Cardiovascular risk factors, such as diabetes and high blood pressure, increase the risk of dementia. That is not new information, but a long-term funded study by the National Institutes of Health found that not only is diabetes almost as strong a predictor of dementia as the APOE4 gene, but also prehypertension.

The researchers analyzed data on 15,744 participants aged 45 to 64 years in the Atherosclerosis Risk in Communities (ARIC) study. Over 25 years, the participants were examined 4 times, including being given cognitive tests during all but the first and third exams.

Over an average of 23 follow-up years, 1,516 people were diagnosed with dementia. During the time of the first exams, the risk of dementia increased most strongly with age, followed by the presence of APOE4. But as time went on, the link between cardiovascular risk factors and dementia became clearer. A separate study of an ARIC subgroup found that the presence of ≥ 1 vascular risk factor during midlife was associated with higher levels of beta amyloid, a protein that often accumulates in the brains of Alzheimer patients. The relationship was not affected by the presence of the APOE4 gene.

When the researchers reanalyzed the data according to who had a stroke, they found similar results: Diabetes, hypertension, prehypertension, and smoking raised the risk of dementia for people who had a stroke and those who had not.

“Our results contribute to a growing body of evidence linking midlife vascular health to dementia,” said study leader Rebecca Gottesman, MD, PhD, professor of neurology at Johns Hopkins University in Maryland. “These are modifiable risk factors. Our hope is that by addressing these types of factors early, people can reduce the chances that they will suffer from dementia later in life.”

Cardiovascular risk factors, such as diabetes and high blood pressure, increase the risk of dementia. That is not new information, but a long-term funded study by the National Institutes of Health found that not only is diabetes almost as strong a predictor of dementia as the APOE4 gene, but also prehypertension.

The researchers analyzed data on 15,744 participants aged 45 to 64 years in the Atherosclerosis Risk in Communities (ARIC) study. Over 25 years, the participants were examined 4 times, including being given cognitive tests during all but the first and third exams.

Over an average of 23 follow-up years, 1,516 people were diagnosed with dementia. During the time of the first exams, the risk of dementia increased most strongly with age, followed by the presence of APOE4. But as time went on, the link between cardiovascular risk factors and dementia became clearer. A separate study of an ARIC subgroup found that the presence of ≥ 1 vascular risk factor during midlife was associated with higher levels of beta amyloid, a protein that often accumulates in the brains of Alzheimer patients. The relationship was not affected by the presence of the APOE4 gene.

When the researchers reanalyzed the data according to who had a stroke, they found similar results: Diabetes, hypertension, prehypertension, and smoking raised the risk of dementia for people who had a stroke and those who had not.

“Our results contribute to a growing body of evidence linking midlife vascular health to dementia,” said study leader Rebecca Gottesman, MD, PhD, professor of neurology at Johns Hopkins University in Maryland. “These are modifiable risk factors. Our hope is that by addressing these types of factors early, people can reduce the chances that they will suffer from dementia later in life.”

Cardiovascular risk factors, such as diabetes and high blood pressure, increase the risk of dementia. That is not new information, but a long-term funded study by the National Institutes of Health found that not only is diabetes almost as strong a predictor of dementia as the APOE4 gene, but also prehypertension.

The researchers analyzed data on 15,744 participants aged 45 to 64 years in the Atherosclerosis Risk in Communities (ARIC) study. Over 25 years, the participants were examined 4 times, including being given cognitive tests during all but the first and third exams.

Over an average of 23 follow-up years, 1,516 people were diagnosed with dementia. During the time of the first exams, the risk of dementia increased most strongly with age, followed by the presence of APOE4. But as time went on, the link between cardiovascular risk factors and dementia became clearer. A separate study of an ARIC subgroup found that the presence of ≥ 1 vascular risk factor during midlife was associated with higher levels of beta amyloid, a protein that often accumulates in the brains of Alzheimer patients. The relationship was not affected by the presence of the APOE4 gene.

When the researchers reanalyzed the data according to who had a stroke, they found similar results: Diabetes, hypertension, prehypertension, and smoking raised the risk of dementia for people who had a stroke and those who had not.

“Our results contribute to a growing body of evidence linking midlife vascular health to dementia,” said study leader Rebecca Gottesman, MD, PhD, professor of neurology at Johns Hopkins University in Maryland. “These are modifiable risk factors. Our hope is that by addressing these types of factors early, people can reduce the chances that they will suffer from dementia later in life.”

Images courtesy of Jonathan B. Grimm

Chemists have reported the creation of new fluorescent dyes that can be used in cells, tissues, and animals.

The scientists found that swapping out specific chemical building blocks in fluorescent molecules called rhodamines can generate dyes of nearly every color.

Such an expanded palette of dyes could help researchers better illuminate the inner workings of cells, said Luke Lavis, PhD, of the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia.

Dr Lavis and his colleagues used their new dyes to light up cell nuclei, label living brain tissue from fruit fly larvae, and highlight visual cortex neurons in mice that had tiny glass windows fitted into their skulls.

The team detailed their work in Nature Methods.

Dr Lavis noted that scientists used to concoct different dyes mostly by trial and error.

“Now, we’ve figured out the rules, and we can make almost any color,” he said.

Dr Lavis’s team focused their research on rhodamines because they’re especially bright and cell-permeable.

Chemists had been working with rhodamines for more than 100 years but created only a few dozen colors. Most were similar shades ranging from green to orange.

That’s because, until recently, making new rhodamines wasn’t easy. Scientists still used techniques from the earliest days of chemistry, boiling chemical ingredients in sulfuric acid. This forces the molecules to link together in a condensation reaction.

Mixing in different building blocks could yield new and unusual dyes, but ingredients had to be tough enough to survive the boiling acid bath. This didn’t leave a lot of options.

In 2011, Dr Lavis’s team developed a new way to tinker with rhodamines’ structure, under milder conditions. Using a reaction sparked by the metal palladium, the scientists could skip the acid step and construct dyes with more complicated building blocks than had been used before.

Four years later, the team revealed the Janelia Fluor dyes. The secret behind these dyes is a tiny, square-shaped appendage called an azetidine ring.

The scientists found that incorporating 4-membered azetidine rings into classic fluorophore structures elicited “substantial increases in brightness and photostability.” In fact, the Janelia Fluor dyes are up to 50 times brighter than other dyes.

Now, Dr Lavis’s group has figured out how to fine-tune their fluorescent dyes by tweaking rhodamines’ structure even further. The team showed that incorporating 3-substituted azetidine groups allowed them to tune spectral and chemical properties with “unprecedented precision.”

The dyes can be synthesized in a single step with inexpensive ingredients. The low cost has allowed Dr Lavis and his colleagues to share their work, shipping thousands of vials to hundreds of labs around the world.

Images courtesy of Jonathan B. Grimm

Chemists have reported the creation of new fluorescent dyes that can be used in cells, tissues, and animals.

The scientists found that swapping out specific chemical building blocks in fluorescent molecules called rhodamines can generate dyes of nearly every color.

Such an expanded palette of dyes could help researchers better illuminate the inner workings of cells, said Luke Lavis, PhD, of the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia.

Dr Lavis and his colleagues used their new dyes to light up cell nuclei, label living brain tissue from fruit fly larvae, and highlight visual cortex neurons in mice that had tiny glass windows fitted into their skulls.

The team detailed their work in Nature Methods.

Dr Lavis noted that scientists used to concoct different dyes mostly by trial and error.

“Now, we’ve figured out the rules, and we can make almost any color,” he said.

Dr Lavis’s team focused their research on rhodamines because they’re especially bright and cell-permeable.

Chemists had been working with rhodamines for more than 100 years but created only a few dozen colors. Most were similar shades ranging from green to orange.

That’s because, until recently, making new rhodamines wasn’t easy. Scientists still used techniques from the earliest days of chemistry, boiling chemical ingredients in sulfuric acid. This forces the molecules to link together in a condensation reaction.

Mixing in different building blocks could yield new and unusual dyes, but ingredients had to be tough enough to survive the boiling acid bath. This didn’t leave a lot of options.

In 2011, Dr Lavis’s team developed a new way to tinker with rhodamines’ structure, under milder conditions. Using a reaction sparked by the metal palladium, the scientists could skip the acid step and construct dyes with more complicated building blocks than had been used before.

Four years later, the team revealed the Janelia Fluor dyes. The secret behind these dyes is a tiny, square-shaped appendage called an azetidine ring.

The scientists found that incorporating 4-membered azetidine rings into classic fluorophore structures elicited “substantial increases in brightness and photostability.” In fact, the Janelia Fluor dyes are up to 50 times brighter than other dyes.

Now, Dr Lavis’s group has figured out how to fine-tune their fluorescent dyes by tweaking rhodamines’ structure even further. The team showed that incorporating 3-substituted azetidine groups allowed them to tune spectral and chemical properties with “unprecedented precision.”

The dyes can be synthesized in a single step with inexpensive ingredients. The low cost has allowed Dr Lavis and his colleagues to share their work, shipping thousands of vials to hundreds of labs around the world.

Images courtesy of Jonathan B. Grimm

Chemists have reported the creation of new fluorescent dyes that can be used in cells, tissues, and animals.

The scientists found that swapping out specific chemical building blocks in fluorescent molecules called rhodamines can generate dyes of nearly every color.

Such an expanded palette of dyes could help researchers better illuminate the inner workings of cells, said Luke Lavis, PhD, of the Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Virginia.

Dr Lavis and his colleagues used their new dyes to light up cell nuclei, label living brain tissue from fruit fly larvae, and highlight visual cortex neurons in mice that had tiny glass windows fitted into their skulls.

The team detailed their work in Nature Methods.

Dr Lavis noted that scientists used to concoct different dyes mostly by trial and error.

“Now, we’ve figured out the rules, and we can make almost any color,” he said.

Dr Lavis’s team focused their research on rhodamines because they’re especially bright and cell-permeable.

Chemists had been working with rhodamines for more than 100 years but created only a few dozen colors. Most were similar shades ranging from green to orange.

That’s because, until recently, making new rhodamines wasn’t easy. Scientists still used techniques from the earliest days of chemistry, boiling chemical ingredients in sulfuric acid. This forces the molecules to link together in a condensation reaction.

Mixing in different building blocks could yield new and unusual dyes, but ingredients had to be tough enough to survive the boiling acid bath. This didn’t leave a lot of options.

In 2011, Dr Lavis’s team developed a new way to tinker with rhodamines’ structure, under milder conditions. Using a reaction sparked by the metal palladium, the scientists could skip the acid step and construct dyes with more complicated building blocks than had been used before.

Four years later, the team revealed the Janelia Fluor dyes. The secret behind these dyes is a tiny, square-shaped appendage called an azetidine ring.

The scientists found that incorporating 4-membered azetidine rings into classic fluorophore structures elicited “substantial increases in brightness and photostability.” In fact, the Janelia Fluor dyes are up to 50 times brighter than other dyes.

Now, Dr Lavis’s group has figured out how to fine-tune their fluorescent dyes by tweaking rhodamines’ structure even further. The team showed that incorporating 3-substituted azetidine groups allowed them to tune spectral and chemical properties with “unprecedented precision.”

The dyes can be synthesized in a single step with inexpensive ingredients. The low cost has allowed Dr Lavis and his colleagues to share their work, shipping thousands of vials to hundreds of labs around the world.

A 66-year-old man with a history of hypertension and type 2 diabetes is hospitalized for palpitations and dizziness and is diagnosed with atrial fibrillation (A-fib). His heart rate is successfully regulated with a ß-blocker. He has a CHA₂DS₂-VASc score of 3, making him a candidate for anticoagulation. Which agent should you start?

Thromboembolism in patients with A-fib often results in stroke and death, but appropriate use of antithrombotic therapy can reduce risk. Evidence-based guidelines recommend that patients with A-fib at intermediate or high risk for stroke (CHADS₂ score ≥ 2, or prior history of cardioembolic stroke or transient ischemic attack) receive antithrombotic therapy with oral anticoagulation, rather than receive no therapy or therapy with antiplatelets.^2,3

The American College of Chest Physicians also recommends use of the direct oral anticoagulant (DOAC) dabigatran instead of warfarin for those patients with nonvalvular A-fib with an estimated glomerular filtration rate ≥ 15 mL/min/1.73 m².³

A meta-analysis of large randomized controlled trials (RCTs) investigated individual DOACs: dabigatran (a direct thrombin inhibitor) and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. The results revealed similar or lower rates of ischemic stroke and major bleeding (except gastrointestinal bleeds; relative risk, 1.25) when compared with warfarin (at an international normalized ratio [INR] goal of 2-3).⁴ In addition, three separate meta-analyses that pooled results from large RCTs involving dabigatran, apixaban, and rivaroxaban also concluded that these medications significantly reduced incidence of embolic stroke and risk for major bleeds and hemorrhagic stroke, compared with warfarin.^5-7

However, less is known about the comparative effectiveness and safety of the ­DOACs when they are used in clinical practice, and it is not clear which, if any, of these agents is superior to others. Moreover, only about half of the patients in the United States with A-fib who are eligible to take DOACs are currently managed with them.⁸

STUDY SUMMARY

Different DOACs, different benefits

This large cohort study used data from three Danish national databases to assess the effectiveness of three DOACs compared with warfarin. The nearly 62,000 patients had been recently diagnosed with A-fib without valvular disease or venous thromboembolism. Subjects were prescribed either standard doses of dabigatran (150 bid; N = 12,701), rivaroxaban (20 mg/d; N = 7,192), or apixaban (5 mg bid; N = 6,349) or dose-adjusted warfarin to an INR goal of 2 to 3 (N = 35,436). Patients were followed for an average of 1.9 years.

Ischemic stroke, systemic emboli. In the first year of observation, there were 1,702 reports of ischemic stroke or systemic emboli. The incidence of ischemic stroke or systemic embolism was the same or better for each of the three DOAC treatments than for warfarin (2.9-3.9 vs 3.3 events per 100 person-years, respectively). Ischemic stroke or systemic emboli events occurred less frequently in the rivaroxaban group than in the warfarin group at one year (hazard ratio [HR], 0.83) and after 2.5 years (HR, 0.80). The rates of ischemic stroke and systemic emboli for both apixaban and dabigatran were not significantly different than that for warfarin at either end-point.

Bleeding events (defined as intracranial, major gastrointestinal, and traumatic intracranial) were lower in the apixaban group (HR, 0.63) and dabigatran group (HR, 0.61) than in the warfarin group at one year. Significant reductions remained after 2.5 years. There was no difference in bleeding events between rivaroxaban and warfarin.

Risk for death. Compared with warfarin, the risk for death after one year of treatment was lower in the apixaban (HR, 0.65) and dabigatran (HR, 0.63) groups, and there was no significant difference in the rivaroxaban group (HR, 0.92).

WHAT’S NEW

No agent “has it all,” but DOACs have advantages

This comparative effectiveness and safety analysis reveals that all of the DOACs are at least as effective as warfarin in preventing ischemic stroke and systemic emboli, that rivaroxaban may be more effective, and that apixaban and dabigatran have a lower risk for bleeding than warfarin.

CAVEATS

Lacking INR data

This study was a nonrandomized cohort trial. And, while propensity weighting helps, the researchers were unable to completely control for underlying risk factors or unknown confounders.

INR data for patients on warfarin were not provided, so it is not clear how often patients were out of therapeutic range, which could affect the stroke and bleeding results in the warfarin group. This, however, is seen with routine use of warfarin. This study reflects the challenge of maintaining patients in warfarin’s narrow therapeutic range.

CHALLENGES TO IMPLEMENTATION

It comes down to cost

Cost could be a barrier, as health insurance coverage for DOACs varies. Patients with high-deductible health insurance plans, or who find themselves in the Medicare “donut hole,” may be at a particular disadvantage.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[8]:518-519).

A 66-year-old man with a history of hypertension and type 2 diabetes is hospitalized for palpitations and dizziness and is diagnosed with atrial fibrillation (A-fib). His heart rate is successfully regulated with a ß-blocker. He has a CHA₂DS₂-VASc score of 3, making him a candidate for anticoagulation. Which agent should you start?

Thromboembolism in patients with A-fib often results in stroke and death, but appropriate use of antithrombotic therapy can reduce risk. Evidence-based guidelines recommend that patients with A-fib at intermediate or high risk for stroke (CHADS₂ score ≥ 2, or prior history of cardioembolic stroke or transient ischemic attack) receive antithrombotic therapy with oral anticoagulation, rather than receive no therapy or therapy with antiplatelets.^2,3

The American College of Chest Physicians also recommends use of the direct oral anticoagulant (DOAC) dabigatran instead of warfarin for those patients with nonvalvular A-fib with an estimated glomerular filtration rate ≥ 15 mL/min/1.73 m².³

A meta-analysis of large randomized controlled trials (RCTs) investigated individual DOACs: dabigatran (a direct thrombin inhibitor) and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. The results revealed similar or lower rates of ischemic stroke and major bleeding (except gastrointestinal bleeds; relative risk, 1.25) when compared with warfarin (at an international normalized ratio [INR] goal of 2-3).⁴ In addition, three separate meta-analyses that pooled results from large RCTs involving dabigatran, apixaban, and rivaroxaban also concluded that these medications significantly reduced incidence of embolic stroke and risk for major bleeds and hemorrhagic stroke, compared with warfarin.^5-7

However, less is known about the comparative effectiveness and safety of the ­DOACs when they are used in clinical practice, and it is not clear which, if any, of these agents is superior to others. Moreover, only about half of the patients in the United States with A-fib who are eligible to take DOACs are currently managed with them.⁸

STUDY SUMMARY

Different DOACs, different benefits

This large cohort study used data from three Danish national databases to assess the effectiveness of three DOACs compared with warfarin. The nearly 62,000 patients had been recently diagnosed with A-fib without valvular disease or venous thromboembolism. Subjects were prescribed either standard doses of dabigatran (150 bid; N = 12,701), rivaroxaban (20 mg/d; N = 7,192), or apixaban (5 mg bid; N = 6,349) or dose-adjusted warfarin to an INR goal of 2 to 3 (N = 35,436). Patients were followed for an average of 1.9 years.

Ischemic stroke, systemic emboli. In the first year of observation, there were 1,702 reports of ischemic stroke or systemic emboli. The incidence of ischemic stroke or systemic embolism was the same or better for each of the three DOAC treatments than for warfarin (2.9-3.9 vs 3.3 events per 100 person-years, respectively). Ischemic stroke or systemic emboli events occurred less frequently in the rivaroxaban group than in the warfarin group at one year (hazard ratio [HR], 0.83) and after 2.5 years (HR, 0.80). The rates of ischemic stroke and systemic emboli for both apixaban and dabigatran were not significantly different than that for warfarin at either end-point.

Bleeding events (defined as intracranial, major gastrointestinal, and traumatic intracranial) were lower in the apixaban group (HR, 0.63) and dabigatran group (HR, 0.61) than in the warfarin group at one year. Significant reductions remained after 2.5 years. There was no difference in bleeding events between rivaroxaban and warfarin.

Risk for death. Compared with warfarin, the risk for death after one year of treatment was lower in the apixaban (HR, 0.65) and dabigatran (HR, 0.63) groups, and there was no significant difference in the rivaroxaban group (HR, 0.92).

WHAT’S NEW

No agent “has it all,” but DOACs have advantages

This comparative effectiveness and safety analysis reveals that all of the DOACs are at least as effective as warfarin in preventing ischemic stroke and systemic emboli, that rivaroxaban may be more effective, and that apixaban and dabigatran have a lower risk for bleeding than warfarin.

CAVEATS

Lacking INR data

This study was a nonrandomized cohort trial. And, while propensity weighting helps, the researchers were unable to completely control for underlying risk factors or unknown confounders.

INR data for patients on warfarin were not provided, so it is not clear how often patients were out of therapeutic range, which could affect the stroke and bleeding results in the warfarin group. This, however, is seen with routine use of warfarin. This study reflects the challenge of maintaining patients in warfarin’s narrow therapeutic range.

CHALLENGES TO IMPLEMENTATION

It comes down to cost

Cost could be a barrier, as health insurance coverage for DOACs varies. Patients with high-deductible health insurance plans, or who find themselves in the Medicare “donut hole,” may be at a particular disadvantage.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[8]:518-519).

A 66-year-old man with a history of hypertension and type 2 diabetes is hospitalized for palpitations and dizziness and is diagnosed with atrial fibrillation (A-fib). His heart rate is successfully regulated with a ß-blocker. He has a CHA₂DS₂-VASc score of 3, making him a candidate for anticoagulation. Which agent should you start?

Thromboembolism in patients with A-fib often results in stroke and death, but appropriate use of antithrombotic therapy can reduce risk. Evidence-based guidelines recommend that patients with A-fib at intermediate or high risk for stroke (CHADS₂ score ≥ 2, or prior history of cardioembolic stroke or transient ischemic attack) receive antithrombotic therapy with oral anticoagulation, rather than receive no therapy or therapy with antiplatelets.^2,3

The American College of Chest Physicians also recommends use of the direct oral anticoagulant (DOAC) dabigatran instead of warfarin for those patients with nonvalvular A-fib with an estimated glomerular filtration rate ≥ 15 mL/min/1.73 m².³

A meta-analysis of large randomized controlled trials (RCTs) investigated individual DOACs: dabigatran (a direct thrombin inhibitor) and the factor Xa inhibitors rivaroxaban, apixaban, and edoxaban. The results revealed similar or lower rates of ischemic stroke and major bleeding (except gastrointestinal bleeds; relative risk, 1.25) when compared with warfarin (at an international normalized ratio [INR] goal of 2-3).⁴ In addition, three separate meta-analyses that pooled results from large RCTs involving dabigatran, apixaban, and rivaroxaban also concluded that these medications significantly reduced incidence of embolic stroke and risk for major bleeds and hemorrhagic stroke, compared with warfarin.^5-7

However, less is known about the comparative effectiveness and safety of the ­DOACs when they are used in clinical practice, and it is not clear which, if any, of these agents is superior to others. Moreover, only about half of the patients in the United States with A-fib who are eligible to take DOACs are currently managed with them.⁸

STUDY SUMMARY

Different DOACs, different benefits

This large cohort study used data from three Danish national databases to assess the effectiveness of three DOACs compared with warfarin. The nearly 62,000 patients had been recently diagnosed with A-fib without valvular disease or venous thromboembolism. Subjects were prescribed either standard doses of dabigatran (150 bid; N = 12,701), rivaroxaban (20 mg/d; N = 7,192), or apixaban (5 mg bid; N = 6,349) or dose-adjusted warfarin to an INR goal of 2 to 3 (N = 35,436). Patients were followed for an average of 1.9 years.

Ischemic stroke, systemic emboli. In the first year of observation, there were 1,702 reports of ischemic stroke or systemic emboli. The incidence of ischemic stroke or systemic embolism was the same or better for each of the three DOAC treatments than for warfarin (2.9-3.9 vs 3.3 events per 100 person-years, respectively). Ischemic stroke or systemic emboli events occurred less frequently in the rivaroxaban group than in the warfarin group at one year (hazard ratio [HR], 0.83) and after 2.5 years (HR, 0.80). The rates of ischemic stroke and systemic emboli for both apixaban and dabigatran were not significantly different than that for warfarin at either end-point.

Bleeding events (defined as intracranial, major gastrointestinal, and traumatic intracranial) were lower in the apixaban group (HR, 0.63) and dabigatran group (HR, 0.61) than in the warfarin group at one year. Significant reductions remained after 2.5 years. There was no difference in bleeding events between rivaroxaban and warfarin.

Risk for death. Compared with warfarin, the risk for death after one year of treatment was lower in the apixaban (HR, 0.65) and dabigatran (HR, 0.63) groups, and there was no significant difference in the rivaroxaban group (HR, 0.92).

WHAT’S NEW

No agent “has it all,” but DOACs have advantages

This comparative effectiveness and safety analysis reveals that all of the DOACs are at least as effective as warfarin in preventing ischemic stroke and systemic emboli, that rivaroxaban may be more effective, and that apixaban and dabigatran have a lower risk for bleeding than warfarin.

CAVEATS

Lacking INR data

This study was a nonrandomized cohort trial. And, while propensity weighting helps, the researchers were unable to completely control for underlying risk factors or unknown confounders.

INR data for patients on warfarin were not provided, so it is not clear how often patients were out of therapeutic range, which could affect the stroke and bleeding results in the warfarin group. This, however, is seen with routine use of warfarin. This study reflects the challenge of maintaining patients in warfarin’s narrow therapeutic range.

CHALLENGES TO IMPLEMENTATION

It comes down to cost

Cost could be a barrier, as health insurance coverage for DOACs varies. Patients with high-deductible health insurance plans, or who find themselves in the Medicare “donut hole,” may be at a particular disadvantage.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

Copyright © 2017. The Family Physicians Inquiries Network. All rights reserved.

Reprinted with permission from the Family Physicians Inquiries Network and The Journal of Family Practice (2017;66[8]:518-519).

Purdue University/Aniket Pal

Researchers say they have developed self-powered, paper-based electrochemical devices (SPEDs) that can provide sensitive diagnostics in low-resource settings and at the point of care.

The SPEDs can detect biomarkers in the blood and identify conditions such as anemia by performing electrochemical analyses that are powered by the user’s touch.

The devices produce color-coded test results that are easy for non-experts to understand.

“You could consider this a portable laboratory that is just completely made out of paper, is inexpensive, and can be disposed of through incineration,” said Ramses V. Martinez, PhD, of Purdue University in West Lafayette, Indiana.

“We hope these devices will serve untrained people located in remote villages or military bases to test for a variety of diseases without requiring any source of electricity, clean water, or additional equipment.”

Dr Martinez and his colleagues developed the SPEDs and described them in a paper published in Advanced Materials Technologies.

SPED testing is initiated by placing a pinprick of blood in a circular feature on the device, which is less than 2-inches square. The SPEDs also contain “self-pipetting test zones” that can be dipped into a sample instead of using a finger-prick test.

The top layer of each SPED is made of untreated cellulose paper with patterned hydrophobic domains that define channels that wick up blood samples for testing. These microfluidic channels allow for assays that change color to indicate specific test results.

The researchers also created a machine-vision diagnostic application to identify and quantify each of these colorimetric tests from a digital image of the SPED, perhaps taken with a cell phone. This provides rapid results for the user and allows for consultation with a remote expert if necessary.

The bottom layer of the SPED is a triboelectric generator (TEG), which generates the electric current necessary to run the diagnostic test by rubbing or pressing it.

An inexpensive, hand-held device called a potentiostat can be plugged into the SPED to automate the diagnostic tests so they can be performed by untrained users. The battery powering the potentiostat can be recharged using the TEG built into the SPEDs.

“To our knowledge, this work reports the first self-powered, paper-based devices capable of performing rapid, accurate, and sensitive electrochemical assays in combination with a low-cost, portable potentiostat that can be recharged using a paper-based TEG,” Dr Martinez said.

SPEDs can perform multiplexed analyses, enabling the detection of various targets for a range of point-of-care testing applications. In addition, the devices are compatible with mass-printing technologies, such as roll-to-roll printing or spray deposition. And the SPEDs can be used to power other electronic devices to facilitate telemedicine applications in resource-limited settings.

Dr Martinez and his colleagues used the SPEDs to detect biomarkers such as glucose, uric acid and L-lactate, ketones, and white blood cells, which indicate factors related to liver and kidney function, malnutrition, and anemia.

The researchers said future versions of the technology will contain several additional layers for more complex assays to detect diseases such as malaria, dengue fever, yellow fever, hepatitis, and HIV.

Purdue University/Aniket Pal

Researchers say they have developed self-powered, paper-based electrochemical devices (SPEDs) that can provide sensitive diagnostics in low-resource settings and at the point of care.

The SPEDs can detect biomarkers in the blood and identify conditions such as anemia by performing electrochemical analyses that are powered by the user’s touch.

The devices produce color-coded test results that are easy for non-experts to understand.

“You could consider this a portable laboratory that is just completely made out of paper, is inexpensive, and can be disposed of through incineration,” said Ramses V. Martinez, PhD, of Purdue University in West Lafayette, Indiana.

“We hope these devices will serve untrained people located in remote villages or military bases to test for a variety of diseases without requiring any source of electricity, clean water, or additional equipment.”

Dr Martinez and his colleagues developed the SPEDs and described them in a paper published in Advanced Materials Technologies.

SPED testing is initiated by placing a pinprick of blood in a circular feature on the device, which is less than 2-inches square. The SPEDs also contain “self-pipetting test zones” that can be dipped into a sample instead of using a finger-prick test.

The top layer of each SPED is made of untreated cellulose paper with patterned hydrophobic domains that define channels that wick up blood samples for testing. These microfluidic channels allow for assays that change color to indicate specific test results.

The researchers also created a machine-vision diagnostic application to identify and quantify each of these colorimetric tests from a digital image of the SPED, perhaps taken with a cell phone. This provides rapid results for the user and allows for consultation with a remote expert if necessary.

The bottom layer of the SPED is a triboelectric generator (TEG), which generates the electric current necessary to run the diagnostic test by rubbing or pressing it.

An inexpensive, hand-held device called a potentiostat can be plugged into the SPED to automate the diagnostic tests so they can be performed by untrained users. The battery powering the potentiostat can be recharged using the TEG built into the SPEDs.

“To our knowledge, this work reports the first self-powered, paper-based devices capable of performing rapid, accurate, and sensitive electrochemical assays in combination with a low-cost, portable potentiostat that can be recharged using a paper-based TEG,” Dr Martinez said.

SPEDs can perform multiplexed analyses, enabling the detection of various targets for a range of point-of-care testing applications. In addition, the devices are compatible with mass-printing technologies, such as roll-to-roll printing or spray deposition. And the SPEDs can be used to power other electronic devices to facilitate telemedicine applications in resource-limited settings.

Dr Martinez and his colleagues used the SPEDs to detect biomarkers such as glucose, uric acid and L-lactate, ketones, and white blood cells, which indicate factors related to liver and kidney function, malnutrition, and anemia.

The researchers said future versions of the technology will contain several additional layers for more complex assays to detect diseases such as malaria, dengue fever, yellow fever, hepatitis, and HIV.

Purdue University/Aniket Pal

Researchers say they have developed self-powered, paper-based electrochemical devices (SPEDs) that can provide sensitive diagnostics in low-resource settings and at the point of care.

The SPEDs can detect biomarkers in the blood and identify conditions such as anemia by performing electrochemical analyses that are powered by the user’s touch.

The devices produce color-coded test results that are easy for non-experts to understand.

“You could consider this a portable laboratory that is just completely made out of paper, is inexpensive, and can be disposed of through incineration,” said Ramses V. Martinez, PhD, of Purdue University in West Lafayette, Indiana.

“We hope these devices will serve untrained people located in remote villages or military bases to test for a variety of diseases without requiring any source of electricity, clean water, or additional equipment.”

Dr Martinez and his colleagues developed the SPEDs and described them in a paper published in Advanced Materials Technologies.

SPED testing is initiated by placing a pinprick of blood in a circular feature on the device, which is less than 2-inches square. The SPEDs also contain “self-pipetting test zones” that can be dipped into a sample instead of using a finger-prick test.

The top layer of each SPED is made of untreated cellulose paper with patterned hydrophobic domains that define channels that wick up blood samples for testing. These microfluidic channels allow for assays that change color to indicate specific test results.

The researchers also created a machine-vision diagnostic application to identify and quantify each of these colorimetric tests from a digital image of the SPED, perhaps taken with a cell phone. This provides rapid results for the user and allows for consultation with a remote expert if necessary.

The bottom layer of the SPED is a triboelectric generator (TEG), which generates the electric current necessary to run the diagnostic test by rubbing or pressing it.

An inexpensive, hand-held device called a potentiostat can be plugged into the SPED to automate the diagnostic tests so they can be performed by untrained users. The battery powering the potentiostat can be recharged using the TEG built into the SPEDs.

“To our knowledge, this work reports the first self-powered, paper-based devices capable of performing rapid, accurate, and sensitive electrochemical assays in combination with a low-cost, portable potentiostat that can be recharged using a paper-based TEG,” Dr Martinez said.

SPEDs can perform multiplexed analyses, enabling the detection of various targets for a range of point-of-care testing applications. In addition, the devices are compatible with mass-printing technologies, such as roll-to-roll printing or spray deposition. And the SPEDs can be used to power other electronic devices to facilitate telemedicine applications in resource-limited settings.

Dr Martinez and his colleagues used the SPEDs to detect biomarkers such as glucose, uric acid and L-lactate, ketones, and white blood cells, which indicate factors related to liver and kidney function, malnutrition, and anemia.

The researchers said future versions of the technology will contain several additional layers for more complex assays to detect diseases such as malaria, dengue fever, yellow fever, hepatitis, and HIV.

Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experiences on a monthly basis.

I am a third-year medical student at the University of California, San Diego, as well as a recipient of the SHM Longitudinal Scholar Grant. Ultimately, I intend to pursue a career in academic medicine as a clinician-scientist, where I hope to bridge my interests in neuroscience, research, and clinical medicine.

Victor Ekuta is a third-year medical student at the University of California, San Diego.

Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experiences on a monthly basis.

I am a third-year medical student at the University of California, San Diego, as well as a recipient of the SHM Longitudinal Scholar Grant. Ultimately, I intend to pursue a career in academic medicine as a clinician-scientist, where I hope to bridge my interests in neuroscience, research, and clinical medicine.

Victor Ekuta is a third-year medical student at the University of California, San Diego.

Editor’s note: The Society of Hospital Medicine’s (SHM’s) Physician in Training Committee launched a scholarship program in 2015 for medical students to help transform health care and revolutionize patient care. The program has been expanded for the 2017-2018 year, offering two options for students to receive funding and engage in scholarly work during their first, second, and third years of medical school. As a part of the longitudinal (18-month) program, recipients are required to write about their experiences on a monthly basis.

I am a third-year medical student at the University of California, San Diego, as well as a recipient of the SHM Longitudinal Scholar Grant. Ultimately, I intend to pursue a career in academic medicine as a clinician-scientist, where I hope to bridge my interests in neuroscience, research, and clinical medicine.

Victor Ekuta is a third-year medical student at the University of California, San Diego.

Clinical Question: Can the HEART score risk stratify emergency department patients with chest pain?

Background: Many patients with chest pain are subjected to unnecessary admission and testing. The HEART (History, Electrocardiogram, Age, Risk factors, and initial Troponin) score can accurately predict outcomes in chest pain patients, though it has undergone limited evaluation in real world settings.

Dr. Troy is assistant professor in the University of Kentucky division of hospital medicine.

Clinical Question: Can the HEART score risk stratify emergency department patients with chest pain?

Background: Many patients with chest pain are subjected to unnecessary admission and testing. The HEART (History, Electrocardiogram, Age, Risk factors, and initial Troponin) score can accurately predict outcomes in chest pain patients, though it has undergone limited evaluation in real world settings.

Dr. Troy is assistant professor in the University of Kentucky division of hospital medicine.

Clinical Question: Can the HEART score risk stratify emergency department patients with chest pain?

Background: Many patients with chest pain are subjected to unnecessary admission and testing. The HEART (History, Electrocardiogram, Age, Risk factors, and initial Troponin) score can accurately predict outcomes in chest pain patients, though it has undergone limited evaluation in real world settings.

Dr. Troy is assistant professor in the University of Kentucky division of hospital medicine.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved use of gemtuzumab ozogamicin (GO, Mylotarg), a treatment that was initially approved by the agency in 2000 but later pulled from the US market.

GO is an antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.

GO is now approved to treat adults with newly diagnosed, CD33-positive acute myeloid leukemia (AML) and patients age 2 and older with CD33-positive, relapsed or refractory AML.

GO can be given alone or in combination with daunorubicin and cytarabine.

The prescribing information for GO includes a boxed warning detailing the risk of hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome, associated with GO.

GO originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development, and commercialization activities for this molecule.

Market withdrawal and subsequent trials

GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.

In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.

This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.

In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.

Because of the unmet need for effective treatments in AML, investigators expressed an interest in evaluating different doses and schedules of GO.

These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of GO.

The trials—ALFA-0701, AML-19, and MyloFrance-1—supported the new approval of GO. Updated data from these trials are included in the prescribing information, which is available for download at www.mylotarg.com.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved use of gemtuzumab ozogamicin (GO, Mylotarg), a treatment that was initially approved by the agency in 2000 but later pulled from the US market.

GO is an antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.

GO is now approved to treat adults with newly diagnosed, CD33-positive acute myeloid leukemia (AML) and patients age 2 and older with CD33-positive, relapsed or refractory AML.

GO can be given alone or in combination with daunorubicin and cytarabine.

The prescribing information for GO includes a boxed warning detailing the risk of hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome, associated with GO.

GO originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development, and commercialization activities for this molecule.

Market withdrawal and subsequent trials

GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.

In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.

This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.

In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.

Because of the unmet need for effective treatments in AML, investigators expressed an interest in evaluating different doses and schedules of GO.

These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of GO.

The trials—ALFA-0701, AML-19, and MyloFrance-1—supported the new approval of GO. Updated data from these trials are included in the prescribing information, which is available for download at www.mylotarg.com.

Photo by Bill Branson

The US Food and Drug Administration (FDA) has approved use of gemtuzumab ozogamicin (GO, Mylotarg), a treatment that was initially approved by the agency in 2000 but later pulled from the US market.

GO is an antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.

GO is now approved to treat adults with newly diagnosed, CD33-positive acute myeloid leukemia (AML) and patients age 2 and older with CD33-positive, relapsed or refractory AML.

GO can be given alone or in combination with daunorubicin and cytarabine.

The prescribing information for GO includes a boxed warning detailing the risk of hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome, associated with GO.

GO originates from a collaboration between Pfizer and Celltech, now UCB. Pfizer has sole responsibility for all manufacturing, clinical development, and commercialization activities for this molecule.

Market withdrawal and subsequent trials

GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.

In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.

This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.

In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.

Because of the unmet need for effective treatments in AML, investigators expressed an interest in evaluating different doses and schedules of GO.

These independent investigators, with Pfizer’s support, conducted clinical trials that yielded more information on the efficacy and safety of GO.

The trials—ALFA-0701, AML-19, and MyloFrance-1—supported the new approval of GO. Updated data from these trials are included in the prescribing information, which is available for download at www.mylotarg.com.

Since my high school days, I have used some form of artificial sweetener in lieu of sugar. Long believing that sugar avoidance was the key to weight maintenance, I didn’t give much thought to the published ill effects of sugar substitutes—after all, I wasn’t a mouse, and I wasn’t consuming mass doses. Did the artificial sweeteners assist in controlling my weight? Quite honestly, I doubt it—but I was so used to being “sugar free” that I was habituated to using these products.

Several years ago at a luncheon, I was reaching for a packet of artificial sweetener to pour into my iced tea when an NP friend stopped me. She and her husband (a pharmacist) had sworn off these products after noting that he was having issues with his cognition and experiencing increased irritability. With no obvious cause for these symptoms, they investigated his diet. He had, over the previous year, increased his use of aspartame. They found research supporting an association between aspartame and changes in behavior and cognition. When he stopped using the product, they both noticed a return to his former jovial, intellectual self. I acknowledged their research conclusion as an “n = 1” but gave it no further credence.

More recently, friends who had adopted an “all-natural” diet chastised me for drinking sugar-free seltzer. I had switched years ago from diet sodas to this beverage as my primary source of hydration. What could be wrong? It had zero calories, no sodium, and no sugar. Ah, but it contained aspartame! Since switching to a food plan without aspartame, my friends had observed that they were feeling better and more alert. Hmm, sounded familiar … maybe there was something to these claims after all. I did a little research of my own, and was I surprised!

On the exterior, aspartame is a highly studied food additive with decades of research demonstrating its safety for human consumption.¹ But what exactly happens when this sweetener is ingested? First, aspartame breaks down into amino acids and methanol (ie, wood alcohol). The methanol continues to break down into formaldehyde and formic acid, a substance commonly found in bee and ant venom (see Figure). And if that weren’t enough, a potential brain tumor agent (aspartylphenylalanine diketopiperazine) is also a residual byproduct.^2,3 As you might expect, these components and byproducts come with varying adverse effects and potential health risks.

The majority of artificially sweetened beverages (ASBs) contain aspartame. As early as 1984—a mere six months after aspartame was approved for use in soft drinks—the FDA, with the assistance of the CDC, undertook an investigation of consumer complaints related to its use. The research team interviewed 517 complainants; 346 (67%) reported neurologic/behavioral symptoms, including headache, dizziness, and mood alteration.⁴ Despite that statistic, however, the researchers reported no evidence for the existence of serious, widespread, adverse health consequences resulting from aspartame consumption.⁴

Reading these reports reminded me of my friends’ comments and strongly suggested to me that soft drinks containing aspartame may be hard on the brain. Further to this point, a recent study found that ASB consumption is associated with an increased risk for stroke and dementia.⁵

Additional studies—including evaluations of possible associations between aspartame and headaches, seizures, behavior, cognition, and mood, as well as allergic-type reactions and use by potentially sensitive subpopulations—have been conducted. The verdict? Scientists maintain that aspartame is safe and that there are no unresolved questions regarding its safety when used as intended.⁶ Some researchers question the validity of the link between ASB consumption and negative health consequences, suggesting that individuals in worse health consume diet beverages in an effort to slow health deterioration or to lose weight.⁷ Yet, the debate about the effects of aspartame on our organs continues.

The number of epidemiologic studies that document strong associations between frequent ASB consumption and illness suggests that substituting or promoting artificial sweeteners as “healthy alternatives” to sugar may not be advisable.⁸ In fact, the most recent studies indicate that artificial sweeteners—the very compounds marketed to assist with weight control—can lead to weight gain, as they trick our brains into craving high-calorie foods. Moreover, ASB consumption is associated with a 21% increased risk for type 2 diabetes.⁹ Azad and colleagues found that evidence does not clearly support the use of nonnutritive sweeteners for weight management; they recommend using caution with these products until the long-term risks and benefits are fully understood.⁷

Is satisfying your sweet tooth with sugar alternatives worth the potential risk? Most of the studies conducted to support or refute aspartame-related health concerns prove correlation, not causality. A purist might point out that many of the studies have limitations that can lead to faulty conclusions. Be that as it may, it still gives one pause.

Small doses of aspartame each day might not be a tipping point toward the documented health complaints, but the consistent concerns about its effects were enough for me to make the switch to plain water, and sugar for my coffee. I do believe that Mary Poppins was correct—a spoonful of sugar does help—and I, for one, am following her lead.

What do you think? Are these concerns unfounded, or are we sweetening our road to poor health? Share your thoughts with me at [email protected]. 

Since my high school days, I have used some form of artificial sweetener in lieu of sugar. Long believing that sugar avoidance was the key to weight maintenance, I didn’t give much thought to the published ill effects of sugar substitutes—after all, I wasn’t a mouse, and I wasn’t consuming mass doses. Did the artificial sweeteners assist in controlling my weight? Quite honestly, I doubt it—but I was so used to being “sugar free” that I was habituated to using these products.

Several years ago at a luncheon, I was reaching for a packet of artificial sweetener to pour into my iced tea when an NP friend stopped me. She and her husband (a pharmacist) had sworn off these products after noting that he was having issues with his cognition and experiencing increased irritability. With no obvious cause for these symptoms, they investigated his diet. He had, over the previous year, increased his use of aspartame. They found research supporting an association between aspartame and changes in behavior and cognition. When he stopped using the product, they both noticed a return to his former jovial, intellectual self. I acknowledged their research conclusion as an “n = 1” but gave it no further credence.

More recently, friends who had adopted an “all-natural” diet chastised me for drinking sugar-free seltzer. I had switched years ago from diet sodas to this beverage as my primary source of hydration. What could be wrong? It had zero calories, no sodium, and no sugar. Ah, but it contained aspartame! Since switching to a food plan without aspartame, my friends had observed that they were feeling better and more alert. Hmm, sounded familiar … maybe there was something to these claims after all. I did a little research of my own, and was I surprised!

On the exterior, aspartame is a highly studied food additive with decades of research demonstrating its safety for human consumption.¹ But what exactly happens when this sweetener is ingested? First, aspartame breaks down into amino acids and methanol (ie, wood alcohol). The methanol continues to break down into formaldehyde and formic acid, a substance commonly found in bee and ant venom (see Figure). And if that weren’t enough, a potential brain tumor agent (aspartylphenylalanine diketopiperazine) is also a residual byproduct.^2,3 As you might expect, these components and byproducts come with varying adverse effects and potential health risks.

The majority of artificially sweetened beverages (ASBs) contain aspartame. As early as 1984—a mere six months after aspartame was approved for use in soft drinks—the FDA, with the assistance of the CDC, undertook an investigation of consumer complaints related to its use. The research team interviewed 517 complainants; 346 (67%) reported neurologic/behavioral symptoms, including headache, dizziness, and mood alteration.⁴ Despite that statistic, however, the researchers reported no evidence for the existence of serious, widespread, adverse health consequences resulting from aspartame consumption.⁴

Reading these reports reminded me of my friends’ comments and strongly suggested to me that soft drinks containing aspartame may be hard on the brain. Further to this point, a recent study found that ASB consumption is associated with an increased risk for stroke and dementia.⁵

Additional studies—including evaluations of possible associations between aspartame and headaches, seizures, behavior, cognition, and mood, as well as allergic-type reactions and use by potentially sensitive subpopulations—have been conducted. The verdict? Scientists maintain that aspartame is safe and that there are no unresolved questions regarding its safety when used as intended.⁶ Some researchers question the validity of the link between ASB consumption and negative health consequences, suggesting that individuals in worse health consume diet beverages in an effort to slow health deterioration or to lose weight.⁷ Yet, the debate about the effects of aspartame on our organs continues.

The number of epidemiologic studies that document strong associations between frequent ASB consumption and illness suggests that substituting or promoting artificial sweeteners as “healthy alternatives” to sugar may not be advisable.⁸ In fact, the most recent studies indicate that artificial sweeteners—the very compounds marketed to assist with weight control—can lead to weight gain, as they trick our brains into craving high-calorie foods. Moreover, ASB consumption is associated with a 21% increased risk for type 2 diabetes.⁹ Azad and colleagues found that evidence does not clearly support the use of nonnutritive sweeteners for weight management; they recommend using caution with these products until the long-term risks and benefits are fully understood.⁷

Is satisfying your sweet tooth with sugar alternatives worth the potential risk? Most of the studies conducted to support or refute aspartame-related health concerns prove correlation, not causality. A purist might point out that many of the studies have limitations that can lead to faulty conclusions. Be that as it may, it still gives one pause.

Small doses of aspartame each day might not be a tipping point toward the documented health complaints, but the consistent concerns about its effects were enough for me to make the switch to plain water, and sugar for my coffee. I do believe that Mary Poppins was correct—a spoonful of sugar does help—and I, for one, am following her lead.

What do you think? Are these concerns unfounded, or are we sweetening our road to poor health? Share your thoughts with me at [email protected]. 

Since my high school days, I have used some form of artificial sweetener in lieu of sugar. Long believing that sugar avoidance was the key to weight maintenance, I didn’t give much thought to the published ill effects of sugar substitutes—after all, I wasn’t a mouse, and I wasn’t consuming mass doses. Did the artificial sweeteners assist in controlling my weight? Quite honestly, I doubt it—but I was so used to being “sugar free” that I was habituated to using these products.

Several years ago at a luncheon, I was reaching for a packet of artificial sweetener to pour into my iced tea when an NP friend stopped me. She and her husband (a pharmacist) had sworn off these products after noting that he was having issues with his cognition and experiencing increased irritability. With no obvious cause for these symptoms, they investigated his diet. He had, over the previous year, increased his use of aspartame. They found research supporting an association between aspartame and changes in behavior and cognition. When he stopped using the product, they both noticed a return to his former jovial, intellectual self. I acknowledged their research conclusion as an “n = 1” but gave it no further credence.

More recently, friends who had adopted an “all-natural” diet chastised me for drinking sugar-free seltzer. I had switched years ago from diet sodas to this beverage as my primary source of hydration. What could be wrong? It had zero calories, no sodium, and no sugar. Ah, but it contained aspartame! Since switching to a food plan without aspartame, my friends had observed that they were feeling better and more alert. Hmm, sounded familiar … maybe there was something to these claims after all. I did a little research of my own, and was I surprised!

On the exterior, aspartame is a highly studied food additive with decades of research demonstrating its safety for human consumption.¹ But what exactly happens when this sweetener is ingested? First, aspartame breaks down into amino acids and methanol (ie, wood alcohol). The methanol continues to break down into formaldehyde and formic acid, a substance commonly found in bee and ant venom (see Figure). And if that weren’t enough, a potential brain tumor agent (aspartylphenylalanine diketopiperazine) is also a residual byproduct.^2,3 As you might expect, these components and byproducts come with varying adverse effects and potential health risks.

The majority of artificially sweetened beverages (ASBs) contain aspartame. As early as 1984—a mere six months after aspartame was approved for use in soft drinks—the FDA, with the assistance of the CDC, undertook an investigation of consumer complaints related to its use. The research team interviewed 517 complainants; 346 (67%) reported neurologic/behavioral symptoms, including headache, dizziness, and mood alteration.⁴ Despite that statistic, however, the researchers reported no evidence for the existence of serious, widespread, adverse health consequences resulting from aspartame consumption.⁴

Reading these reports reminded me of my friends’ comments and strongly suggested to me that soft drinks containing aspartame may be hard on the brain. Further to this point, a recent study found that ASB consumption is associated with an increased risk for stroke and dementia.⁵

Additional studies—including evaluations of possible associations between aspartame and headaches, seizures, behavior, cognition, and mood, as well as allergic-type reactions and use by potentially sensitive subpopulations—have been conducted. The verdict? Scientists maintain that aspartame is safe and that there are no unresolved questions regarding its safety when used as intended.⁶ Some researchers question the validity of the link between ASB consumption and negative health consequences, suggesting that individuals in worse health consume diet beverages in an effort to slow health deterioration or to lose weight.⁷ Yet, the debate about the effects of aspartame on our organs continues.

The number of epidemiologic studies that document strong associations between frequent ASB consumption and illness suggests that substituting or promoting artificial sweeteners as “healthy alternatives” to sugar may not be advisable.⁸ In fact, the most recent studies indicate that artificial sweeteners—the very compounds marketed to assist with weight control—can lead to weight gain, as they trick our brains into craving high-calorie foods. Moreover, ASB consumption is associated with a 21% increased risk for type 2 diabetes.⁹ Azad and colleagues found that evidence does not clearly support the use of nonnutritive sweeteners for weight management; they recommend using caution with these products until the long-term risks and benefits are fully understood.⁷

Is satisfying your sweet tooth with sugar alternatives worth the potential risk? Most of the studies conducted to support or refute aspartame-related health concerns prove correlation, not causality. A purist might point out that many of the studies have limitations that can lead to faulty conclusions. Be that as it may, it still gives one pause.

Small doses of aspartame each day might not be a tipping point toward the documented health complaints, but the consistent concerns about its effects were enough for me to make the switch to plain water, and sugar for my coffee. I do believe that Mary Poppins was correct—a spoonful of sugar does help—and I, for one, am following her lead.

What do you think? Are these concerns unfounded, or are we sweetening our road to poor health? Share your thoughts with me at [email protected].