Mary Ann Moon

Maintenance therapy with sertraline prevents a recurrence of major depression in diabetic patients whose mood disorder initially responds well to the drug, reported Patrick J. Lustman, Ph.D., of Washington University, St. Louis.

Clinical depression has been reported to occur in one-fourth of people with diabetes, and recurrent episodes are common. Depression not only impairs their function and quality of life but also increases their risk of death—largely by accelerating coronary heart disease—and their risk of diabetes complications, Dr. Lustman and his associates said.

Pharmacotherapy and psychotherapy improve both mood and glycemic control in depressed diabetic patients, but the benefits appear to be short-lived, with up to 60% of such patients developing a recurrence in the year following successful treatment. Maintenance therapy is known to reduce recurrences in 15%–30% of nondiabetic depressed patients but had not been assessed in diabetic patients until this study was done.

The researchers evaluated maintenance therapy in 152 patients with either type 1 or type 2 diabetes and major depressive disorder. The study subjects had a mean of five previous episodes of depression.

The current episode had resolved with sertraline therapy, at a mean dose of 118 mg per day (range of 50–200 mg per day). Subjects were then randomly assigned to either continue with the same dosage of sertraline that had induced recovery (79 subjects) or to switch to placebo (73 subjects), and were followed for 12 months or until depression recurred.

Depression symptoms and glycemic control were monitored in monthly office visits and via telephone interviews at every midpoint between office visits, to permit rapid detection of recurrences. Both the Beck Depression Inventory and the Hamilton Depression Rating scale were used to measure depression symptoms.

Sertraline was significantly more effective than placebo at prolonging the depression-free interval. At 1 year, the calculated rate of nonrecurrence was 66% in patients treated with sertraline, compared with 48% for those who received placebo, the investigators wrote (Arch. Gen. Psychiatry 2006;63:521–9).

The interval until one-third of the subjects developed a recurrence was 226 days in those taking sertraline, compared with 57 days in those taking placebo. The median time to recurrence exceeded 365 days, the maximum duration of follow-up, for subjects taking sertraline, compared with 251 days for those taking placebo.

This study was supported in part by Pfizer Inc., which provided the sertraline for study subjects.

Maintenance therapy with sertraline prevents a recurrence of major depression in diabetic patients whose mood disorder initially responds well to the drug, reported Patrick J. Lustman, Ph.D., of Washington University, St. Louis.

Clinical depression has been reported to occur in one-fourth of people with diabetes, and recurrent episodes are common. Depression not only impairs their function and quality of life but also increases their risk of death—largely by accelerating coronary heart disease—and their risk of diabetes complications, Dr. Lustman and his associates said.

Pharmacotherapy and psychotherapy improve both mood and glycemic control in depressed diabetic patients, but the benefits appear to be short-lived, with up to 60% of such patients developing a recurrence in the year following successful treatment. Maintenance therapy is known to reduce recurrences in 15%–30% of nondiabetic depressed patients but had not been assessed in diabetic patients until this study was done.

The researchers evaluated maintenance therapy in 152 patients with either type 1 or type 2 diabetes and major depressive disorder. The study subjects had a mean of five previous episodes of depression.

The current episode had resolved with sertraline therapy, at a mean dose of 118 mg per day (range of 50–200 mg per day). Subjects were then randomly assigned to either continue with the same dosage of sertraline that had induced recovery (79 subjects) or to switch to placebo (73 subjects), and were followed for 12 months or until depression recurred.

Depression symptoms and glycemic control were monitored in monthly office visits and via telephone interviews at every midpoint between office visits, to permit rapid detection of recurrences. Both the Beck Depression Inventory and the Hamilton Depression Rating scale were used to measure depression symptoms.

Sertraline was significantly more effective than placebo at prolonging the depression-free interval. At 1 year, the calculated rate of nonrecurrence was 66% in patients treated with sertraline, compared with 48% for those who received placebo, the investigators wrote (Arch. Gen. Psychiatry 2006;63:521–9).

The interval until one-third of the subjects developed a recurrence was 226 days in those taking sertraline, compared with 57 days in those taking placebo. The median time to recurrence exceeded 365 days, the maximum duration of follow-up, for subjects taking sertraline, compared with 251 days for those taking placebo.

This study was supported in part by Pfizer Inc., which provided the sertraline for study subjects.

Maintenance therapy with sertraline prevents a recurrence of major depression in diabetic patients whose mood disorder initially responds well to the drug, reported Patrick J. Lustman, Ph.D., of Washington University, St. Louis.

Clinical depression has been reported to occur in one-fourth of people with diabetes, and recurrent episodes are common. Depression not only impairs their function and quality of life but also increases their risk of death—largely by accelerating coronary heart disease—and their risk of diabetes complications, Dr. Lustman and his associates said.

Pharmacotherapy and psychotherapy improve both mood and glycemic control in depressed diabetic patients, but the benefits appear to be short-lived, with up to 60% of such patients developing a recurrence in the year following successful treatment. Maintenance therapy is known to reduce recurrences in 15%–30% of nondiabetic depressed patients but had not been assessed in diabetic patients until this study was done.

The researchers evaluated maintenance therapy in 152 patients with either type 1 or type 2 diabetes and major depressive disorder. The study subjects had a mean of five previous episodes of depression.

The current episode had resolved with sertraline therapy, at a mean dose of 118 mg per day (range of 50–200 mg per day). Subjects were then randomly assigned to either continue with the same dosage of sertraline that had induced recovery (79 subjects) or to switch to placebo (73 subjects), and were followed for 12 months or until depression recurred.

Depression symptoms and glycemic control were monitored in monthly office visits and via telephone interviews at every midpoint between office visits, to permit rapid detection of recurrences. Both the Beck Depression Inventory and the Hamilton Depression Rating scale were used to measure depression symptoms.

Sertraline was significantly more effective than placebo at prolonging the depression-free interval. At 1 year, the calculated rate of nonrecurrence was 66% in patients treated with sertraline, compared with 48% for those who received placebo, the investigators wrote (Arch. Gen. Psychiatry 2006;63:521–9).

The interval until one-third of the subjects developed a recurrence was 226 days in those taking sertraline, compared with 57 days in those taking placebo. The median time to recurrence exceeded 365 days, the maximum duration of follow-up, for subjects taking sertraline, compared with 251 days for those taking placebo.

This study was supported in part by Pfizer Inc., which provided the sertraline for study subjects.

Despite 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, compared all randomized, placebo-controlled trials of nonhormonal treatments for hot flashes with the efficacy and adverse effects of agents other than estrogens, progestins, progesterone, or androgens (JAMA 2006;295:2057–71).

A metaanalysis was conducted using 24 of 43 selected studies. Overall, there was some evidence that selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), clonidine, and gabapentin reduce the severity and frequency of hot flashes. However, none of these agents approached the effectiveness of hormone therapy, Dr. Nelson and her associated noted.

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 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, compared all randomized, placebo-controlled trials of nonhormonal treatments for hot flashes with the efficacy and adverse effects of agents other than estrogens, progestins, progesterone, or androgens (JAMA 2006;295:2057–71).

A metaanalysis was conducted using 24 of 43 selected studies. Overall, there was some evidence that selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), clonidine, and gabapentin reduce the severity and frequency of hot flashes. However, none of these agents approached the effectiveness of hormone therapy, Dr. Nelson and her associated noted.

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 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, compared all randomized, placebo-controlled trials of nonhormonal treatments for hot flashes with the efficacy and adverse effects of agents other than estrogens, progestins, progesterone, or androgens (JAMA 2006;295:2057–71).

A metaanalysis was conducted using 24 of 43 selected studies. Overall, there was some evidence that selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), clonidine, and gabapentin reduce the severity and frequency of hot flashes. However, none of these agents approached the effectiveness of hormone therapy, Dr. Nelson and her associated noted.

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.

Atorvastatin raised the number of circulating endothelial precursors in a pilot study of 14 patients with systemic sclerosis, significantly improving the symptoms of Raynaud's phenomenon, reported Dr. Masataka Kuwana of Keio University, Tokyo, and associates.

Compared with healthy control subjects, patients with scleroderma had a markedly reduced number of circulating endothelial precursors (CEPs), and their CEPs tended to have an impaired maturation potential when stimulated by angiogenic factors.

Dr. Kuwana and associates theorized that “insufficient mechanisms of vascular repair, due to defective vasculogenesis, contribute to the pathogenic process” underlying scleroderma patients' Raynaud's symptoms, digital ulcers, and gangrene. If so, raising the number of CEPs and stimulating CEP kinetics might improve the vasculopathy.

Statins have been shown to increase CEPs and stimulate their kinetics in patients with coronary heart disease, so the researchers conducted a prospective pilot study to assess whether statins would have the same effect in scleroderma. They assessed 14 women aged 36–75 years (mean age, 57 years), half of whom had diffuse systemic sclerosis and half of whom had limited cutaneous systemic sclerosis. All the patients had Raynaud's phenomenon.

Atorvastatin treatment resulted in a statistically significant 1.7- to 8.0-fold increase in the number of CEPs. The CEP numbers returned to extremely low baseline levels after cessation of atorvastatin, however.

In addition, “reductions in the up-regulated levels of angiogenic factors and vascular endothelial activation/injury markers were observed during treatment,” Dr. Kuwana and associates noted.

Raynaud's symptoms improved significantly during treatment, along with patients' activity levels and ratings of disability and pain. No patient developed new ulcers during treatment. These symptoms recurred when therapy was stopped, however, and patients quickly began developing new digital ulcers.

All but one patient completed the 12-week course of once-daily atorvastatin (10 mg) while continuing on their regular medication regimens. None had any adverse events, but one woman withdrew from the study because her total cholesterol level declined excessively, to less than 100 mg/dL, the investigators said (Arthritis Rheum. 2006;54:1946–51). These beneficial drug effects are likely due to the recruitment of CEPs into the periphery and the repair of injured endothelium. Statins may increase both the proliferation and the mobilization of CEPs and may prevent CEP senescence and apoptosis within the bone marrow, the researchers reported.

“However, it is also possible that the observed clinical changes were mediated through other effects of statins, such as anti-inflammation mechanisms and the improvement of mature endothelial function,” Dr. Kuwana and colleagues noted.

Although the number of CEPs increased dramatically with atorvastatin, it never reached the level reported in healthy subjects. Also, atorvastatin failed to improve the impaired maturation potential of the CEPs, the researchers acknowledged. “These observations indicate that although atorvastatin is certainly capable of improving CEP dysfunction in systemic sclerosis patients, its effects are limited.

“In addition to statins, … drugs that exert potent stimulatory effects on CEP kinetics, such as granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor, could augment vasculogenesis as a therapeutic intervention for ischemic complications in patients with systemic sclerosis,” according to Dr. Kuwana and associates.

CEPs, which are derived from bone marrow, are required for the formation of blood vessels and also contribute to vascular healing at sites of vascular injury or ischemia by working together with existing mature endothelial cells.

Atorvastatin raised the number of circulating endothelial precursors in a pilot study of 14 patients with systemic sclerosis, significantly improving the symptoms of Raynaud's phenomenon, reported Dr. Masataka Kuwana of Keio University, Tokyo, and associates.

Compared with healthy control subjects, patients with scleroderma had a markedly reduced number of circulating endothelial precursors (CEPs), and their CEPs tended to have an impaired maturation potential when stimulated by angiogenic factors.

Dr. Kuwana and associates theorized that “insufficient mechanisms of vascular repair, due to defective vasculogenesis, contribute to the pathogenic process” underlying scleroderma patients' Raynaud's symptoms, digital ulcers, and gangrene. If so, raising the number of CEPs and stimulating CEP kinetics might improve the vasculopathy.

Statins have been shown to increase CEPs and stimulate their kinetics in patients with coronary heart disease, so the researchers conducted a prospective pilot study to assess whether statins would have the same effect in scleroderma. They assessed 14 women aged 36–75 years (mean age, 57 years), half of whom had diffuse systemic sclerosis and half of whom had limited cutaneous systemic sclerosis. All the patients had Raynaud's phenomenon.

Atorvastatin treatment resulted in a statistically significant 1.7- to 8.0-fold increase in the number of CEPs. The CEP numbers returned to extremely low baseline levels after cessation of atorvastatin, however.

In addition, “reductions in the up-regulated levels of angiogenic factors and vascular endothelial activation/injury markers were observed during treatment,” Dr. Kuwana and associates noted.

Raynaud's symptoms improved significantly during treatment, along with patients' activity levels and ratings of disability and pain. No patient developed new ulcers during treatment. These symptoms recurred when therapy was stopped, however, and patients quickly began developing new digital ulcers.

All but one patient completed the 12-week course of once-daily atorvastatin (10 mg) while continuing on their regular medication regimens. None had any adverse events, but one woman withdrew from the study because her total cholesterol level declined excessively, to less than 100 mg/dL, the investigators said (Arthritis Rheum. 2006;54:1946–51). These beneficial drug effects are likely due to the recruitment of CEPs into the periphery and the repair of injured endothelium. Statins may increase both the proliferation and the mobilization of CEPs and may prevent CEP senescence and apoptosis within the bone marrow, the researchers reported.

“However, it is also possible that the observed clinical changes were mediated through other effects of statins, such as anti-inflammation mechanisms and the improvement of mature endothelial function,” Dr. Kuwana and colleagues noted.

Although the number of CEPs increased dramatically with atorvastatin, it never reached the level reported in healthy subjects. Also, atorvastatin failed to improve the impaired maturation potential of the CEPs, the researchers acknowledged. “These observations indicate that although atorvastatin is certainly capable of improving CEP dysfunction in systemic sclerosis patients, its effects are limited.

“In addition to statins, … drugs that exert potent stimulatory effects on CEP kinetics, such as granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor, could augment vasculogenesis as a therapeutic intervention for ischemic complications in patients with systemic sclerosis,” according to Dr. Kuwana and associates.

CEPs, which are derived from bone marrow, are required for the formation of blood vessels and also contribute to vascular healing at sites of vascular injury or ischemia by working together with existing mature endothelial cells.

Atorvastatin raised the number of circulating endothelial precursors in a pilot study of 14 patients with systemic sclerosis, significantly improving the symptoms of Raynaud's phenomenon, reported Dr. Masataka Kuwana of Keio University, Tokyo, and associates.

Compared with healthy control subjects, patients with scleroderma had a markedly reduced number of circulating endothelial precursors (CEPs), and their CEPs tended to have an impaired maturation potential when stimulated by angiogenic factors.

Dr. Kuwana and associates theorized that “insufficient mechanisms of vascular repair, due to defective vasculogenesis, contribute to the pathogenic process” underlying scleroderma patients' Raynaud's symptoms, digital ulcers, and gangrene. If so, raising the number of CEPs and stimulating CEP kinetics might improve the vasculopathy.

Statins have been shown to increase CEPs and stimulate their kinetics in patients with coronary heart disease, so the researchers conducted a prospective pilot study to assess whether statins would have the same effect in scleroderma. They assessed 14 women aged 36–75 years (mean age, 57 years), half of whom had diffuse systemic sclerosis and half of whom had limited cutaneous systemic sclerosis. All the patients had Raynaud's phenomenon.

Atorvastatin treatment resulted in a statistically significant 1.7- to 8.0-fold increase in the number of CEPs. The CEP numbers returned to extremely low baseline levels after cessation of atorvastatin, however.

In addition, “reductions in the up-regulated levels of angiogenic factors and vascular endothelial activation/injury markers were observed during treatment,” Dr. Kuwana and associates noted.

Raynaud's symptoms improved significantly during treatment, along with patients' activity levels and ratings of disability and pain. No patient developed new ulcers during treatment. These symptoms recurred when therapy was stopped, however, and patients quickly began developing new digital ulcers.

All but one patient completed the 12-week course of once-daily atorvastatin (10 mg) while continuing on their regular medication regimens. None had any adverse events, but one woman withdrew from the study because her total cholesterol level declined excessively, to less than 100 mg/dL, the investigators said (Arthritis Rheum. 2006;54:1946–51). These beneficial drug effects are likely due to the recruitment of CEPs into the periphery and the repair of injured endothelium. Statins may increase both the proliferation and the mobilization of CEPs and may prevent CEP senescence and apoptosis within the bone marrow, the researchers reported.

“However, it is also possible that the observed clinical changes were mediated through other effects of statins, such as anti-inflammation mechanisms and the improvement of mature endothelial function,” Dr. Kuwana and colleagues noted.

Although the number of CEPs increased dramatically with atorvastatin, it never reached the level reported in healthy subjects. Also, atorvastatin failed to improve the impaired maturation potential of the CEPs, the researchers acknowledged. “These observations indicate that although atorvastatin is certainly capable of improving CEP dysfunction in systemic sclerosis patients, its effects are limited.

“In addition to statins, … drugs that exert potent stimulatory effects on CEP kinetics, such as granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor, could augment vasculogenesis as a therapeutic intervention for ischemic complications in patients with systemic sclerosis,” according to Dr. Kuwana and associates.

CEPs, which are derived from bone marrow, are required for the formation of blood vessels and also contribute to vascular healing at sites of vascular injury or ischemia by working together with existing mature endothelial cells.

A new system for scoring the severity of foot ulcers in diabetic patients helps predict the likelihood of healing, hospitalization, local surgery, and amputation, according to Dr. Stefan Beckert and his associates at the University of Tübingen (Germany).

Although other researchers have made attempts to establish classification systems that help gauge the severity of foot ulcers, most have been too complicated for widespread clinical application. Some systems required extensive work-ups and complex grading schedules, and no simple severity scores have been adopted into routine clinical practice, the investigators said.

Dr. Beckert and his associates followed 1,000 consecutive diabetic patients with foot ulcers to develop such a score, which they termed the Diabetic Ulcer Severity Score (DUSS), and to test its practical use in predicting outcomes.

The median subject age was 69 years, and subjects were followed for up to 1 year after presenting for outpatient foot ulcer care. Treatment was given by an interdisciplinary team of a general and vascular surgeon, a radiologist, a diabetologist, an orthotist, and a wound care nurse. It consisted of sharp debridement, advanced local surgery such as limited bone resections if necessary, moist wound therapy, and adequate pressure off-loading.

Four factors—pedal pulses, bone involvement, site of ulceration, and number of ulcerations—were found to predict outcome, and a simple scoring system was developed to rate these factors, the investigators said (Diabetes Care 2006;29:988–92).

Absent pedal pulses were scored as 1, while present pedal pulses were scored as 0. Bone involvement, defined as the ability to probe the ulcer to the bone, was scored as 1, lack of bone involvement, a 0. Ulceration was scored as 0 if it involved only the toe; 1 if it involved the foot. Multiple wounds were scored as 1 while single wounds were scored as 0.

The overall DUSS was determined by adding these four components, so possible scores ranged from 0 to 4.

Patients with a DUSS of 0 had a 93% probability of healing. The probability of healing decreased steadily with increasing DUSS, to a low of 57% for scores of 4.

Local surgery was required for 9% of patients with a DUSS of 0, 17% of those with a DUSS of 1, 27% for those with a score of 2, 37% for those with a DUSS of 3, and 50% of those with a DUSS of 4. Similarly, hospitalization was required for 39% of patients with a DUSS of 0, 49% of those with a DUSS of 1, 63% of those with a DUSS of 2, 72% of those with a DUSS of 3, and 92% of those with a DUSS of 4.

The likelihood of amputation followed this same pattern for the most part. Patients with a DUSS of 0 had no risk of amputation, those with a DUSS of 1 had a 2% risk, those with a DUSS of 2 had an 8% risk, and those with a DUSS of 3 had an 11% risk. However, the pattern did not hold for patients with a DUSS of 4 (4% risk), most likely because of the small number of patients in this subgroup and the low number of amputations overall, the researchers said.

A new system for scoring the severity of foot ulcers in diabetic patients helps predict the likelihood of healing, hospitalization, local surgery, and amputation, according to Dr. Stefan Beckert and his associates at the University of Tübingen (Germany).

Although other researchers have made attempts to establish classification systems that help gauge the severity of foot ulcers, most have been too complicated for widespread clinical application. Some systems required extensive work-ups and complex grading schedules, and no simple severity scores have been adopted into routine clinical practice, the investigators said.

Dr. Beckert and his associates followed 1,000 consecutive diabetic patients with foot ulcers to develop such a score, which they termed the Diabetic Ulcer Severity Score (DUSS), and to test its practical use in predicting outcomes.

The median subject age was 69 years, and subjects were followed for up to 1 year after presenting for outpatient foot ulcer care. Treatment was given by an interdisciplinary team of a general and vascular surgeon, a radiologist, a diabetologist, an orthotist, and a wound care nurse. It consisted of sharp debridement, advanced local surgery such as limited bone resections if necessary, moist wound therapy, and adequate pressure off-loading.

Four factors—pedal pulses, bone involvement, site of ulceration, and number of ulcerations—were found to predict outcome, and a simple scoring system was developed to rate these factors, the investigators said (Diabetes Care 2006;29:988–92).

Absent pedal pulses were scored as 1, while present pedal pulses were scored as 0. Bone involvement, defined as the ability to probe the ulcer to the bone, was scored as 1, lack of bone involvement, a 0. Ulceration was scored as 0 if it involved only the toe; 1 if it involved the foot. Multiple wounds were scored as 1 while single wounds were scored as 0.

The overall DUSS was determined by adding these four components, so possible scores ranged from 0 to 4.

Patients with a DUSS of 0 had a 93% probability of healing. The probability of healing decreased steadily with increasing DUSS, to a low of 57% for scores of 4.

Local surgery was required for 9% of patients with a DUSS of 0, 17% of those with a DUSS of 1, 27% for those with a score of 2, 37% for those with a DUSS of 3, and 50% of those with a DUSS of 4. Similarly, hospitalization was required for 39% of patients with a DUSS of 0, 49% of those with a DUSS of 1, 63% of those with a DUSS of 2, 72% of those with a DUSS of 3, and 92% of those with a DUSS of 4.

The likelihood of amputation followed this same pattern for the most part. Patients with a DUSS of 0 had no risk of amputation, those with a DUSS of 1 had a 2% risk, those with a DUSS of 2 had an 8% risk, and those with a DUSS of 3 had an 11% risk. However, the pattern did not hold for patients with a DUSS of 4 (4% risk), most likely because of the small number of patients in this subgroup and the low number of amputations overall, the researchers said.

A new system for scoring the severity of foot ulcers in diabetic patients helps predict the likelihood of healing, hospitalization, local surgery, and amputation, according to Dr. Stefan Beckert and his associates at the University of Tübingen (Germany).

Although other researchers have made attempts to establish classification systems that help gauge the severity of foot ulcers, most have been too complicated for widespread clinical application. Some systems required extensive work-ups and complex grading schedules, and no simple severity scores have been adopted into routine clinical practice, the investigators said.

Dr. Beckert and his associates followed 1,000 consecutive diabetic patients with foot ulcers to develop such a score, which they termed the Diabetic Ulcer Severity Score (DUSS), and to test its practical use in predicting outcomes.

The median subject age was 69 years, and subjects were followed for up to 1 year after presenting for outpatient foot ulcer care. Treatment was given by an interdisciplinary team of a general and vascular surgeon, a radiologist, a diabetologist, an orthotist, and a wound care nurse. It consisted of sharp debridement, advanced local surgery such as limited bone resections if necessary, moist wound therapy, and adequate pressure off-loading.

Four factors—pedal pulses, bone involvement, site of ulceration, and number of ulcerations—were found to predict outcome, and a simple scoring system was developed to rate these factors, the investigators said (Diabetes Care 2006;29:988–92).

Absent pedal pulses were scored as 1, while present pedal pulses were scored as 0. Bone involvement, defined as the ability to probe the ulcer to the bone, was scored as 1, lack of bone involvement, a 0. Ulceration was scored as 0 if it involved only the toe; 1 if it involved the foot. Multiple wounds were scored as 1 while single wounds were scored as 0.

The overall DUSS was determined by adding these four components, so possible scores ranged from 0 to 4.

Patients with a DUSS of 0 had a 93% probability of healing. The probability of healing decreased steadily with increasing DUSS, to a low of 57% for scores of 4.

Local surgery was required for 9% of patients with a DUSS of 0, 17% of those with a DUSS of 1, 27% for those with a score of 2, 37% for those with a DUSS of 3, and 50% of those with a DUSS of 4. Similarly, hospitalization was required for 39% of patients with a DUSS of 0, 49% of those with a DUSS of 1, 63% of those with a DUSS of 2, 72% of those with a DUSS of 3, and 92% of those with a DUSS of 4.

The likelihood of amputation followed this same pattern for the most part. Patients with a DUSS of 0 had no risk of amputation, those with a DUSS of 1 had a 2% risk, those with a DUSS of 2 had an 8% risk, and those with a DUSS of 3 had an 11% risk. However, the pattern did not hold for patients with a DUSS of 4 (4% risk), most likely because of the small number of patients in this subgroup and the low number of amputations overall, the researchers said.

Older white men who have an optimistic nature have about half the risk of dying from cardiovascular causes as their less optimistic peers, according to Dr. Erik J. Giltay of the Institute of Mental Health, Delft, the Netherlands, and his associates.

The researchers used data from a large, prospective study of cardiovascular disease (CVD) in healthy, middle-aged Dutch men to examine a possible link with dispositional optimism. Their study differed from previous research in that it adjusted for classic CVD risk factors, socioeconomic characteristics, and depression.

Dispositional optimism was defined as having “generalized positive expectancies for one's future.” It was measured using a four-item questionnaire in which subjects rated their agreement with the following statements: “I still expect much from life,” “I do not look forward to what lies ahead for me in the years to come,” “My days seem to be passing by slowly,” and “I am still full of plans.”

A total of 545 healthy men aged 64–84 years in 1985 began the study and were followed up at 5-year intervals until 2000. During that time, 373 (68.4%) died, including 187 (50.1%) who died of cardiovascular causes.

“Compared with men in the lowest tertile of dispositional optimism, those in the top tertile had a 55% lower multivariate-adjusted hazard ratio of cardiovascular mortality,” the investigators said (Arch. Intern. Med. 2006;166:431–6).

Optimism was not related to CVD risk factors such as body mass index, hypertension, diabetes, or HDL cholesterol levels. It also proved to be a relatively constant personality trait through the years.

“Our results demonstrate a strong and consistent association between dispositional optimism and an about 50% lower risk of cardiovascular mortality in elderly men during 15 years of follow-up,” Dr. Giltay and his associates said.

“A low subjectively perceived level of optimism should be added to the list of independent risk markers for cardiovascular mortality in elderly men,” they said. The study findings may not be generalizable to women or to other ethnic groups, as all of the subjects were white men, the researchers noted.

Older white men who have an optimistic nature have about half the risk of dying from cardiovascular causes as their less optimistic peers, according to Dr. Erik J. Giltay of the Institute of Mental Health, Delft, the Netherlands, and his associates.

The researchers used data from a large, prospective study of cardiovascular disease (CVD) in healthy, middle-aged Dutch men to examine a possible link with dispositional optimism. Their study differed from previous research in that it adjusted for classic CVD risk factors, socioeconomic characteristics, and depression.

Dispositional optimism was defined as having “generalized positive expectancies for one's future.” It was measured using a four-item questionnaire in which subjects rated their agreement with the following statements: “I still expect much from life,” “I do not look forward to what lies ahead for me in the years to come,” “My days seem to be passing by slowly,” and “I am still full of plans.”

A total of 545 healthy men aged 64–84 years in 1985 began the study and were followed up at 5-year intervals until 2000. During that time, 373 (68.4%) died, including 187 (50.1%) who died of cardiovascular causes.

“Compared with men in the lowest tertile of dispositional optimism, those in the top tertile had a 55% lower multivariate-adjusted hazard ratio of cardiovascular mortality,” the investigators said (Arch. Intern. Med. 2006;166:431–6).

Optimism was not related to CVD risk factors such as body mass index, hypertension, diabetes, or HDL cholesterol levels. It also proved to be a relatively constant personality trait through the years.

“Our results demonstrate a strong and consistent association between dispositional optimism and an about 50% lower risk of cardiovascular mortality in elderly men during 15 years of follow-up,” Dr. Giltay and his associates said.

“A low subjectively perceived level of optimism should be added to the list of independent risk markers for cardiovascular mortality in elderly men,” they said. The study findings may not be generalizable to women or to other ethnic groups, as all of the subjects were white men, the researchers noted.

Older white men who have an optimistic nature have about half the risk of dying from cardiovascular causes as their less optimistic peers, according to Dr. Erik J. Giltay of the Institute of Mental Health, Delft, the Netherlands, and his associates.

The researchers used data from a large, prospective study of cardiovascular disease (CVD) in healthy, middle-aged Dutch men to examine a possible link with dispositional optimism. Their study differed from previous research in that it adjusted for classic CVD risk factors, socioeconomic characteristics, and depression.

Dispositional optimism was defined as having “generalized positive expectancies for one's future.” It was measured using a four-item questionnaire in which subjects rated their agreement with the following statements: “I still expect much from life,” “I do not look forward to what lies ahead for me in the years to come,” “My days seem to be passing by slowly,” and “I am still full of plans.”

A total of 545 healthy men aged 64–84 years in 1985 began the study and were followed up at 5-year intervals until 2000. During that time, 373 (68.4%) died, including 187 (50.1%) who died of cardiovascular causes.

“Compared with men in the lowest tertile of dispositional optimism, those in the top tertile had a 55% lower multivariate-adjusted hazard ratio of cardiovascular mortality,” the investigators said (Arch. Intern. Med. 2006;166:431–6).

Optimism was not related to CVD risk factors such as body mass index, hypertension, diabetes, or HDL cholesterol levels. It also proved to be a relatively constant personality trait through the years.

“Our results demonstrate a strong and consistent association between dispositional optimism and an about 50% lower risk of cardiovascular mortality in elderly men during 15 years of follow-up,” Dr. Giltay and his associates said.

“A low subjectively perceived level of optimism should be added to the list of independent risk markers for cardiovascular mortality in elderly men,” they said. The study findings may not be generalizable to women or to other ethnic groups, as all of the subjects were white men, the researchers noted.

Cognitive impairment was found in 30% of patients with amyotrophic lateral sclerosis in a study designed to assess the prevalence of cognitive involvement in what used to be considered a disease restricted to the motor system, according to Dr. Gregory A. Rippon and his associates.

In an editorial comment accompanying this report, Dr. Michael J. Strong of the University of Western Ontario, London, said that the 30% prevalence of dementia found in this study may actually underestimate the prevalence in the general population.

These subjects were evaluated “long before the institution of detailed tests of frontotemporal lobe dysfunction,” which would likely have detected dementia in more of them. Moreover, subjects with a family history of neurodegenerative diseases were excluded from this study, which again may have led to an underrepresentation of dementia cases, he said.

Dr. Rippon agreed that estimates must be considered unreliable at best, since the studies from which they were derived were flawed by small sample sizes, selection bias, widely varying definitions of cognitive impairment, and very different methods for assessing cognition.

As ALS is increasingly recognized as a multisystem neurodegenerative disorder, researchers have revised their estimates of cognitive involvement from 2% up to as much as 52%.

In what Dr. Rippon and his associates at Columbia University College of Physicians and Surgeons, New York, described as one of the largest studies of the issue to date, the researchers assessed 40 consecutively treated patients with classic ALS seen in a 1-year period at the university's Neurological Institute. These patients, along with 80 control subjects matched for age, sex, and education level, underwent a battery of neuropsychologic tests that evaluated learning and memory, executive function, attention and psychomotor speed, language, and visuospatial ability.

Twelve of the ALS patients (30%) showed cognitive impairment, including 9 (23%) who met the criteria for dementia.

Free recall, executive function, and naming were the areas of most severe impairment, while language comprehension was preserved and attention, processing speed, and visuospatial function remained normal.

This pattern is consistent with frontotemporal lobar dementia, the investigators said (Arch. Neurol. 2006;63:345–52).

Among the ALS patients, there was no difference between those with and without dementia in terms of age, sex, education level, site of symptom onset, emotional lability, subjective memory loss, or family history.

This finding is contrary to that of other researchers who suggested that patients with bulbar-onset ALS are particularly susceptible to dementia, Dr. Rippon and his associates noted.

ALS symptom severity did not seem to affect test performance. As a group, the ALS patients performed better than control subjects on most of the tasks tested.

Survival was the same in ALS patients with dementia as in those without dementia, but this study was underpowered to detect a survival difference of less than 3 years.

Previous studies have demonstrated a shorter survival time in ALS patients with frontotemporal dementia.

“Larger prospective studies with interval cognitive assessments would more fully address the possibility of differential survival,” they added.

In his editorial, Dr. Strong noted that the study's findings may provoke controversy over the clinical relevance of cognitive impairment in most ALS patients (Arch. Neurol. 2006;63:319–20).

Most cognitive impairment associated with ALS in the literature is “subtle,” not a fulminant dementia.

Cognitive impairment was found in 30% of patients with amyotrophic lateral sclerosis in a study designed to assess the prevalence of cognitive involvement in what used to be considered a disease restricted to the motor system, according to Dr. Gregory A. Rippon and his associates.

In an editorial comment accompanying this report, Dr. Michael J. Strong of the University of Western Ontario, London, said that the 30% prevalence of dementia found in this study may actually underestimate the prevalence in the general population.

These subjects were evaluated “long before the institution of detailed tests of frontotemporal lobe dysfunction,” which would likely have detected dementia in more of them. Moreover, subjects with a family history of neurodegenerative diseases were excluded from this study, which again may have led to an underrepresentation of dementia cases, he said.

Dr. Rippon agreed that estimates must be considered unreliable at best, since the studies from which they were derived were flawed by small sample sizes, selection bias, widely varying definitions of cognitive impairment, and very different methods for assessing cognition.

As ALS is increasingly recognized as a multisystem neurodegenerative disorder, researchers have revised their estimates of cognitive involvement from 2% up to as much as 52%.

In what Dr. Rippon and his associates at Columbia University College of Physicians and Surgeons, New York, described as one of the largest studies of the issue to date, the researchers assessed 40 consecutively treated patients with classic ALS seen in a 1-year period at the university's Neurological Institute. These patients, along with 80 control subjects matched for age, sex, and education level, underwent a battery of neuropsychologic tests that evaluated learning and memory, executive function, attention and psychomotor speed, language, and visuospatial ability.

Twelve of the ALS patients (30%) showed cognitive impairment, including 9 (23%) who met the criteria for dementia.

Free recall, executive function, and naming were the areas of most severe impairment, while language comprehension was preserved and attention, processing speed, and visuospatial function remained normal.

This pattern is consistent with frontotemporal lobar dementia, the investigators said (Arch. Neurol. 2006;63:345–52).

Among the ALS patients, there was no difference between those with and without dementia in terms of age, sex, education level, site of symptom onset, emotional lability, subjective memory loss, or family history.

This finding is contrary to that of other researchers who suggested that patients with bulbar-onset ALS are particularly susceptible to dementia, Dr. Rippon and his associates noted.

ALS symptom severity did not seem to affect test performance. As a group, the ALS patients performed better than control subjects on most of the tasks tested.

Survival was the same in ALS patients with dementia as in those without dementia, but this study was underpowered to detect a survival difference of less than 3 years.

Previous studies have demonstrated a shorter survival time in ALS patients with frontotemporal dementia.

“Larger prospective studies with interval cognitive assessments would more fully address the possibility of differential survival,” they added.

In his editorial, Dr. Strong noted that the study's findings may provoke controversy over the clinical relevance of cognitive impairment in most ALS patients (Arch. Neurol. 2006;63:319–20).

Most cognitive impairment associated with ALS in the literature is “subtle,” not a fulminant dementia.

Cognitive impairment was found in 30% of patients with amyotrophic lateral sclerosis in a study designed to assess the prevalence of cognitive involvement in what used to be considered a disease restricted to the motor system, according to Dr. Gregory A. Rippon and his associates.

In an editorial comment accompanying this report, Dr. Michael J. Strong of the University of Western Ontario, London, said that the 30% prevalence of dementia found in this study may actually underestimate the prevalence in the general population.

These subjects were evaluated “long before the institution of detailed tests of frontotemporal lobe dysfunction,” which would likely have detected dementia in more of them. Moreover, subjects with a family history of neurodegenerative diseases were excluded from this study, which again may have led to an underrepresentation of dementia cases, he said.

Dr. Rippon agreed that estimates must be considered unreliable at best, since the studies from which they were derived were flawed by small sample sizes, selection bias, widely varying definitions of cognitive impairment, and very different methods for assessing cognition.

As ALS is increasingly recognized as a multisystem neurodegenerative disorder, researchers have revised their estimates of cognitive involvement from 2% up to as much as 52%.

In what Dr. Rippon and his associates at Columbia University College of Physicians and Surgeons, New York, described as one of the largest studies of the issue to date, the researchers assessed 40 consecutively treated patients with classic ALS seen in a 1-year period at the university's Neurological Institute. These patients, along with 80 control subjects matched for age, sex, and education level, underwent a battery of neuropsychologic tests that evaluated learning and memory, executive function, attention and psychomotor speed, language, and visuospatial ability.

Twelve of the ALS patients (30%) showed cognitive impairment, including 9 (23%) who met the criteria for dementia.

Free recall, executive function, and naming were the areas of most severe impairment, while language comprehension was preserved and attention, processing speed, and visuospatial function remained normal.

This pattern is consistent with frontotemporal lobar dementia, the investigators said (Arch. Neurol. 2006;63:345–52).

Among the ALS patients, there was no difference between those with and without dementia in terms of age, sex, education level, site of symptom onset, emotional lability, subjective memory loss, or family history.

This finding is contrary to that of other researchers who suggested that patients with bulbar-onset ALS are particularly susceptible to dementia, Dr. Rippon and his associates noted.

ALS symptom severity did not seem to affect test performance. As a group, the ALS patients performed better than control subjects on most of the tasks tested.

Survival was the same in ALS patients with dementia as in those without dementia, but this study was underpowered to detect a survival difference of less than 3 years.

Previous studies have demonstrated a shorter survival time in ALS patients with frontotemporal dementia.

“Larger prospective studies with interval cognitive assessments would more fully address the possibility of differential survival,” they added.

In his editorial, Dr. Strong noted that the study's findings may provoke controversy over the clinical relevance of cognitive impairment in most ALS patients (Arch. Neurol. 2006;63:319–20).

Most cognitive impairment associated with ALS in the literature is “subtle,” not a fulminant dementia.

Older people with poor physical function are at higher risk for developing dementia than those with good physical function, reported Li Wang of the Veterans Affairs Puget Sound Health Care System, Seattle, and her associates.

In a study of 2,288 people aged 65 and older, patients with poor standing balance, slowed gait, and poor handgrip had an increased risk of cognitive impairment, dementia, or Alzheimer's disease (AD) developing during 6-year follow-up. The findings suggest physical decline may precede onset of dementia, which may in turn explain why other research has found that physical exercise appears to have a protective effect against dementia, the investigators said.

Ms. Wang and her associates used data from a population-based longitudinal study of aging to examine whether decline in motor function might be linked to progression to dementia. The study subjects were drawn from a random sample of patients enrolled in an HMO who were 65 or older from 1994 to 1996 (Arch. Intern. Med. 2006;166:1115–20).

All subjects had normal cognitive function on a battery of assessments at their initial screening. Attention, concentration, orientation, short-term memory, long-term memory, language ability, visual construction, list-generating fluency, abstraction, and judgment were assessed.

Subjects also underwent four physical performance tests: a 10-foot timed walk, timing of the interval required to rise from a seated position, standing balance, and grip strength. They were reexamined every 2 years to identify incident dementia and AD, the investigators said.

During a 6-year follow-up, 1,422 subjects remained free of dementia, 362 died, 185 withdrew from the study, and 319 developed dementia–221 with AD, 55 with vascular dementia, and 43 with other types of dementia.

The incidence of dementia was 53/1,000 person-years for subjects who had poorer physical function at baseline (below the 25th percentile), compared with 17/1,000 person-years for those with better physical function.

Similarly, among subjects with the highest physical function scores at baseline, the incidence of dementia was 15/1,000 person-years, compared with an incidence of 58/1,000 person-years among those with lower scores.

When the results of each physical function test were considered separately, gait slowing and poor balance developed early, before any signs of cognitive impairment. Poor grip strength developed somewhat later, when cognitive impairment was just beginning to emerge.

“Gait and balance require integration of motor, sensory, and cerebellar activities, whereas grip requires a simpler motor activity. The more 'brain-challenging' tasks of gait and balance could be affected earlier in the course of dementia, whereas a simpler motor task such as grip would likely be preserved until later in the disease course,” Ms. Wang and her associates said.

If their findings are confirmed in future studies, it would indicate that gait slowing and poor balance are earlier markers and poor handgrip a later marker of preclinical dementia, they added.

Until then, “we speculate that physical decline and cognitive decline may be inseparable during the development of dementia,” they said.

Older people with poor physical function are at higher risk for developing dementia than those with good physical function, reported Li Wang of the Veterans Affairs Puget Sound Health Care System, Seattle, and her associates.

In a study of 2,288 people aged 65 and older, patients with poor standing balance, slowed gait, and poor handgrip had an increased risk of cognitive impairment, dementia, or Alzheimer's disease (AD) developing during 6-year follow-up. The findings suggest physical decline may precede onset of dementia, which may in turn explain why other research has found that physical exercise appears to have a protective effect against dementia, the investigators said.

Ms. Wang and her associates used data from a population-based longitudinal study of aging to examine whether decline in motor function might be linked to progression to dementia. The study subjects were drawn from a random sample of patients enrolled in an HMO who were 65 or older from 1994 to 1996 (Arch. Intern. Med. 2006;166:1115–20).

All subjects had normal cognitive function on a battery of assessments at their initial screening. Attention, concentration, orientation, short-term memory, long-term memory, language ability, visual construction, list-generating fluency, abstraction, and judgment were assessed.

Subjects also underwent four physical performance tests: a 10-foot timed walk, timing of the interval required to rise from a seated position, standing balance, and grip strength. They were reexamined every 2 years to identify incident dementia and AD, the investigators said.

During a 6-year follow-up, 1,422 subjects remained free of dementia, 362 died, 185 withdrew from the study, and 319 developed dementia–221 with AD, 55 with vascular dementia, and 43 with other types of dementia.

The incidence of dementia was 53/1,000 person-years for subjects who had poorer physical function at baseline (below the 25th percentile), compared with 17/1,000 person-years for those with better physical function.

Similarly, among subjects with the highest physical function scores at baseline, the incidence of dementia was 15/1,000 person-years, compared with an incidence of 58/1,000 person-years among those with lower scores.

When the results of each physical function test were considered separately, gait slowing and poor balance developed early, before any signs of cognitive impairment. Poor grip strength developed somewhat later, when cognitive impairment was just beginning to emerge.

“Gait and balance require integration of motor, sensory, and cerebellar activities, whereas grip requires a simpler motor activity. The more 'brain-challenging' tasks of gait and balance could be affected earlier in the course of dementia, whereas a simpler motor task such as grip would likely be preserved until later in the disease course,” Ms. Wang and her associates said.

If their findings are confirmed in future studies, it would indicate that gait slowing and poor balance are earlier markers and poor handgrip a later marker of preclinical dementia, they added.

Until then, “we speculate that physical decline and cognitive decline may be inseparable during the development of dementia,” they said.

Older people with poor physical function are at higher risk for developing dementia than those with good physical function, reported Li Wang of the Veterans Affairs Puget Sound Health Care System, Seattle, and her associates.

In a study of 2,288 people aged 65 and older, patients with poor standing balance, slowed gait, and poor handgrip had an increased risk of cognitive impairment, dementia, or Alzheimer's disease (AD) developing during 6-year follow-up. The findings suggest physical decline may precede onset of dementia, which may in turn explain why other research has found that physical exercise appears to have a protective effect against dementia, the investigators said.

Ms. Wang and her associates used data from a population-based longitudinal study of aging to examine whether decline in motor function might be linked to progression to dementia. The study subjects were drawn from a random sample of patients enrolled in an HMO who were 65 or older from 1994 to 1996 (Arch. Intern. Med. 2006;166:1115–20).

All subjects had normal cognitive function on a battery of assessments at their initial screening. Attention, concentration, orientation, short-term memory, long-term memory, language ability, visual construction, list-generating fluency, abstraction, and judgment were assessed.

Subjects also underwent four physical performance tests: a 10-foot timed walk, timing of the interval required to rise from a seated position, standing balance, and grip strength. They were reexamined every 2 years to identify incident dementia and AD, the investigators said.

During a 6-year follow-up, 1,422 subjects remained free of dementia, 362 died, 185 withdrew from the study, and 319 developed dementia–221 with AD, 55 with vascular dementia, and 43 with other types of dementia.

The incidence of dementia was 53/1,000 person-years for subjects who had poorer physical function at baseline (below the 25th percentile), compared with 17/1,000 person-years for those with better physical function.

Similarly, among subjects with the highest physical function scores at baseline, the incidence of dementia was 15/1,000 person-years, compared with an incidence of 58/1,000 person-years among those with lower scores.

When the results of each physical function test were considered separately, gait slowing and poor balance developed early, before any signs of cognitive impairment. Poor grip strength developed somewhat later, when cognitive impairment was just beginning to emerge.

“Gait and balance require integration of motor, sensory, and cerebellar activities, whereas grip requires a simpler motor activity. The more 'brain-challenging' tasks of gait and balance could be affected earlier in the course of dementia, whereas a simpler motor task such as grip would likely be preserved until later in the disease course,” Ms. Wang and her associates said.

If their findings are confirmed in future studies, it would indicate that gait slowing and poor balance are earlier markers and poor handgrip a later marker of preclinical dementia, they added.

Until then, “we speculate that physical decline and cognitive decline may be inseparable during the development of dementia,” they said.

When a mother's depression remits, her child's clinical state also improves, and children of mothers who remain depressed are likely to deteriorate, reported Myrna M. Weissman, Ph.D., and her associates in the pediatric portion of the Sequenced Treatment Alternative to Relieve Depression study.

Maternal depression is one of the most consistent risk factors for childhood anxiety, depression, and disruptive behavior disorders. However, the researchers said, to their knowledge, this is the first published study documenting prospectively the relationship between the remission of a mother's depression and a child's clinical state.

“These findings are intriguing because they suggest that an environmental influence … had a measurable impact on the child's psychopathology,” the investigators noted.

The Sequenced Treatment Alternative to Relieve Depression (STAR

In the ancillary pediatric study, Dr. Weissman and her associates assessed 114 mother-child pairs. This report details their findings at baseline and at the first of several planned follow-up evaluations (JAMA 2006;295:1389–98).

All the mothers were initially treated with citalopram (Celexa). Those who did not respond or did not tolerate the antidepressant went on to be randomly assigned to subsequent steps in treatment, said Dr. Weissman, of Columbia University and the New York State Psychiatric Institute, New York, and her associates.

Many of the children, aged 7–17 years, were acutely symptomatic at baseline. “Over a third had a current psychiatric disorder including anxiety (16%), depressive (10%), or disruptive behavior disorders (22%); almost half had a past psychiatric disorder. These high rates are consistent with findings from numerous studies of children with depressed parents,” the investigators said.

The maternal remission rate at 3 months was 33%. At that time, children of the 34 mothers who remitted showed an 11% decline in rates of those diagnoses, from 35% (12 of 34 children) at baseline to 24% (8 of 34). In contrast, there was an 8% increase in diagnoses among children of mothers with continuing depression, from 35% (25 of 71 children) to 43% (30 of 71 children) during that interval.

There were 68 children who had no psychiatric disorder at baseline. All of those in whom maternal depression remitted remained free of psychiatric disorders at the 3-month follow-up. In contrast, 17% (8 of 46) of the children of mothers who remained depressed developed an onset or a relapse of psychiatric disorders by the 3-month follow-up.

The change in rates of child diagnoses was inversely related to the magnitude of the mother's response to treatment. An improvement of at least 50% was necessary before any improvement could be discerned in the children. After that threshold was reached, greater maternal improvements had a direct linear association with decreases in child diagnoses. Conversely, children of mothers who responded at a rate of less than 50% showed an increase in psychiatric diagnoses at 3 months.

It is important to note that although many of the children in this study had a current or past psychiatric disorder, they showed improvement in a relatively short time (3 months)–even though most of them were not receiving direct treatment–simply because their mothers improved.

“Even more interesting” was the finding of a possible preventive effect of maternal improvement: None of the children of remitting mothers had any onset or recurrence of psychiatric symptoms, the researchers noted.

These results suggest that “a reduction in stress associated with maternal remission may reverse the long-standing symptoms in children who are likely to be genetically vulnerable,” they added.

ELSEVIER GLOBAL MEDICAL NEWS

When a mother's depression remits, her child's clinical state also improves, and children of mothers who remain depressed are likely to deteriorate, reported Myrna M. Weissman, Ph.D., and her associates in the pediatric portion of the Sequenced Treatment Alternative to Relieve Depression study.

Maternal depression is one of the most consistent risk factors for childhood anxiety, depression, and disruptive behavior disorders. However, the researchers said, to their knowledge, this is the first published study documenting prospectively the relationship between the remission of a mother's depression and a child's clinical state.

“These findings are intriguing because they suggest that an environmental influence … had a measurable impact on the child's psychopathology,” the investigators noted.

The Sequenced Treatment Alternative to Relieve Depression (STAR

In the ancillary pediatric study, Dr. Weissman and her associates assessed 114 mother-child pairs. This report details their findings at baseline and at the first of several planned follow-up evaluations (JAMA 2006;295:1389–98).

All the mothers were initially treated with citalopram (Celexa). Those who did not respond or did not tolerate the antidepressant went on to be randomly assigned to subsequent steps in treatment, said Dr. Weissman, of Columbia University and the New York State Psychiatric Institute, New York, and her associates.

Many of the children, aged 7–17 years, were acutely symptomatic at baseline. “Over a third had a current psychiatric disorder including anxiety (16%), depressive (10%), or disruptive behavior disorders (22%); almost half had a past psychiatric disorder. These high rates are consistent with findings from numerous studies of children with depressed parents,” the investigators said.

The maternal remission rate at 3 months was 33%. At that time, children of the 34 mothers who remitted showed an 11% decline in rates of those diagnoses, from 35% (12 of 34 children) at baseline to 24% (8 of 34). In contrast, there was an 8% increase in diagnoses among children of mothers with continuing depression, from 35% (25 of 71 children) to 43% (30 of 71 children) during that interval.

There were 68 children who had no psychiatric disorder at baseline. All of those in whom maternal depression remitted remained free of psychiatric disorders at the 3-month follow-up. In contrast, 17% (8 of 46) of the children of mothers who remained depressed developed an onset or a relapse of psychiatric disorders by the 3-month follow-up.

The change in rates of child diagnoses was inversely related to the magnitude of the mother's response to treatment. An improvement of at least 50% was necessary before any improvement could be discerned in the children. After that threshold was reached, greater maternal improvements had a direct linear association with decreases in child diagnoses. Conversely, children of mothers who responded at a rate of less than 50% showed an increase in psychiatric diagnoses at 3 months.

It is important to note that although many of the children in this study had a current or past psychiatric disorder, they showed improvement in a relatively short time (3 months)–even though most of them were not receiving direct treatment–simply because their mothers improved.

“Even more interesting” was the finding of a possible preventive effect of maternal improvement: None of the children of remitting mothers had any onset or recurrence of psychiatric symptoms, the researchers noted.

These results suggest that “a reduction in stress associated with maternal remission may reverse the long-standing symptoms in children who are likely to be genetically vulnerable,” they added.

ELSEVIER GLOBAL MEDICAL NEWS

When a mother's depression remits, her child's clinical state also improves, and children of mothers who remain depressed are likely to deteriorate, reported Myrna M. Weissman, Ph.D., and her associates in the pediatric portion of the Sequenced Treatment Alternative to Relieve Depression study.

Maternal depression is one of the most consistent risk factors for childhood anxiety, depression, and disruptive behavior disorders. However, the researchers said, to their knowledge, this is the first published study documenting prospectively the relationship between the remission of a mother's depression and a child's clinical state.

“These findings are intriguing because they suggest that an environmental influence … had a measurable impact on the child's psychopathology,” the investigators noted.

The Sequenced Treatment Alternative to Relieve Depression (STAR

In the ancillary pediatric study, Dr. Weissman and her associates assessed 114 mother-child pairs. This report details their findings at baseline and at the first of several planned follow-up evaluations (JAMA 2006;295:1389–98).

All the mothers were initially treated with citalopram (Celexa). Those who did not respond or did not tolerate the antidepressant went on to be randomly assigned to subsequent steps in treatment, said Dr. Weissman, of Columbia University and the New York State Psychiatric Institute, New York, and her associates.

Many of the children, aged 7–17 years, were acutely symptomatic at baseline. “Over a third had a current psychiatric disorder including anxiety (16%), depressive (10%), or disruptive behavior disorders (22%); almost half had a past psychiatric disorder. These high rates are consistent with findings from numerous studies of children with depressed parents,” the investigators said.

The maternal remission rate at 3 months was 33%. At that time, children of the 34 mothers who remitted showed an 11% decline in rates of those diagnoses, from 35% (12 of 34 children) at baseline to 24% (8 of 34). In contrast, there was an 8% increase in diagnoses among children of mothers with continuing depression, from 35% (25 of 71 children) to 43% (30 of 71 children) during that interval.

There were 68 children who had no psychiatric disorder at baseline. All of those in whom maternal depression remitted remained free of psychiatric disorders at the 3-month follow-up. In contrast, 17% (8 of 46) of the children of mothers who remained depressed developed an onset or a relapse of psychiatric disorders by the 3-month follow-up.

The change in rates of child diagnoses was inversely related to the magnitude of the mother's response to treatment. An improvement of at least 50% was necessary before any improvement could be discerned in the children. After that threshold was reached, greater maternal improvements had a direct linear association with decreases in child diagnoses. Conversely, children of mothers who responded at a rate of less than 50% showed an increase in psychiatric diagnoses at 3 months.

It is important to note that although many of the children in this study had a current or past psychiatric disorder, they showed improvement in a relatively short time (3 months)–even though most of them were not receiving direct treatment–simply because their mothers improved.

“Even more interesting” was the finding of a possible preventive effect of maternal improvement: None of the children of remitting mothers had any onset or recurrence of psychiatric symptoms, the researchers noted.

These results suggest that “a reduction in stress associated with maternal remission may reverse the long-standing symptoms in children who are likely to be genetically vulnerable,” they added.

ELSEVIER GLOBAL MEDICAL NEWS

Two studies that addressed unrelated, lingering questions about colonoscopy screening should help physicians decide when to recommend the procedure and should help patients decide when to undergo it.

One group of researchers investigated whether it is reasonable to recommend a screening interval of 10 years after a colonoscopy yields negative results. This interval has been widely adopted “based on the estimate of the time it takes for an adenomatous polyp to transform into carcinoma,” but no one has ever demonstrated how long cancer risk remains decreased after a negative colonoscopy.

The second study assessed the value of performing screening colonoscopy in people aged 80 years or older. Current guidelines do not specify when it is reasonable to stop performing the procedure in aging patients, even though the benefits are limited because of their diminishing life expectancies and because the elderly have lower procedural completion rates and higher complication rates than do patients in their 50s or 60s.

In the first study, Dr. Harminder Singh and his associates at the University of Manitoba, Winnipeg, found that the likelihood that colorectal cancer will develop after a screening colonoscopy yields negative results remains low for more than 10 years.

They identified 32,203 members of the general population in Manitoba who had undergone colonoscopy with negative results between 1989 and 2003 and had been followed for at least 6 months for the development of colorectal cancer.

The researchers calculated that the incidence of colorectal cancer (CRC) in these patients was at most 60%–70% of the risk in the general population. “If a patient has a single negative colonoscopy result and does not require further colonoscopy for a particular indication, the likelihood of developing CRC is extremely low, and for this group a screening interval … can be reasonably set at more than 10 years,” Dr. Singh and his associates wrote (JAMA 2006;295:2366–73).

In the second study, Dr. Otto S. Lin of Virginia Mason Medical Center, Seattle, and his associates estimated the mean extension in life expectancy after colonoscopy screening in 1,244 patients who underwent screening between 2002 and 2005. The subjects were categorized by age: 1,034 were aged 50–54 years, 147 were aged 75–79 years, and 63 were aged 80 years or older. The prevalence of neoplasias increased with age. The oldest group had 14% prevalence, compared with 3% in the youngest group.

Nevertheless, screening colonoscopy extended life expectancy only by a mean of about 1 month in the oldest patients, compared with a mean of nearly 1 year in the youngest group. This is because the oldest patients “are much more likely to die of 'natural' causes before an adenoma turns into cancer, thus negating any potential benefits of colonoscopy and polypectomy,” Dr. Lin and his associates wrote (JAMA 2006;295:2357–65).

“Currently, very elderly patients and their physicians are using individual judgment to decide whether to undergo screening. These decisions are based on scant data regarding the impact of screening colonoscopy on life expectancy,” the authors noted.

Physicians and patients should keep in mind not only that the gain in life expectancy may be small but also that procedure times are longer, rates of completed cecal intubation are lower, risks of bowel perforation are higher, and suboptimal bowel preparation is more likely in the elderly, the researchers added.

Two studies that addressed unrelated, lingering questions about colonoscopy screening should help physicians decide when to recommend the procedure and should help patients decide when to undergo it.

One group of researchers investigated whether it is reasonable to recommend a screening interval of 10 years after a colonoscopy yields negative results. This interval has been widely adopted “based on the estimate of the time it takes for an adenomatous polyp to transform into carcinoma,” but no one has ever demonstrated how long cancer risk remains decreased after a negative colonoscopy.

The second study assessed the value of performing screening colonoscopy in people aged 80 years or older. Current guidelines do not specify when it is reasonable to stop performing the procedure in aging patients, even though the benefits are limited because of their diminishing life expectancies and because the elderly have lower procedural completion rates and higher complication rates than do patients in their 50s or 60s.

In the first study, Dr. Harminder Singh and his associates at the University of Manitoba, Winnipeg, found that the likelihood that colorectal cancer will develop after a screening colonoscopy yields negative results remains low for more than 10 years.

They identified 32,203 members of the general population in Manitoba who had undergone colonoscopy with negative results between 1989 and 2003 and had been followed for at least 6 months for the development of colorectal cancer.

The researchers calculated that the incidence of colorectal cancer (CRC) in these patients was at most 60%–70% of the risk in the general population. “If a patient has a single negative colonoscopy result and does not require further colonoscopy for a particular indication, the likelihood of developing CRC is extremely low, and for this group a screening interval … can be reasonably set at more than 10 years,” Dr. Singh and his associates wrote (JAMA 2006;295:2366–73).

In the second study, Dr. Otto S. Lin of Virginia Mason Medical Center, Seattle, and his associates estimated the mean extension in life expectancy after colonoscopy screening in 1,244 patients who underwent screening between 2002 and 2005. The subjects were categorized by age: 1,034 were aged 50–54 years, 147 were aged 75–79 years, and 63 were aged 80 years or older. The prevalence of neoplasias increased with age. The oldest group had 14% prevalence, compared with 3% in the youngest group.

Nevertheless, screening colonoscopy extended life expectancy only by a mean of about 1 month in the oldest patients, compared with a mean of nearly 1 year in the youngest group. This is because the oldest patients “are much more likely to die of 'natural' causes before an adenoma turns into cancer, thus negating any potential benefits of colonoscopy and polypectomy,” Dr. Lin and his associates wrote (JAMA 2006;295:2357–65).

“Currently, very elderly patients and their physicians are using individual judgment to decide whether to undergo screening. These decisions are based on scant data regarding the impact of screening colonoscopy on life expectancy,” the authors noted.

Physicians and patients should keep in mind not only that the gain in life expectancy may be small but also that procedure times are longer, rates of completed cecal intubation are lower, risks of bowel perforation are higher, and suboptimal bowel preparation is more likely in the elderly, the researchers added.

Two studies that addressed unrelated, lingering questions about colonoscopy screening should help physicians decide when to recommend the procedure and should help patients decide when to undergo it.

One group of researchers investigated whether it is reasonable to recommend a screening interval of 10 years after a colonoscopy yields negative results. This interval has been widely adopted “based on the estimate of the time it takes for an adenomatous polyp to transform into carcinoma,” but no one has ever demonstrated how long cancer risk remains decreased after a negative colonoscopy.

The second study assessed the value of performing screening colonoscopy in people aged 80 years or older. Current guidelines do not specify when it is reasonable to stop performing the procedure in aging patients, even though the benefits are limited because of their diminishing life expectancies and because the elderly have lower procedural completion rates and higher complication rates than do patients in their 50s or 60s.

In the first study, Dr. Harminder Singh and his associates at the University of Manitoba, Winnipeg, found that the likelihood that colorectal cancer will develop after a screening colonoscopy yields negative results remains low for more than 10 years.

They identified 32,203 members of the general population in Manitoba who had undergone colonoscopy with negative results between 1989 and 2003 and had been followed for at least 6 months for the development of colorectal cancer.

The researchers calculated that the incidence of colorectal cancer (CRC) in these patients was at most 60%–70% of the risk in the general population. “If a patient has a single negative colonoscopy result and does not require further colonoscopy for a particular indication, the likelihood of developing CRC is extremely low, and for this group a screening interval … can be reasonably set at more than 10 years,” Dr. Singh and his associates wrote (JAMA 2006;295:2366–73).

In the second study, Dr. Otto S. Lin of Virginia Mason Medical Center, Seattle, and his associates estimated the mean extension in life expectancy after colonoscopy screening in 1,244 patients who underwent screening between 2002 and 2005. The subjects were categorized by age: 1,034 were aged 50–54 years, 147 were aged 75–79 years, and 63 were aged 80 years or older. The prevalence of neoplasias increased with age. The oldest group had 14% prevalence, compared with 3% in the youngest group.

Nevertheless, screening colonoscopy extended life expectancy only by a mean of about 1 month in the oldest patients, compared with a mean of nearly 1 year in the youngest group. This is because the oldest patients “are much more likely to die of 'natural' causes before an adenoma turns into cancer, thus negating any potential benefits of colonoscopy and polypectomy,” Dr. Lin and his associates wrote (JAMA 2006;295:2357–65).

“Currently, very elderly patients and their physicians are using individual judgment to decide whether to undergo screening. These decisions are based on scant data regarding the impact of screening colonoscopy on life expectancy,” the authors noted.

Physicians and patients should keep in mind not only that the gain in life expectancy may be small but also that procedure times are longer, rates of completed cecal intubation are lower, risks of bowel perforation are higher, and suboptimal bowel preparation is more likely in the elderly, the researchers added.

Intravenous acyclovir significantly reduced postherpetic neuralgia in half of the older patients who received it in an open-label pilot study, reported Dr. Dianna Quan and her associates at the University of Colorado Health Sciences Center, Denver.

These “promising” results will pave the way for a large clinical trial of the drug, the researchers said.

For most patients who develop herpes zoster (shingles) decades after childhood varicella infection, pain resolves within 4–6 weeks. But among patients over age 70, 40% have postherpetic neuralgia that persists for months or years. The exact cause is unknown, but there is evidence that low-grade varicella infection within the ganglia is a contributing factor. Noting that postherpetic neuralgia may reflect such chronic infection, Dr. Quan and her associates assessed whether antiviral therapy would help to quiet any low-grade infection and diminish pain.

They treated 12 men and 3 women aged 53–82 years whose postherpetic neuralgia had persisted for a median of 1 year and had not responded to numerous treatments including opioids, tricyclic antidepressants, and gabapentin. The subjects received 10 mg/kg IV acyclovir every 8 hours for 14 days. Three subjects withdrew from the study: one who had mild, reversible creatinine elevation likely caused by the drug, one who became ill from unrelated causes, and one who could not tolerate the IV.

The remaining 12 subjects completed the intravenous therapy and then received a 1-month course of oral valacyclovir. It was hoped that the oral antiviral would provide continued viral suppression and prolong the period of pain relief (Arch. Neurol. 2006;63:[doi:10.1001/archneur.63.7.noc60049]).

In the intention-to-treat analysis, 7 of the 15 subjects (47%) reported clinically significant pain relief after the intravenous therapy. At the conclusion of the study after the course of valacyclovir, 8 of 15 (53%) reported clinically significant pain relief.

“Based on our findings, we now believe that a large, randomized, double-blind, placebo-controlled trial is warranted,” the authors said.

Intravenous acyclovir significantly reduced postherpetic neuralgia in half of the older patients who received it in an open-label pilot study, reported Dr. Dianna Quan and her associates at the University of Colorado Health Sciences Center, Denver.

These “promising” results will pave the way for a large clinical trial of the drug, the researchers said.

For most patients who develop herpes zoster (shingles) decades after childhood varicella infection, pain resolves within 4–6 weeks. But among patients over age 70, 40% have postherpetic neuralgia that persists for months or years. The exact cause is unknown, but there is evidence that low-grade varicella infection within the ganglia is a contributing factor. Noting that postherpetic neuralgia may reflect such chronic infection, Dr. Quan and her associates assessed whether antiviral therapy would help to quiet any low-grade infection and diminish pain.

They treated 12 men and 3 women aged 53–82 years whose postherpetic neuralgia had persisted for a median of 1 year and had not responded to numerous treatments including opioids, tricyclic antidepressants, and gabapentin. The subjects received 10 mg/kg IV acyclovir every 8 hours for 14 days. Three subjects withdrew from the study: one who had mild, reversible creatinine elevation likely caused by the drug, one who became ill from unrelated causes, and one who could not tolerate the IV.

The remaining 12 subjects completed the intravenous therapy and then received a 1-month course of oral valacyclovir. It was hoped that the oral antiviral would provide continued viral suppression and prolong the period of pain relief (Arch. Neurol. 2006;63:[doi:10.1001/archneur.63.7.noc60049]).

In the intention-to-treat analysis, 7 of the 15 subjects (47%) reported clinically significant pain relief after the intravenous therapy. At the conclusion of the study after the course of valacyclovir, 8 of 15 (53%) reported clinically significant pain relief.

“Based on our findings, we now believe that a large, randomized, double-blind, placebo-controlled trial is warranted,” the authors said.

Intravenous acyclovir significantly reduced postherpetic neuralgia in half of the older patients who received it in an open-label pilot study, reported Dr. Dianna Quan and her associates at the University of Colorado Health Sciences Center, Denver.

These “promising” results will pave the way for a large clinical trial of the drug, the researchers said.

For most patients who develop herpes zoster (shingles) decades after childhood varicella infection, pain resolves within 4–6 weeks. But among patients over age 70, 40% have postherpetic neuralgia that persists for months or years. The exact cause is unknown, but there is evidence that low-grade varicella infection within the ganglia is a contributing factor. Noting that postherpetic neuralgia may reflect such chronic infection, Dr. Quan and her associates assessed whether antiviral therapy would help to quiet any low-grade infection and diminish pain.

They treated 12 men and 3 women aged 53–82 years whose postherpetic neuralgia had persisted for a median of 1 year and had not responded to numerous treatments including opioids, tricyclic antidepressants, and gabapentin. The subjects received 10 mg/kg IV acyclovir every 8 hours for 14 days. Three subjects withdrew from the study: one who had mild, reversible creatinine elevation likely caused by the drug, one who became ill from unrelated causes, and one who could not tolerate the IV.

The remaining 12 subjects completed the intravenous therapy and then received a 1-month course of oral valacyclovir. It was hoped that the oral antiviral would provide continued viral suppression and prolong the period of pain relief (Arch. Neurol. 2006;63:[doi:10.1001/archneur.63.7.noc60049]).

In the intention-to-treat analysis, 7 of the 15 subjects (47%) reported clinically significant pain relief after the intravenous therapy. At the conclusion of the study after the course of valacyclovir, 8 of 15 (53%) reported clinically significant pain relief.

“Based on our findings, we now believe that a large, randomized, double-blind, placebo-controlled trial is warranted,” the authors said.