Hormone therapy in postmenopausal women does not prevent heart disease but does increase the risk of stroke and blood clots, according to a recently updated Cochrane review.

“Our review findings provide strong evidence that treatment with hormone therapy in postmenopausal women for either primary or secondary prevention of cardiovascular disease events has little if any benefit overall, and causes an increase in the risk of stroke, or venous thromboembolic events,” reported Dr. Henry Boardman of the University of Oxford John Radcliffe Hospital, and his associates.

The researchers updated a review published in 2013 with data from an additional six randomized controlled trials. The total of 19 trials, involving 40,410 postmenopausal women, all compared orally-administered estrogen, with or without progestogen, to a placebo or no treatment for a minimum of 6 months (Cochrane Database Syst. Rev. 2015 March 10 [doi:10.1002/14651858.CD002229.pub4]).

The average age of the women in the studies, mostly from the United States, was older than 60 years, and the women received hormone therapy anywhere from 7 months to 10 years across the studies. The overall quality of the studies was “good” with a low risk of bias.

The sharp rise in cardiovascular disease rates in women after menopause had been hypothesized to be related to a decline in hormone levels that causes a higher androgen-to-estradiol ratio, and observational studies starting in the 1980s showed lower mortality rates and cardiovascular events in women receiving hormone therapy – previously called hormone replacement therapy – compared to those not receiving hormone therapy.

Two subsequent randomized controlled trials contradicted these observational findings, though, leading to further study. In this review, hormone therapy showed no risk reduction for all-cause mortality, cardiovascular death, nonfatal myocardial infarction, angina, or revascularization.

However, the overall risk of stroke for those receiving hormone therapy for both primary and secondary prevention was 24% higher than that of women receiving placebo treatment (relative risk 1.24), with an absolute risk of 6 additional strokes per 1,000 women.

Venous thromboembolic events occurred 92% more and pulmonary emboli occurred 81% more in the hormone treatment groups (RR 1.92 and 1.81, respectively), with increased absolute risks of 8 per 1,000 women and 4 per 1,000 women, respectively.

The researchers calculated the number needed to treat for an additional harm (NNTH) at 165 women for stroke, 118 for venous thromboembolism, and 242 for pulmonary embolism.

Further analysis revealed that the relative risks or protection hormone therapy conferred depended on how long after menopause women started treatment.

Mortality was reduced 30% and coronary heart disease was reduced 48% in women who began hormone therapy less than 10 years after menopause (RR 0.70 and RR 0.52, respectively); these women still faced a 74% increased risk of venous thromboembolism, but no increased risk of stroke.

Meanwhile, women who started hormone therapy more than 10 years after menopause had a 21% increased risk of stroke and a 96% increased risk of venous thromboembolism, but no reduced risk on overall death or coronary heart disease.

“It is worth noting that the benefit seen in survival and coronary heart disease for the group starting treatment less than 10 years after the menopause is from combining five trials all performed in primary prevention populations and all with quite long follow-up, ranging from 3.4 to 10.1 years,” the authors wrote.

These results may reflect the possibility of a time interaction, with coronary heart disease events occurring earlier in predisposed women, making it impossible to say whether short duration therapy is beneficial in this population or not, the researchers wrote .

Eighteen of the 19 trials included in the analysis reported the funding source. One study was exclusively funded by Wyeth-Ayerst. Two studies received partial funding from Novo-Nordisk Pharmaceutical, and one study was funded by the National Institutes of Health with support from Wyeth-Ayerst, Hoffman-LaRoche, Pharmacia, and Upjohn. Eight other studies used medication provided by various pharmaceutical companies.

Hormone therapy in postmenopausal women does not prevent heart disease but does increase the risk of stroke and blood clots, according to a recently updated Cochrane review.

“Our review findings provide strong evidence that treatment with hormone therapy in postmenopausal women for either primary or secondary prevention of cardiovascular disease events has little if any benefit overall, and causes an increase in the risk of stroke, or venous thromboembolic events,” reported Dr. Henry Boardman of the University of Oxford John Radcliffe Hospital, and his associates.

The researchers updated a review published in 2013 with data from an additional six randomized controlled trials. The total of 19 trials, involving 40,410 postmenopausal women, all compared orally-administered estrogen, with or without progestogen, to a placebo or no treatment for a minimum of 6 months (Cochrane Database Syst. Rev. 2015 March 10 [doi:10.1002/14651858.CD002229.pub4]).

The average age of the women in the studies, mostly from the United States, was older than 60 years, and the women received hormone therapy anywhere from 7 months to 10 years across the studies. The overall quality of the studies was “good” with a low risk of bias.

The sharp rise in cardiovascular disease rates in women after menopause had been hypothesized to be related to a decline in hormone levels that causes a higher androgen-to-estradiol ratio, and observational studies starting in the 1980s showed lower mortality rates and cardiovascular events in women receiving hormone therapy – previously called hormone replacement therapy – compared to those not receiving hormone therapy.

Two subsequent randomized controlled trials contradicted these observational findings, though, leading to further study. In this review, hormone therapy showed no risk reduction for all-cause mortality, cardiovascular death, nonfatal myocardial infarction, angina, or revascularization.

However, the overall risk of stroke for those receiving hormone therapy for both primary and secondary prevention was 24% higher than that of women receiving placebo treatment (relative risk 1.24), with an absolute risk of 6 additional strokes per 1,000 women.

Venous thromboembolic events occurred 92% more and pulmonary emboli occurred 81% more in the hormone treatment groups (RR 1.92 and 1.81, respectively), with increased absolute risks of 8 per 1,000 women and 4 per 1,000 women, respectively.

The researchers calculated the number needed to treat for an additional harm (NNTH) at 165 women for stroke, 118 for venous thromboembolism, and 242 for pulmonary embolism.

Further analysis revealed that the relative risks or protection hormone therapy conferred depended on how long after menopause women started treatment.

Mortality was reduced 30% and coronary heart disease was reduced 48% in women who began hormone therapy less than 10 years after menopause (RR 0.70 and RR 0.52, respectively); these women still faced a 74% increased risk of venous thromboembolism, but no increased risk of stroke.

Meanwhile, women who started hormone therapy more than 10 years after menopause had a 21% increased risk of stroke and a 96% increased risk of venous thromboembolism, but no reduced risk on overall death or coronary heart disease.

“It is worth noting that the benefit seen in survival and coronary heart disease for the group starting treatment less than 10 years after the menopause is from combining five trials all performed in primary prevention populations and all with quite long follow-up, ranging from 3.4 to 10.1 years,” the authors wrote.

These results may reflect the possibility of a time interaction, with coronary heart disease events occurring earlier in predisposed women, making it impossible to say whether short duration therapy is beneficial in this population or not, the researchers wrote .

Eighteen of the 19 trials included in the analysis reported the funding source. One study was exclusively funded by Wyeth-Ayerst. Two studies received partial funding from Novo-Nordisk Pharmaceutical, and one study was funded by the National Institutes of Health with support from Wyeth-Ayerst, Hoffman-LaRoche, Pharmacia, and Upjohn. Eight other studies used medication provided by various pharmaceutical companies.

Hormone therapy in postmenopausal women does not prevent heart disease but does increase the risk of stroke and blood clots, according to a recently updated Cochrane review.

“Our review findings provide strong evidence that treatment with hormone therapy in postmenopausal women for either primary or secondary prevention of cardiovascular disease events has little if any benefit overall, and causes an increase in the risk of stroke, or venous thromboembolic events,” reported Dr. Henry Boardman of the University of Oxford John Radcliffe Hospital, and his associates.

The researchers updated a review published in 2013 with data from an additional six randomized controlled trials. The total of 19 trials, involving 40,410 postmenopausal women, all compared orally-administered estrogen, with or without progestogen, to a placebo or no treatment for a minimum of 6 months (Cochrane Database Syst. Rev. 2015 March 10 [doi:10.1002/14651858.CD002229.pub4]).

The average age of the women in the studies, mostly from the United States, was older than 60 years, and the women received hormone therapy anywhere from 7 months to 10 years across the studies. The overall quality of the studies was “good” with a low risk of bias.

The sharp rise in cardiovascular disease rates in women after menopause had been hypothesized to be related to a decline in hormone levels that causes a higher androgen-to-estradiol ratio, and observational studies starting in the 1980s showed lower mortality rates and cardiovascular events in women receiving hormone therapy – previously called hormone replacement therapy – compared to those not receiving hormone therapy.

Two subsequent randomized controlled trials contradicted these observational findings, though, leading to further study. In this review, hormone therapy showed no risk reduction for all-cause mortality, cardiovascular death, nonfatal myocardial infarction, angina, or revascularization.

However, the overall risk of stroke for those receiving hormone therapy for both primary and secondary prevention was 24% higher than that of women receiving placebo treatment (relative risk 1.24), with an absolute risk of 6 additional strokes per 1,000 women.

Venous thromboembolic events occurred 92% more and pulmonary emboli occurred 81% more in the hormone treatment groups (RR 1.92 and 1.81, respectively), with increased absolute risks of 8 per 1,000 women and 4 per 1,000 women, respectively.

The researchers calculated the number needed to treat for an additional harm (NNTH) at 165 women for stroke, 118 for venous thromboembolism, and 242 for pulmonary embolism.

Further analysis revealed that the relative risks or protection hormone therapy conferred depended on how long after menopause women started treatment.

Mortality was reduced 30% and coronary heart disease was reduced 48% in women who began hormone therapy less than 10 years after menopause (RR 0.70 and RR 0.52, respectively); these women still faced a 74% increased risk of venous thromboembolism, but no increased risk of stroke.

Meanwhile, women who started hormone therapy more than 10 years after menopause had a 21% increased risk of stroke and a 96% increased risk of venous thromboembolism, but no reduced risk on overall death or coronary heart disease.

“It is worth noting that the benefit seen in survival and coronary heart disease for the group starting treatment less than 10 years after the menopause is from combining five trials all performed in primary prevention populations and all with quite long follow-up, ranging from 3.4 to 10.1 years,” the authors wrote.

These results may reflect the possibility of a time interaction, with coronary heart disease events occurring earlier in predisposed women, making it impossible to say whether short duration therapy is beneficial in this population or not, the researchers wrote .

Eighteen of the 19 trials included in the analysis reported the funding source. One study was exclusively funded by Wyeth-Ayerst. Two studies received partial funding from Novo-Nordisk Pharmaceutical, and one study was funded by the National Institutes of Health with support from Wyeth-Ayerst, Hoffman-LaRoche, Pharmacia, and Upjohn. Eight other studies used medication provided by various pharmaceutical companies.

SAN DIEGO – Researchers at the University of Arkansas for Medical Sciences in Little Rock are teaching dogs to detect thyroid cancer from urine samples.

The dogs become alert on samples if they detect cancer, but remain passive if they don’t. The first graduate of the program, a German shepherd mix named Frankie, got it right in 30 of 34 cases, matching final surgical pathology results with a sensitivity of 86.6% and a specificity of 89.5%.

With results like those, it might not be too long before Frankie and his colleagues are providing inexpensive adjunct diagnostic services when test results are uncertain, and helping underserved areas with limited diagnostic capacity, the researchers noted.

At the Endocrine Society meeting, investigator Dr. Andrew Hinson shared clips of Frankie and another recent graduate, a border collie mix named Sophie, and explained the project’s next steps.

Frankie was rescued by principal investigator Dr. Arny Ferrando. Sophie and other dogs in the program were also rescued from local animal shelters.

More information is available at www.thefrankiefoundation.org.

[email protected] 


SAN DIEGO – Researchers at the University of Arkansas for Medical Sciences in Little Rock are teaching dogs to detect thyroid cancer from urine samples.

The dogs become alert on samples if they detect cancer, but remain passive if they don’t. The first graduate of the program, a German shepherd mix named Frankie, got it right in 30 of 34 cases, matching final surgical pathology results with a sensitivity of 86.6% and a specificity of 89.5%.

With results like those, it might not be too long before Frankie and his colleagues are providing inexpensive adjunct diagnostic services when test results are uncertain, and helping underserved areas with limited diagnostic capacity, the researchers noted.

At the Endocrine Society meeting, investigator Dr. Andrew Hinson shared clips of Frankie and another recent graduate, a border collie mix named Sophie, and explained the project’s next steps.

Frankie was rescued by principal investigator Dr. Arny Ferrando. Sophie and other dogs in the program were also rescued from local animal shelters.

More information is available at www.thefrankiefoundation.org.

[email protected] 


SAN DIEGO – Researchers at the University of Arkansas for Medical Sciences in Little Rock are teaching dogs to detect thyroid cancer from urine samples.

The dogs become alert on samples if they detect cancer, but remain passive if they don’t. The first graduate of the program, a German shepherd mix named Frankie, got it right in 30 of 34 cases, matching final surgical pathology results with a sensitivity of 86.6% and a specificity of 89.5%.

With results like those, it might not be too long before Frankie and his colleagues are providing inexpensive adjunct diagnostic services when test results are uncertain, and helping underserved areas with limited diagnostic capacity, the researchers noted.

At the Endocrine Society meeting, investigator Dr. Andrew Hinson shared clips of Frankie and another recent graduate, a border collie mix named Sophie, and explained the project’s next steps.

Frankie was rescued by principal investigator Dr. Arny Ferrando. Sophie and other dogs in the program were also rescued from local animal shelters.

More information is available at www.thefrankiefoundation.org.

[email protected] 


Venous thromboembolisms affected 6.4% of patients who underwent radical cystectomy, even though all patients received heparin in the hospital as recommended by the American Urological Association, researchers reported.

“Using an in-house, heparin-based anticoagulation protocol consistent with current AUA guidelines has not decreased the rate of venous thromboembolism compared to historical warfarin use,” wrote Dr. Andrew Sun and his colleagues at the University of Southern California Institute of Urology in Los Angeles. Most episodes of VTE occurred after patients were discharged home, and “future studies are needed to establish the benefits of extended-duration [VTE] prophylaxis regimens that cover the critical posthospitalization period,” the researchers added (J. UroL 2015;193:565-9).

Previous studies have reported venous thromboembolism rates of 3%-6% in cystectomy patients, a rate that is more than double that reported for nephrectomy or prostatectomy patients. For their study, the investigators retrospectively assessed 2,316 patients who underwent open radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer between 1971 and 2012. Symptomatic VTE developed among 109 patients overall (4.7%), compared with 6.4% of those who received the modern, heparin-based protocol implemented in 2009 (P = .089).

Furthermore, 58% of all cases occurred after patients stopped anticoagulation therapy and were discharged home. The median time of onset was 20 days after surgery (range, 2-91 days), and VTE was significantly more common among patients with a higher body mass index, prolonged hospital stays, positive surgical margins and orthotopic diversion procedures, compared with other patients. Surgical techniques remained consistent throughout the study.

The study was retrospective, and thus “could not prove any cause and effect relationships. This underscores the need for additional prospective data in this area of research,” said the investigators. “We focused only on open radical cystectomy, and thus, findings may not be generalizable to minimally invasive modalities, on which there is even a greater paucity of data.”

Senior author Dr. Siamak Daneshmand reported financial or other relationships with Endo and Cubist. The authors reported no funding sources or other relevant conflicts of interest.

Venous thromboembolisms affected 6.4% of patients who underwent radical cystectomy, even though all patients received heparin in the hospital as recommended by the American Urological Association, researchers reported.

“Using an in-house, heparin-based anticoagulation protocol consistent with current AUA guidelines has not decreased the rate of venous thromboembolism compared to historical warfarin use,” wrote Dr. Andrew Sun and his colleagues at the University of Southern California Institute of Urology in Los Angeles. Most episodes of VTE occurred after patients were discharged home, and “future studies are needed to establish the benefits of extended-duration [VTE] prophylaxis regimens that cover the critical posthospitalization period,” the researchers added (J. UroL 2015;193:565-9).

Previous studies have reported venous thromboembolism rates of 3%-6% in cystectomy patients, a rate that is more than double that reported for nephrectomy or prostatectomy patients. For their study, the investigators retrospectively assessed 2,316 patients who underwent open radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer between 1971 and 2012. Symptomatic VTE developed among 109 patients overall (4.7%), compared with 6.4% of those who received the modern, heparin-based protocol implemented in 2009 (P = .089).

Furthermore, 58% of all cases occurred after patients stopped anticoagulation therapy and were discharged home. The median time of onset was 20 days after surgery (range, 2-91 days), and VTE was significantly more common among patients with a higher body mass index, prolonged hospital stays, positive surgical margins and orthotopic diversion procedures, compared with other patients. Surgical techniques remained consistent throughout the study.

The study was retrospective, and thus “could not prove any cause and effect relationships. This underscores the need for additional prospective data in this area of research,” said the investigators. “We focused only on open radical cystectomy, and thus, findings may not be generalizable to minimally invasive modalities, on which there is even a greater paucity of data.”

Senior author Dr. Siamak Daneshmand reported financial or other relationships with Endo and Cubist. The authors reported no funding sources or other relevant conflicts of interest.

Venous thromboembolisms affected 6.4% of patients who underwent radical cystectomy, even though all patients received heparin in the hospital as recommended by the American Urological Association, researchers reported.

“Using an in-house, heparin-based anticoagulation protocol consistent with current AUA guidelines has not decreased the rate of venous thromboembolism compared to historical warfarin use,” wrote Dr. Andrew Sun and his colleagues at the University of Southern California Institute of Urology in Los Angeles. Most episodes of VTE occurred after patients were discharged home, and “future studies are needed to establish the benefits of extended-duration [VTE] prophylaxis regimens that cover the critical posthospitalization period,” the researchers added (J. UroL 2015;193:565-9).

Previous studies have reported venous thromboembolism rates of 3%-6% in cystectomy patients, a rate that is more than double that reported for nephrectomy or prostatectomy patients. For their study, the investigators retrospectively assessed 2,316 patients who underwent open radical cystectomy and extended pelvic lymph node dissection for urothelial bladder cancer between 1971 and 2012. Symptomatic VTE developed among 109 patients overall (4.7%), compared with 6.4% of those who received the modern, heparin-based protocol implemented in 2009 (P = .089).

Furthermore, 58% of all cases occurred after patients stopped anticoagulation therapy and were discharged home. The median time of onset was 20 days after surgery (range, 2-91 days), and VTE was significantly more common among patients with a higher body mass index, prolonged hospital stays, positive surgical margins and orthotopic diversion procedures, compared with other patients. Surgical techniques remained consistent throughout the study.

The study was retrospective, and thus “could not prove any cause and effect relationships. This underscores the need for additional prospective data in this area of research,” said the investigators. “We focused only on open radical cystectomy, and thus, findings may not be generalizable to minimally invasive modalities, on which there is even a greater paucity of data.”

Senior author Dr. Siamak Daneshmand reported financial or other relationships with Endo and Cubist. The authors reported no funding sources or other relevant conflicts of interest.

The TPA ambulance, armed with its own CT scanner, has arrived in the United States after several successful years in Germany.

Now what?

Like all new advances, it’s a difficult balance between costs and benefits. The money, in the end, is what it really comes down to. Will the cost of a CT ambulance, the equipment needed to send images to a radiologist, the extra training for EMTs, the price of stocking TPA on board, and maybe even having a neurologist on the ride (or telemedicine for one to see the patient) be offset by money saved on rehabilitation costs, better recoveries, fewer complications, even returning a patient to work?

I have no idea. I’m not sure anyone else does, either.

Certainly, I support the idea of improved stroke care. Although far from ideal, TPA is the only thing we have right now, and the sooner it’s given, the better. Most neurologists will agree. But who’s going to pay for this?

The insurance companies, obviously. But money is finite. What if we upgrade all these ambulances, only to find that there’s no significant cost savings on rehab and recovery when TPA is used in the field? Then the money comes out of doctors’ and nurses’ salaries, higher premiums for everyone, and a cutback in treatment for some other disorder. I’m pretty sure it won’t be taken out of an insurance executive’s year-end bonus.

And just try explaining that to the family of a stroke victim.

It’s not practical to put a CT scanner in every ambulance, so where do we put those so equipped? Again, there’s no easy answer. In areas with large retirement communities? Seems like a safe bet, but young people have strokes, too. Only in cities? More people live in cities, but those in rural areas may be too far from a hospital to receive TPA early. Shouldn’t they have one, too?

Who’s going to make the decision to send the TPA ambulance vs. the regular ambulance? That’s another tough question. The layman who calls in usually isn’t sure what’s going on, only that an ambulance is needed. The dispatcher often can’t tell over the phone if the patient has had a stroke, seizure, or psychogenic event. Should a neurologist or emergency medicine physician make the decision? Maybe, but how much extra time will it take to get one on the line? And, even then, they’ll be making a critical decision with sparse, secondhand information. What if the special ambulance is mistakenly sent to deal with a conversion disorder, only to have a legitimate stroke occur elsewhere when it’s no longer immediately available? That, inevitably, will lead to a lawsuit because the wrong ambulance was sent.

I’m not against the stroke ambulance – far from it – but there are still a lot questions to be answered. Putting a CT scanner and TPA in an ambulance is, comparatively, the easiest part.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The TPA ambulance, armed with its own CT scanner, has arrived in the United States after several successful years in Germany.

Now what?

Like all new advances, it’s a difficult balance between costs and benefits. The money, in the end, is what it really comes down to. Will the cost of a CT ambulance, the equipment needed to send images to a radiologist, the extra training for EMTs, the price of stocking TPA on board, and maybe even having a neurologist on the ride (or telemedicine for one to see the patient) be offset by money saved on rehabilitation costs, better recoveries, fewer complications, even returning a patient to work?

I have no idea. I’m not sure anyone else does, either.

Certainly, I support the idea of improved stroke care. Although far from ideal, TPA is the only thing we have right now, and the sooner it’s given, the better. Most neurologists will agree. But who’s going to pay for this?

The insurance companies, obviously. But money is finite. What if we upgrade all these ambulances, only to find that there’s no significant cost savings on rehab and recovery when TPA is used in the field? Then the money comes out of doctors’ and nurses’ salaries, higher premiums for everyone, and a cutback in treatment for some other disorder. I’m pretty sure it won’t be taken out of an insurance executive’s year-end bonus.

And just try explaining that to the family of a stroke victim.

It’s not practical to put a CT scanner in every ambulance, so where do we put those so equipped? Again, there’s no easy answer. In areas with large retirement communities? Seems like a safe bet, but young people have strokes, too. Only in cities? More people live in cities, but those in rural areas may be too far from a hospital to receive TPA early. Shouldn’t they have one, too?

Who’s going to make the decision to send the TPA ambulance vs. the regular ambulance? That’s another tough question. The layman who calls in usually isn’t sure what’s going on, only that an ambulance is needed. The dispatcher often can’t tell over the phone if the patient has had a stroke, seizure, or psychogenic event. Should a neurologist or emergency medicine physician make the decision? Maybe, but how much extra time will it take to get one on the line? And, even then, they’ll be making a critical decision with sparse, secondhand information. What if the special ambulance is mistakenly sent to deal with a conversion disorder, only to have a legitimate stroke occur elsewhere when it’s no longer immediately available? That, inevitably, will lead to a lawsuit because the wrong ambulance was sent.

I’m not against the stroke ambulance – far from it – but there are still a lot questions to be answered. Putting a CT scanner and TPA in an ambulance is, comparatively, the easiest part.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The TPA ambulance, armed with its own CT scanner, has arrived in the United States after several successful years in Germany.

Now what?

Like all new advances, it’s a difficult balance between costs and benefits. The money, in the end, is what it really comes down to. Will the cost of a CT ambulance, the equipment needed to send images to a radiologist, the extra training for EMTs, the price of stocking TPA on board, and maybe even having a neurologist on the ride (or telemedicine for one to see the patient) be offset by money saved on rehabilitation costs, better recoveries, fewer complications, even returning a patient to work?

I have no idea. I’m not sure anyone else does, either.

Certainly, I support the idea of improved stroke care. Although far from ideal, TPA is the only thing we have right now, and the sooner it’s given, the better. Most neurologists will agree. But who’s going to pay for this?

The insurance companies, obviously. But money is finite. What if we upgrade all these ambulances, only to find that there’s no significant cost savings on rehab and recovery when TPA is used in the field? Then the money comes out of doctors’ and nurses’ salaries, higher premiums for everyone, and a cutback in treatment for some other disorder. I’m pretty sure it won’t be taken out of an insurance executive’s year-end bonus.

And just try explaining that to the family of a stroke victim.

It’s not practical to put a CT scanner in every ambulance, so where do we put those so equipped? Again, there’s no easy answer. In areas with large retirement communities? Seems like a safe bet, but young people have strokes, too. Only in cities? More people live in cities, but those in rural areas may be too far from a hospital to receive TPA early. Shouldn’t they have one, too?

Who’s going to make the decision to send the TPA ambulance vs. the regular ambulance? That’s another tough question. The layman who calls in usually isn’t sure what’s going on, only that an ambulance is needed. The dispatcher often can’t tell over the phone if the patient has had a stroke, seizure, or psychogenic event. Should a neurologist or emergency medicine physician make the decision? Maybe, but how much extra time will it take to get one on the line? And, even then, they’ll be making a critical decision with sparse, secondhand information. What if the special ambulance is mistakenly sent to deal with a conversion disorder, only to have a legitimate stroke occur elsewhere when it’s no longer immediately available? That, inevitably, will lead to a lawsuit because the wrong ambulance was sent.

I’m not against the stroke ambulance – far from it – but there are still a lot questions to be answered. Putting a CT scanner and TPA in an ambulance is, comparatively, the easiest part.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Plasma for transfusion

Photo by Cristina Granados

The US Food and Drug Administration (FDA) has approved a revised label for the pooled plasma product Octaplas, increasing the product’s shelf life.

The new label says Octaplas can now be stored frozen, at or below -18°C (-0.4°F), for 3 years from the date of manufacture.

And thawed Octaplas should be used within 24 hours if refrigerated (between 1°C and 6°C/33.8°F to 42.8°F) or within 8 hours if stored at room temperature (between 20°C and 25°C/68°F to 77°F)

The previous product label said frozen Octaplas could be stored for 2 years, and thawed Octaplas should be used within 12 hours if stored between 2°C and 4°C (35.6°F to 39.2°F) or within 3 hours if stored between 20°C and 25°C (68°F to 77°F).

About Octaplas

Octaplas is a sterile, frozen solution of human plasma from several donors that has been treated with a solvent detergent process to minimize the risk of serious virus transmission. The plasma is collected from US donors who have been screened and tested for diseases transmitted by blood.

Octaplas gained FDA approval in January 2013. The product is indicated for the replacement of multiple coagulation factors in patients with acquired deficiencies due to liver disease or undergoing cardiac surgery or liver transplant. Octaplas can also be used for plasma exchange in patients with thrombotic thrombocytopenic purpura.

Octaplas is contraindicated in patients with immunoglobulin A deficiency, severe deficiency of protein S, history of hypersensitivity to fresh-frozen plasma or to plasma-derived products including any plasma protein, or a history of hypersensitivity reaction to Octaplas.

Serious adverse events observed in clinical trials of Octaplas were anaphylactic shock, citrate toxicity, and severe hypotension. The most common adverse events observed in 1% of patients or more included pruritus, urticaria, nausea, headache, and paresthesia.

Transfusion reactions can occur with ABO blood group mismatches. High infusion rates can induce hypervolemia with consequent pulmonary edema or cardiac failure. Excessive bleeding due to hyperfibrinolysis can occur due to low levels of alpha2-antiplasmin.

Thrombosis can occur due to low levels of protein S. Citrate toxicity can occur with transfusion rates exceeding 1 mL/kg/min of Octaplas. As Octaplas is made from human plasma, it may carry a risk of transmitting infectious agents, such as viruses, the variant Creutzfeldt-Jakob disease agent, and, theoretically, the Creutzfeldt-Jakob disease agent.

For more details on Octaplas, see the complete prescribing information.

Plasma for transfusion

Photo by Cristina Granados

The US Food and Drug Administration (FDA) has approved a revised label for the pooled plasma product Octaplas, increasing the product’s shelf life.

The new label says Octaplas can now be stored frozen, at or below -18°C (-0.4°F), for 3 years from the date of manufacture.

And thawed Octaplas should be used within 24 hours if refrigerated (between 1°C and 6°C/33.8°F to 42.8°F) or within 8 hours if stored at room temperature (between 20°C and 25°C/68°F to 77°F)

The previous product label said frozen Octaplas could be stored for 2 years, and thawed Octaplas should be used within 12 hours if stored between 2°C and 4°C (35.6°F to 39.2°F) or within 3 hours if stored between 20°C and 25°C (68°F to 77°F).

About Octaplas

Octaplas is a sterile, frozen solution of human plasma from several donors that has been treated with a solvent detergent process to minimize the risk of serious virus transmission. The plasma is collected from US donors who have been screened and tested for diseases transmitted by blood.

Octaplas gained FDA approval in January 2013. The product is indicated for the replacement of multiple coagulation factors in patients with acquired deficiencies due to liver disease or undergoing cardiac surgery or liver transplant. Octaplas can also be used for plasma exchange in patients with thrombotic thrombocytopenic purpura.

Octaplas is contraindicated in patients with immunoglobulin A deficiency, severe deficiency of protein S, history of hypersensitivity to fresh-frozen plasma or to plasma-derived products including any plasma protein, or a history of hypersensitivity reaction to Octaplas.

Serious adverse events observed in clinical trials of Octaplas were anaphylactic shock, citrate toxicity, and severe hypotension. The most common adverse events observed in 1% of patients or more included pruritus, urticaria, nausea, headache, and paresthesia.

Transfusion reactions can occur with ABO blood group mismatches. High infusion rates can induce hypervolemia with consequent pulmonary edema or cardiac failure. Excessive bleeding due to hyperfibrinolysis can occur due to low levels of alpha2-antiplasmin.

Thrombosis can occur due to low levels of protein S. Citrate toxicity can occur with transfusion rates exceeding 1 mL/kg/min of Octaplas. As Octaplas is made from human plasma, it may carry a risk of transmitting infectious agents, such as viruses, the variant Creutzfeldt-Jakob disease agent, and, theoretically, the Creutzfeldt-Jakob disease agent.

For more details on Octaplas, see the complete prescribing information.

Plasma for transfusion

Photo by Cristina Granados

The US Food and Drug Administration (FDA) has approved a revised label for the pooled plasma product Octaplas, increasing the product’s shelf life.

The new label says Octaplas can now be stored frozen, at or below -18°C (-0.4°F), for 3 years from the date of manufacture.

And thawed Octaplas should be used within 24 hours if refrigerated (between 1°C and 6°C/33.8°F to 42.8°F) or within 8 hours if stored at room temperature (between 20°C and 25°C/68°F to 77°F)

The previous product label said frozen Octaplas could be stored for 2 years, and thawed Octaplas should be used within 12 hours if stored between 2°C and 4°C (35.6°F to 39.2°F) or within 3 hours if stored between 20°C and 25°C (68°F to 77°F).

About Octaplas

Octaplas is a sterile, frozen solution of human plasma from several donors that has been treated with a solvent detergent process to minimize the risk of serious virus transmission. The plasma is collected from US donors who have been screened and tested for diseases transmitted by blood.

Octaplas gained FDA approval in January 2013. The product is indicated for the replacement of multiple coagulation factors in patients with acquired deficiencies due to liver disease or undergoing cardiac surgery or liver transplant. Octaplas can also be used for plasma exchange in patients with thrombotic thrombocytopenic purpura.

Octaplas is contraindicated in patients with immunoglobulin A deficiency, severe deficiency of protein S, history of hypersensitivity to fresh-frozen plasma or to plasma-derived products including any plasma protein, or a history of hypersensitivity reaction to Octaplas.

Serious adverse events observed in clinical trials of Octaplas were anaphylactic shock, citrate toxicity, and severe hypotension. The most common adverse events observed in 1% of patients or more included pruritus, urticaria, nausea, headache, and paresthesia.

Transfusion reactions can occur with ABO blood group mismatches. High infusion rates can induce hypervolemia with consequent pulmonary edema or cardiac failure. Excessive bleeding due to hyperfibrinolysis can occur due to low levels of alpha2-antiplasmin.

Thrombosis can occur due to low levels of protein S. Citrate toxicity can occur with transfusion rates exceeding 1 mL/kg/min of Octaplas. As Octaplas is made from human plasma, it may carry a risk of transmitting infectious agents, such as viruses, the variant Creutzfeldt-Jakob disease agent, and, theoretically, the Creutzfeldt-Jakob disease agent.

For more details on Octaplas, see the complete prescribing information.

Rendering of fibrin forming

a blood clot, with PolySTAT

(blue) binding strands together

Image by William Walker–

University of Washington

Preclinical research suggests an injectable polymer known as PolySTAT may one day be able to halt life-threatening bleeding in soldiers and trauma patients.

Once injected, this hemostatic polymer circulates in the blood, homes to sites of vascular injury, and promotes the formation of blood clots.

In experiments with rats, 100% of animals injected with PolySTAT survived a typically lethal injury to the femoral artery. In comparison, 0% to 40% of controls survived.

“Most of the patients who die from bleeding die quickly,” said Nathan White, MD, of the University of Washington in Seattle.

“[PolySTAT] is something you could potentially put in a syringe inside a backpack and give right away to reduce blood loss and keep people alive long enough to make it to medical care.”

Dr White and his colleagues described their work with PolySTAT in Science Translational Medicine. A related Focus article addressed the promises and challenges of advancing PolySTAT and other clotting approaches from proof-of-principle to clinical development.

PolySTAT induces hemostasis by cross-linking the fibrin matrix within blood clots, just as factor XIII does. But the researchers said PolySTAT offers greater protection against natural enzymes that dissolve blood clots.

That’s because PolySTAT binds to fibrin monomers and is uniformly integrated into fibrin fibers during polymerization. This produces a fortified, hybrid polymer network that can resist enzymatic degradation.

In vitro experiments showed that PolySTAT accelerated clotting kinetics, increased the strength of blood clots, and delayed clot breakdown.

The researchers also assessed how PolySTAT affected rats following a femoral artery injury, comparing results with PolySTAT to those with volume control (0.9% saline), a nonbinding scrambled control polymer (PolySCRAM), rat albumin, and human FXIIIa.

The team found that PolySTAT conferred superior survival by reducing blood loss and fluid resuscitation requirements.

All of the rats treated with PolySTAT (5/5) survived to the end of the experiment, compared to none of the rats that received albumin, 20% that received PolySCRAM or FXIIIa, and 40% that received volume control.

The researchers said PolySTAT’s initial safety profile looks promising, but they are still planning to test the polymer on larger animals and conduct additional screening to find out if PolySTAT binds to any other unintended substances.

The team also plans to investigate PolySTAT’s potential for treating hemophilia and for integration into bandages.

Rendering of fibrin forming

a blood clot, with PolySTAT

(blue) binding strands together

Image by William Walker–

University of Washington

Preclinical research suggests an injectable polymer known as PolySTAT may one day be able to halt life-threatening bleeding in soldiers and trauma patients.

Once injected, this hemostatic polymer circulates in the blood, homes to sites of vascular injury, and promotes the formation of blood clots.

In experiments with rats, 100% of animals injected with PolySTAT survived a typically lethal injury to the femoral artery. In comparison, 0% to 40% of controls survived.

“Most of the patients who die from bleeding die quickly,” said Nathan White, MD, of the University of Washington in Seattle.

“[PolySTAT] is something you could potentially put in a syringe inside a backpack and give right away to reduce blood loss and keep people alive long enough to make it to medical care.”

Dr White and his colleagues described their work with PolySTAT in Science Translational Medicine. A related Focus article addressed the promises and challenges of advancing PolySTAT and other clotting approaches from proof-of-principle to clinical development.

PolySTAT induces hemostasis by cross-linking the fibrin matrix within blood clots, just as factor XIII does. But the researchers said PolySTAT offers greater protection against natural enzymes that dissolve blood clots.

That’s because PolySTAT binds to fibrin monomers and is uniformly integrated into fibrin fibers during polymerization. This produces a fortified, hybrid polymer network that can resist enzymatic degradation.

In vitro experiments showed that PolySTAT accelerated clotting kinetics, increased the strength of blood clots, and delayed clot breakdown.

The researchers also assessed how PolySTAT affected rats following a femoral artery injury, comparing results with PolySTAT to those with volume control (0.9% saline), a nonbinding scrambled control polymer (PolySCRAM), rat albumin, and human FXIIIa.

The team found that PolySTAT conferred superior survival by reducing blood loss and fluid resuscitation requirements.

All of the rats treated with PolySTAT (5/5) survived to the end of the experiment, compared to none of the rats that received albumin, 20% that received PolySCRAM or FXIIIa, and 40% that received volume control.

The researchers said PolySTAT’s initial safety profile looks promising, but they are still planning to test the polymer on larger animals and conduct additional screening to find out if PolySTAT binds to any other unintended substances.

The team also plans to investigate PolySTAT’s potential for treating hemophilia and for integration into bandages.

Rendering of fibrin forming

a blood clot, with PolySTAT

(blue) binding strands together

Image by William Walker–

University of Washington

Preclinical research suggests an injectable polymer known as PolySTAT may one day be able to halt life-threatening bleeding in soldiers and trauma patients.

Once injected, this hemostatic polymer circulates in the blood, homes to sites of vascular injury, and promotes the formation of blood clots.

In experiments with rats, 100% of animals injected with PolySTAT survived a typically lethal injury to the femoral artery. In comparison, 0% to 40% of controls survived.

“Most of the patients who die from bleeding die quickly,” said Nathan White, MD, of the University of Washington in Seattle.

“[PolySTAT] is something you could potentially put in a syringe inside a backpack and give right away to reduce blood loss and keep people alive long enough to make it to medical care.”

Dr White and his colleagues described their work with PolySTAT in Science Translational Medicine. A related Focus article addressed the promises and challenges of advancing PolySTAT and other clotting approaches from proof-of-principle to clinical development.

PolySTAT induces hemostasis by cross-linking the fibrin matrix within blood clots, just as factor XIII does. But the researchers said PolySTAT offers greater protection against natural enzymes that dissolve blood clots.

That’s because PolySTAT binds to fibrin monomers and is uniformly integrated into fibrin fibers during polymerization. This produces a fortified, hybrid polymer network that can resist enzymatic degradation.

In vitro experiments showed that PolySTAT accelerated clotting kinetics, increased the strength of blood clots, and delayed clot breakdown.

The researchers also assessed how PolySTAT affected rats following a femoral artery injury, comparing results with PolySTAT to those with volume control (0.9% saline), a nonbinding scrambled control polymer (PolySCRAM), rat albumin, and human FXIIIa.

The team found that PolySTAT conferred superior survival by reducing blood loss and fluid resuscitation requirements.

All of the rats treated with PolySTAT (5/5) survived to the end of the experiment, compared to none of the rats that received albumin, 20% that received PolySCRAM or FXIIIa, and 40% that received volume control.

The researchers said PolySTAT’s initial safety profile looks promising, but they are still planning to test the polymer on larger animals and conduct additional screening to find out if PolySTAT binds to any other unintended substances.

The team also plans to investigate PolySTAT’s potential for treating hemophilia and for integration into bandages.

Red blood cells

A new analysis indicates that patients hospitalized for severe sepsis are often readmitted within 90 days, and many of these readmissions may be preventable.

About 43% of the patients studied were readmitted to the hospital within 90 days of their sepsis hospitalization.

And 42% of these hospitalizations were due to conditions that could potentially be prevented or treated early to avoid hospitalization, according to researchers.

Hallie C. Prescott, MD, of the University of Michigan, Ann Arbor, and her colleagues reported these findings in JAMA.

The researchers analyzed participants in the nationally representative US Health and Retirement Study, a sample of households with adults 50 years of age or older that is linked to Medicare claims (1998-2010).

The team examined the most common readmission diagnoses among patients who were hospitalized for severe sepsis, the extent to which readmissions might have been preventable, and whether the pattern of readmission diagnoses differed compared with that of other acute medical conditions.

To gauge what proportion of rehospitalizations might have been preventable, the researchers looked at ambulatory-care-sensitive conditions (ACSCs) identified by the Agency for Healthcare Research and Quality. They also expanded the definition of ACSCs to include conditions that aren’t common among the general population but arise more often in sepsis survivors.

So their potentially preventable readmission diagnoses included pneumonia, hypertension, dehydration, asthma, urinary tract infection, chronic obstructive pulmonary disease exacerbation, perforated appendix, diabetes, angina, congestive heart failure, sepsis, acute renal failure, skin or soft tissue infection, and aspiration pneumonitis.

Dr Prescott and her colleagues identified 2617 hospitalizations for severe sepsis that could be matched to hospitalizations for other acute medical conditions. And they found that 1115 of the severe sepsis survivors (42.6%) were rehospitalized within 90 days.

The 10 most common readmission diagnoses following severe sepsis were sepsis (6.4%), congestive heart failure (5.5%), pneumonia (3.5%), acute renal failure (3.3%), rehabilitation (2.8%), respiratory failure (2.5%), complication related to a device, implant, or graft (2%), exacerbation of chronic obstructive pulmonary disorder (1.9%), aspiration pneumonitis (1.8%), and urinary tract infection (1.7%).

Readmissions for a primary diagnosis of infection (sepsis, pneumonia, urinary tract, and skin or soft tissue infection) occurred in 11.9% of severe sepsis survivors and 8.0% of patients with acute medical conditions (P<0.001).

Likewise, readmissions for ACSCs were more common after severe sepsis than for patients with acute conditions—21.6% and 19.1%, respectively (P=0.02)—and accounted for a greater proportion of all 90-day readmissions—41.6% and 37%.1, respectively (P=0.009).

“Many of these conditions can be managed if the patient can get in to see a doctor at the start of the illness, meaning that we potentially avoid hospitalization,” Dr Prescott said. “We need to assess their vulnerability and design a better landing pad for patients when they leave the hospital, and avoid the second hit that derails recovery.”

Red blood cells

A new analysis indicates that patients hospitalized for severe sepsis are often readmitted within 90 days, and many of these readmissions may be preventable.

About 43% of the patients studied were readmitted to the hospital within 90 days of their sepsis hospitalization.

And 42% of these hospitalizations were due to conditions that could potentially be prevented or treated early to avoid hospitalization, according to researchers.

Hallie C. Prescott, MD, of the University of Michigan, Ann Arbor, and her colleagues reported these findings in JAMA.

The researchers analyzed participants in the nationally representative US Health and Retirement Study, a sample of households with adults 50 years of age or older that is linked to Medicare claims (1998-2010).

The team examined the most common readmission diagnoses among patients who were hospitalized for severe sepsis, the extent to which readmissions might have been preventable, and whether the pattern of readmission diagnoses differed compared with that of other acute medical conditions.

To gauge what proportion of rehospitalizations might have been preventable, the researchers looked at ambulatory-care-sensitive conditions (ACSCs) identified by the Agency for Healthcare Research and Quality. They also expanded the definition of ACSCs to include conditions that aren’t common among the general population but arise more often in sepsis survivors.

So their potentially preventable readmission diagnoses included pneumonia, hypertension, dehydration, asthma, urinary tract infection, chronic obstructive pulmonary disease exacerbation, perforated appendix, diabetes, angina, congestive heart failure, sepsis, acute renal failure, skin or soft tissue infection, and aspiration pneumonitis.

Dr Prescott and her colleagues identified 2617 hospitalizations for severe sepsis that could be matched to hospitalizations for other acute medical conditions. And they found that 1115 of the severe sepsis survivors (42.6%) were rehospitalized within 90 days.

The 10 most common readmission diagnoses following severe sepsis were sepsis (6.4%), congestive heart failure (5.5%), pneumonia (3.5%), acute renal failure (3.3%), rehabilitation (2.8%), respiratory failure (2.5%), complication related to a device, implant, or graft (2%), exacerbation of chronic obstructive pulmonary disorder (1.9%), aspiration pneumonitis (1.8%), and urinary tract infection (1.7%).

Readmissions for a primary diagnosis of infection (sepsis, pneumonia, urinary tract, and skin or soft tissue infection) occurred in 11.9% of severe sepsis survivors and 8.0% of patients with acute medical conditions (P<0.001).

Likewise, readmissions for ACSCs were more common after severe sepsis than for patients with acute conditions—21.6% and 19.1%, respectively (P=0.02)—and accounted for a greater proportion of all 90-day readmissions—41.6% and 37%.1, respectively (P=0.009).

“Many of these conditions can be managed if the patient can get in to see a doctor at the start of the illness, meaning that we potentially avoid hospitalization,” Dr Prescott said. “We need to assess their vulnerability and design a better landing pad for patients when they leave the hospital, and avoid the second hit that derails recovery.”

Red blood cells

A new analysis indicates that patients hospitalized for severe sepsis are often readmitted within 90 days, and many of these readmissions may be preventable.

About 43% of the patients studied were readmitted to the hospital within 90 days of their sepsis hospitalization.

And 42% of these hospitalizations were due to conditions that could potentially be prevented or treated early to avoid hospitalization, according to researchers.

Hallie C. Prescott, MD, of the University of Michigan, Ann Arbor, and her colleagues reported these findings in JAMA.

The researchers analyzed participants in the nationally representative US Health and Retirement Study, a sample of households with adults 50 years of age or older that is linked to Medicare claims (1998-2010).

The team examined the most common readmission diagnoses among patients who were hospitalized for severe sepsis, the extent to which readmissions might have been preventable, and whether the pattern of readmission diagnoses differed compared with that of other acute medical conditions.

To gauge what proportion of rehospitalizations might have been preventable, the researchers looked at ambulatory-care-sensitive conditions (ACSCs) identified by the Agency for Healthcare Research and Quality. They also expanded the definition of ACSCs to include conditions that aren’t common among the general population but arise more often in sepsis survivors.

So their potentially preventable readmission diagnoses included pneumonia, hypertension, dehydration, asthma, urinary tract infection, chronic obstructive pulmonary disease exacerbation, perforated appendix, diabetes, angina, congestive heart failure, sepsis, acute renal failure, skin or soft tissue infection, and aspiration pneumonitis.

Dr Prescott and her colleagues identified 2617 hospitalizations for severe sepsis that could be matched to hospitalizations for other acute medical conditions. And they found that 1115 of the severe sepsis survivors (42.6%) were rehospitalized within 90 days.

The 10 most common readmission diagnoses following severe sepsis were sepsis (6.4%), congestive heart failure (5.5%), pneumonia (3.5%), acute renal failure (3.3%), rehabilitation (2.8%), respiratory failure (2.5%), complication related to a device, implant, or graft (2%), exacerbation of chronic obstructive pulmonary disorder (1.9%), aspiration pneumonitis (1.8%), and urinary tract infection (1.7%).

Readmissions for a primary diagnosis of infection (sepsis, pneumonia, urinary tract, and skin or soft tissue infection) occurred in 11.9% of severe sepsis survivors and 8.0% of patients with acute medical conditions (P<0.001).

Likewise, readmissions for ACSCs were more common after severe sepsis than for patients with acute conditions—21.6% and 19.1%, respectively (P=0.02)—and accounted for a greater proportion of all 90-day readmissions—41.6% and 37%.1, respectively (P=0.009).

“Many of these conditions can be managed if the patient can get in to see a doctor at the start of the illness, meaning that we potentially avoid hospitalization,” Dr Prescott said. “We need to assess their vulnerability and design a better landing pad for patients when they leave the hospital, and avoid the second hit that derails recovery.”

RBCs grown from edited iPSCs

Image by Ying Wang–

Johns Hopkins Medicine

Researchers say they have devised a technique for generating normal, mature red blood cells (RBCs) from patients with sickle cell disease (SCD).

The team hopes that, ultimately, the RBCs could be transfused back into the patients from which they are derived and eliminate the need for donor transfusion in SCD.

Linzhao Cheng, PhD, of the Johns Hopkins School of Medicine in Baltimore, Maryland, and his colleagues described the technique in Stem Cells.

Dr Cheng noted that SCD patients often require RBC transfusions, but over time, their bodies may begin to mount an immune response against the foreign blood.

“Their bodies quickly kill off the blood cells,” Dr Cheng said. “So they have to get transfusions more and more frequently.”

A solution, Dr Cheng and his colleagues thought, would be to generate RBCs for transfusion using a patient’s own cells.

To do this, the researchers first took hematopoietic cells from an SCD patient and generated induced pluripotent stem cells (iPSCs).

Then, the team used the gene-editing technique CRISPR/Cas9 to target the homozygous SCD mutation (nt. 69A>T) in the HBB gene and ensure the RBCs they generated would not be sickled.

Finally, they coaxed the iPSCs into mature RBCs that expressed the corrected HBB gene. The edited iPSCs generated RBCs just as efficiently as iPSCs that hadn’t been subjected to CRISPR/Cas9.

And the level of HBB protein expression in the RBCs derived from edited iPSCs was similar to that of RBCs generated from unedited iPSCs.

Dr Cheng noted that, to become medically useful, this method will have to be made more efficient and scaled up significantly. And the cells would need to be tested for safety.

“[Nevertheless,] this study shows it may be possible in the not-too-distant future to provide patients with sickle cell disease with an exciting new treatment option,” Dr Cheng said.

He and his colleagues believe this method of RBC generation may also be applicable for other blood disorders. And they think it might be possible to edit cells from healthy individuals so they can resist malaria and other infectious agents.

Another research group has reported the ability to correct the SCD mutation using zinc-finger nucleases.

RBCs grown from edited iPSCs

Image by Ying Wang–

Johns Hopkins Medicine

Researchers say they have devised a technique for generating normal, mature red blood cells (RBCs) from patients with sickle cell disease (SCD).

The team hopes that, ultimately, the RBCs could be transfused back into the patients from which they are derived and eliminate the need for donor transfusion in SCD.

Linzhao Cheng, PhD, of the Johns Hopkins School of Medicine in Baltimore, Maryland, and his colleagues described the technique in Stem Cells.

Dr Cheng noted that SCD patients often require RBC transfusions, but over time, their bodies may begin to mount an immune response against the foreign blood.

“Their bodies quickly kill off the blood cells,” Dr Cheng said. “So they have to get transfusions more and more frequently.”

A solution, Dr Cheng and his colleagues thought, would be to generate RBCs for transfusion using a patient’s own cells.

To do this, the researchers first took hematopoietic cells from an SCD patient and generated induced pluripotent stem cells (iPSCs).

Then, the team used the gene-editing technique CRISPR/Cas9 to target the homozygous SCD mutation (nt. 69A>T) in the HBB gene and ensure the RBCs they generated would not be sickled.

Finally, they coaxed the iPSCs into mature RBCs that expressed the corrected HBB gene. The edited iPSCs generated RBCs just as efficiently as iPSCs that hadn’t been subjected to CRISPR/Cas9.

And the level of HBB protein expression in the RBCs derived from edited iPSCs was similar to that of RBCs generated from unedited iPSCs.

Dr Cheng noted that, to become medically useful, this method will have to be made more efficient and scaled up significantly. And the cells would need to be tested for safety.

“[Nevertheless,] this study shows it may be possible in the not-too-distant future to provide patients with sickle cell disease with an exciting new treatment option,” Dr Cheng said.

He and his colleagues believe this method of RBC generation may also be applicable for other blood disorders. And they think it might be possible to edit cells from healthy individuals so they can resist malaria and other infectious agents.

Another research group has reported the ability to correct the SCD mutation using zinc-finger nucleases.

RBCs grown from edited iPSCs

Image by Ying Wang–

Johns Hopkins Medicine

Researchers say they have devised a technique for generating normal, mature red blood cells (RBCs) from patients with sickle cell disease (SCD).

The team hopes that, ultimately, the RBCs could be transfused back into the patients from which they are derived and eliminate the need for donor transfusion in SCD.

Linzhao Cheng, PhD, of the Johns Hopkins School of Medicine in Baltimore, Maryland, and his colleagues described the technique in Stem Cells.

Dr Cheng noted that SCD patients often require RBC transfusions, but over time, their bodies may begin to mount an immune response against the foreign blood.

“Their bodies quickly kill off the blood cells,” Dr Cheng said. “So they have to get transfusions more and more frequently.”

A solution, Dr Cheng and his colleagues thought, would be to generate RBCs for transfusion using a patient’s own cells.

To do this, the researchers first took hematopoietic cells from an SCD patient and generated induced pluripotent stem cells (iPSCs).

Then, the team used the gene-editing technique CRISPR/Cas9 to target the homozygous SCD mutation (nt. 69A>T) in the HBB gene and ensure the RBCs they generated would not be sickled.

Finally, they coaxed the iPSCs into mature RBCs that expressed the corrected HBB gene. The edited iPSCs generated RBCs just as efficiently as iPSCs that hadn’t been subjected to CRISPR/Cas9.

And the level of HBB protein expression in the RBCs derived from edited iPSCs was similar to that of RBCs generated from unedited iPSCs.

Dr Cheng noted that, to become medically useful, this method will have to be made more efficient and scaled up significantly. And the cells would need to be tested for safety.

“[Nevertheless,] this study shows it may be possible in the not-too-distant future to provide patients with sickle cell disease with an exciting new treatment option,” Dr Cheng said.

He and his colleagues believe this method of RBC generation may also be applicable for other blood disorders. And they think it might be possible to edit cells from healthy individuals so they can resist malaria and other infectious agents.

Another research group has reported the ability to correct the SCD mutation using zinc-finger nucleases.

BALTIMORE – If all Americans eligible for statins under new American College of Cardiology/American Heart Association guidelines actually took them, thousands of deaths per year from cardiovascular disease might be prevented but at a cost of increased incidence of diabetes and myopathy.

The 2013 ACC/AHA guidelines expand criteria for the use of statins for primary prevention of CVD to more Americans (Circulation 2015;131:A05). Compliance with those guidelines would save 7,930 lives per year that would have been lost to CVD, according to Quanhe Yang, Ph.D., of the Centers for Disease Control and Prevention’s Division for Heart Disease and Stroke Prevention, and colleagues from the CDC and Emory University, Atlanta. Dr. Yang presented the findings at the American Heart Association Epidemiology and Prevention, Lifestyle and Cardiometabolic Health 2015 Scientific Sessions.

Statins are now indicated for primary prevention of CVD for anyone with an LDL cholesterol level greater than or equal to 190 mg/dL, for individuals aged 40-75 years with diabetes, and for those aged 40-75 years with LDL cholesterol greater than or equal to 70 mg/dL but less than 190 mg/dL who have at least a 7.5% estimated 10-year risk of developing atherosclerotic CVD. This means that an additional 24.2 million Americans are now eligible for statins but are not taking one, according to Dr. Yang and coinvestigators. However, “no study has assessed the potential impact of statin therapy under the new guidelines,” said Dr. Yang.

In order to obtain treatment group-specific atherosclerotic CVD, investigators first estimated hazard ratios for each treatment group by sex from the National Health and Nutrition Examination Survey III (NHANES III)–linked Mortality files. These hazard ratios were then applied to data from NHANES 2005-2010, the 2010 Multiple Cause of Death file, and the 2010 U.S. census to obtain age/race/sex-specific atherosclerotic CVD for each treatment group.

Applying the per-group hazard ratios, Dr. Yang and colleagues calculated that an annual 7,930 atherosclerotic CVD deaths would be prevented with full statin compliance, a reduction of 12.6%. However, modeling predicted an additional 16,400 additional cases of diabetes caused by statin use, he cautioned. More cases of myopathy would also occur, though the estimated number depends on whether the rate is derived from randomized, controlled trials (RCTs) or from population-based reports of myopathy. If the RCT data are used, just 1,510 excess cases of myopathy would be seen, in contrast to the 36,100 cases predicted by population-based data.

The study could model deaths caused by CVD only and not the reduction in disease burden of CVD that would result if all of the additional 24.2 million Americans took a statin, Dr Yang noted. Other limitations of the study included the lack of agreement in incidence of myopathy between RCTs and population-based studies, as well as the likelihood that the risk of diabetes increases with age and higher statin dose – effects not accounted for in the study.

Questioning after the talk focused on sex-specific differences in statin takers. For example, statin-associated diabetes is more common in women than men, another effect not accounted for in the study’s modeling, noted an audience member. Additionally, given that women have been underrepresented in clinical trials in general and in those for CVD in particular, some modeling assumptions in the present study may also lack full generalizability to women at risk for CVD.

BALTIMORE – If all Americans eligible for statins under new American College of Cardiology/American Heart Association guidelines actually took them, thousands of deaths per year from cardiovascular disease might be prevented but at a cost of increased incidence of diabetes and myopathy.

The 2013 ACC/AHA guidelines expand criteria for the use of statins for primary prevention of CVD to more Americans (Circulation 2015;131:A05). Compliance with those guidelines would save 7,930 lives per year that would have been lost to CVD, according to Quanhe Yang, Ph.D., of the Centers for Disease Control and Prevention’s Division for Heart Disease and Stroke Prevention, and colleagues from the CDC and Emory University, Atlanta. Dr. Yang presented the findings at the American Heart Association Epidemiology and Prevention, Lifestyle and Cardiometabolic Health 2015 Scientific Sessions.

Statins are now indicated for primary prevention of CVD for anyone with an LDL cholesterol level greater than or equal to 190 mg/dL, for individuals aged 40-75 years with diabetes, and for those aged 40-75 years with LDL cholesterol greater than or equal to 70 mg/dL but less than 190 mg/dL who have at least a 7.5% estimated 10-year risk of developing atherosclerotic CVD. This means that an additional 24.2 million Americans are now eligible for statins but are not taking one, according to Dr. Yang and coinvestigators. However, “no study has assessed the potential impact of statin therapy under the new guidelines,” said Dr. Yang.

In order to obtain treatment group-specific atherosclerotic CVD, investigators first estimated hazard ratios for each treatment group by sex from the National Health and Nutrition Examination Survey III (NHANES III)–linked Mortality files. These hazard ratios were then applied to data from NHANES 2005-2010, the 2010 Multiple Cause of Death file, and the 2010 U.S. census to obtain age/race/sex-specific atherosclerotic CVD for each treatment group.

Applying the per-group hazard ratios, Dr. Yang and colleagues calculated that an annual 7,930 atherosclerotic CVD deaths would be prevented with full statin compliance, a reduction of 12.6%. However, modeling predicted an additional 16,400 additional cases of diabetes caused by statin use, he cautioned. More cases of myopathy would also occur, though the estimated number depends on whether the rate is derived from randomized, controlled trials (RCTs) or from population-based reports of myopathy. If the RCT data are used, just 1,510 excess cases of myopathy would be seen, in contrast to the 36,100 cases predicted by population-based data.

The study could model deaths caused by CVD only and not the reduction in disease burden of CVD that would result if all of the additional 24.2 million Americans took a statin, Dr Yang noted. Other limitations of the study included the lack of agreement in incidence of myopathy between RCTs and population-based studies, as well as the likelihood that the risk of diabetes increases with age and higher statin dose – effects not accounted for in the study.

Questioning after the talk focused on sex-specific differences in statin takers. For example, statin-associated diabetes is more common in women than men, another effect not accounted for in the study’s modeling, noted an audience member. Additionally, given that women have been underrepresented in clinical trials in general and in those for CVD in particular, some modeling assumptions in the present study may also lack full generalizability to women at risk for CVD.

BALTIMORE – If all Americans eligible for statins under new American College of Cardiology/American Heart Association guidelines actually took them, thousands of deaths per year from cardiovascular disease might be prevented but at a cost of increased incidence of diabetes and myopathy.

The 2013 ACC/AHA guidelines expand criteria for the use of statins for primary prevention of CVD to more Americans (Circulation 2015;131:A05). Compliance with those guidelines would save 7,930 lives per year that would have been lost to CVD, according to Quanhe Yang, Ph.D., of the Centers for Disease Control and Prevention’s Division for Heart Disease and Stroke Prevention, and colleagues from the CDC and Emory University, Atlanta. Dr. Yang presented the findings at the American Heart Association Epidemiology and Prevention, Lifestyle and Cardiometabolic Health 2015 Scientific Sessions.

Statins are now indicated for primary prevention of CVD for anyone with an LDL cholesterol level greater than or equal to 190 mg/dL, for individuals aged 40-75 years with diabetes, and for those aged 40-75 years with LDL cholesterol greater than or equal to 70 mg/dL but less than 190 mg/dL who have at least a 7.5% estimated 10-year risk of developing atherosclerotic CVD. This means that an additional 24.2 million Americans are now eligible for statins but are not taking one, according to Dr. Yang and coinvestigators. However, “no study has assessed the potential impact of statin therapy under the new guidelines,” said Dr. Yang.

In order to obtain treatment group-specific atherosclerotic CVD, investigators first estimated hazard ratios for each treatment group by sex from the National Health and Nutrition Examination Survey III (NHANES III)–linked Mortality files. These hazard ratios were then applied to data from NHANES 2005-2010, the 2010 Multiple Cause of Death file, and the 2010 U.S. census to obtain age/race/sex-specific atherosclerotic CVD for each treatment group.

Applying the per-group hazard ratios, Dr. Yang and colleagues calculated that an annual 7,930 atherosclerotic CVD deaths would be prevented with full statin compliance, a reduction of 12.6%. However, modeling predicted an additional 16,400 additional cases of diabetes caused by statin use, he cautioned. More cases of myopathy would also occur, though the estimated number depends on whether the rate is derived from randomized, controlled trials (RCTs) or from population-based reports of myopathy. If the RCT data are used, just 1,510 excess cases of myopathy would be seen, in contrast to the 36,100 cases predicted by population-based data.

The study could model deaths caused by CVD only and not the reduction in disease burden of CVD that would result if all of the additional 24.2 million Americans took a statin, Dr Yang noted. Other limitations of the study included the lack of agreement in incidence of myopathy between RCTs and population-based studies, as well as the likelihood that the risk of diabetes increases with age and higher statin dose – effects not accounted for in the study.

Questioning after the talk focused on sex-specific differences in statin takers. For example, statin-associated diabetes is more common in women than men, another effect not accounted for in the study’s modeling, noted an audience member. Additionally, given that women have been underrepresented in clinical trials in general and in those for CVD in particular, some modeling assumptions in the present study may also lack full generalizability to women at risk for CVD.