effects (Diabetes Care 2006;29:1039–45).

The drug's mechanism of action is not yet understood. It is known that “oxidative stress and local inflammatory activity play key roles in the pathogenesis of endothelial dysfunction in diabetes,” and the glitazones may reduce the production or availability of nitric oxide as well as decreasing inflammatory factors.

“We suggest our findings justify further research into possible direct effects of glitazones in the vascular wall, as well as into the possible role of endothelial function to predict treatment-induced vascular benefit in glitazone-treated patients,” they said.

For patients with coronary artery disease who develop diabetes, pioglitazone improves endothelial dysfunction independently of its beneficial effects on insulin resistance and glycemia, reported Dr. Harald Sourij and his associates at the Medical University of Graz, Austria.

This added benefit is important because “better endothelial function is associated with improved cardiovascular outcome in patients with manifest CAD,” the investigators noted.

Preliminary research indicated glitazones, “a new class of antidiabetic drugs that primarily act via amelioration of insulin resistance,” might also influence endothelial function. The researchers assessed endothelial function in 42 patients with stable CAD and newly diagnosed type 2 diabetes. Their mean age was 60 years.

All participants had profoundly impaired endothelial function when they entered the study. They were randomly assigned to treatment with 30 mg pioglitazone or a placebo once daily for 12 weeks.

Only pioglitazone significantly improved endothelial function. Although the drug also improved insulin resistance and β-cell function, its effects on endothelial function were independent of those metabolic effects (Diabetes Care 2006;29:1039–45).

The drug's mechanism of action is not yet understood. It is known that “oxidative stress and local inflammatory activity play key roles in the pathogenesis of endothelial dysfunction in diabetes,” and the glitazones may reduce the production or availability of nitric oxide as well as decreasing inflammatory factors.

“We suggest our findings justify further research into possible direct effects of glitazones in the vascular wall, as well as into the possible role of endothelial function to predict treatment-induced vascular benefit in glitazone-treated patients,” they said.

For patients with coronary artery disease who develop diabetes, pioglitazone improves endothelial dysfunction independently of its beneficial effects on insulin resistance and glycemia, reported Dr. Harald Sourij and his associates at the Medical University of Graz, Austria.

This added benefit is important because “better endothelial function is associated with improved cardiovascular outcome in patients with manifest CAD,” the investigators noted.

Preliminary research indicated glitazones, “a new class of antidiabetic drugs that primarily act via amelioration of insulin resistance,” might also influence endothelial function. The researchers assessed endothelial function in 42 patients with stable CAD and newly diagnosed type 2 diabetes. Their mean age was 60 years.

All participants had profoundly impaired endothelial function when they entered the study. They were randomly assigned to treatment with 30 mg pioglitazone or a placebo once daily for 12 weeks.

Only pioglitazone significantly improved endothelial function. Although the drug also improved insulin resistance and β-cell function, its effects on endothelial function were independent of those metabolic effects (Diabetes Care 2006;29:1039–45).

The drug's mechanism of action is not yet understood. It is known that “oxidative stress and local inflammatory activity play key roles in the pathogenesis of endothelial dysfunction in diabetes,” and the glitazones may reduce the production or availability of nitric oxide as well as decreasing inflammatory factors.

“We suggest our findings justify further research into possible direct effects of glitazones in the vascular wall, as well as into the possible role of endothelial function to predict treatment-induced vascular benefit in glitazone-treated patients,” they said.

Both thiazide diuretics and β-blockers taken to treat hypertension appear to raise the risk of type 2 diabetes, reported Dr. Eric N. Taylor of Harvard Medical School, Boston, and his associates.

The researchers used data from three large cohort studies to determine whether various antihypertensive agents were associated with incident cases of type 2 diabetes. They analyzed data on more than 14,000 younger women (aged 25–42 at baseline) in the Nurses' Health Study II, more than 41,000 older women (aged 30–55 years at baseline) in the Nurses' Health Study I, and more than 19,000 men (aged 40–75 years at baseline) in the Health Professionals Follow-Up Study.

All the subjects were taking medication for hypertension. During follow-ups of 10 years (NHS II participants), 8 years (NHS I participants), and 16 years (HPFS participants), 3,589 developed type 2 diabetes.

The use of thiazide diuretics significantly raised the risk of incident diabetes in all three cohorts. The use of β-blockers was not assessed separately from other antihypertensives in the younger women, but it significantly raised the risk of incident diabetes in the older women and in the men, Dr. Taylor and his associates wrote (Diabetes Care 2006;29:1065–70).

There was no link between the use of calcium channel blockers or other antihypertensive medications and diabetes risks. The results suggest that patients whose hypertension is treated with thiazide diuretics or β-blockers “merit increased surveillance for diabetes,” the investigators said.

Both thiazide diuretics and β-blockers taken to treat hypertension appear to raise the risk of type 2 diabetes, reported Dr. Eric N. Taylor of Harvard Medical School, Boston, and his associates.

The researchers used data from three large cohort studies to determine whether various antihypertensive agents were associated with incident cases of type 2 diabetes. They analyzed data on more than 14,000 younger women (aged 25–42 at baseline) in the Nurses' Health Study II, more than 41,000 older women (aged 30–55 years at baseline) in the Nurses' Health Study I, and more than 19,000 men (aged 40–75 years at baseline) in the Health Professionals Follow-Up Study.

All the subjects were taking medication for hypertension. During follow-ups of 10 years (NHS II participants), 8 years (NHS I participants), and 16 years (HPFS participants), 3,589 developed type 2 diabetes.

The use of thiazide diuretics significantly raised the risk of incident diabetes in all three cohorts. The use of β-blockers was not assessed separately from other antihypertensives in the younger women, but it significantly raised the risk of incident diabetes in the older women and in the men, Dr. Taylor and his associates wrote (Diabetes Care 2006;29:1065–70).

There was no link between the use of calcium channel blockers or other antihypertensive medications and diabetes risks. The results suggest that patients whose hypertension is treated with thiazide diuretics or β-blockers “merit increased surveillance for diabetes,” the investigators said.

Both thiazide diuretics and β-blockers taken to treat hypertension appear to raise the risk of type 2 diabetes, reported Dr. Eric N. Taylor of Harvard Medical School, Boston, and his associates.

The researchers used data from three large cohort studies to determine whether various antihypertensive agents were associated with incident cases of type 2 diabetes. They analyzed data on more than 14,000 younger women (aged 25–42 at baseline) in the Nurses' Health Study II, more than 41,000 older women (aged 30–55 years at baseline) in the Nurses' Health Study I, and more than 19,000 men (aged 40–75 years at baseline) in the Health Professionals Follow-Up Study.

All the subjects were taking medication for hypertension. During follow-ups of 10 years (NHS II participants), 8 years (NHS I participants), and 16 years (HPFS participants), 3,589 developed type 2 diabetes.

The use of thiazide diuretics significantly raised the risk of incident diabetes in all three cohorts. The use of β-blockers was not assessed separately from other antihypertensives in the younger women, but it significantly raised the risk of incident diabetes in the older women and in the men, Dr. Taylor and his associates wrote (Diabetes Care 2006;29:1065–70).

There was no link between the use of calcium channel blockers or other antihypertensive medications and diabetes risks. The results suggest that patients whose hypertension is treated with thiazide diuretics or β-blockers “merit increased surveillance for diabetes,” the investigators said.

Most, if not all, elderly people with diabetes have at least one indication for ACE inhibitors or angiotensin receptor blockers, but only about 40% are receiving the drugs, according to a national survey.

“Given that indications for ACE/ARB therapy are so prevalent in this population, it may be time to simplify our treatment algorithms by expanding indications … to include all older individuals with diabetes regardless of their measured risk factors,” said Dr. Allison B. Rosen of the University of Michigan Health Systems, Ann Arbor.

Dr. Rosen analyzed data from 4 years of the National Health and Nutrition Examination Survey to calculate the proportion of older diabetic patients with clinical indications for ACE inhibitors or ARBs. Her study sample included 742 respondents who represented over 8 million Americans aged 55 years or older who have diabetes.

A total of 92% of the respondents had at least one indication besides diabetes for the medications, according to several sets of guidelines. These indications included albuminuria, cardiovascular disease, congestive heart failure, and hypertension.

Two other risk factors—hyperlipidemia and smoking—are listed as indications on some guidelines, and patients with these risk factors are believed to benefit from ACE inhibitor or ARB therapy. When these indications were added to the list, 100% of the respondents had at least one indication for the medications, Dr. Rosen said.

Yet despite this “nearly universal” indication for treatment, only 43% of the respondents were taking an ACE inhibitor or an ARB, she said (J. Gen. Intern. Med. 2006;DOI:10.1111/j.1525–1497.2006.00351.x).

Of particular note, 53% of those with diabetes and four or more additional indications were taking the drugs, a “disturbingly low” rate for such high-risk patients. The likelihood that these clearly needy patients would actually be receiving appropriate medication “was not much higher than the toss of a coin,” she commented.

Moreover, patients with albuminuria and preexisting cardiovascular disease, two key indications that should invariably prompt a physician to prescribe ACE inhibitors or ARBs, had the same low rate of use as patients who didn't have these crucial risk factors.

Dr. Rosen described her study as “the first nationally representative study to ask what proportion of older patients with diabetes would benefit from renin-angiotensin system blockade.”

Most, if not all, elderly people with diabetes have at least one indication for ACE inhibitors or angiotensin receptor blockers, but only about 40% are receiving the drugs, according to a national survey.

“Given that indications for ACE/ARB therapy are so prevalent in this population, it may be time to simplify our treatment algorithms by expanding indications … to include all older individuals with diabetes regardless of their measured risk factors,” said Dr. Allison B. Rosen of the University of Michigan Health Systems, Ann Arbor.

Dr. Rosen analyzed data from 4 years of the National Health and Nutrition Examination Survey to calculate the proportion of older diabetic patients with clinical indications for ACE inhibitors or ARBs. Her study sample included 742 respondents who represented over 8 million Americans aged 55 years or older who have diabetes.

A total of 92% of the respondents had at least one indication besides diabetes for the medications, according to several sets of guidelines. These indications included albuminuria, cardiovascular disease, congestive heart failure, and hypertension.

Two other risk factors—hyperlipidemia and smoking—are listed as indications on some guidelines, and patients with these risk factors are believed to benefit from ACE inhibitor or ARB therapy. When these indications were added to the list, 100% of the respondents had at least one indication for the medications, Dr. Rosen said.

Yet despite this “nearly universal” indication for treatment, only 43% of the respondents were taking an ACE inhibitor or an ARB, she said (J. Gen. Intern. Med. 2006;DOI:10.1111/j.1525–1497.2006.00351.x).

Of particular note, 53% of those with diabetes and four or more additional indications were taking the drugs, a “disturbingly low” rate for such high-risk patients. The likelihood that these clearly needy patients would actually be receiving appropriate medication “was not much higher than the toss of a coin,” she commented.

Moreover, patients with albuminuria and preexisting cardiovascular disease, two key indications that should invariably prompt a physician to prescribe ACE inhibitors or ARBs, had the same low rate of use as patients who didn't have these crucial risk factors.

Dr. Rosen described her study as “the first nationally representative study to ask what proportion of older patients with diabetes would benefit from renin-angiotensin system blockade.”

Most, if not all, elderly people with diabetes have at least one indication for ACE inhibitors or angiotensin receptor blockers, but only about 40% are receiving the drugs, according to a national survey.

“Given that indications for ACE/ARB therapy are so prevalent in this population, it may be time to simplify our treatment algorithms by expanding indications … to include all older individuals with diabetes regardless of their measured risk factors,” said Dr. Allison B. Rosen of the University of Michigan Health Systems, Ann Arbor.

Dr. Rosen analyzed data from 4 years of the National Health and Nutrition Examination Survey to calculate the proportion of older diabetic patients with clinical indications for ACE inhibitors or ARBs. Her study sample included 742 respondents who represented over 8 million Americans aged 55 years or older who have diabetes.

A total of 92% of the respondents had at least one indication besides diabetes for the medications, according to several sets of guidelines. These indications included albuminuria, cardiovascular disease, congestive heart failure, and hypertension.

Two other risk factors—hyperlipidemia and smoking—are listed as indications on some guidelines, and patients with these risk factors are believed to benefit from ACE inhibitor or ARB therapy. When these indications were added to the list, 100% of the respondents had at least one indication for the medications, Dr. Rosen said.

Yet despite this “nearly universal” indication for treatment, only 43% of the respondents were taking an ACE inhibitor or an ARB, she said (J. Gen. Intern. Med. 2006;DOI:10.1111/j.1525–1497.2006.00351.x).

Of particular note, 53% of those with diabetes and four or more additional indications were taking the drugs, a “disturbingly low” rate for such high-risk patients. The likelihood that these clearly needy patients would actually be receiving appropriate medication “was not much higher than the toss of a coin,” she commented.

Moreover, patients with albuminuria and preexisting cardiovascular disease, two key indications that should invariably prompt a physician to prescribe ACE inhibitors or ARBs, had the same low rate of use as patients who didn't have these crucial risk factors.

Dr. Rosen described her study as “the first nationally representative study to ask what proportion of older patients with diabetes would benefit from renin-angiotensin system blockade.”

Simvastatin increases retinal blood flow and decreases intraocular pressure in healthy subjects, making it a potential treatment for diabetic retinopathy and glaucoma, according to Dr. Taiji Nagaoka of Asahikawa (Japan) Medical College and associates.

Noting that long-term statin use has been reported to reduce the risk of retinal ischemic diseases, the researchers assessed the effect of simvastatin on the retinal circulation and on intraocular pressure in 12 healthy volunteers.

The subjects were nonsmoking Japanese men aged 19–23 years. They were examined 90 minutes after a single 20-mg dose of the drug on one occasion and after taking a placebo on a separate occasion. They also underwent similar assessments after taking daily doses of either simvastatin or placebo for 1 week.

Retinal blood flow increased significantly, by 20% in the retinal arteries and by 23% in the retinal veins, after 1 week of simvastatin therapy. Intraocular pressure decreased significantly, from 14.3 mm Hg at baseline to 12.6 mm Hg after a single dose of the drug and to 12.4 mm Hg after 1 week of therapy. Plasma nitrite/nitrate levels also rose by 60% after 1 week on simvastatin.

In contrast, all retinal measurements remained unchanged after administration of the placebo.

This is the first study to show that simvastatin increases retinal blood flow, “probably via the increase in nitric oxide,” the investigators said (Arch. Ophthalmol. 2006;124:665–70).

The increase appears to be exerted mainly on the more downstream vessels in the retinal microvascular network, notably the capillaries, they added.

A previous study involving six subjects suggested that statins might improve hard exudates and microaneurysms in diabetic retinopathy. “Although the findings in the present study are obtained from healthy men whose physiological response to simvastatin may be different from that of patients with diabetes, the increased retinal blood flow associated with treatment with simvastatin may be a potential therapy for diabetic retinopathy,” Dr. Nagaoka and associates said.

Similarly, another study recently reported that statin use appears to reduce the risk for glaucoma but did not measure intraocular pressure. “In the present study, we document for the first time … that the intraocular pressure was slightly but significantly decreased by simvastatin,” they added.

“Further study among more subjects is needed to examine the effects of age, sex, and systemic disorders such as hyperlipidemia, hypertension, and diabetes mellitus, on the retinal circulation that are associated with systemic administration of simvastatin,” they said.

Simvastatin increases retinal blood flow and decreases intraocular pressure in healthy subjects, making it a potential treatment for diabetic retinopathy and glaucoma, according to Dr. Taiji Nagaoka of Asahikawa (Japan) Medical College and associates.

Noting that long-term statin use has been reported to reduce the risk of retinal ischemic diseases, the researchers assessed the effect of simvastatin on the retinal circulation and on intraocular pressure in 12 healthy volunteers.

The subjects were nonsmoking Japanese men aged 19–23 years. They were examined 90 minutes after a single 20-mg dose of the drug on one occasion and after taking a placebo on a separate occasion. They also underwent similar assessments after taking daily doses of either simvastatin or placebo for 1 week.

Retinal blood flow increased significantly, by 20% in the retinal arteries and by 23% in the retinal veins, after 1 week of simvastatin therapy. Intraocular pressure decreased significantly, from 14.3 mm Hg at baseline to 12.6 mm Hg after a single dose of the drug and to 12.4 mm Hg after 1 week of therapy. Plasma nitrite/nitrate levels also rose by 60% after 1 week on simvastatin.

In contrast, all retinal measurements remained unchanged after administration of the placebo.

This is the first study to show that simvastatin increases retinal blood flow, “probably via the increase in nitric oxide,” the investigators said (Arch. Ophthalmol. 2006;124:665–70).

The increase appears to be exerted mainly on the more downstream vessels in the retinal microvascular network, notably the capillaries, they added.

A previous study involving six subjects suggested that statins might improve hard exudates and microaneurysms in diabetic retinopathy. “Although the findings in the present study are obtained from healthy men whose physiological response to simvastatin may be different from that of patients with diabetes, the increased retinal blood flow associated with treatment with simvastatin may be a potential therapy for diabetic retinopathy,” Dr. Nagaoka and associates said.

Similarly, another study recently reported that statin use appears to reduce the risk for glaucoma but did not measure intraocular pressure. “In the present study, we document for the first time … that the intraocular pressure was slightly but significantly decreased by simvastatin,” they added.

“Further study among more subjects is needed to examine the effects of age, sex, and systemic disorders such as hyperlipidemia, hypertension, and diabetes mellitus, on the retinal circulation that are associated with systemic administration of simvastatin,” they said.

Simvastatin increases retinal blood flow and decreases intraocular pressure in healthy subjects, making it a potential treatment for diabetic retinopathy and glaucoma, according to Dr. Taiji Nagaoka of Asahikawa (Japan) Medical College and associates.

Noting that long-term statin use has been reported to reduce the risk of retinal ischemic diseases, the researchers assessed the effect of simvastatin on the retinal circulation and on intraocular pressure in 12 healthy volunteers.

The subjects were nonsmoking Japanese men aged 19–23 years. They were examined 90 minutes after a single 20-mg dose of the drug on one occasion and after taking a placebo on a separate occasion. They also underwent similar assessments after taking daily doses of either simvastatin or placebo for 1 week.

Retinal blood flow increased significantly, by 20% in the retinal arteries and by 23% in the retinal veins, after 1 week of simvastatin therapy. Intraocular pressure decreased significantly, from 14.3 mm Hg at baseline to 12.6 mm Hg after a single dose of the drug and to 12.4 mm Hg after 1 week of therapy. Plasma nitrite/nitrate levels also rose by 60% after 1 week on simvastatin.

In contrast, all retinal measurements remained unchanged after administration of the placebo.

This is the first study to show that simvastatin increases retinal blood flow, “probably via the increase in nitric oxide,” the investigators said (Arch. Ophthalmol. 2006;124:665–70).

The increase appears to be exerted mainly on the more downstream vessels in the retinal microvascular network, notably the capillaries, they added.

A previous study involving six subjects suggested that statins might improve hard exudates and microaneurysms in diabetic retinopathy. “Although the findings in the present study are obtained from healthy men whose physiological response to simvastatin may be different from that of patients with diabetes, the increased retinal blood flow associated with treatment with simvastatin may be a potential therapy for diabetic retinopathy,” Dr. Nagaoka and associates said.

Similarly, another study recently reported that statin use appears to reduce the risk for glaucoma but did not measure intraocular pressure. “In the present study, we document for the first time … that the intraocular pressure was slightly but significantly decreased by simvastatin,” they added.

“Further study among more subjects is needed to examine the effects of age, sex, and systemic disorders such as hyperlipidemia, hypertension, and diabetes mellitus, on the retinal circulation that are associated with systemic administration of simvastatin,” they said.

A relatively simple screening tool helps determine whether patients who present with adult-onset diabetes have type 2 disease or latent autoimmune diabetes, according to Dr. Spiros Fourlanos and his associates at the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria (Australia).

Latent autoimmune diabetes, which is believed to signal slowly progressive autoimmune β-cell destruction, is a form of type 1 disease characterized by adult onset; circulating islet cell antibodies and glutamic acid decarboxylase antibodies; and no initial need for insulin therapy. However, patients often have dramatic loss of β-cell function within 3 years of diagnosis, which quickly leads to insulin dependence.

“We believe that physicians need to be aware that patients with [latent autoimmune diabetes] are prone to insulin deficiency and often require rapid escalation of oral hypoglycemic treatment or commencement of insulin earlier than islet antibody-negative patients,” Dr. Fourlanos and his associates said (Diabetes Care 2006;29:970–5).

Despite the frequency of the disorder and the difficulty in distinguishing it from type 2 diabetes, “there are no universal recommendations regarding testing for islet antibodies in adult-onset diabetes. Currently, many physicians test for islet antibodies only if they suspect [latent autoimmune diabetes],” the researchers said. Since most physicians also assume that this disorder affects only normal-weight individuals, overweight adults who are diagnosed as having diabetes are presumed to have type 2 disease and are not tested.

The investigators conducted a retrospective study of 102 patients with latent autoimmune diabetes and 111 with type 2 diabetes to determine which clinical features distinguished the two groups so that they could develop a simple screening tool for physicians in clinical practice.

The subjects with latent autoimmune diabetes were significantly younger at diagnosis (median age 46 years vs. 61 years). Most (67%) had acute symptoms, such as polydipsia, polyuria, or unintentional weight loss, whereas only a minority of patients with type 2 diabetes (28%) were symptomatic. The median body mass index (BMI) was lower in the subjects with latent autoimmune diabetes, but a majority of them still qualified as overweight or obese. Finally, most also had a personal or family history of autoimmune disease, whereas subjects with type 2 diabetes did not.

Dr. Fourlanos and his associates used these five clinical traits to fashion a screening tool, and validated its usefulness in a prospective study of 130 subjects aged 30–75 years with recently diagnosed diabetes who didn't require insulin therapy. Subjects who had at least two of the five clinical features—age of onset older than 50, acute symptoms, BMI (kg/m

If these patients are not tested and identified, “our experience is that suboptimal glycemia in such patients is frequently prolonged because it is not attributed to autoimmune diabetes and insulin deficiency,” they noted.

The screening also proved highly reliable at excluding a diagnosis of latent autoimmune diabetes in patients who had none or one of these features, with a negative predictive value of 99%. A score of 0 or 1 on this screen will exclude the autoimmune disorder and thus the need for antibody testing in approximately two-thirds of adults with diabetes, they added.

“This clinical screening method is superior to the current popular clinical practice of only screening patients with [a low] BMI … because a majority of subjects with [latent autoimmune diabetes] are overweight or obese,” the investigators said.

Use of this screening tool should increase the identification of autoimmune diabetes and improve clinical management, they said.

A relatively simple screening tool helps determine whether patients who present with adult-onset diabetes have type 2 disease or latent autoimmune diabetes, according to Dr. Spiros Fourlanos and his associates at the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria (Australia).

Latent autoimmune diabetes, which is believed to signal slowly progressive autoimmune β-cell destruction, is a form of type 1 disease characterized by adult onset; circulating islet cell antibodies and glutamic acid decarboxylase antibodies; and no initial need for insulin therapy. However, patients often have dramatic loss of β-cell function within 3 years of diagnosis, which quickly leads to insulin dependence.

“We believe that physicians need to be aware that patients with [latent autoimmune diabetes] are prone to insulin deficiency and often require rapid escalation of oral hypoglycemic treatment or commencement of insulin earlier than islet antibody-negative patients,” Dr. Fourlanos and his associates said (Diabetes Care 2006;29:970–5).

Despite the frequency of the disorder and the difficulty in distinguishing it from type 2 diabetes, “there are no universal recommendations regarding testing for islet antibodies in adult-onset diabetes. Currently, many physicians test for islet antibodies only if they suspect [latent autoimmune diabetes],” the researchers said. Since most physicians also assume that this disorder affects only normal-weight individuals, overweight adults who are diagnosed as having diabetes are presumed to have type 2 disease and are not tested.

The investigators conducted a retrospective study of 102 patients with latent autoimmune diabetes and 111 with type 2 diabetes to determine which clinical features distinguished the two groups so that they could develop a simple screening tool for physicians in clinical practice.

The subjects with latent autoimmune diabetes were significantly younger at diagnosis (median age 46 years vs. 61 years). Most (67%) had acute symptoms, such as polydipsia, polyuria, or unintentional weight loss, whereas only a minority of patients with type 2 diabetes (28%) were symptomatic. The median body mass index (BMI) was lower in the subjects with latent autoimmune diabetes, but a majority of them still qualified as overweight or obese. Finally, most also had a personal or family history of autoimmune disease, whereas subjects with type 2 diabetes did not.

Dr. Fourlanos and his associates used these five clinical traits to fashion a screening tool, and validated its usefulness in a prospective study of 130 subjects aged 30–75 years with recently diagnosed diabetes who didn't require insulin therapy. Subjects who had at least two of the five clinical features—age of onset older than 50, acute symptoms, BMI (kg/m

If these patients are not tested and identified, “our experience is that suboptimal glycemia in such patients is frequently prolonged because it is not attributed to autoimmune diabetes and insulin deficiency,” they noted.

The screening also proved highly reliable at excluding a diagnosis of latent autoimmune diabetes in patients who had none or one of these features, with a negative predictive value of 99%. A score of 0 or 1 on this screen will exclude the autoimmune disorder and thus the need for antibody testing in approximately two-thirds of adults with diabetes, they added.

“This clinical screening method is superior to the current popular clinical practice of only screening patients with [a low] BMI … because a majority of subjects with [latent autoimmune diabetes] are overweight or obese,” the investigators said.

Use of this screening tool should increase the identification of autoimmune diabetes and improve clinical management, they said.

A relatively simple screening tool helps determine whether patients who present with adult-onset diabetes have type 2 disease or latent autoimmune diabetes, according to Dr. Spiros Fourlanos and his associates at the Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria (Australia).

Latent autoimmune diabetes, which is believed to signal slowly progressive autoimmune β-cell destruction, is a form of type 1 disease characterized by adult onset; circulating islet cell antibodies and glutamic acid decarboxylase antibodies; and no initial need for insulin therapy. However, patients often have dramatic loss of β-cell function within 3 years of diagnosis, which quickly leads to insulin dependence.

“We believe that physicians need to be aware that patients with [latent autoimmune diabetes] are prone to insulin deficiency and often require rapid escalation of oral hypoglycemic treatment or commencement of insulin earlier than islet antibody-negative patients,” Dr. Fourlanos and his associates said (Diabetes Care 2006;29:970–5).

Despite the frequency of the disorder and the difficulty in distinguishing it from type 2 diabetes, “there are no universal recommendations regarding testing for islet antibodies in adult-onset diabetes. Currently, many physicians test for islet antibodies only if they suspect [latent autoimmune diabetes],” the researchers said. Since most physicians also assume that this disorder affects only normal-weight individuals, overweight adults who are diagnosed as having diabetes are presumed to have type 2 disease and are not tested.

The investigators conducted a retrospective study of 102 patients with latent autoimmune diabetes and 111 with type 2 diabetes to determine which clinical features distinguished the two groups so that they could develop a simple screening tool for physicians in clinical practice.

The subjects with latent autoimmune diabetes were significantly younger at diagnosis (median age 46 years vs. 61 years). Most (67%) had acute symptoms, such as polydipsia, polyuria, or unintentional weight loss, whereas only a minority of patients with type 2 diabetes (28%) were symptomatic. The median body mass index (BMI) was lower in the subjects with latent autoimmune diabetes, but a majority of them still qualified as overweight or obese. Finally, most also had a personal or family history of autoimmune disease, whereas subjects with type 2 diabetes did not.

Dr. Fourlanos and his associates used these five clinical traits to fashion a screening tool, and validated its usefulness in a prospective study of 130 subjects aged 30–75 years with recently diagnosed diabetes who didn't require insulin therapy. Subjects who had at least two of the five clinical features—age of onset older than 50, acute symptoms, BMI (kg/m

If these patients are not tested and identified, “our experience is that suboptimal glycemia in such patients is frequently prolonged because it is not attributed to autoimmune diabetes and insulin deficiency,” they noted.

The screening also proved highly reliable at excluding a diagnosis of latent autoimmune diabetes in patients who had none or one of these features, with a negative predictive value of 99%. A score of 0 or 1 on this screen will exclude the autoimmune disorder and thus the need for antibody testing in approximately two-thirds of adults with diabetes, they added.

“This clinical screening method is superior to the current popular clinical practice of only screening patients with [a low] BMI … because a majority of subjects with [latent autoimmune diabetes] are overweight or obese,” the investigators said.

Use of this screening tool should increase the identification of autoimmune diabetes and improve clinical management, they said.