Mary Ann Moon

The use of nonsteroidal anti-inflammatory drugs does not reduce the risk of cutaneous squamous cell carcinoma, according to the findings of a retrospective study.

In a case-control study involving more than 800 subjects, the dose, duration, and type of NSAID exposure exerted “no clear effect” on the risk of developing squamous cell cancer (SCC), said Dr. Maryam M. Asgari of Kaiser Permanente of Northern California, Oakland, and associates.

NSAIDs block the synthesis of proinflammatory prostaglandins and “inhibit neoplastic proliferation by inducing apoptosis and inhibiting angiogenesis,” the authors wrote. They have been reported to protect against colorectal, breast, prostate, and lung cancer, and have shown activity against SCCs both in animal and in vitro studies. However, human studies have produced conflicting results.

Dr. Asgari and her colleagues assessed NSAID use during the preceding decade in 415 patients with pathologically confirmed SCC who were diagnosed in 2004 and 415 control subjects matched for age, sex, and race. Only cases of extragenital and nonmucosal SCC were included.

The subjects (aged 43-85 years) completed 3-page questionnaires detailing medication use, health history, skin cancer history, and risk factors. NSAID use was analyzed by four categories: any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs. Regular use was defined as taking the medication at least once per week for at least 1 year.

Most of the subjects (61%) reported regular use of NSAIDs at some time during the preceding 10 years, most commonly aspirin (48%), followed by ibuprofen (18%), naproxen (5%), and nabumetone (4%).

There was no association between self-reported NSAID use and SCC risk.

This finding was validated in a separate analysis of pharmacy records of NSAIDs that were dispensed to the same group of subjects, the investigators said (Arch. Dermatol. 2010 Feb. 15 [doi:10.1001/archdermatol.2009.374]).

Dose and duration of exposure had no effect on the results.

“Our results are largely consistent with” three of the four published articles examining the association of NSAIDs with SCC risk, they added.

Disclosures: This study was funded by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases and the National Cancer Institute. One of Dr. Asgari's associates reported serving on an advisory committee for Roche Laboratories and consulting for law firms serving both plaintiffs and Ortho-McNeil-Janssen Pharmaceuticals in legal cases. No other potential conflicts of interest were reported.

The use of nonsteroidal anti-inflammatory drugs does not reduce the risk of cutaneous squamous cell carcinoma, according to the findings of a retrospective study.

In a case-control study involving more than 800 subjects, the dose, duration, and type of NSAID exposure exerted “no clear effect” on the risk of developing squamous cell cancer (SCC), said Dr. Maryam M. Asgari of Kaiser Permanente of Northern California, Oakland, and associates.

NSAIDs block the synthesis of proinflammatory prostaglandins and “inhibit neoplastic proliferation by inducing apoptosis and inhibiting angiogenesis,” the authors wrote. They have been reported to protect against colorectal, breast, prostate, and lung cancer, and have shown activity against SCCs both in animal and in vitro studies. However, human studies have produced conflicting results.

Dr. Asgari and her colleagues assessed NSAID use during the preceding decade in 415 patients with pathologically confirmed SCC who were diagnosed in 2004 and 415 control subjects matched for age, sex, and race. Only cases of extragenital and nonmucosal SCC were included.

The subjects (aged 43-85 years) completed 3-page questionnaires detailing medication use, health history, skin cancer history, and risk factors. NSAID use was analyzed by four categories: any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs. Regular use was defined as taking the medication at least once per week for at least 1 year.

Most of the subjects (61%) reported regular use of NSAIDs at some time during the preceding 10 years, most commonly aspirin (48%), followed by ibuprofen (18%), naproxen (5%), and nabumetone (4%).

There was no association between self-reported NSAID use and SCC risk.

This finding was validated in a separate analysis of pharmacy records of NSAIDs that were dispensed to the same group of subjects, the investigators said (Arch. Dermatol. 2010 Feb. 15 [doi:10.1001/archdermatol.2009.374]).

Dose and duration of exposure had no effect on the results.

“Our results are largely consistent with” three of the four published articles examining the association of NSAIDs with SCC risk, they added.

Disclosures: This study was funded by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases and the National Cancer Institute. One of Dr. Asgari's associates reported serving on an advisory committee for Roche Laboratories and consulting for law firms serving both plaintiffs and Ortho-McNeil-Janssen Pharmaceuticals in legal cases. No other potential conflicts of interest were reported.

The use of nonsteroidal anti-inflammatory drugs does not reduce the risk of cutaneous squamous cell carcinoma, according to the findings of a retrospective study.

In a case-control study involving more than 800 subjects, the dose, duration, and type of NSAID exposure exerted “no clear effect” on the risk of developing squamous cell cancer (SCC), said Dr. Maryam M. Asgari of Kaiser Permanente of Northern California, Oakland, and associates.

NSAIDs block the synthesis of proinflammatory prostaglandins and “inhibit neoplastic proliferation by inducing apoptosis and inhibiting angiogenesis,” the authors wrote. They have been reported to protect against colorectal, breast, prostate, and lung cancer, and have shown activity against SCCs both in animal and in vitro studies. However, human studies have produced conflicting results.

Dr. Asgari and her colleagues assessed NSAID use during the preceding decade in 415 patients with pathologically confirmed SCC who were diagnosed in 2004 and 415 control subjects matched for age, sex, and race. Only cases of extragenital and nonmucosal SCC were included.

The subjects (aged 43-85 years) completed 3-page questionnaires detailing medication use, health history, skin cancer history, and risk factors. NSAID use was analyzed by four categories: any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs. Regular use was defined as taking the medication at least once per week for at least 1 year.

Most of the subjects (61%) reported regular use of NSAIDs at some time during the preceding 10 years, most commonly aspirin (48%), followed by ibuprofen (18%), naproxen (5%), and nabumetone (4%).

There was no association between self-reported NSAID use and SCC risk.

This finding was validated in a separate analysis of pharmacy records of NSAIDs that were dispensed to the same group of subjects, the investigators said (Arch. Dermatol. 2010 Feb. 15 [doi:10.1001/archdermatol.2009.374]).

Dose and duration of exposure had no effect on the results.

“Our results are largely consistent with” three of the four published articles examining the association of NSAIDs with SCC risk, they added.

Disclosures: This study was funded by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases and the National Cancer Institute. One of Dr. Asgari's associates reported serving on an advisory committee for Roche Laboratories and consulting for law firms serving both plaintiffs and Ortho-McNeil-Janssen Pharmaceuticals in legal cases. No other potential conflicts of interest were reported.

A single negative whole-leg compression ultrasound may safely identify which patients with suspected deep vein thrombosis can forego anticoagulation therapy because they are at low risk for venous thromboembolism, according to a meta-analysis.

But the authors of an accompanying editorial cautioned against drawing firm clinical conclusions from the meta-analysis.

For patients assessed for possible DVT, practice guidelines currently recommend serial compression ultrasound imaging of the proximal veins after an initial negative result. Such imaging may minimize the risk that distal DVT is present and could propagate into the proximal veins, putting the patient at risk for VTE. However, only 1%-2% of these repeat studies detect thrombus propagation, making many studies ultimately unnecessary.

In addition, “because many distal thrombi appear to resolve without use of anticoagulant therapy, it may be argued that detection and treatment of distal DVT is unnecessary because it may place patients at undue risk for anticoagulant-related complications,” wrote Dr. Stacy A. Johnson of the University of Utah, Salt Lake City, and associates (JAMA 2010;303:438-45).

Whole-leg compression ultrasound (CUS) has been proposed as an alternative strategy to improve initial detection of distal DVT and obviate repeat compression ultrasound. But many clinicians are reluctant to rely on a single whole-leg CUS for that purpose, citing concerns about the technical feasibility and safety of such an approach, the investigators noted.

The researchers performed a meta-analysis “to address the safety of withholding anticoagulation after a negative whole-leg CUS by providing estimates of the incidence of symptomatic VTE during the 3 months after a single negative result.” They reviewed 156 studies and narrowed the meta-analysis to 6 prospective cohort studies and 1 randomized clinical trial. Outcomes from 4,731 patients were included.

The combined end point of confirmed VTE and mortality possibly related to VTE developed in 34 (0.7%) of the patients. There were 11 cases of distal VTE, 7 cases of proximal DVT, and 7 cases of nonfatal PE.

There were nine deaths possibly related to VTE, but no necropsies were done to establish the causes of death. None of the deaths was attributed to VTE, and all occurred in acutely ill hospitalized patients or patients with advanced cancer. “Overall, the risk for symptomatic VTE was low, with a pooled VTE event rate of 0.57%,” Dr. Johnson and colleagues said. “To our knowledge, these results represent the first reported pooled risk assessment of VTE following a negative lower-extremity whole-leg CUS result.”

However, “summary statements from meta-analyses should not be used to guide patient care,” cautioned Dr. Robert A. McNutt, Ph.D., of Rush University Medical Center, Chicago, and Dr. Edward H. Livingston of the University of Texas Southwestern Medical Center, Dallas, in an editorial comment accompanying the report.

“Such conclusions are not helpful when the clinical studies are combined and averaged in a way that reduces the complex world of medical care to overly simple and consequently not clinically useful statistical summaries,” they said (JAMA 2010;303:454-5).

“Generalizing the findings related to a diagnostic test or treatment regimen beyond the specific context from which a study was performed is fraught with danger,” Dr. McNutt and Dr. Livingston noted. “For instance, based on the meta-analysis by Dr. Johnson and associates, clinicians may infer that not initiating anticoagulation treatment after a negative CUS result in some surgical or ambulatory patients at low risk of having VTE may be appropriate; however, that inference may not be true for hospitalized patients or those with cancer.

Dr. Johnson's associates reported receiving consulting and speakers' fees from AGEN Biomedical, Janssen-Ortho, Boehringer-Ingelheim, Sanofi-Aventis, AstraZeneca, Pfizer, and Leo Pharma. The editorialists reported that they had no financial disclosures.

A single negative whole-leg compression ultrasound may safely identify which patients with suspected deep vein thrombosis can forego anticoagulation therapy because they are at low risk for venous thromboembolism, according to a meta-analysis.

But the authors of an accompanying editorial cautioned against drawing firm clinical conclusions from the meta-analysis.

For patients assessed for possible DVT, practice guidelines currently recommend serial compression ultrasound imaging of the proximal veins after an initial negative result. Such imaging may minimize the risk that distal DVT is present and could propagate into the proximal veins, putting the patient at risk for VTE. However, only 1%-2% of these repeat studies detect thrombus propagation, making many studies ultimately unnecessary.

In addition, “because many distal thrombi appear to resolve without use of anticoagulant therapy, it may be argued that detection and treatment of distal DVT is unnecessary because it may place patients at undue risk for anticoagulant-related complications,” wrote Dr. Stacy A. Johnson of the University of Utah, Salt Lake City, and associates (JAMA 2010;303:438-45).

Whole-leg compression ultrasound (CUS) has been proposed as an alternative strategy to improve initial detection of distal DVT and obviate repeat compression ultrasound. But many clinicians are reluctant to rely on a single whole-leg CUS for that purpose, citing concerns about the technical feasibility and safety of such an approach, the investigators noted.

The researchers performed a meta-analysis “to address the safety of withholding anticoagulation after a negative whole-leg CUS by providing estimates of the incidence of symptomatic VTE during the 3 months after a single negative result.” They reviewed 156 studies and narrowed the meta-analysis to 6 prospective cohort studies and 1 randomized clinical trial. Outcomes from 4,731 patients were included.

The combined end point of confirmed VTE and mortality possibly related to VTE developed in 34 (0.7%) of the patients. There were 11 cases of distal VTE, 7 cases of proximal DVT, and 7 cases of nonfatal PE.

There were nine deaths possibly related to VTE, but no necropsies were done to establish the causes of death. None of the deaths was attributed to VTE, and all occurred in acutely ill hospitalized patients or patients with advanced cancer. “Overall, the risk for symptomatic VTE was low, with a pooled VTE event rate of 0.57%,” Dr. Johnson and colleagues said. “To our knowledge, these results represent the first reported pooled risk assessment of VTE following a negative lower-extremity whole-leg CUS result.”

However, “summary statements from meta-analyses should not be used to guide patient care,” cautioned Dr. Robert A. McNutt, Ph.D., of Rush University Medical Center, Chicago, and Dr. Edward H. Livingston of the University of Texas Southwestern Medical Center, Dallas, in an editorial comment accompanying the report.

“Such conclusions are not helpful when the clinical studies are combined and averaged in a way that reduces the complex world of medical care to overly simple and consequently not clinically useful statistical summaries,” they said (JAMA 2010;303:454-5).

“Generalizing the findings related to a diagnostic test or treatment regimen beyond the specific context from which a study was performed is fraught with danger,” Dr. McNutt and Dr. Livingston noted. “For instance, based on the meta-analysis by Dr. Johnson and associates, clinicians may infer that not initiating anticoagulation treatment after a negative CUS result in some surgical or ambulatory patients at low risk of having VTE may be appropriate; however, that inference may not be true for hospitalized patients or those with cancer.

Dr. Johnson's associates reported receiving consulting and speakers' fees from AGEN Biomedical, Janssen-Ortho, Boehringer-Ingelheim, Sanofi-Aventis, AstraZeneca, Pfizer, and Leo Pharma. The editorialists reported that they had no financial disclosures.

A single negative whole-leg compression ultrasound may safely identify which patients with suspected deep vein thrombosis can forego anticoagulation therapy because they are at low risk for venous thromboembolism, according to a meta-analysis.

But the authors of an accompanying editorial cautioned against drawing firm clinical conclusions from the meta-analysis.

For patients assessed for possible DVT, practice guidelines currently recommend serial compression ultrasound imaging of the proximal veins after an initial negative result. Such imaging may minimize the risk that distal DVT is present and could propagate into the proximal veins, putting the patient at risk for VTE. However, only 1%-2% of these repeat studies detect thrombus propagation, making many studies ultimately unnecessary.

In addition, “because many distal thrombi appear to resolve without use of anticoagulant therapy, it may be argued that detection and treatment of distal DVT is unnecessary because it may place patients at undue risk for anticoagulant-related complications,” wrote Dr. Stacy A. Johnson of the University of Utah, Salt Lake City, and associates (JAMA 2010;303:438-45).

Whole-leg compression ultrasound (CUS) has been proposed as an alternative strategy to improve initial detection of distal DVT and obviate repeat compression ultrasound. But many clinicians are reluctant to rely on a single whole-leg CUS for that purpose, citing concerns about the technical feasibility and safety of such an approach, the investigators noted.

The researchers performed a meta-analysis “to address the safety of withholding anticoagulation after a negative whole-leg CUS by providing estimates of the incidence of symptomatic VTE during the 3 months after a single negative result.” They reviewed 156 studies and narrowed the meta-analysis to 6 prospective cohort studies and 1 randomized clinical trial. Outcomes from 4,731 patients were included.

The combined end point of confirmed VTE and mortality possibly related to VTE developed in 34 (0.7%) of the patients. There were 11 cases of distal VTE, 7 cases of proximal DVT, and 7 cases of nonfatal PE.

There were nine deaths possibly related to VTE, but no necropsies were done to establish the causes of death. None of the deaths was attributed to VTE, and all occurred in acutely ill hospitalized patients or patients with advanced cancer. “Overall, the risk for symptomatic VTE was low, with a pooled VTE event rate of 0.57%,” Dr. Johnson and colleagues said. “To our knowledge, these results represent the first reported pooled risk assessment of VTE following a negative lower-extremity whole-leg CUS result.”

However, “summary statements from meta-analyses should not be used to guide patient care,” cautioned Dr. Robert A. McNutt, Ph.D., of Rush University Medical Center, Chicago, and Dr. Edward H. Livingston of the University of Texas Southwestern Medical Center, Dallas, in an editorial comment accompanying the report.

“Such conclusions are not helpful when the clinical studies are combined and averaged in a way that reduces the complex world of medical care to overly simple and consequently not clinically useful statistical summaries,” they said (JAMA 2010;303:454-5).

“Generalizing the findings related to a diagnostic test or treatment regimen beyond the specific context from which a study was performed is fraught with danger,” Dr. McNutt and Dr. Livingston noted. “For instance, based on the meta-analysis by Dr. Johnson and associates, clinicians may infer that not initiating anticoagulation treatment after a negative CUS result in some surgical or ambulatory patients at low risk of having VTE may be appropriate; however, that inference may not be true for hospitalized patients or those with cancer.

Dr. Johnson's associates reported receiving consulting and speakers' fees from AGEN Biomedical, Janssen-Ortho, Boehringer-Ingelheim, Sanofi-Aventis, AstraZeneca, Pfizer, and Leo Pharma. The editorialists reported that they had no financial disclosures.

Older women with metabolic syndrome are at increased risk of developing cognitive impairment, including dementia, a report in the Archives of Neurology shows.

Given the high rate of metabolic syndrome among Americans, “even a modest association with cognitive impairment could have large public health implications,” said Dr. Kristine Yaffe of the University of California, San Francisco, and her associates.

The researchers assessed the development of cognitive impairment in 4,895 postmenopausal women participating in a clinical trial of osteoporosis that was conducted at 180 clinical centers in 25 countries. The trial included an ancillary study of cognitive impairment.

The participants were screened for the five components of metabolic syndrome–abdominal obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, and high fasting glucose or diabetes–and followed for 4 years. A total of 497 women (10%) had metabolic syndrome.

The study participants underwent screening for dementia and a battery of cognitive tests at baseline and each year afterward. During that time, 217 women (4%) developed cognitive impairment.

The rate of cognitive impairment was 7% among women who had metabolic syndrome, compared with 4% among those who did not have the syndrome, Dr. Yaffe and her colleagues said (Arch. Neurol. 2009;66:324-8).

The investigators also individually analyzed the five components of metabolic syndrome to assess their individual effects on cognitive risk. They found that only a high fasting glucose level/diabetes raised that risk.

“Our findings add to a growing body of literature that suggests the metabolic syndrome is associated with accelerated cognitive aging,” the researchers said.

The mechanism by which metabolic syndrome raises cognitive risk is not yet known. It is possible that the syndrome raises cerebrovascular risk in the same way in which it is known to raise cardiovascular risk, or that the increased inflammation that often accompanies metabolic syndrome affects brain function as well.

In addition, insulin resistance might accelerate beta-amyloid aggregation, deposition, or clearance. And obesity has been linked to increased neuronal degradation and brain atrophy, they noted.

Future research should determine whether more aggressive clinical control of the components of metabolic syndrome might lessen cognitive risk, the investigators added.

Dr. Yaffe reported no financial disclosures. The parent study was funded by Eli Lilly & Co.

Older women with metabolic syndrome are at increased risk of developing cognitive impairment, including dementia, a report in the Archives of Neurology shows.

Given the high rate of metabolic syndrome among Americans, “even a modest association with cognitive impairment could have large public health implications,” said Dr. Kristine Yaffe of the University of California, San Francisco, and her associates.

The researchers assessed the development of cognitive impairment in 4,895 postmenopausal women participating in a clinical trial of osteoporosis that was conducted at 180 clinical centers in 25 countries. The trial included an ancillary study of cognitive impairment.

The participants were screened for the five components of metabolic syndrome–abdominal obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, and high fasting glucose or diabetes–and followed for 4 years. A total of 497 women (10%) had metabolic syndrome.

The study participants underwent screening for dementia and a battery of cognitive tests at baseline and each year afterward. During that time, 217 women (4%) developed cognitive impairment.

The rate of cognitive impairment was 7% among women who had metabolic syndrome, compared with 4% among those who did not have the syndrome, Dr. Yaffe and her colleagues said (Arch. Neurol. 2009;66:324-8).

The investigators also individually analyzed the five components of metabolic syndrome to assess their individual effects on cognitive risk. They found that only a high fasting glucose level/diabetes raised that risk.

“Our findings add to a growing body of literature that suggests the metabolic syndrome is associated with accelerated cognitive aging,” the researchers said.

The mechanism by which metabolic syndrome raises cognitive risk is not yet known. It is possible that the syndrome raises cerebrovascular risk in the same way in which it is known to raise cardiovascular risk, or that the increased inflammation that often accompanies metabolic syndrome affects brain function as well.

In addition, insulin resistance might accelerate beta-amyloid aggregation, deposition, or clearance. And obesity has been linked to increased neuronal degradation and brain atrophy, they noted.

Future research should determine whether more aggressive clinical control of the components of metabolic syndrome might lessen cognitive risk, the investigators added.

Dr. Yaffe reported no financial disclosures. The parent study was funded by Eli Lilly & Co.

Older women with metabolic syndrome are at increased risk of developing cognitive impairment, including dementia, a report in the Archives of Neurology shows.

Given the high rate of metabolic syndrome among Americans, “even a modest association with cognitive impairment could have large public health implications,” said Dr. Kristine Yaffe of the University of California, San Francisco, and her associates.

The researchers assessed the development of cognitive impairment in 4,895 postmenopausal women participating in a clinical trial of osteoporosis that was conducted at 180 clinical centers in 25 countries. The trial included an ancillary study of cognitive impairment.

The participants were screened for the five components of metabolic syndrome–abdominal obesity, hypertriglyceridemia, low HDL cholesterol, hypertension, and high fasting glucose or diabetes–and followed for 4 years. A total of 497 women (10%) had metabolic syndrome.

The study participants underwent screening for dementia and a battery of cognitive tests at baseline and each year afterward. During that time, 217 women (4%) developed cognitive impairment.

The rate of cognitive impairment was 7% among women who had metabolic syndrome, compared with 4% among those who did not have the syndrome, Dr. Yaffe and her colleagues said (Arch. Neurol. 2009;66:324-8).

The investigators also individually analyzed the five components of metabolic syndrome to assess their individual effects on cognitive risk. They found that only a high fasting glucose level/diabetes raised that risk.

“Our findings add to a growing body of literature that suggests the metabolic syndrome is associated with accelerated cognitive aging,” the researchers said.

The mechanism by which metabolic syndrome raises cognitive risk is not yet known. It is possible that the syndrome raises cerebrovascular risk in the same way in which it is known to raise cardiovascular risk, or that the increased inflammation that often accompanies metabolic syndrome affects brain function as well.

In addition, insulin resistance might accelerate beta-amyloid aggregation, deposition, or clearance. And obesity has been linked to increased neuronal degradation and brain atrophy, they noted.

Future research should determine whether more aggressive clinical control of the components of metabolic syndrome might lessen cognitive risk, the investigators added.

Dr. Yaffe reported no financial disclosures. The parent study was funded by Eli Lilly & Co.

Three drug classes–sedatives and hypnotics, benzodiazepines, and antidepressants–substantially raise the risk of falling in the elderly, according to a meta-analysis in the Archives of Internal Medicine.

The findings underscore “the need for caution when prescribing these medications to seniors,” said John C. Woolcott of the University of British Columbia, Vancouver, and associates. “Falls and fall-related complications are the fifth leading cause of death in the developed world, and more than 30% of persons older than 65 years will fall at least once annually.”

In performing their meta-analysis, Mr. Woolcott and his colleagues updated the results of two previous meta-analyses conducted by Dr. Rosanne M. Leipzig and her colleagues that included papers published between 1966 and 1996 (Arch. Intern. Med. 2009;169:1952-60).

Mr. Woolcott and his colleagues conducted a Bayesian meta-analysis incorporating the results of this previous meta-analysis with studies published afterward, between 1996 and 2007.

The 22 studies in this meta-analysis included 10 cohort studies, 5 case-control studies, and 7 cross-sectional studies involving 79,081 subjects aged 60 years or older. None of the 22 studies was a randomized, controlled trial. Falls deemed to be “a consequence of sustaining a violent blow, loss of consciousness, sudden onset of paralysis as in a stroke, or an epileptic seizure” were excluded.

The use of sedatives and hypnotics, antidepressants, and benzodiazepines was significantly associated with falling. Of those three drug classes, the investigators found that antidepressants had the strongest association with a fall experience, with an updated Bayesian odds ratio of 1.68.

In contrast, the use of six other classes of drugs–neuroleptics and antipsychotics, antihypertensives, diuretics, beta-blockers, narcotics, and nonsteroidal anti-inflammatory drugs–did not significantly raise the risk of falling, the investigators said. Drugs in the narcotics class had an OR point estimate of 0.96, which means narcotics had the lowest association with a fall experience.

These findings were consistent across the studies reviewed, regardless of whether subjects lived in long-term care facilities, the investigators commented.

Mr. Woolcott and his colleagues reported that a strength of their meta-analysis is its use of Bayesian methodology, which allowed the investigators to incorporate information from the previous meta-analysis with more recently completed studies. However, they cited the relatively small number of studies meeting their inclusion criteria of using falls as an outcome as a key limitation.

The investigators hope that future research in this area is able to be completed with larger sample sizes in community and long-term care settings, Mr. Woolcott wrote.

The study was funded partly by the Canadian Institutes of Health Research. The investigators reported no financial disclosures.

Three drug classes–sedatives and hypnotics, benzodiazepines, and antidepressants–substantially raise the risk of falling in the elderly, according to a meta-analysis in the Archives of Internal Medicine.

The findings underscore “the need for caution when prescribing these medications to seniors,” said John C. Woolcott of the University of British Columbia, Vancouver, and associates. “Falls and fall-related complications are the fifth leading cause of death in the developed world, and more than 30% of persons older than 65 years will fall at least once annually.”

In performing their meta-analysis, Mr. Woolcott and his colleagues updated the results of two previous meta-analyses conducted by Dr. Rosanne M. Leipzig and her colleagues that included papers published between 1966 and 1996 (Arch. Intern. Med. 2009;169:1952-60).

Mr. Woolcott and his colleagues conducted a Bayesian meta-analysis incorporating the results of this previous meta-analysis with studies published afterward, between 1996 and 2007.

The 22 studies in this meta-analysis included 10 cohort studies, 5 case-control studies, and 7 cross-sectional studies involving 79,081 subjects aged 60 years or older. None of the 22 studies was a randomized, controlled trial. Falls deemed to be “a consequence of sustaining a violent blow, loss of consciousness, sudden onset of paralysis as in a stroke, or an epileptic seizure” were excluded.

The use of sedatives and hypnotics, antidepressants, and benzodiazepines was significantly associated with falling. Of those three drug classes, the investigators found that antidepressants had the strongest association with a fall experience, with an updated Bayesian odds ratio of 1.68.

In contrast, the use of six other classes of drugs–neuroleptics and antipsychotics, antihypertensives, diuretics, beta-blockers, narcotics, and nonsteroidal anti-inflammatory drugs–did not significantly raise the risk of falling, the investigators said. Drugs in the narcotics class had an OR point estimate of 0.96, which means narcotics had the lowest association with a fall experience.

These findings were consistent across the studies reviewed, regardless of whether subjects lived in long-term care facilities, the investigators commented.

Mr. Woolcott and his colleagues reported that a strength of their meta-analysis is its use of Bayesian methodology, which allowed the investigators to incorporate information from the previous meta-analysis with more recently completed studies. However, they cited the relatively small number of studies meeting their inclusion criteria of using falls as an outcome as a key limitation.

The investigators hope that future research in this area is able to be completed with larger sample sizes in community and long-term care settings, Mr. Woolcott wrote.

The study was funded partly by the Canadian Institutes of Health Research. The investigators reported no financial disclosures.

Three drug classes–sedatives and hypnotics, benzodiazepines, and antidepressants–substantially raise the risk of falling in the elderly, according to a meta-analysis in the Archives of Internal Medicine.

The findings underscore “the need for caution when prescribing these medications to seniors,” said John C. Woolcott of the University of British Columbia, Vancouver, and associates. “Falls and fall-related complications are the fifth leading cause of death in the developed world, and more than 30% of persons older than 65 years will fall at least once annually.”

In performing their meta-analysis, Mr. Woolcott and his colleagues updated the results of two previous meta-analyses conducted by Dr. Rosanne M. Leipzig and her colleagues that included papers published between 1966 and 1996 (Arch. Intern. Med. 2009;169:1952-60).

Mr. Woolcott and his colleagues conducted a Bayesian meta-analysis incorporating the results of this previous meta-analysis with studies published afterward, between 1996 and 2007.

The 22 studies in this meta-analysis included 10 cohort studies, 5 case-control studies, and 7 cross-sectional studies involving 79,081 subjects aged 60 years or older. None of the 22 studies was a randomized, controlled trial. Falls deemed to be “a consequence of sustaining a violent blow, loss of consciousness, sudden onset of paralysis as in a stroke, or an epileptic seizure” were excluded.

The use of sedatives and hypnotics, antidepressants, and benzodiazepines was significantly associated with falling. Of those three drug classes, the investigators found that antidepressants had the strongest association with a fall experience, with an updated Bayesian odds ratio of 1.68.

In contrast, the use of six other classes of drugs–neuroleptics and antipsychotics, antihypertensives, diuretics, beta-blockers, narcotics, and nonsteroidal anti-inflammatory drugs–did not significantly raise the risk of falling, the investigators said. Drugs in the narcotics class had an OR point estimate of 0.96, which means narcotics had the lowest association with a fall experience.

These findings were consistent across the studies reviewed, regardless of whether subjects lived in long-term care facilities, the investigators commented.

Mr. Woolcott and his colleagues reported that a strength of their meta-analysis is its use of Bayesian methodology, which allowed the investigators to incorporate information from the previous meta-analysis with more recently completed studies. However, they cited the relatively small number of studies meeting their inclusion criteria of using falls as an outcome as a key limitation.

The investigators hope that future research in this area is able to be completed with larger sample sizes in community and long-term care settings, Mr. Woolcott wrote.

The study was funded partly by the Canadian Institutes of Health Research. The investigators reported no financial disclosures.

A simpler method to monitor tissue oxygenation in severe sepsis led to short-term survival rates similar to those of the standard approach, and could ease initial management of critically ill patients, according to a report in JAMA.

Central venous oxygen saturation (ScvO₂) monitoring is the third step in the protocol for early goal-directed therapy in severe sepsis, which is a complicated strategy for titrating intravenous fluids, pressors, inotropes such as dobutamine, and transfusions to quickly correct the imbalances associated with the disorder. With that approach, ScvO₂ monitoring is used to assess whether dobutamine or red blood cell transfusions are restoring tissue oxygen delivery to a target value of at least 70%.

But ScvO₂ monitoring is technically difficult, requiring expertise and special equipment that are not available in many emergency departments, the investigators noted, as well as “real-time calibration and troubleshooting that can divert attention from the patient.” A simpler and more generalizable method for monitoring the adequacy of tissue oxygen delivery is needed, said Dr. Alan E. Jones of the emergency department at Carolinas Medical Center, Charlotte, N.C., and his associates.

The researchers proposed using lactate clearance as such an alternative. Clearance of serum lactate is derived by calculating the change in lactate level from two blood specimens drawn at different times. A clearance of at least 10% can be used as a marker of adequate tissue oxygen delivery.

Dr. Jones and his colleagues performed a prospective, nonblinded clinical trial comparing the two methods in 300 patients who presented with severe sepsis or septic shock at emergency departments in three large urban medical centers. The study subjects were randomly assigned in equal numbers to receive either ScvO₂ (central) monitoring or lactate clearance (serum) monitoring.

The primary end point of the study—the absolute in-hospital mortality rate—slightly favored the lactate clearance method (17% mortality) over ScvO₂ (23% mortality). Thus, the less-invasive method was found to be noninferior, the investigators reported (JAMA 2010;303:739–46). “These data support the substitution of lactate measurements in peripheral venous blood as a safe and efficacious alternative to a [centrally placed] computerized spectrophotometric catheter in the resuscitation of sepsis,” they said.

Early goal-directed therapy and its constituent components “are currently being reevaluated in a number of large prospective clinical trials,” noted Dr. Roger J. Lewis of Harbor-UCLA Medical Center, Los Angeles, in an editorial comment. The study “is an important first step to identifying less burdensome approaches to the initial management of critically ill patients with severe sepsis and septic shock,” he wrote (JAMA 2010;303:777–9).

Disclosures: The study was supported by grants from the National Institutes of Health. Dr. Jones reported receiving research support from Critical Biologics Corp. and Hutchinson Technology Inc., and serving on an advisory board for Brahms Inc. and Siemens. Dr. Lewis chairs the data and safety monitoring board for the Protocolized Care for Early Septic Shock trial funded by NIH, and serves as a consultant to Berry Consultants LLC.

A simpler method to monitor tissue oxygenation in severe sepsis led to short-term survival rates similar to those of the standard approach, and could ease initial management of critically ill patients, according to a report in JAMA.

Central venous oxygen saturation (ScvO₂) monitoring is the third step in the protocol for early goal-directed therapy in severe sepsis, which is a complicated strategy for titrating intravenous fluids, pressors, inotropes such as dobutamine, and transfusions to quickly correct the imbalances associated with the disorder. With that approach, ScvO₂ monitoring is used to assess whether dobutamine or red blood cell transfusions are restoring tissue oxygen delivery to a target value of at least 70%.

But ScvO₂ monitoring is technically difficult, requiring expertise and special equipment that are not available in many emergency departments, the investigators noted, as well as “real-time calibration and troubleshooting that can divert attention from the patient.” A simpler and more generalizable method for monitoring the adequacy of tissue oxygen delivery is needed, said Dr. Alan E. Jones of the emergency department at Carolinas Medical Center, Charlotte, N.C., and his associates.

The researchers proposed using lactate clearance as such an alternative. Clearance of serum lactate is derived by calculating the change in lactate level from two blood specimens drawn at different times. A clearance of at least 10% can be used as a marker of adequate tissue oxygen delivery.

Dr. Jones and his colleagues performed a prospective, nonblinded clinical trial comparing the two methods in 300 patients who presented with severe sepsis or septic shock at emergency departments in three large urban medical centers. The study subjects were randomly assigned in equal numbers to receive either ScvO₂ (central) monitoring or lactate clearance (serum) monitoring.

The primary end point of the study—the absolute in-hospital mortality rate—slightly favored the lactate clearance method (17% mortality) over ScvO₂ (23% mortality). Thus, the less-invasive method was found to be noninferior, the investigators reported (JAMA 2010;303:739–46). “These data support the substitution of lactate measurements in peripheral venous blood as a safe and efficacious alternative to a [centrally placed] computerized spectrophotometric catheter in the resuscitation of sepsis,” they said.

Early goal-directed therapy and its constituent components “are currently being reevaluated in a number of large prospective clinical trials,” noted Dr. Roger J. Lewis of Harbor-UCLA Medical Center, Los Angeles, in an editorial comment. The study “is an important first step to identifying less burdensome approaches to the initial management of critically ill patients with severe sepsis and septic shock,” he wrote (JAMA 2010;303:777–9).

Disclosures: The study was supported by grants from the National Institutes of Health. Dr. Jones reported receiving research support from Critical Biologics Corp. and Hutchinson Technology Inc., and serving on an advisory board for Brahms Inc. and Siemens. Dr. Lewis chairs the data and safety monitoring board for the Protocolized Care for Early Septic Shock trial funded by NIH, and serves as a consultant to Berry Consultants LLC.

A simpler method to monitor tissue oxygenation in severe sepsis led to short-term survival rates similar to those of the standard approach, and could ease initial management of critically ill patients, according to a report in JAMA.

Central venous oxygen saturation (ScvO₂) monitoring is the third step in the protocol for early goal-directed therapy in severe sepsis, which is a complicated strategy for titrating intravenous fluids, pressors, inotropes such as dobutamine, and transfusions to quickly correct the imbalances associated with the disorder. With that approach, ScvO₂ monitoring is used to assess whether dobutamine or red blood cell transfusions are restoring tissue oxygen delivery to a target value of at least 70%.

But ScvO₂ monitoring is technically difficult, requiring expertise and special equipment that are not available in many emergency departments, the investigators noted, as well as “real-time calibration and troubleshooting that can divert attention from the patient.” A simpler and more generalizable method for monitoring the adequacy of tissue oxygen delivery is needed, said Dr. Alan E. Jones of the emergency department at Carolinas Medical Center, Charlotte, N.C., and his associates.

The researchers proposed using lactate clearance as such an alternative. Clearance of serum lactate is derived by calculating the change in lactate level from two blood specimens drawn at different times. A clearance of at least 10% can be used as a marker of adequate tissue oxygen delivery.

Dr. Jones and his colleagues performed a prospective, nonblinded clinical trial comparing the two methods in 300 patients who presented with severe sepsis or septic shock at emergency departments in three large urban medical centers. The study subjects were randomly assigned in equal numbers to receive either ScvO₂ (central) monitoring or lactate clearance (serum) monitoring.

The primary end point of the study—the absolute in-hospital mortality rate—slightly favored the lactate clearance method (17% mortality) over ScvO₂ (23% mortality). Thus, the less-invasive method was found to be noninferior, the investigators reported (JAMA 2010;303:739–46). “These data support the substitution of lactate measurements in peripheral venous blood as a safe and efficacious alternative to a [centrally placed] computerized spectrophotometric catheter in the resuscitation of sepsis,” they said.

Early goal-directed therapy and its constituent components “are currently being reevaluated in a number of large prospective clinical trials,” noted Dr. Roger J. Lewis of Harbor-UCLA Medical Center, Los Angeles, in an editorial comment. The study “is an important first step to identifying less burdensome approaches to the initial management of critically ill patients with severe sepsis and septic shock,” he wrote (JAMA 2010;303:777–9).

Disclosures: The study was supported by grants from the National Institutes of Health. Dr. Jones reported receiving research support from Critical Biologics Corp. and Hutchinson Technology Inc., and serving on an advisory board for Brahms Inc. and Siemens. Dr. Lewis chairs the data and safety monitoring board for the Protocolized Care for Early Septic Shock trial funded by NIH, and serves as a consultant to Berry Consultants LLC.

Three clinical factors help estimate which thin melanomas are likely to harbor occult nodal metastases, and thus aid in selecting which patients would benefit most from sentinel node biopsy, according to a report in the February issue of the Archives of Surgery.

The three factors--patient sex, patient age at diagnosis, and lesion Breslow thickness--were used to develop a scoring system for estimating the risk of nodal recurrence. "This risk assessment is not intended to mandate what risk level is appropriate for sentinel node evaluation, but it allows for a better informed discussion with the patient newly diagnosed as having melanoma.

"Such information could be used to reassure extremely low-risk patients who may be anxious about the possibility of metastases or convince patients at higher risk of the need to consider biopsy," said Dr. Mark B. Faries of the John Wayne Cancer Institute, Santa Monica, Calif., and his associates (Arch. Surg. 2010;145:137-42) .

The use of sentinel node biopsy in patients with thin melanoma is controversial, since most such cases are at low risk for metastasis but the disease is usually fatal for the few patients who do develop recurrence. Doing the procedure in every case "would be prohibitively expensive and would expose a large number of patients with an extremely low risk of nodal disease to the real, albeit low, risk of toxic effects related to the procedure," they noted.

Dr. Faries and his colleagues reviewed the records in a prospective database of over 13,000 cases of thin (<1 mm) melanoma treated in 1971-2005 with wide excision but no nodal staging or lymphadenectomy. A total of 1,732 subjects were enrolled in the study. They were followed every 3 months for 2 years, every 4-6 months for the next 3 years, and annually thereafter.

During a median follow-up of 13 years, 51 patients (3%) developed nodal metastases. The median time to such recurrence was 38 months.

A variety of clinical factors were assessed to identify which ones were the strongest predictors of metastasis. Male sex, younger age at diagnosis, and greater tumor Breslow thickness were strongly predictive of metastasis, while factors such as tumor site and Clark level were not.

The investigators developed a scoring system using these 3 factors. Applying it to the study subjects, they found that the system predicted a 0.1% risk of metastasis in the lowest-risk subjects, compared with predicting a 17% risk of metastasis in the highest-risk subjects.

Tumor ulceration was predictive of nodal recurrence, with an 8% rate of metastasis in cases of ulcerated lesions compared to a 3% rate in cases without ulceration. However, ulceration was not included in the scoring system because information on ulceration often was not included in patient records, and a small proportion (approximately 2%) of this subset of patients showed lesion ulceration.

"Although such ulcerated lesions clearly deserve greater concern and evaluation, the rarity of this finding decreases the utility of including it in a prediction scheme," Dr. Faries and his associates said.

This study was funded in part by the National Cancer Institute and the Amyx Foundation. No financial conflicts of interest were reported.

Three clinical factors help estimate which thin melanomas are likely to harbor occult nodal metastases, and thus aid in selecting which patients would benefit most from sentinel node biopsy, according to a report in the February issue of the Archives of Surgery.

The three factors--patient sex, patient age at diagnosis, and lesion Breslow thickness--were used to develop a scoring system for estimating the risk of nodal recurrence. "This risk assessment is not intended to mandate what risk level is appropriate for sentinel node evaluation, but it allows for a better informed discussion with the patient newly diagnosed as having melanoma.

"Such information could be used to reassure extremely low-risk patients who may be anxious about the possibility of metastases or convince patients at higher risk of the need to consider biopsy," said Dr. Mark B. Faries of the John Wayne Cancer Institute, Santa Monica, Calif., and his associates (Arch. Surg. 2010;145:137-42) .

The use of sentinel node biopsy in patients with thin melanoma is controversial, since most such cases are at low risk for metastasis but the disease is usually fatal for the few patients who do develop recurrence. Doing the procedure in every case "would be prohibitively expensive and would expose a large number of patients with an extremely low risk of nodal disease to the real, albeit low, risk of toxic effects related to the procedure," they noted.

Dr. Faries and his colleagues reviewed the records in a prospective database of over 13,000 cases of thin (<1 mm) melanoma treated in 1971-2005 with wide excision but no nodal staging or lymphadenectomy. A total of 1,732 subjects were enrolled in the study. They were followed every 3 months for 2 years, every 4-6 months for the next 3 years, and annually thereafter.

During a median follow-up of 13 years, 51 patients (3%) developed nodal metastases. The median time to such recurrence was 38 months.

A variety of clinical factors were assessed to identify which ones were the strongest predictors of metastasis. Male sex, younger age at diagnosis, and greater tumor Breslow thickness were strongly predictive of metastasis, while factors such as tumor site and Clark level were not.

The investigators developed a scoring system using these 3 factors. Applying it to the study subjects, they found that the system predicted a 0.1% risk of metastasis in the lowest-risk subjects, compared with predicting a 17% risk of metastasis in the highest-risk subjects.

Tumor ulceration was predictive of nodal recurrence, with an 8% rate of metastasis in cases of ulcerated lesions compared to a 3% rate in cases without ulceration. However, ulceration was not included in the scoring system because information on ulceration often was not included in patient records, and a small proportion (approximately 2%) of this subset of patients showed lesion ulceration.

"Although such ulcerated lesions clearly deserve greater concern and evaluation, the rarity of this finding decreases the utility of including it in a prediction scheme," Dr. Faries and his associates said.

This study was funded in part by the National Cancer Institute and the Amyx Foundation. No financial conflicts of interest were reported.

Three clinical factors help estimate which thin melanomas are likely to harbor occult nodal metastases, and thus aid in selecting which patients would benefit most from sentinel node biopsy, according to a report in the February issue of the Archives of Surgery.

The three factors--patient sex, patient age at diagnosis, and lesion Breslow thickness--were used to develop a scoring system for estimating the risk of nodal recurrence. "This risk assessment is not intended to mandate what risk level is appropriate for sentinel node evaluation, but it allows for a better informed discussion with the patient newly diagnosed as having melanoma.

"Such information could be used to reassure extremely low-risk patients who may be anxious about the possibility of metastases or convince patients at higher risk of the need to consider biopsy," said Dr. Mark B. Faries of the John Wayne Cancer Institute, Santa Monica, Calif., and his associates (Arch. Surg. 2010;145:137-42) .

The use of sentinel node biopsy in patients with thin melanoma is controversial, since most such cases are at low risk for metastasis but the disease is usually fatal for the few patients who do develop recurrence. Doing the procedure in every case "would be prohibitively expensive and would expose a large number of patients with an extremely low risk of nodal disease to the real, albeit low, risk of toxic effects related to the procedure," they noted.

Dr. Faries and his colleagues reviewed the records in a prospective database of over 13,000 cases of thin (<1 mm) melanoma treated in 1971-2005 with wide excision but no nodal staging or lymphadenectomy. A total of 1,732 subjects were enrolled in the study. They were followed every 3 months for 2 years, every 4-6 months for the next 3 years, and annually thereafter.

During a median follow-up of 13 years, 51 patients (3%) developed nodal metastases. The median time to such recurrence was 38 months.

A variety of clinical factors were assessed to identify which ones were the strongest predictors of metastasis. Male sex, younger age at diagnosis, and greater tumor Breslow thickness were strongly predictive of metastasis, while factors such as tumor site and Clark level were not.

The investigators developed a scoring system using these 3 factors. Applying it to the study subjects, they found that the system predicted a 0.1% risk of metastasis in the lowest-risk subjects, compared with predicting a 17% risk of metastasis in the highest-risk subjects.

Tumor ulceration was predictive of nodal recurrence, with an 8% rate of metastasis in cases of ulcerated lesions compared to a 3% rate in cases without ulceration. However, ulceration was not included in the scoring system because information on ulceration often was not included in patient records, and a small proportion (approximately 2%) of this subset of patients showed lesion ulceration.

"Although such ulcerated lesions clearly deserve greater concern and evaluation, the rarity of this finding decreases the utility of including it in a prediction scheme," Dr. Faries and his associates said.

This study was funded in part by the National Cancer Institute and the Amyx Foundation. No financial conflicts of interest were reported.

The use of nonsteroidal anti-inflammatory drugs does not reduce the risk of cutaneous squamous cell carcinoma, according to a study published online Feb. 15 in the Archives of Dermatology.

In a retrospective case-control study involving more than 800 subjects, the dose, duration, and type of NSAID exposure exerted "no clear effect" on the risk of developing squamous cell carcinoma (SCC), said Dr. Maryam M. Asgari of Kaiser Permanente of Northern California, Oakland, and associates.

NSAIDs block the synthesis of proinflammatory prostaglandins and "inhibit neoplastic proliferation by inducing apoptosis and inhibiting angiogenesis," the authors wrote. They have been reported to protect against colorectal, breast, prostate, and lung cancer, and have shown activity against SCCs both in animal and in vitro studies. However, human studies have produced conflicting results.

Dr. Asgari and her colleagues assessed NSAID use during the preceding decade in 415 patients with pathologically confirmed SCC who were diagnosed in 2004 and 415 control subjects matched for age, sex, and race. Only cases of extragenital and nonmucosal SCC were included.

The subjects (aged 43-85 years) completed 3-page questionnaires detailing medication use, health history, skin cancer history, and risk factors. NSAID use was analyzed by four categories: any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs. Regular use was defined as taking the medication at least once per week for at least 1 year.

Most of the subjects (61%) reported regular use of NSAIDs at some time during the preceding 10 years, most commonly aspirin (48%), followed by ibuprofen (18%), naproxen (5%), and nabumetone (4%).

There was no association between self-reported NSAID use and SCC risk.

This finding was validated in a separate analysis of pharmacy records of NSAIDs dispensed to the same group of subjects, the investigators said (Arch. Dermatol. 2010 Feb. 15 [doi:10.1001/archdermatol.2009.374]).

Dose and duration of exposure had no effect on the results.

"Our results are largely consistent with" three of the four published articles examining the association of NSAIDs with SCC risk, they added.

Disclosures: This study was funded by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases and the National Cancer Institute. One of Dr. Asgari's associates reported serving on an advisory committee for Roche Laboratories and consulting for law firms serving both plaintiffs and Ortho-McNeil-Janssen Pharmaceuticals in legal cases. No other potential conflicts of interest were reported.

The use of nonsteroidal anti-inflammatory drugs does not reduce the risk of cutaneous squamous cell carcinoma, according to a study published online Feb. 15 in the Archives of Dermatology.

In a retrospective case-control study involving more than 800 subjects, the dose, duration, and type of NSAID exposure exerted "no clear effect" on the risk of developing squamous cell carcinoma (SCC), said Dr. Maryam M. Asgari of Kaiser Permanente of Northern California, Oakland, and associates.

NSAIDs block the synthesis of proinflammatory prostaglandins and "inhibit neoplastic proliferation by inducing apoptosis and inhibiting angiogenesis," the authors wrote. They have been reported to protect against colorectal, breast, prostate, and lung cancer, and have shown activity against SCCs both in animal and in vitro studies. However, human studies have produced conflicting results.

Dr. Asgari and her colleagues assessed NSAID use during the preceding decade in 415 patients with pathologically confirmed SCC who were diagnosed in 2004 and 415 control subjects matched for age, sex, and race. Only cases of extragenital and nonmucosal SCC were included.

The subjects (aged 43-85 years) completed 3-page questionnaires detailing medication use, health history, skin cancer history, and risk factors. NSAID use was analyzed by four categories: any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs. Regular use was defined as taking the medication at least once per week for at least 1 year.

Most of the subjects (61%) reported regular use of NSAIDs at some time during the preceding 10 years, most commonly aspirin (48%), followed by ibuprofen (18%), naproxen (5%), and nabumetone (4%).

There was no association between self-reported NSAID use and SCC risk.

This finding was validated in a separate analysis of pharmacy records of NSAIDs dispensed to the same group of subjects, the investigators said (Arch. Dermatol. 2010 Feb. 15 [doi:10.1001/archdermatol.2009.374]).

Dose and duration of exposure had no effect on the results.

"Our results are largely consistent with" three of the four published articles examining the association of NSAIDs with SCC risk, they added.

Disclosures: This study was funded by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases and the National Cancer Institute. One of Dr. Asgari's associates reported serving on an advisory committee for Roche Laboratories and consulting for law firms serving both plaintiffs and Ortho-McNeil-Janssen Pharmaceuticals in legal cases. No other potential conflicts of interest were reported.

The use of nonsteroidal anti-inflammatory drugs does not reduce the risk of cutaneous squamous cell carcinoma, according to a study published online Feb. 15 in the Archives of Dermatology.

In a retrospective case-control study involving more than 800 subjects, the dose, duration, and type of NSAID exposure exerted "no clear effect" on the risk of developing squamous cell carcinoma (SCC), said Dr. Maryam M. Asgari of Kaiser Permanente of Northern California, Oakland, and associates.

NSAIDs block the synthesis of proinflammatory prostaglandins and "inhibit neoplastic proliferation by inducing apoptosis and inhibiting angiogenesis," the authors wrote. They have been reported to protect against colorectal, breast, prostate, and lung cancer, and have shown activity against SCCs both in animal and in vitro studies. However, human studies have produced conflicting results.

Dr. Asgari and her colleagues assessed NSAID use during the preceding decade in 415 patients with pathologically confirmed SCC who were diagnosed in 2004 and 415 control subjects matched for age, sex, and race. Only cases of extragenital and nonmucosal SCC were included.

The subjects (aged 43-85 years) completed 3-page questionnaires detailing medication use, health history, skin cancer history, and risk factors. NSAID use was analyzed by four categories: any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs. Regular use was defined as taking the medication at least once per week for at least 1 year.

Most of the subjects (61%) reported regular use of NSAIDs at some time during the preceding 10 years, most commonly aspirin (48%), followed by ibuprofen (18%), naproxen (5%), and nabumetone (4%).

There was no association between self-reported NSAID use and SCC risk.

This finding was validated in a separate analysis of pharmacy records of NSAIDs dispensed to the same group of subjects, the investigators said (Arch. Dermatol. 2010 Feb. 15 [doi:10.1001/archdermatol.2009.374]).

Dose and duration of exposure had no effect on the results.

"Our results are largely consistent with" three of the four published articles examining the association of NSAIDs with SCC risk, they added.

Disclosures: This study was funded by the National Institute of Arthritis, Musculoskeletal, and Skin Diseases and the National Cancer Institute. One of Dr. Asgari's associates reported serving on an advisory committee for Roche Laboratories and consulting for law firms serving both plaintiffs and Ortho-McNeil-Janssen Pharmaceuticals in legal cases. No other potential conflicts of interest were reported.

Fingolimod and cladribine, the first oral formulations for treating relapsing-remitting multiple sclerosis, proved effective in three phase III clinical trials.

The two drugs have different mechanisms of action, but both target lymphocytes that are potentially autoaggressive against the CNS and both also are believed to promote neuroprotective and reparative processes. In separate multicenter, randomized, double-blind, placebo-controlled clinical trials, both oral medications reduced the rate of multiple sclerosis (MS) relapse, slowed the progression of disability, and decreased the number and severity of brain lesions on MRI.

In one of the studies, fingolimod outperformed interferon beta-1a injections, a widely used treatment for MS. “It is likely that the two oral therapies will be at least as effective as other currently available disease-modifying therapies,” Dr. William M. Carroll wrote in an editorial (N. Engl. J. Med. 2010 Jan. 20 [doi:10.1056/NEJMe0912019

Both fingolimod and cladribine had acceptable safety profiles with low rates of adverse events leading to discontinuation of the drugs. However, these rates still were twice as high with active therapy as with placebo (ranging from 8% to 14%), and were associated with patient death in at least two cases.

“Clinicians and patients will need to evaluate the risks and benefits of each of these drugs,” and long-term safety remains a concern because patients may need to take them their whole lives, according to Dr. Carroll of Sir Charles Gairdner Hospital, Perth, Australia.

In the first study, which was funded by Novartis Pharma, Dr. Ludwig Kappos of the University of Basel (Switzerland) and his associates compared two doses of daily fingolimod capsules (0.5 mg and 1.25 mg) with a matching placebo in 1,272 patients followed for 2 years at medical centers in 22 countries. The primary end point—the rate of relapse—was 54% lower with the lower dose of the drug and 60% lower with the higher dose, relative to placebo.

Fingolimod was equally effective in patients who had never been treated and those who had already received other treatments for MS. The time to first relapse was significantly longer with active treatment than with placebo, and more patients in the active-treatment group remained relapse free at 2-year follow-up.

Both doses of fingolimod also reduced the risk of disability progression and the time to progression. Scores on two measures of disability either remained stable or improved slightly with fingolimod, but worsened with placebo.

MRI scans showed significantly fewer brain lesions, as well as fewer new or enlarged lesions and a smaller overall volume of lesions, with fingolimod than with placebo. In addition, characteristic reductions in brain volume were 30% smaller with fingolimod, Dr. Kappos and his colleagues reported (N. Engl. J. Med. 2010 Jan. 20 [doi:10.1056/NEJMoa0907839

In the second study, which also was funded by Novartis Pharma, Dr. Jeffrey A. Cohen of the Cleveland Clinic's Mellen Center and his associates compared the same two doses of daily oral fingolimod with intramuscular injections of interferon beta-1a (Avonex). The investigators conducted follow-up for 1 year with 1,292 patients treated at 172 medical centers in 18 countries.

Compared with interferon beta-1a, the relapse rate was 38% lower with low-dose and 52% lower with high-dose fingolimod. The time to relapse, proportion of relapse-free patients, and proportion with multiple relapses also favored fingolimod.

Fingolimod-treated patients also experienced a similar rate of disability progression, time to disability progression, and MRI findings as those that were reported in the trial conducted by Dr. Kappos and his associates.

In these two studies, serious adverse events were more frequent with fingolimod than with the comparator, and they appeared to be more common at the higher dose of the drug. Adverse events tended to fall into the categories expected for any immunomodulatory agent: lymphocytopenia, CV effects, increased rates of infection, macular edema, liver-enzyme abnormalities, and neoplasms.

Fingolimod caused transient and often asymptomatic bradycardia and atrioventricular block, which likely reflects the drug's ability to bind to receptors in cardiac tissue. The long-term relevance of this effect is not yet known.

The drug also raised the rate of infection, including pneumonia. Several patients developed herpes infections, two of which were fatal, and reactivation of latent herpes remains a concern.

Both research groups emphasized that longer studies are needed to assess safety issues adequately.

In the third study, sponsored by Merck Serono, Dr. Gavin Giovannoni of Queen Mary University, London, and his associates compared two doses of oral cladribine with a matching placebo in 1,326 patients who were followed for 96 weeks at 155 centers in 32 countries.

The agents were given in two or four short courses for 48 weeks, then again in two short courses at weeks 48 and 52, for a total of 8-20 treatment days per year. This schedule allowed for an extended hematopoietic recovery period during the interval before the second round of treatment courses.

Both doses of cladribine significantly reduced the relapse rate by 55%–58%. In addition, the drug lengthened the time to relapse and decreased the rate of disability progression by approximately one-third.

Cladribine also reduced measures of MS inflammatory activity on MRI brain imaging.

The rate of serious adverse events was 8% with low-dose cladribine and 9% with high-dose cladribine, compared with 6% with placebo. The types of adverse events were similar to those with other immunomodulatory agents: lymphocytopenia, infection, and neoplasms.

Twenty patients had reactivation of latent herpes infections, and 1 had a reactivation of latent tuberculosis that proved fatal. “Cancers were isolated cases across different organ systems, and given the small number, it is not possible to establish a risk for the use of cladribine,” Dr. Giovannoni and his colleagues wrote (N. Engl. J. Med. 2010 Jan. 20 [doi:10.1056/NEJMoa0902533

As with fingolimod, the risks of treatment with cladribine must be carefully weighed against the benefits, and longer follow-up is essential, the investigators added.

All three clinical trials were well conducted and “provide a new horizon for patients with relapsing-remitting MS and a welcome increase in the range of treatment options,” Dr. Carroll noted.

All three first authors and many of their coauthors reported receiving consulting or lecture fees or research support from many manufacturers of drugs for MS, including Biogen Idec, Merck Serono, EMD Serono, and Novartis.

Fingolimod and cladribine, the first oral formulations for treating relapsing-remitting multiple sclerosis, proved effective in three phase III clinical trials.

The two drugs have different mechanisms of action, but both target lymphocytes that are potentially autoaggressive against the CNS and both also are believed to promote neuroprotective and reparative processes. In separate multicenter, randomized, double-blind, placebo-controlled clinical trials, both oral medications reduced the rate of multiple sclerosis (MS) relapse, slowed the progression of disability, and decreased the number and severity of brain lesions on MRI.

In one of the studies, fingolimod outperformed interferon beta-1a injections, a widely used treatment for MS. “It is likely that the two oral therapies will be at least as effective as other currently available disease-modifying therapies,” Dr. William M. Carroll wrote in an editorial (N. Engl. J. Med. 2010 Jan. 20 [doi:10.1056/NEJMe0912019

Both fingolimod and cladribine had acceptable safety profiles with low rates of adverse events leading to discontinuation of the drugs. However, these rates still were twice as high with active therapy as with placebo (ranging from 8% to 14%), and were associated with patient death in at least two cases.

“Clinicians and patients will need to evaluate the risks and benefits of each of these drugs,” and long-term safety remains a concern because patients may need to take them their whole lives, according to Dr. Carroll of Sir Charles Gairdner Hospital, Perth, Australia.

In the first study, which was funded by Novartis Pharma, Dr. Ludwig Kappos of the University of Basel (Switzerland) and his associates compared two doses of daily fingolimod capsules (0.5 mg and 1.25 mg) with a matching placebo in 1,272 patients followed for 2 years at medical centers in 22 countries. The primary end point—the rate of relapse—was 54% lower with the lower dose of the drug and 60% lower with the higher dose, relative to placebo.

Fingolimod was equally effective in patients who had never been treated and those who had already received other treatments for MS. The time to first relapse was significantly longer with active treatment than with placebo, and more patients in the active-treatment group remained relapse free at 2-year follow-up.

Both doses of fingolimod also reduced the risk of disability progression and the time to progression. Scores on two measures of disability either remained stable or improved slightly with fingolimod, but worsened with placebo.

MRI scans showed significantly fewer brain lesions, as well as fewer new or enlarged lesions and a smaller overall volume of lesions, with fingolimod than with placebo. In addition, characteristic reductions in brain volume were 30% smaller with fingolimod, Dr. Kappos and his colleagues reported (N. Engl. J. Med. 2010 Jan. 20 [doi:10.1056/NEJMoa0907839

In the second study, which also was funded by Novartis Pharma, Dr. Jeffrey A. Cohen of the Cleveland Clinic's Mellen Center and his associates compared the same two doses of daily oral fingolimod with intramuscular injections of interferon beta-1a (Avonex). The investigators conducted follow-up for 1 year with 1,292 patients treated at 172 medical centers in 18 countries.

Compared with interferon beta-1a, the relapse rate was 38% lower with low-dose and 52% lower with high-dose fingolimod. The time to relapse, proportion of relapse-free patients, and proportion with multiple relapses also favored fingolimod.

Fingolimod-treated patients also experienced a similar rate of disability progression, time to disability progression, and MRI findings as those that were reported in the trial conducted by Dr. Kappos and his associates.

In these two studies, serious adverse events were more frequent with fingolimod than with the comparator, and they appeared to be more common at the higher dose of the drug. Adverse events tended to fall into the categories expected for any immunomodulatory agent: lymphocytopenia, CV effects, increased rates of infection, macular edema, liver-enzyme abnormalities, and neoplasms.

Fingolimod caused transient and often asymptomatic bradycardia and atrioventricular block, which likely reflects the drug's ability to bind to receptors in cardiac tissue. The long-term relevance of this effect is not yet known.

The drug also raised the rate of infection, including pneumonia. Several patients developed herpes infections, two of which were fatal, and reactivation of latent herpes remains a concern.

Both research groups emphasized that longer studies are needed to assess safety issues adequately.

In the third study, sponsored by Merck Serono, Dr. Gavin Giovannoni of Queen Mary University, London, and his associates compared two doses of oral cladribine with a matching placebo in 1,326 patients who were followed for 96 weeks at 155 centers in 32 countries.

The agents were given in two or four short courses for 48 weeks, then again in two short courses at weeks 48 and 52, for a total of 8-20 treatment days per year. This schedule allowed for an extended hematopoietic recovery period during the interval before the second round of treatment courses.

Both doses of cladribine significantly reduced the relapse rate by 55%–58%. In addition, the drug lengthened the time to relapse and decreased the rate of disability progression by approximately one-third.

Cladribine also reduced measures of MS inflammatory activity on MRI brain imaging.

The rate of serious adverse events was 8% with low-dose cladribine and 9% with high-dose cladribine, compared with 6% with placebo. The types of adverse events were similar to those with other immunomodulatory agents: lymphocytopenia, infection, and neoplasms.

Twenty patients had reactivation of latent herpes infections, and 1 had a reactivation of latent tuberculosis that proved fatal. “Cancers were isolated cases across different organ systems, and given the small number, it is not possible to establish a risk for the use of cladribine,” Dr. Giovannoni and his colleagues wrote (N. Engl. J. Med. 2010 Jan. 20 [doi:10.1056/NEJMoa0902533

As with fingolimod, the risks of treatment with cladribine must be carefully weighed against the benefits, and longer follow-up is essential, the investigators added.

All three clinical trials were well conducted and “provide a new horizon for patients with relapsing-remitting MS and a welcome increase in the range of treatment options,” Dr. Carroll noted.

All three first authors and many of their coauthors reported receiving consulting or lecture fees or research support from many manufacturers of drugs for MS, including Biogen Idec, Merck Serono, EMD Serono, and Novartis.

Fingolimod and cladribine, the first oral formulations for treating relapsing-remitting multiple sclerosis, proved effective in three phase III clinical trials.

The two drugs have different mechanisms of action, but both target lymphocytes that are potentially autoaggressive against the CNS and both also are believed to promote neuroprotective and reparative processes. In separate multicenter, randomized, double-blind, placebo-controlled clinical trials, both oral medications reduced the rate of multiple sclerosis (MS) relapse, slowed the progression of disability, and decreased the number and severity of brain lesions on MRI.

In one of the studies, fingolimod outperformed interferon beta-1a injections, a widely used treatment for MS. “It is likely that the two oral therapies will be at least as effective as other currently available disease-modifying therapies,” Dr. William M. Carroll wrote in an editorial (N. Engl. J. Med. 2010 Jan. 20 [doi:10.1056/NEJMe0912019

Both fingolimod and cladribine had acceptable safety profiles with low rates of adverse events leading to discontinuation of the drugs. However, these rates still were twice as high with active therapy as with placebo (ranging from 8% to 14%), and were associated with patient death in at least two cases.

“Clinicians and patients will need to evaluate the risks and benefits of each of these drugs,” and long-term safety remains a concern because patients may need to take them their whole lives, according to Dr. Carroll of Sir Charles Gairdner Hospital, Perth, Australia.

In the first study, which was funded by Novartis Pharma, Dr. Ludwig Kappos of the University of Basel (Switzerland) and his associates compared two doses of daily fingolimod capsules (0.5 mg and 1.25 mg) with a matching placebo in 1,272 patients followed for 2 years at medical centers in 22 countries. The primary end point—the rate of relapse—was 54% lower with the lower dose of the drug and 60% lower with the higher dose, relative to placebo.

Fingolimod was equally effective in patients who had never been treated and those who had already received other treatments for MS. The time to first relapse was significantly longer with active treatment than with placebo, and more patients in the active-treatment group remained relapse free at 2-year follow-up.

Both doses of fingolimod also reduced the risk of disability progression and the time to progression. Scores on two measures of disability either remained stable or improved slightly with fingolimod, but worsened with placebo.

MRI scans showed significantly fewer brain lesions, as well as fewer new or enlarged lesions and a smaller overall volume of lesions, with fingolimod than with placebo. In addition, characteristic reductions in brain volume were 30% smaller with fingolimod, Dr. Kappos and his colleagues reported (N. Engl. J. Med. 2010 Jan. 20 [doi:10.1056/NEJMoa0907839

In the second study, which also was funded by Novartis Pharma, Dr. Jeffrey A. Cohen of the Cleveland Clinic's Mellen Center and his associates compared the same two doses of daily oral fingolimod with intramuscular injections of interferon beta-1a (Avonex). The investigators conducted follow-up for 1 year with 1,292 patients treated at 172 medical centers in 18 countries.

Compared with interferon beta-1a, the relapse rate was 38% lower with low-dose and 52% lower with high-dose fingolimod. The time to relapse, proportion of relapse-free patients, and proportion with multiple relapses also favored fingolimod.

Fingolimod-treated patients also experienced a similar rate of disability progression, time to disability progression, and MRI findings as those that were reported in the trial conducted by Dr. Kappos and his associates.

In these two studies, serious adverse events were more frequent with fingolimod than with the comparator, and they appeared to be more common at the higher dose of the drug. Adverse events tended to fall into the categories expected for any immunomodulatory agent: lymphocytopenia, CV effects, increased rates of infection, macular edema, liver-enzyme abnormalities, and neoplasms.

Fingolimod caused transient and often asymptomatic bradycardia and atrioventricular block, which likely reflects the drug's ability to bind to receptors in cardiac tissue. The long-term relevance of this effect is not yet known.

The drug also raised the rate of infection, including pneumonia. Several patients developed herpes infections, two of which were fatal, and reactivation of latent herpes remains a concern.

Both research groups emphasized that longer studies are needed to assess safety issues adequately.

In the third study, sponsored by Merck Serono, Dr. Gavin Giovannoni of Queen Mary University, London, and his associates compared two doses of oral cladribine with a matching placebo in 1,326 patients who were followed for 96 weeks at 155 centers in 32 countries.

The agents were given in two or four short courses for 48 weeks, then again in two short courses at weeks 48 and 52, for a total of 8-20 treatment days per year. This schedule allowed for an extended hematopoietic recovery period during the interval before the second round of treatment courses.

Both doses of cladribine significantly reduced the relapse rate by 55%–58%. In addition, the drug lengthened the time to relapse and decreased the rate of disability progression by approximately one-third.

Cladribine also reduced measures of MS inflammatory activity on MRI brain imaging.

The rate of serious adverse events was 8% with low-dose cladribine and 9% with high-dose cladribine, compared with 6% with placebo. The types of adverse events were similar to those with other immunomodulatory agents: lymphocytopenia, infection, and neoplasms.

Twenty patients had reactivation of latent herpes infections, and 1 had a reactivation of latent tuberculosis that proved fatal. “Cancers were isolated cases across different organ systems, and given the small number, it is not possible to establish a risk for the use of cladribine,” Dr. Giovannoni and his colleagues wrote (N. Engl. J. Med. 2010 Jan. 20 [doi:10.1056/NEJMoa0902533

As with fingolimod, the risks of treatment with cladribine must be carefully weighed against the benefits, and longer follow-up is essential, the investigators added.

All three clinical trials were well conducted and “provide a new horizon for patients with relapsing-remitting MS and a welcome increase in the range of treatment options,” Dr. Carroll noted.

All three first authors and many of their coauthors reported receiving consulting or lecture fees or research support from many manufacturers of drugs for MS, including Biogen Idec, Merck Serono, EMD Serono, and Novartis.

Women who are physically active at midlife, including those whose only exercise is walking, are more likely than sedentary women to have exceptionally good health in older age, according to an analysis of more than 2 decades of data from the Nurses' Health Study.

Researchers led by Dr. Qi Sun of the Harvard School of Public Health, Boston, studied how women might reach “successful survival.” The team defined that goal as living to at least age 70 with no impairment in cognitive function, no limitations on moderate activities, only moderate limitations on demanding physical activities, no mental health limitations, and no serious diseases.

The researchers wrote that their study “documented a strong, positive association between midlife leisure-time physical activity and the odds of successful survival or exceptional overall health in later life.” Even moderate-intensity walking raised the likelihood that women would “maintain physical and cognitive integrity and remain free of major chronic illnesses,” the team reported (Arch. Intern. Med. 2010;170:194-201).

Previous studies have not addressed the relationship between activity and healthy aging in women specifically, even though women tend to live longer than men and stand to benefit more from successful survival. “The notion that physical activity can promote successful survival rather than simply extend the lifespan may provide particularly strong motivation for initiating activity,” Dr. Sun and his colleagues noted.

The investigators analyzed data on 13,535 women participating in the Nurses' Health Study. The participants were assessed initially in 1976, when they were aged 30-55 years, and have been followed ever since. The type, timing, and intensity of their physical activity were calculated in 1986, when their mean age was 60 years.

At follow-up during 1995-2001, 1,456 (approximately 11%) of these women were found to be successful survivors.

The positive association between physical activity during midlife and successful survival was strong within each group of women categorized by body mass index, indicating that physical activity contributes to optimal health in both lean and overweight women, Dr. Sun and his colleagues said.

Several activities were individually associated with successful survival, including jogging, running, playing tennis, doing aerobics, and walking. Independently of total physical activity levels, walking pace was strongly associated with health in old age. “Compared with women whose walking pace was easy, women with a moderate walking pace had a 90% increase in the odds of successful aging; women whose walking pace was brisk or very brisk had a 2.68-fold increased odds,” the researchers said.

In their report, they noted that an estimated 85% of Americans do not engage in any regular vigorous physical activity, but nearly 50% at least walk for exercise. “Given that walking is a sustainable exercise that can often be easily incorporated into people's daily schedules, our observations provide initial support for the consideration of walking in broad public health recommendations,” Dr. Sun and his colleagues added.

The study was limited in that the participants were primarily of European ancestry and “largely healthy” at age 60, so the findings may not be applicable to other populations, the researchers said.

The study was supported by grants from NIH and the Boston Obesity Nutrition Research Center. Dr. Sun disclosed a postdoctoral fellowship supported by Unilever Corporate Research.

Women who are physically active at midlife, including those whose only exercise is walking, are more likely than sedentary women to have exceptionally good health in older age, according to an analysis of more than 2 decades of data from the Nurses' Health Study.

Researchers led by Dr. Qi Sun of the Harvard School of Public Health, Boston, studied how women might reach “successful survival.” The team defined that goal as living to at least age 70 with no impairment in cognitive function, no limitations on moderate activities, only moderate limitations on demanding physical activities, no mental health limitations, and no serious diseases.

The researchers wrote that their study “documented a strong, positive association between midlife leisure-time physical activity and the odds of successful survival or exceptional overall health in later life.” Even moderate-intensity walking raised the likelihood that women would “maintain physical and cognitive integrity and remain free of major chronic illnesses,” the team reported (Arch. Intern. Med. 2010;170:194-201).

Previous studies have not addressed the relationship between activity and healthy aging in women specifically, even though women tend to live longer than men and stand to benefit more from successful survival. “The notion that physical activity can promote successful survival rather than simply extend the lifespan may provide particularly strong motivation for initiating activity,” Dr. Sun and his colleagues noted.

The investigators analyzed data on 13,535 women participating in the Nurses' Health Study. The participants were assessed initially in 1976, when they were aged 30-55 years, and have been followed ever since. The type, timing, and intensity of their physical activity were calculated in 1986, when their mean age was 60 years.

At follow-up during 1995-2001, 1,456 (approximately 11%) of these women were found to be successful survivors.

The positive association between physical activity during midlife and successful survival was strong within each group of women categorized by body mass index, indicating that physical activity contributes to optimal health in both lean and overweight women, Dr. Sun and his colleagues said.

Several activities were individually associated with successful survival, including jogging, running, playing tennis, doing aerobics, and walking. Independently of total physical activity levels, walking pace was strongly associated with health in old age. “Compared with women whose walking pace was easy, women with a moderate walking pace had a 90% increase in the odds of successful aging; women whose walking pace was brisk or very brisk had a 2.68-fold increased odds,” the researchers said.

In their report, they noted that an estimated 85% of Americans do not engage in any regular vigorous physical activity, but nearly 50% at least walk for exercise. “Given that walking is a sustainable exercise that can often be easily incorporated into people's daily schedules, our observations provide initial support for the consideration of walking in broad public health recommendations,” Dr. Sun and his colleagues added.

The study was limited in that the participants were primarily of European ancestry and “largely healthy” at age 60, so the findings may not be applicable to other populations, the researchers said.

The study was supported by grants from NIH and the Boston Obesity Nutrition Research Center. Dr. Sun disclosed a postdoctoral fellowship supported by Unilever Corporate Research.

Women who are physically active at midlife, including those whose only exercise is walking, are more likely than sedentary women to have exceptionally good health in older age, according to an analysis of more than 2 decades of data from the Nurses' Health Study.

Researchers led by Dr. Qi Sun of the Harvard School of Public Health, Boston, studied how women might reach “successful survival.” The team defined that goal as living to at least age 70 with no impairment in cognitive function, no limitations on moderate activities, only moderate limitations on demanding physical activities, no mental health limitations, and no serious diseases.

The researchers wrote that their study “documented a strong, positive association between midlife leisure-time physical activity and the odds of successful survival or exceptional overall health in later life.” Even moderate-intensity walking raised the likelihood that women would “maintain physical and cognitive integrity and remain free of major chronic illnesses,” the team reported (Arch. Intern. Med. 2010;170:194-201).

Previous studies have not addressed the relationship between activity and healthy aging in women specifically, even though women tend to live longer than men and stand to benefit more from successful survival. “The notion that physical activity can promote successful survival rather than simply extend the lifespan may provide particularly strong motivation for initiating activity,” Dr. Sun and his colleagues noted.

The investigators analyzed data on 13,535 women participating in the Nurses' Health Study. The participants were assessed initially in 1976, when they were aged 30-55 years, and have been followed ever since. The type, timing, and intensity of their physical activity were calculated in 1986, when their mean age was 60 years.

At follow-up during 1995-2001, 1,456 (approximately 11%) of these women were found to be successful survivors.

The positive association between physical activity during midlife and successful survival was strong within each group of women categorized by body mass index, indicating that physical activity contributes to optimal health in both lean and overweight women, Dr. Sun and his colleagues said.

Several activities were individually associated with successful survival, including jogging, running, playing tennis, doing aerobics, and walking. Independently of total physical activity levels, walking pace was strongly associated with health in old age. “Compared with women whose walking pace was easy, women with a moderate walking pace had a 90% increase in the odds of successful aging; women whose walking pace was brisk or very brisk had a 2.68-fold increased odds,” the researchers said.

In their report, they noted that an estimated 85% of Americans do not engage in any regular vigorous physical activity, but nearly 50% at least walk for exercise. “Given that walking is a sustainable exercise that can often be easily incorporated into people's daily schedules, our observations provide initial support for the consideration of walking in broad public health recommendations,” Dr. Sun and his colleagues added.

The study was limited in that the participants were primarily of European ancestry and “largely healthy” at age 60, so the findings may not be applicable to other populations, the researchers said.

The study was supported by grants from NIH and the Boston Obesity Nutrition Research Center. Dr. Sun disclosed a postdoctoral fellowship supported by Unilever Corporate Research.

Major Finding: High-normal fasting plasma glucose levels in childhood may predict prediabetes and diabetes in young adulthood.

Data Source: Data from the Bogalusa Heart Study involving 1,849 subjects who were 4-18 years at the initiation of the trial.

Disclosures: Dr. Nguyen's study was supported by the National Institute on Aging and the American Heart Association, and Dr. Gillman's involved funding from the National Institutes of Health. Both Dr. Nguyen and Dr. Gillman reported no relevant conflicts of interest.

Elevated fasting plasma glucose levels during childhood—even when they remain within the normoglycemic range—appear to predict prediabetes and diabetes in young adulthood, according to a new report.

Moreover, high-normal fasting plasma glucose predicts later diabetes status independently of other traditional risk factors, said Dr. Quoc Manh Nguyen and associates at Tulane University, New Orleans.

The investigators used data from the Bogalusa Heart Study to assess diabetes risk over a 2-decade span. The study subjects were aged 4-18 years at its inception in 1978 and have been followed for a mean of 21 years. At the last survey, 1,723 subjects were classified as normoglycemic, 79 as prediabetic, and 47 as diabetic.

Subjects who had high-normal levels of fasting plasma glucose at baseline, defined as 86-99 mg/dL, were more than twice as likely to develop prediabetes or diabetes in young adulthood as were those with lower levels of fasting plasma glucose at baseline.

Moreover, fasting plasma glucose level predicted later diabetes risk even after the data were controlled for other cardiometabolic risk factors, Dr. Nguyen and colleagues said (Arch. Ped. Adolesc. Med. 2010;164:124-8).

In an editorial comment accompanying this report, Dr. Matthew W. Gillman of Harvard Medical School, Boston, noted that the prevalence of prediabetes was 6%–7% among adult subjects whose childhood glucose exceeded 86 mg/dL, but was only 2% for those whose childhood glucose levels were lower.

Nevertheless, it would be premature to recommend using high-normal childhood glucose levels to predict later prediabetes. It would not be “sensible” to label all such children as at risk when only 7% are likely to develop the disorder, Dr. Gillman noted (Arch. Ped. Adolesc. Med. 2010;164:198-9).

Major Finding: High-normal fasting plasma glucose levels in childhood may predict prediabetes and diabetes in young adulthood.

Data Source: Data from the Bogalusa Heart Study involving 1,849 subjects who were 4-18 years at the initiation of the trial.

Disclosures: Dr. Nguyen's study was supported by the National Institute on Aging and the American Heart Association, and Dr. Gillman's involved funding from the National Institutes of Health. Both Dr. Nguyen and Dr. Gillman reported no relevant conflicts of interest.

Elevated fasting plasma glucose levels during childhood—even when they remain within the normoglycemic range—appear to predict prediabetes and diabetes in young adulthood, according to a new report.

Moreover, high-normal fasting plasma glucose predicts later diabetes status independently of other traditional risk factors, said Dr. Quoc Manh Nguyen and associates at Tulane University, New Orleans.

The investigators used data from the Bogalusa Heart Study to assess diabetes risk over a 2-decade span. The study subjects were aged 4-18 years at its inception in 1978 and have been followed for a mean of 21 years. At the last survey, 1,723 subjects were classified as normoglycemic, 79 as prediabetic, and 47 as diabetic.

Subjects who had high-normal levels of fasting plasma glucose at baseline, defined as 86-99 mg/dL, were more than twice as likely to develop prediabetes or diabetes in young adulthood as were those with lower levels of fasting plasma glucose at baseline.

Moreover, fasting plasma glucose level predicted later diabetes risk even after the data were controlled for other cardiometabolic risk factors, Dr. Nguyen and colleagues said (Arch. Ped. Adolesc. Med. 2010;164:124-8).

In an editorial comment accompanying this report, Dr. Matthew W. Gillman of Harvard Medical School, Boston, noted that the prevalence of prediabetes was 6%–7% among adult subjects whose childhood glucose exceeded 86 mg/dL, but was only 2% for those whose childhood glucose levels were lower.

Nevertheless, it would be premature to recommend using high-normal childhood glucose levels to predict later prediabetes. It would not be “sensible” to label all such children as at risk when only 7% are likely to develop the disorder, Dr. Gillman noted (Arch. Ped. Adolesc. Med. 2010;164:198-9).

Major Finding: High-normal fasting plasma glucose levels in childhood may predict prediabetes and diabetes in young adulthood.

Data Source: Data from the Bogalusa Heart Study involving 1,849 subjects who were 4-18 years at the initiation of the trial.

Disclosures: Dr. Nguyen's study was supported by the National Institute on Aging and the American Heart Association, and Dr. Gillman's involved funding from the National Institutes of Health. Both Dr. Nguyen and Dr. Gillman reported no relevant conflicts of interest.

Elevated fasting plasma glucose levels during childhood—even when they remain within the normoglycemic range—appear to predict prediabetes and diabetes in young adulthood, according to a new report.

Moreover, high-normal fasting plasma glucose predicts later diabetes status independently of other traditional risk factors, said Dr. Quoc Manh Nguyen and associates at Tulane University, New Orleans.

The investigators used data from the Bogalusa Heart Study to assess diabetes risk over a 2-decade span. The study subjects were aged 4-18 years at its inception in 1978 and have been followed for a mean of 21 years. At the last survey, 1,723 subjects were classified as normoglycemic, 79 as prediabetic, and 47 as diabetic.

Subjects who had high-normal levels of fasting plasma glucose at baseline, defined as 86-99 mg/dL, were more than twice as likely to develop prediabetes or diabetes in young adulthood as were those with lower levels of fasting plasma glucose at baseline.

Moreover, fasting plasma glucose level predicted later diabetes risk even after the data were controlled for other cardiometabolic risk factors, Dr. Nguyen and colleagues said (Arch. Ped. Adolesc. Med. 2010;164:124-8).

In an editorial comment accompanying this report, Dr. Matthew W. Gillman of Harvard Medical School, Boston, noted that the prevalence of prediabetes was 6%–7% among adult subjects whose childhood glucose exceeded 86 mg/dL, but was only 2% for those whose childhood glucose levels were lower.

Nevertheless, it would be premature to recommend using high-normal childhood glucose levels to predict later prediabetes. It would not be “sensible” to label all such children as at risk when only 7% are likely to develop the disorder, Dr. Gillman noted (Arch. Ped. Adolesc. Med. 2010;164:198-9).