Illustrative case

A 74-year-old woman with chronic lower extremity edema seeks treatment for a nonhealing venous stasis ulcer. For the past 9 months, she’s been wearing compression stockings and receiving intermittent home-based wound care, but nothing seems to help. She asks if there’s anything else she can try.

Venous stasis ulcers affect 1% of US adults and lead to substantial morbidity and more than $2 billion in annual health care expenditures.^1,2 Edema management—generally limb elevation and compression therapy—has been the mainstay of therapy. Treatment can be lengthy, and ulcer recurrences are common.^2,3

Statins have been found to help wound healing through their diverse physiologic (pleiotropic) effects. Evidence shows they can be beneficial for treating diabetic foot ulcers,⁴ pressure ulcers,⁵ and ulcerations associated with systemic sclerosis and Raynaud’s phenomenon.⁶ Evangelista et al¹ investigated whether adding a statin to standard wound care and compression could improve venous stasis ulcer healing.

STUDY SUMMARY: Ulcers are more likely to close when a statin is added to standard care

This randomized, double-blind, placebo-controlled trial was performed at a large medical center in the Philippines. It was designed to assess the efficacy and safety of simvastatin 40 mg/d for venous ulcer healing when combined with standard treatment (compression therapy, limb elevation, and standard wound care).¹

Researchers randomized 66 patients ages 41 to 71 who’d had one or more venous ulcers for at least 3 months to receive either simvastatin 40 mg/d (N=32) or an identical appearing placebo (N=34). Patients were excluded if they were pregnant, had an ulcer that was infected or >10 cm in diameter, or were taking any medication that could interact with a statin. Patients were stratified according to ulcer diameter (≤5 cm and >5 cm). There was no statistically significant difference between the 2 groups in the duration of venous ulceration (3.80 years in the placebo group vs 3.93 years in the simvastatin group) or incidence of diabetes (5% in the placebo group vs 3% in the simvastatin group).

The primary outcome was the proportion of patients whose ulcers completely healed at 10 weeks. Secondary outcomes were measures of the total surface area healed and healing time, and Dermatology Life Quality Index (DLQI) scores. Baseline ulcer diameter and surface area and DLQI scores were obtained prior to therapy. The same dermatologist, who was blinded to the patients’ assigned group, evaluated all patients every 2 weeks until wound closure or for a maximum of 10 weeks.

Overall, 90% of the patients who received simvastatin had complete ulcer closure at 10 weeks, compared with 34% of patients in the control group (relative risk [RR]=0.16; 95% confidence interval [CI], 0.05-0.47; number needed to treat [NNT]=2).

Sixty-seven percent of ulcers >5 cm in the simvastatin group had closure, while none of those in the control group did. Among patients with ulcers ≤5 cm, 100% of the ulcers healed in the simvastatin group, compared to 50% in the control group (RR=0.10; 95% CI, 0.01-0.71; NNT=2). Perhaps more importantly, in patients with ulcers >5 cm, 67% of the ulcers in the simvastatin group had closure with a mean healing time of 9 weeks, whereas none of the ulcers of this size closed in the control group (RR=0.33; 95% CI, 0.12-0.84; NNT=1.5), and the mean healed area was significantly larger in patients who received simvastatin (28.9 cm² vs 19.6 cm²; P=.03).

In addition, in the simvastatin group, healing times were significantly reduced (7.53±1.34 weeks vs 8.55±1.13 weeks) and quality of life (as evaluated by DLQI scoring) significantly improved compared to the control group.

Study dropouts (8%; 2 in the placebo group and 3 in the intervention group) were minimal. Using intention-to-treat analysis and worst-case scenarios for dropouts did not affect the primary outcome. There were no withdrawals for adverse reactions.

WHAT’S NEW: Statins offer significant benefits for treating venous stasis ulcers

This is the first human study to investigate the use of a statin in venous stasis ulcer healing. This intervention demonstrated significant improvements in healing rate and time, a very small NNT for benefit, and improved patient quality of life compared to placebo.

CAVEATS: Results were found in a carefully selected group of patients

Many wounds will heal with compression therapy alone, as occurred in this study, where 50% of ulcers ≤5 cm treated with standard therapy healed, albeit at a somewhat slower rate. Adding another medication to the regimen when these patients generally have multiple comorbidities should always prompt caution.

The study by Evangelista et al¹ was performed in a select population, and the exclusion criteria included the use of some commonly prescribed medications, such as angiotensin-converting enzyme inhibitors. No data were collected on patient body mass index, which is a risk factor for delayed healing. The prevalence of obesity is lower in the Philippines than in the United States, and it is uncertain what role this difference would have in the statin’s effectiveness. Further studies, especially those conducted with a less selective population, would better clarify the generalizability of this intervention.

We found the results of this study impressive. The methods reported are rigorous and consistent with standard RCT methodologies. This is the only study of a statin in human venous stasis disease, but studies in animals—and studies of statins for other types of ulcers in humans—have consistently suggested benefit. It seems hard to argue against adding this low-cost, low-risk intervention.

CHALLENGES TO IMPLEMENTATION

There are no known barriers to implementing this practice.

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.

Illustrative case

A 74-year-old woman with chronic lower extremity edema seeks treatment for a nonhealing venous stasis ulcer. For the past 9 months, she’s been wearing compression stockings and receiving intermittent home-based wound care, but nothing seems to help. She asks if there’s anything else she can try.

Venous stasis ulcers affect 1% of US adults and lead to substantial morbidity and more than $2 billion in annual health care expenditures.^1,2 Edema management—generally limb elevation and compression therapy—has been the mainstay of therapy. Treatment can be lengthy, and ulcer recurrences are common.^2,3

Statins have been found to help wound healing through their diverse physiologic (pleiotropic) effects. Evidence shows they can be beneficial for treating diabetic foot ulcers,⁴ pressure ulcers,⁵ and ulcerations associated with systemic sclerosis and Raynaud’s phenomenon.⁶ Evangelista et al¹ investigated whether adding a statin to standard wound care and compression could improve venous stasis ulcer healing.

STUDY SUMMARY: Ulcers are more likely to close when a statin is added to standard care

This randomized, double-blind, placebo-controlled trial was performed at a large medical center in the Philippines. It was designed to assess the efficacy and safety of simvastatin 40 mg/d for venous ulcer healing when combined with standard treatment (compression therapy, limb elevation, and standard wound care).¹

Researchers randomized 66 patients ages 41 to 71 who’d had one or more venous ulcers for at least 3 months to receive either simvastatin 40 mg/d (N=32) or an identical appearing placebo (N=34). Patients were excluded if they were pregnant, had an ulcer that was infected or >10 cm in diameter, or were taking any medication that could interact with a statin. Patients were stratified according to ulcer diameter (≤5 cm and >5 cm). There was no statistically significant difference between the 2 groups in the duration of venous ulceration (3.80 years in the placebo group vs 3.93 years in the simvastatin group) or incidence of diabetes (5% in the placebo group vs 3% in the simvastatin group).

The primary outcome was the proportion of patients whose ulcers completely healed at 10 weeks. Secondary outcomes were measures of the total surface area healed and healing time, and Dermatology Life Quality Index (DLQI) scores. Baseline ulcer diameter and surface area and DLQI scores were obtained prior to therapy. The same dermatologist, who was blinded to the patients’ assigned group, evaluated all patients every 2 weeks until wound closure or for a maximum of 10 weeks.

Overall, 90% of the patients who received simvastatin had complete ulcer closure at 10 weeks, compared with 34% of patients in the control group (relative risk [RR]=0.16; 95% confidence interval [CI], 0.05-0.47; number needed to treat [NNT]=2).

Sixty-seven percent of ulcers >5 cm in the simvastatin group had closure, while none of those in the control group did. Among patients with ulcers ≤5 cm, 100% of the ulcers healed in the simvastatin group, compared to 50% in the control group (RR=0.10; 95% CI, 0.01-0.71; NNT=2). Perhaps more importantly, in patients with ulcers >5 cm, 67% of the ulcers in the simvastatin group had closure with a mean healing time of 9 weeks, whereas none of the ulcers of this size closed in the control group (RR=0.33; 95% CI, 0.12-0.84; NNT=1.5), and the mean healed area was significantly larger in patients who received simvastatin (28.9 cm² vs 19.6 cm²; P=.03).

In addition, in the simvastatin group, healing times were significantly reduced (7.53±1.34 weeks vs 8.55±1.13 weeks) and quality of life (as evaluated by DLQI scoring) significantly improved compared to the control group.

Study dropouts (8%; 2 in the placebo group and 3 in the intervention group) were minimal. Using intention-to-treat analysis and worst-case scenarios for dropouts did not affect the primary outcome. There were no withdrawals for adverse reactions.

WHAT’S NEW: Statins offer significant benefits for treating venous stasis ulcers

This is the first human study to investigate the use of a statin in venous stasis ulcer healing. This intervention demonstrated significant improvements in healing rate and time, a very small NNT for benefit, and improved patient quality of life compared to placebo.

CAVEATS: Results were found in a carefully selected group of patients

Many wounds will heal with compression therapy alone, as occurred in this study, where 50% of ulcers ≤5 cm treated with standard therapy healed, albeit at a somewhat slower rate. Adding another medication to the regimen when these patients generally have multiple comorbidities should always prompt caution.

The study by Evangelista et al¹ was performed in a select population, and the exclusion criteria included the use of some commonly prescribed medications, such as angiotensin-converting enzyme inhibitors. No data were collected on patient body mass index, which is a risk factor for delayed healing. The prevalence of obesity is lower in the Philippines than in the United States, and it is uncertain what role this difference would have in the statin’s effectiveness. Further studies, especially those conducted with a less selective population, would better clarify the generalizability of this intervention.

We found the results of this study impressive. The methods reported are rigorous and consistent with standard RCT methodologies. This is the only study of a statin in human venous stasis disease, but studies in animals—and studies of statins for other types of ulcers in humans—have consistently suggested benefit. It seems hard to argue against adding this low-cost, low-risk intervention.

CHALLENGES TO IMPLEMENTATION

There are no known barriers to implementing this practice.

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.

Illustrative case

A 74-year-old woman with chronic lower extremity edema seeks treatment for a nonhealing venous stasis ulcer. For the past 9 months, she’s been wearing compression stockings and receiving intermittent home-based wound care, but nothing seems to help. She asks if there’s anything else she can try.

Venous stasis ulcers affect 1% of US adults and lead to substantial morbidity and more than $2 billion in annual health care expenditures.^1,2 Edema management—generally limb elevation and compression therapy—has been the mainstay of therapy. Treatment can be lengthy, and ulcer recurrences are common.^2,3

Statins have been found to help wound healing through their diverse physiologic (pleiotropic) effects. Evidence shows they can be beneficial for treating diabetic foot ulcers,⁴ pressure ulcers,⁵ and ulcerations associated with systemic sclerosis and Raynaud’s phenomenon.⁶ Evangelista et al¹ investigated whether adding a statin to standard wound care and compression could improve venous stasis ulcer healing.

STUDY SUMMARY: Ulcers are more likely to close when a statin is added to standard care

This randomized, double-blind, placebo-controlled trial was performed at a large medical center in the Philippines. It was designed to assess the efficacy and safety of simvastatin 40 mg/d for venous ulcer healing when combined with standard treatment (compression therapy, limb elevation, and standard wound care).¹

Researchers randomized 66 patients ages 41 to 71 who’d had one or more venous ulcers for at least 3 months to receive either simvastatin 40 mg/d (N=32) or an identical appearing placebo (N=34). Patients were excluded if they were pregnant, had an ulcer that was infected or >10 cm in diameter, or were taking any medication that could interact with a statin. Patients were stratified according to ulcer diameter (≤5 cm and >5 cm). There was no statistically significant difference between the 2 groups in the duration of venous ulceration (3.80 years in the placebo group vs 3.93 years in the simvastatin group) or incidence of diabetes (5% in the placebo group vs 3% in the simvastatin group).

The primary outcome was the proportion of patients whose ulcers completely healed at 10 weeks. Secondary outcomes were measures of the total surface area healed and healing time, and Dermatology Life Quality Index (DLQI) scores. Baseline ulcer diameter and surface area and DLQI scores were obtained prior to therapy. The same dermatologist, who was blinded to the patients’ assigned group, evaluated all patients every 2 weeks until wound closure or for a maximum of 10 weeks.

Overall, 90% of the patients who received simvastatin had complete ulcer closure at 10 weeks, compared with 34% of patients in the control group (relative risk [RR]=0.16; 95% confidence interval [CI], 0.05-0.47; number needed to treat [NNT]=2).

Sixty-seven percent of ulcers >5 cm in the simvastatin group had closure, while none of those in the control group did. Among patients with ulcers ≤5 cm, 100% of the ulcers healed in the simvastatin group, compared to 50% in the control group (RR=0.10; 95% CI, 0.01-0.71; NNT=2). Perhaps more importantly, in patients with ulcers >5 cm, 67% of the ulcers in the simvastatin group had closure with a mean healing time of 9 weeks, whereas none of the ulcers of this size closed in the control group (RR=0.33; 95% CI, 0.12-0.84; NNT=1.5), and the mean healed area was significantly larger in patients who received simvastatin (28.9 cm² vs 19.6 cm²; P=.03).

In addition, in the simvastatin group, healing times were significantly reduced (7.53±1.34 weeks vs 8.55±1.13 weeks) and quality of life (as evaluated by DLQI scoring) significantly improved compared to the control group.

Study dropouts (8%; 2 in the placebo group and 3 in the intervention group) were minimal. Using intention-to-treat analysis and worst-case scenarios for dropouts did not affect the primary outcome. There were no withdrawals for adverse reactions.

WHAT’S NEW: Statins offer significant benefits for treating venous stasis ulcers

This is the first human study to investigate the use of a statin in venous stasis ulcer healing. This intervention demonstrated significant improvements in healing rate and time, a very small NNT for benefit, and improved patient quality of life compared to placebo.

CAVEATS: Results were found in a carefully selected group of patients

Many wounds will heal with compression therapy alone, as occurred in this study, where 50% of ulcers ≤5 cm treated with standard therapy healed, albeit at a somewhat slower rate. Adding another medication to the regimen when these patients generally have multiple comorbidities should always prompt caution.

The study by Evangelista et al¹ was performed in a select population, and the exclusion criteria included the use of some commonly prescribed medications, such as angiotensin-converting enzyme inhibitors. No data were collected on patient body mass index, which is a risk factor for delayed healing. The prevalence of obesity is lower in the Philippines than in the United States, and it is uncertain what role this difference would have in the statin’s effectiveness. Further studies, especially those conducted with a less selective population, would better clarify the generalizability of this intervention.

We found the results of this study impressive. The methods reported are rigorous and consistent with standard RCT methodologies. This is the only study of a statin in human venous stasis disease, but studies in animals—and studies of statins for other types of ulcers in humans—have consistently suggested benefit. It seems hard to argue against adding this low-cost, low-risk intervention.

CHALLENGES TO IMPLEMENTATION

There are no known barriers to implementing this practice.

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.

Preparing for HSCT

Photo by Chad McNeeley

A retrospective study has shown that, since the 1980s, the world has seen a substantial increase in the use of hematopoietic stem cell transplants (HSCTs) and a significant rise in the number of donor registries.

Still, it seems many patients who would benefit from HSCT do not undergo the procedure due to a chronic shortage of resources and donors.

Dietger Niederwieser, MD, of the University Hospital Leipzig in Germany, and his colleagues recounted these findings in The Lancet Haematology.

Using data collected by the Worldwide Network for Blood and Marrow Transplantation (WBMT), the researchers systematically analyzed the growth of HSCT and changes in its use in 194 WHO member countries since the first HSCT was performed in 1957.

The team also examined the link between macroeconomic factors (eg, gross national income and healthcare expenditure) and transplant frequencies per 10 million inhabitants in each country.

The data showed that about 10,000 HSCTs had been performed by 1985, but that number rose to around 100,000 by 1995. By December 2012, nearly 1 million HSCTs—42% allogeneic and 58% autologous—had been performed at 1516 transplant centers across 75 countries.

Transplants were more common in countries with greater financial resources, more transplant teams, and an unrelated donor infrastructure. Most transplants were performed in Europe (53%), followed by the Americas (31%), South East Asia and the Western Pacific (15%), and the Eastern Mediterranean and Africa (2%).

The use of allogeneic HSCT has grown rapidly in all regions, without any signs of saturation. This likely reflects substantial underuse of this therapy, according to the researchers. And it suggests more patients would have received allogeneic transplants if they were accessible or suitable donors were available.

On the other hand, the researchers found that the number of countries with donor registries increased from 2 in 1987 to 57 in 2012. And the number of volunteer donors rose from 3072 in 1987 to over 22 million in 2012.

The international exchange of stem cell products also increased to more than 10,000 a year between 2006 and 2012, with substantial differences between countries in the amount of stem cells they import or export.

Despite these increases, the researchers noted that there are still too many patients who are unable to find a suitable donor. At any time, more than 37,000 people worldwide are waiting for an HSC donation.

“Patients, many of them children, are facing a life-and-death situation,” Dr Niederwieser said. “Ultimately, they will die if they cannot get the treatment they need. All countries need to provide adequate infrastructure for patients and donors to make sure that everyone who needs a transplant gets one, rather than the present situation in which access remains restricted to countries and people with sufficient resources.”

Preparing for HSCT

Photo by Chad McNeeley

A retrospective study has shown that, since the 1980s, the world has seen a substantial increase in the use of hematopoietic stem cell transplants (HSCTs) and a significant rise in the number of donor registries.

Still, it seems many patients who would benefit from HSCT do not undergo the procedure due to a chronic shortage of resources and donors.

Dietger Niederwieser, MD, of the University Hospital Leipzig in Germany, and his colleagues recounted these findings in The Lancet Haematology.

Using data collected by the Worldwide Network for Blood and Marrow Transplantation (WBMT), the researchers systematically analyzed the growth of HSCT and changes in its use in 194 WHO member countries since the first HSCT was performed in 1957.

The team also examined the link between macroeconomic factors (eg, gross national income and healthcare expenditure) and transplant frequencies per 10 million inhabitants in each country.

The data showed that about 10,000 HSCTs had been performed by 1985, but that number rose to around 100,000 by 1995. By December 2012, nearly 1 million HSCTs—42% allogeneic and 58% autologous—had been performed at 1516 transplant centers across 75 countries.

Transplants were more common in countries with greater financial resources, more transplant teams, and an unrelated donor infrastructure. Most transplants were performed in Europe (53%), followed by the Americas (31%), South East Asia and the Western Pacific (15%), and the Eastern Mediterranean and Africa (2%).

The use of allogeneic HSCT has grown rapidly in all regions, without any signs of saturation. This likely reflects substantial underuse of this therapy, according to the researchers. And it suggests more patients would have received allogeneic transplants if they were accessible or suitable donors were available.

On the other hand, the researchers found that the number of countries with donor registries increased from 2 in 1987 to 57 in 2012. And the number of volunteer donors rose from 3072 in 1987 to over 22 million in 2012.

The international exchange of stem cell products also increased to more than 10,000 a year between 2006 and 2012, with substantial differences between countries in the amount of stem cells they import or export.

Despite these increases, the researchers noted that there are still too many patients who are unable to find a suitable donor. At any time, more than 37,000 people worldwide are waiting for an HSC donation.

“Patients, many of them children, are facing a life-and-death situation,” Dr Niederwieser said. “Ultimately, they will die if they cannot get the treatment they need. All countries need to provide adequate infrastructure for patients and donors to make sure that everyone who needs a transplant gets one, rather than the present situation in which access remains restricted to countries and people with sufficient resources.”

Preparing for HSCT

Photo by Chad McNeeley

A retrospective study has shown that, since the 1980s, the world has seen a substantial increase in the use of hematopoietic stem cell transplants (HSCTs) and a significant rise in the number of donor registries.

Still, it seems many patients who would benefit from HSCT do not undergo the procedure due to a chronic shortage of resources and donors.

Dietger Niederwieser, MD, of the University Hospital Leipzig in Germany, and his colleagues recounted these findings in The Lancet Haematology.

Using data collected by the Worldwide Network for Blood and Marrow Transplantation (WBMT), the researchers systematically analyzed the growth of HSCT and changes in its use in 194 WHO member countries since the first HSCT was performed in 1957.

The team also examined the link between macroeconomic factors (eg, gross national income and healthcare expenditure) and transplant frequencies per 10 million inhabitants in each country.

The data showed that about 10,000 HSCTs had been performed by 1985, but that number rose to around 100,000 by 1995. By December 2012, nearly 1 million HSCTs—42% allogeneic and 58% autologous—had been performed at 1516 transplant centers across 75 countries.

Transplants were more common in countries with greater financial resources, more transplant teams, and an unrelated donor infrastructure. Most transplants were performed in Europe (53%), followed by the Americas (31%), South East Asia and the Western Pacific (15%), and the Eastern Mediterranean and Africa (2%).

The use of allogeneic HSCT has grown rapidly in all regions, without any signs of saturation. This likely reflects substantial underuse of this therapy, according to the researchers. And it suggests more patients would have received allogeneic transplants if they were accessible or suitable donors were available.

On the other hand, the researchers found that the number of countries with donor registries increased from 2 in 1987 to 57 in 2012. And the number of volunteer donors rose from 3072 in 1987 to over 22 million in 2012.

The international exchange of stem cell products also increased to more than 10,000 a year between 2006 and 2012, with substantial differences between countries in the amount of stem cells they import or export.

Despite these increases, the researchers noted that there are still too many patients who are unable to find a suitable donor. At any time, more than 37,000 people worldwide are waiting for an HSC donation.

“Patients, many of them children, are facing a life-and-death situation,” Dr Niederwieser said. “Ultimately, they will die if they cannot get the treatment they need. All countries need to provide adequate infrastructure for patients and donors to make sure that everyone who needs a transplant gets one, rather than the present situation in which access remains restricted to countries and people with sufficient resources.”

Hematopoietic stem cells

in the bone marrow

The incidence of clonal hematopoiesis in the general population may be higher than we thought and appears to increase dramatically with age, according to research published in Cell Reports.

Investigators used ultra-deep sequencing to search for evidence of clonal hematopoiesis driven by 15 recurrent leukemogenic mutations.

They sequenced DNA from more than 4000 subjects who had no evidence of hematologic malignancy.

And the incidence of clonal hematopoiesis was higher than has been observed in previous, exome-sequencing studies—0.8% in subjects under 60, rising to 19.5% in subjects ages 90 to 98.

“Ultra-deep sequencing has allowed us to see the very beginnings of cancer,” said study author George Vassiliou, MD, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“These mutations will be harmless for the majority of people, but, for a few unlucky carriers, they will take the body on a journey towards leukemia. We are now beginning to understand the major landmarks on that journey.”

The investigators found that mutations affecting 2 genes, SF3B1 and SRSF2, appeared exclusively in 70-year-olds.

This suggests these mutations only confer a growth benefit for cells later in life, when there is less competition. And it explains why myelodysplastic syndromes, which are associated with these genes, appear almost exclusively in the elderly.

None of the 4219 subjects studied had mutations in the NPM1 gene, which is mutated in up to 40% of leukemia cases.

This unexpected result suggests that mutations in NPM1 behave as gatekeepers for leukemia, the investigators said. Once a mutation in this gene occurs in a cell with particular, previously accumulated, pre-leukemic mutations, leukemia will develop.

“The significance of mutations in this gene is astonishingly clear from these results: it simply doesn’t exist where there is no leukemia,” said study author Naomi Park, PhD, of the Wellcome Trust Sanger Institute.

“When it is mutated in the appropriate cell, the floodgates open, and leukemia is then very likely to develop. This fits with studies we’ve conducted in the past in which we found that the gene primes blood stem cells for leukemic transformation.”

Hematopoietic stem cells

in the bone marrow

The incidence of clonal hematopoiesis in the general population may be higher than we thought and appears to increase dramatically with age, according to research published in Cell Reports.

Investigators used ultra-deep sequencing to search for evidence of clonal hematopoiesis driven by 15 recurrent leukemogenic mutations.

They sequenced DNA from more than 4000 subjects who had no evidence of hematologic malignancy.

And the incidence of clonal hematopoiesis was higher than has been observed in previous, exome-sequencing studies—0.8% in subjects under 60, rising to 19.5% in subjects ages 90 to 98.

“Ultra-deep sequencing has allowed us to see the very beginnings of cancer,” said study author George Vassiliou, MD, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“These mutations will be harmless for the majority of people, but, for a few unlucky carriers, they will take the body on a journey towards leukemia. We are now beginning to understand the major landmarks on that journey.”

The investigators found that mutations affecting 2 genes, SF3B1 and SRSF2, appeared exclusively in 70-year-olds.

This suggests these mutations only confer a growth benefit for cells later in life, when there is less competition. And it explains why myelodysplastic syndromes, which are associated with these genes, appear almost exclusively in the elderly.

None of the 4219 subjects studied had mutations in the NPM1 gene, which is mutated in up to 40% of leukemia cases.

This unexpected result suggests that mutations in NPM1 behave as gatekeepers for leukemia, the investigators said. Once a mutation in this gene occurs in a cell with particular, previously accumulated, pre-leukemic mutations, leukemia will develop.

“The significance of mutations in this gene is astonishingly clear from these results: it simply doesn’t exist where there is no leukemia,” said study author Naomi Park, PhD, of the Wellcome Trust Sanger Institute.

“When it is mutated in the appropriate cell, the floodgates open, and leukemia is then very likely to develop. This fits with studies we’ve conducted in the past in which we found that the gene primes blood stem cells for leukemic transformation.”

Hematopoietic stem cells

in the bone marrow

The incidence of clonal hematopoiesis in the general population may be higher than we thought and appears to increase dramatically with age, according to research published in Cell Reports.

Investigators used ultra-deep sequencing to search for evidence of clonal hematopoiesis driven by 15 recurrent leukemogenic mutations.

They sequenced DNA from more than 4000 subjects who had no evidence of hematologic malignancy.

And the incidence of clonal hematopoiesis was higher than has been observed in previous, exome-sequencing studies—0.8% in subjects under 60, rising to 19.5% in subjects ages 90 to 98.

“Ultra-deep sequencing has allowed us to see the very beginnings of cancer,” said study author George Vassiliou, MD, PhD, of the Wellcome Trust Sanger Institute in Cambridge, UK.

“These mutations will be harmless for the majority of people, but, for a few unlucky carriers, they will take the body on a journey towards leukemia. We are now beginning to understand the major landmarks on that journey.”

The investigators found that mutations affecting 2 genes, SF3B1 and SRSF2, appeared exclusively in 70-year-olds.

This suggests these mutations only confer a growth benefit for cells later in life, when there is less competition. And it explains why myelodysplastic syndromes, which are associated with these genes, appear almost exclusively in the elderly.

None of the 4219 subjects studied had mutations in the NPM1 gene, which is mutated in up to 40% of leukemia cases.

This unexpected result suggests that mutations in NPM1 behave as gatekeepers for leukemia, the investigators said. Once a mutation in this gene occurs in a cell with particular, previously accumulated, pre-leukemic mutations, leukemia will develop.

“The significance of mutations in this gene is astonishingly clear from these results: it simply doesn’t exist where there is no leukemia,” said study author Naomi Park, PhD, of the Wellcome Trust Sanger Institute.

“When it is mutated in the appropriate cell, the floodgates open, and leukemia is then very likely to develop. This fits with studies we’ve conducted in the past in which we found that the gene primes blood stem cells for leukemic transformation.”

Lab mouse

The use of animals in experimental research conducted at leading US laboratories has risen by more than 70% in recent years, according to a study published in the Journal of Medical Ethics.

The data contradict industry claims of reduced animal use and are at odds with government policies designed to curb and replace the use of animals in experiments, according to researchers.

The US is the world’s largest user of animals in experiments. And government data show declines in the use of cats, dogs, primates, rabbits, hamsters, and other larger mammals.

But the exclusion of the species most commonly used in laboratory research—mice, rats, birds, and all cold-blooded animals—from federal regulations has resulted in an absence of published data on how many of these animals are used in experiments.

To fill this gap, researchers at People for the Ethical Treatment of Animals (PETA) analyzed previously unpublished data collected by the National Institutes of Health (NIH) on the use of all vertebrate species at the top 25 institutions in receipt of NIH grants.

This includes such institutions as Harvard University, Yale University, Columbia University, the University of California-San Francisco, the University of Wisconsin-Madison, and Johns Hopkins University. Together, these institutions account for 27% of all NIH grants disbursed.

PETA’s analysis showed that the use of animals in laboratory research at these facilities rose by 72.7% between 1997 and 2012. This increase was largely driven by an increase in the use of mice. The use of other species remained mostly unchanged.

This study is the first ever to document figures on the use of mice, rats, birds, fish, reptiles, and amphibians in US laboratories. These species are not protected under the federal law governing the treatment of animals used in experiments—the Animal Welfare Act—and therefore are excluded from the law’s reporting requirements.

PETA’s study showed that these unregulated species comprise 98.8% of animals in laboratories.

The researchers said possible explanations for these results include personal and legal biases toward certain animal species. But the figures highlight a need for greater efforts to curb the use of animals in scientific research and more transparency in reporting on whether such efforts are succeeding.

A linked viewpoint article acknowledges the ongoing tensions between scientists and animal rights advocates but suggests that people on both sides of the divide do want to better understand one another.

It recommends that institutional policies be updated to better inform the public about the use of animals in scientific research, as well as opening up dialogue between a broad base of players to replace the often poorly informed and emotionally charged debate.

Lab mouse

The use of animals in experimental research conducted at leading US laboratories has risen by more than 70% in recent years, according to a study published in the Journal of Medical Ethics.

The data contradict industry claims of reduced animal use and are at odds with government policies designed to curb and replace the use of animals in experiments, according to researchers.

The US is the world’s largest user of animals in experiments. And government data show declines in the use of cats, dogs, primates, rabbits, hamsters, and other larger mammals.

But the exclusion of the species most commonly used in laboratory research—mice, rats, birds, and all cold-blooded animals—from federal regulations has resulted in an absence of published data on how many of these animals are used in experiments.

To fill this gap, researchers at People for the Ethical Treatment of Animals (PETA) analyzed previously unpublished data collected by the National Institutes of Health (NIH) on the use of all vertebrate species at the top 25 institutions in receipt of NIH grants.

This includes such institutions as Harvard University, Yale University, Columbia University, the University of California-San Francisco, the University of Wisconsin-Madison, and Johns Hopkins University. Together, these institutions account for 27% of all NIH grants disbursed.

PETA’s analysis showed that the use of animals in laboratory research at these facilities rose by 72.7% between 1997 and 2012. This increase was largely driven by an increase in the use of mice. The use of other species remained mostly unchanged.

This study is the first ever to document figures on the use of mice, rats, birds, fish, reptiles, and amphibians in US laboratories. These species are not protected under the federal law governing the treatment of animals used in experiments—the Animal Welfare Act—and therefore are excluded from the law’s reporting requirements.

PETA’s study showed that these unregulated species comprise 98.8% of animals in laboratories.

The researchers said possible explanations for these results include personal and legal biases toward certain animal species. But the figures highlight a need for greater efforts to curb the use of animals in scientific research and more transparency in reporting on whether such efforts are succeeding.

A linked viewpoint article acknowledges the ongoing tensions between scientists and animal rights advocates but suggests that people on both sides of the divide do want to better understand one another.

It recommends that institutional policies be updated to better inform the public about the use of animals in scientific research, as well as opening up dialogue between a broad base of players to replace the often poorly informed and emotionally charged debate.

Lab mouse

The use of animals in experimental research conducted at leading US laboratories has risen by more than 70% in recent years, according to a study published in the Journal of Medical Ethics.

The data contradict industry claims of reduced animal use and are at odds with government policies designed to curb and replace the use of animals in experiments, according to researchers.

The US is the world’s largest user of animals in experiments. And government data show declines in the use of cats, dogs, primates, rabbits, hamsters, and other larger mammals.

But the exclusion of the species most commonly used in laboratory research—mice, rats, birds, and all cold-blooded animals—from federal regulations has resulted in an absence of published data on how many of these animals are used in experiments.

To fill this gap, researchers at People for the Ethical Treatment of Animals (PETA) analyzed previously unpublished data collected by the National Institutes of Health (NIH) on the use of all vertebrate species at the top 25 institutions in receipt of NIH grants.

This includes such institutions as Harvard University, Yale University, Columbia University, the University of California-San Francisco, the University of Wisconsin-Madison, and Johns Hopkins University. Together, these institutions account for 27% of all NIH grants disbursed.

PETA’s analysis showed that the use of animals in laboratory research at these facilities rose by 72.7% between 1997 and 2012. This increase was largely driven by an increase in the use of mice. The use of other species remained mostly unchanged.

This study is the first ever to document figures on the use of mice, rats, birds, fish, reptiles, and amphibians in US laboratories. These species are not protected under the federal law governing the treatment of animals used in experiments—the Animal Welfare Act—and therefore are excluded from the law’s reporting requirements.

PETA’s study showed that these unregulated species comprise 98.8% of animals in laboratories.

The researchers said possible explanations for these results include personal and legal biases toward certain animal species. But the figures highlight a need for greater efforts to curb the use of animals in scientific research and more transparency in reporting on whether such efforts are succeeding.

A linked viewpoint article acknowledges the ongoing tensions between scientists and animal rights advocates but suggests that people on both sides of the divide do want to better understand one another.

It recommends that institutional policies be updated to better inform the public about the use of animals in scientific research, as well as opening up dialogue between a broad base of players to replace the often poorly informed and emotionally charged debate.

Doctor evaluating a patient

Photo courtesy of CDC

In reviewing 4 clinical trials of ibrutinib, researchers found that a quarter of chronic lymphocytic leukemia (CLL) patients discontinued treatment with the Bruton tyrosine kinase (BTK) inhibitor.

Ten percent of patients stopped taking the drug due to disease progression, and 15% stopped because of adverse and medical events.

Sequencing data indicated that mutations in BTK and PLCG2 were associated with CLL progression but not Richter’s transformation (RT).

Jennifer A. Woyach, MD, of Ohio State University in Columbus, and her colleagues detailed these discoveries in JAMA Oncology.

The researchers evaluated 308 patients participating in 4 trials conducted at a single institution. The team described the characteristics and outcomes of the patients who discontinued treatment with ibrutinib.

At a median follow-up of 20 months, 232 of the patients studied (75%) remained on therapy, including 7 patients who went off study to undergo stem cell transplant or receive ibrutinib commercially at another center.

Forty-five patients (15%) discontinued treatment following adverse or medical events—28 due to infection, 8 for other adverse events, and 9 due to other medical events. This included 2 patients who needed anticoagulation, 2 with comorbid medical conditions, 1 case of progressive multifocal leukoencephalopathy in a patient who had received rituximab, 1 case of noncompliance, 1 failure to thrive, 1 sudden cardiac death, and 1 cerebrovascular event.

Thirty-one patients (10%) discontinued treatment due to disease progression. Progression included RT or progressive CLL. RT appeared to occur early and CLL progression later. The median survival was 3.5 months after RT and 17.6 months after CLL progression.

Deep sequencing performed on 11 patients with CLL progression revealed BTK or PLCG2 mutations in all of them. But sequencing data on peripheral blood from 8 patients with RT showed that only 2 patients had mutations in BTK, and a lymph node sample showed no mutations in BTK or PLCG2.

Doctor evaluating a patient

Photo courtesy of CDC

In reviewing 4 clinical trials of ibrutinib, researchers found that a quarter of chronic lymphocytic leukemia (CLL) patients discontinued treatment with the Bruton tyrosine kinase (BTK) inhibitor.

Ten percent of patients stopped taking the drug due to disease progression, and 15% stopped because of adverse and medical events.

Sequencing data indicated that mutations in BTK and PLCG2 were associated with CLL progression but not Richter’s transformation (RT).

Jennifer A. Woyach, MD, of Ohio State University in Columbus, and her colleagues detailed these discoveries in JAMA Oncology.

The researchers evaluated 308 patients participating in 4 trials conducted at a single institution. The team described the characteristics and outcomes of the patients who discontinued treatment with ibrutinib.

At a median follow-up of 20 months, 232 of the patients studied (75%) remained on therapy, including 7 patients who went off study to undergo stem cell transplant or receive ibrutinib commercially at another center.

Forty-five patients (15%) discontinued treatment following adverse or medical events—28 due to infection, 8 for other adverse events, and 9 due to other medical events. This included 2 patients who needed anticoagulation, 2 with comorbid medical conditions, 1 case of progressive multifocal leukoencephalopathy in a patient who had received rituximab, 1 case of noncompliance, 1 failure to thrive, 1 sudden cardiac death, and 1 cerebrovascular event.

Thirty-one patients (10%) discontinued treatment due to disease progression. Progression included RT or progressive CLL. RT appeared to occur early and CLL progression later. The median survival was 3.5 months after RT and 17.6 months after CLL progression.

Deep sequencing performed on 11 patients with CLL progression revealed BTK or PLCG2 mutations in all of them. But sequencing data on peripheral blood from 8 patients with RT showed that only 2 patients had mutations in BTK, and a lymph node sample showed no mutations in BTK or PLCG2.

Doctor evaluating a patient

Photo courtesy of CDC

In reviewing 4 clinical trials of ibrutinib, researchers found that a quarter of chronic lymphocytic leukemia (CLL) patients discontinued treatment with the Bruton tyrosine kinase (BTK) inhibitor.

Ten percent of patients stopped taking the drug due to disease progression, and 15% stopped because of adverse and medical events.

Sequencing data indicated that mutations in BTK and PLCG2 were associated with CLL progression but not Richter’s transformation (RT).

Jennifer A. Woyach, MD, of Ohio State University in Columbus, and her colleagues detailed these discoveries in JAMA Oncology.

The researchers evaluated 308 patients participating in 4 trials conducted at a single institution. The team described the characteristics and outcomes of the patients who discontinued treatment with ibrutinib.

At a median follow-up of 20 months, 232 of the patients studied (75%) remained on therapy, including 7 patients who went off study to undergo stem cell transplant or receive ibrutinib commercially at another center.

Forty-five patients (15%) discontinued treatment following adverse or medical events—28 due to infection, 8 for other adverse events, and 9 due to other medical events. This included 2 patients who needed anticoagulation, 2 with comorbid medical conditions, 1 case of progressive multifocal leukoencephalopathy in a patient who had received rituximab, 1 case of noncompliance, 1 failure to thrive, 1 sudden cardiac death, and 1 cerebrovascular event.

Thirty-one patients (10%) discontinued treatment due to disease progression. Progression included RT or progressive CLL. RT appeared to occur early and CLL progression later. The median survival was 3.5 months after RT and 17.6 months after CLL progression.

Deep sequencing performed on 11 patients with CLL progression revealed BTK or PLCG2 mutations in all of them. But sequencing data on peripheral blood from 8 patients with RT showed that only 2 patients had mutations in BTK, and a lymph node sample showed no mutations in BTK or PLCG2.

EVIDENCE SUMMARY

A systematic review of 7 RCTs with a total of 477 adults that examined the efficacy of ICS compared with placebo for treating subacute (3-8 weeks) and chronic (>8 weeks) cough found inconsistent, but mostly negative results.¹ Most trials combined patients with nonspecific subacute and chronic cough.

The evaluated steroids included beclomethasone, budesonide, fluticasone, and mometasone; daily “budesonide equivalent” doses ranged from 320 mcg to 1600 mcg. Six of the 7 trials found that ICS didn’t improve cough. The seventh didn’t treat patients with postviral cough. The authors of the review couldn’t pool data because of heterogeneity.

Steroids don’t affect methacholine challenge in teens

A double-blind, placebo-controlled RCT of 56 adolescents found that giving ICS after viral upper respiratory infection didn’t change the methacholine dosing necessary to produce a 20% reduction in the forced expiratory volume in one second (FEV₁).² Investigators included patients if they had a previous diagnosis of asthma but no use of asthma medications in 2 years, a baseline FEV₁ greater than 70% of predicted, and a concentration of methacholine that produced a 20% fall in FEV₁ less than 8 mg/mL.

They randomized patients to inhaled budesonide (2 200-mcg puffs bid) or placebo (2 500-mcg puffs micronized lactose bid). Patients underwent spirometry and methacholine challenge testing every 3 months over a 9-month period. The groups didn’t differ in bronchial hyperresponsiveness or FEV₁.

Lower respiratory symptoms don’t respond to ICS in nonasthmatic children

A systematic review of 5 RCTs with a total of 339 patients found that in 4 of the 5, ICS didn’t improve lower respiratory symptoms in children with episodic viral wheeze and no history of asthma.³ Investigators evaluated ICS efficacy using lower respiratory symptom scores (based primarily on cough and wheeze) and decreased use of oral steroids or reduced emergency room visits.

Four trials found no benefit from ICS; one trial (52 children with viral-induced wheeze) found that nebulized budesonide (400 mg qid for 2 days, then bid for 7 days) decreased respiratory symptom scores (weighted mean difference= -0.17; 95% confidence interval, -0.34 to -0.003) compared with placebo. Investigators didn’t assess cough separately from wheezing, however.

EVIDENCE SUMMARY

A systematic review of 7 RCTs with a total of 477 adults that examined the efficacy of ICS compared with placebo for treating subacute (3-8 weeks) and chronic (>8 weeks) cough found inconsistent, but mostly negative results.¹ Most trials combined patients with nonspecific subacute and chronic cough.

The evaluated steroids included beclomethasone, budesonide, fluticasone, and mometasone; daily “budesonide equivalent” doses ranged from 320 mcg to 1600 mcg. Six of the 7 trials found that ICS didn’t improve cough. The seventh didn’t treat patients with postviral cough. The authors of the review couldn’t pool data because of heterogeneity.

Steroids don’t affect methacholine challenge in teens

A double-blind, placebo-controlled RCT of 56 adolescents found that giving ICS after viral upper respiratory infection didn’t change the methacholine dosing necessary to produce a 20% reduction in the forced expiratory volume in one second (FEV₁).² Investigators included patients if they had a previous diagnosis of asthma but no use of asthma medications in 2 years, a baseline FEV₁ greater than 70% of predicted, and a concentration of methacholine that produced a 20% fall in FEV₁ less than 8 mg/mL.

They randomized patients to inhaled budesonide (2 200-mcg puffs bid) or placebo (2 500-mcg puffs micronized lactose bid). Patients underwent spirometry and methacholine challenge testing every 3 months over a 9-month period. The groups didn’t differ in bronchial hyperresponsiveness or FEV₁.

Lower respiratory symptoms don’t respond to ICS in nonasthmatic children

A systematic review of 5 RCTs with a total of 339 patients found that in 4 of the 5, ICS didn’t improve lower respiratory symptoms in children with episodic viral wheeze and no history of asthma.³ Investigators evaluated ICS efficacy using lower respiratory symptom scores (based primarily on cough and wheeze) and decreased use of oral steroids or reduced emergency room visits.

Four trials found no benefit from ICS; one trial (52 children with viral-induced wheeze) found that nebulized budesonide (400 mg qid for 2 days, then bid for 7 days) decreased respiratory symptom scores (weighted mean difference= -0.17; 95% confidence interval, -0.34 to -0.003) compared with placebo. Investigators didn’t assess cough separately from wheezing, however.

EVIDENCE SUMMARY

A systematic review of 7 RCTs with a total of 477 adults that examined the efficacy of ICS compared with placebo for treating subacute (3-8 weeks) and chronic (>8 weeks) cough found inconsistent, but mostly negative results.¹ Most trials combined patients with nonspecific subacute and chronic cough.

The evaluated steroids included beclomethasone, budesonide, fluticasone, and mometasone; daily “budesonide equivalent” doses ranged from 320 mcg to 1600 mcg. Six of the 7 trials found that ICS didn’t improve cough. The seventh didn’t treat patients with postviral cough. The authors of the review couldn’t pool data because of heterogeneity.

Steroids don’t affect methacholine challenge in teens

A double-blind, placebo-controlled RCT of 56 adolescents found that giving ICS after viral upper respiratory infection didn’t change the methacholine dosing necessary to produce a 20% reduction in the forced expiratory volume in one second (FEV₁).² Investigators included patients if they had a previous diagnosis of asthma but no use of asthma medications in 2 years, a baseline FEV₁ greater than 70% of predicted, and a concentration of methacholine that produced a 20% fall in FEV₁ less than 8 mg/mL.

They randomized patients to inhaled budesonide (2 200-mcg puffs bid) or placebo (2 500-mcg puffs micronized lactose bid). Patients underwent spirometry and methacholine challenge testing every 3 months over a 9-month period. The groups didn’t differ in bronchial hyperresponsiveness or FEV₁.

Lower respiratory symptoms don’t respond to ICS in nonasthmatic children

A systematic review of 5 RCTs with a total of 339 patients found that in 4 of the 5, ICS didn’t improve lower respiratory symptoms in children with episodic viral wheeze and no history of asthma.³ Investigators evaluated ICS efficacy using lower respiratory symptom scores (based primarily on cough and wheeze) and decreased use of oral steroids or reduced emergency room visits.

Four trials found no benefit from ICS; one trial (52 children with viral-induced wheeze) found that nebulized budesonide (400 mg qid for 2 days, then bid for 7 days) decreased respiratory symptom scores (weighted mean difference= -0.17; 95% confidence interval, -0.34 to -0.003) compared with placebo. Investigators didn’t assess cough separately from wheezing, however.

EVIDENCE SUMMARY

A review of 3 double-blind, placebo-controlled RCTs compared topical, oral, and IV acyclovir in patients with a first episode of genital herpes.¹ Researchers recruited a total of 138 patients and randomized them to receive either placebo or one of the following: oral acyclovir (200 mg 5 times daily for 10 days), IV acyclovir (5 mg/kg dose, 3 times daily for 5 days), or 5% topical acyclovir in polyethylene glycol (4 times daily for 6 days).

All treatments shortened duration of pain compared with placebo: oral (3 days vs 7 days, P<.01), IV (5 days vs 9 days, P<.05), and topical (5 days vs 7 days, P<.05).

A subsequent RCT with 50 patients found that adding topical acyclovir to oral acyclovir was no more effective than oral acyclovir alone.²

Oral acyclovir, valacyclovir, and famciclovir work equally well

Head-to-head trials comparing acyclovir with valacyclovir or famciclovir show no difference in decreased duration of pain caused by primary genital herpes. An RCT of 643 adults found valacyclovir (1000 mg twice daily for 10 days) to be as effective and well-tolerated as acyclovir (200 mg 5 times daily for 10 days).³ An RCT of  951 adults demonstrated that famciclovir (250 mg 3 times daily for either 5 or 10 days) worked as well as acyclovir (200 mg 5 times daily for 10 days).⁴

General treatment measures

Expert opinion recommends the following general treatment measures for genital herpes lesions: keeping the affected area clean and dry, wearing dry, loose-fitting clothing and cotton underwear, and not touching the lesions. Additional symptomatic treatments for local pain include ice packs, baking soda compresses, warm baths, oral analgesics, topical anesthetics, and drying the affected area with cool air.^5-8

CAM approaches lack evidence of efficacy

A 2005 nonsystematic review of available scientific data on complementary and alternative medicine found a lack of evidence or conflicting evidence concerning the use of aloe vera, echinacea, L-lysine, bee products (honey pollen), zinc, and eleuthero for the treatment of pain in genital herpes.⁹

RECOMMENDATIONS

Clinical practice guidelines recommend prescribing oral antiviral therapy for patients with a first episode of genital herpes because patients with mild clinical findings at onset may develop severe or prolonged symptoms. Choices include a 7- to 10-day course of valacyclovir 1 g twice a day, famciclovir 250 mg 3 times a day, acyclovir 400 mg 3 times a day, or acyclovir 400 mg 5 times a day.^5,10

The guidelines recommend treating patients with severe disease (such as disseminated infection, pneumonitis, hepatitis, or meningoencephalitis) with IV acyclovir (5-10 mg/kg every 8 hours for 2-7 days or until clinical improvement), followed by oral acyclovir for at least 10 days.

EVIDENCE SUMMARY

A review of 3 double-blind, placebo-controlled RCTs compared topical, oral, and IV acyclovir in patients with a first episode of genital herpes.¹ Researchers recruited a total of 138 patients and randomized them to receive either placebo or one of the following: oral acyclovir (200 mg 5 times daily for 10 days), IV acyclovir (5 mg/kg dose, 3 times daily for 5 days), or 5% topical acyclovir in polyethylene glycol (4 times daily for 6 days).

All treatments shortened duration of pain compared with placebo: oral (3 days vs 7 days, P<.01), IV (5 days vs 9 days, P<.05), and topical (5 days vs 7 days, P<.05).

A subsequent RCT with 50 patients found that adding topical acyclovir to oral acyclovir was no more effective than oral acyclovir alone.²

Oral acyclovir, valacyclovir, and famciclovir work equally well

Head-to-head trials comparing acyclovir with valacyclovir or famciclovir show no difference in decreased duration of pain caused by primary genital herpes. An RCT of 643 adults found valacyclovir (1000 mg twice daily for 10 days) to be as effective and well-tolerated as acyclovir (200 mg 5 times daily for 10 days).³ An RCT of  951 adults demonstrated that famciclovir (250 mg 3 times daily for either 5 or 10 days) worked as well as acyclovir (200 mg 5 times daily for 10 days).⁴

General treatment measures

Expert opinion recommends the following general treatment measures for genital herpes lesions: keeping the affected area clean and dry, wearing dry, loose-fitting clothing and cotton underwear, and not touching the lesions. Additional symptomatic treatments for local pain include ice packs, baking soda compresses, warm baths, oral analgesics, topical anesthetics, and drying the affected area with cool air.^5-8

CAM approaches lack evidence of efficacy

A 2005 nonsystematic review of available scientific data on complementary and alternative medicine found a lack of evidence or conflicting evidence concerning the use of aloe vera, echinacea, L-lysine, bee products (honey pollen), zinc, and eleuthero for the treatment of pain in genital herpes.⁹

RECOMMENDATIONS

Clinical practice guidelines recommend prescribing oral antiviral therapy for patients with a first episode of genital herpes because patients with mild clinical findings at onset may develop severe or prolonged symptoms. Choices include a 7- to 10-day course of valacyclovir 1 g twice a day, famciclovir 250 mg 3 times a day, acyclovir 400 mg 3 times a day, or acyclovir 400 mg 5 times a day.^5,10

The guidelines recommend treating patients with severe disease (such as disseminated infection, pneumonitis, hepatitis, or meningoencephalitis) with IV acyclovir (5-10 mg/kg every 8 hours for 2-7 days or until clinical improvement), followed by oral acyclovir for at least 10 days.

EVIDENCE SUMMARY

A review of 3 double-blind, placebo-controlled RCTs compared topical, oral, and IV acyclovir in patients with a first episode of genital herpes.¹ Researchers recruited a total of 138 patients and randomized them to receive either placebo or one of the following: oral acyclovir (200 mg 5 times daily for 10 days), IV acyclovir (5 mg/kg dose, 3 times daily for 5 days), or 5% topical acyclovir in polyethylene glycol (4 times daily for 6 days).

All treatments shortened duration of pain compared with placebo: oral (3 days vs 7 days, P<.01), IV (5 days vs 9 days, P<.05), and topical (5 days vs 7 days, P<.05).

A subsequent RCT with 50 patients found that adding topical acyclovir to oral acyclovir was no more effective than oral acyclovir alone.²

Oral acyclovir, valacyclovir, and famciclovir work equally well

Head-to-head trials comparing acyclovir with valacyclovir or famciclovir show no difference in decreased duration of pain caused by primary genital herpes. An RCT of 643 adults found valacyclovir (1000 mg twice daily for 10 days) to be as effective and well-tolerated as acyclovir (200 mg 5 times daily for 10 days).³ An RCT of  951 adults demonstrated that famciclovir (250 mg 3 times daily for either 5 or 10 days) worked as well as acyclovir (200 mg 5 times daily for 10 days).⁴

General treatment measures

Expert opinion recommends the following general treatment measures for genital herpes lesions: keeping the affected area clean and dry, wearing dry, loose-fitting clothing and cotton underwear, and not touching the lesions. Additional symptomatic treatments for local pain include ice packs, baking soda compresses, warm baths, oral analgesics, topical anesthetics, and drying the affected area with cool air.^5-8

CAM approaches lack evidence of efficacy

A 2005 nonsystematic review of available scientific data on complementary and alternative medicine found a lack of evidence or conflicting evidence concerning the use of aloe vera, echinacea, L-lysine, bee products (honey pollen), zinc, and eleuthero for the treatment of pain in genital herpes.⁹

RECOMMENDATIONS

Clinical practice guidelines recommend prescribing oral antiviral therapy for patients with a first episode of genital herpes because patients with mild clinical findings at onset may develop severe or prolonged symptoms. Choices include a 7- to 10-day course of valacyclovir 1 g twice a day, famciclovir 250 mg 3 times a day, acyclovir 400 mg 3 times a day, or acyclovir 400 mg 5 times a day.^5,10

The guidelines recommend treating patients with severe disease (such as disseminated infection, pneumonitis, hepatitis, or meningoencephalitis) with IV acyclovir (5-10 mg/kg every 8 hours for 2-7 days or until clinical improvement), followed by oral acyclovir for at least 10 days.

For about one in five patients with known atherosclerotic coronary artery disease, standard-dose therapy with statins did not result in significant lowering of LDL cholesterol.

Furthermore, the results of this large pooled data sample showed that for statin hyporesponders, statin therapy did not prevent progression of intravascular plaque volume as measured by grayscale intravascular ultrasound.

Patients exhibit a wide range of response to standard statin dosing, and the effect of minimal LDL-C lowering on atherosclerotic disease progression had not previously been determined, according to Dr. Yu Kataoka of the University of Adelaide, Australia, and his colleagues (Arterioscler. Thromb. Vasc. Biol. 2015 [doi:10.1161/ATVBAHA.114.304477]).

Investigators pooled data from seven clinical trials that examined 647 total patients with angiographically confirmed CAD who were initiated on statins and followed by serial intravascular ultrasound. The present study analyzed baseline characteristics, serial lipid profile, and atheroma burden for the group.

In all, 130 patients of the 647 (20%) had minimal LDL-C lowering with statin therapy, showing nonsignificant lowering or even an increase in LDL-C levels during the study period. This group of hyporesponders differed in being slightly younger, more obese, less likely to have hypertension and dyslipidemia, and less likely to be receiving beta-blockers than were the statin responders. Other patient characteristics were similar between the two groups. A variety of agents were used, including atorvastatin, rosuvastatin, simvastatin, and pravastatin. Concurrent administration of other antiatherosclerotic agents was permitted and was similar between the groups. Atheroma burden at baseline was also similar between the two groups.

Measuring serial changes in atheroma burden showed a significant difference between statin responders and hyporesponders. The adjusted change in atheroma volume was –0.21% for the responders, compared with +0.83% for the hyporesponders (P = .006). Lumen volume decreased 11.64 mm³ for the responders, while the reduction was 16.54 mm³ for the hyporesponders (P = .006). Of those who responded to lipid therapy with LDL-C lowering, 29.8% had substantial atheroma regression, while 25.9% had substantial plaque progression; among hyporesponders, however, just 13.8% experienced significant plaque regression, while 37.7% had significant atheroma progression, both significant differences.

Dr. Kataoka and his colleagues emphasized that the factors contributing to poor statin response are not well understood. They noted that for this study, the pooled trials all showed adherence rates over 90%, eliminating patient compliance as a variable. Rigorous statistical techniques were used to control for comorbidities and coadministered medications. There are known genetic polymorphisms and phenotypic variations in statin metabolism, though these were not reported here. Although the results were not statistically significant, C-reactive protein levels were higher for the hyporesponse group, suggesting that another factor may be individual response to the anti-inflammatory effect that is among the known pleiotropic effects of this drug class.

In an interview, lead author Stephen Nicholls noted that many clinicians are still reluctant to treat to full effect. Citing the concept of “clinical inertia,” Dr. Nicholls pointed out that “Even when statins are prescribed, they are often at lower doses than ideal. That translated to more plaque growth, which leads directly to more heart attacks and more revascularization procedures.”

Study limitations included the potential residual confounding effects of pooling data from seven discrete clinical trials, though mixed modeling techniques attempted to correct for this effect. The present study also reported atheroma burden, but not actual clinical events. The study authors noted, however, that they had previously reported a direct relationship between atheroma progression and the occurrence of cardiovascular events.

Dr. Nicholls has received speaking honoraria and research support from many pharmaceutical companies, and from Infraredx. Dr. Steven E. Nissen of the Cleveland Clinic was a coinvestigator and has received research support from and is a consultant/adviser to numerous pharmaceutical companies; all honoraria or consulting fees go directly to charity so that he receives neither income nor a tax deduction. The other authors report no conflicts.

For about one in five patients with known atherosclerotic coronary artery disease, standard-dose therapy with statins did not result in significant lowering of LDL cholesterol.

Furthermore, the results of this large pooled data sample showed that for statin hyporesponders, statin therapy did not prevent progression of intravascular plaque volume as measured by grayscale intravascular ultrasound.

Patients exhibit a wide range of response to standard statin dosing, and the effect of minimal LDL-C lowering on atherosclerotic disease progression had not previously been determined, according to Dr. Yu Kataoka of the University of Adelaide, Australia, and his colleagues (Arterioscler. Thromb. Vasc. Biol. 2015 [doi:10.1161/ATVBAHA.114.304477]).

Investigators pooled data from seven clinical trials that examined 647 total patients with angiographically confirmed CAD who were initiated on statins and followed by serial intravascular ultrasound. The present study analyzed baseline characteristics, serial lipid profile, and atheroma burden for the group.

In all, 130 patients of the 647 (20%) had minimal LDL-C lowering with statin therapy, showing nonsignificant lowering or even an increase in LDL-C levels during the study period. This group of hyporesponders differed in being slightly younger, more obese, less likely to have hypertension and dyslipidemia, and less likely to be receiving beta-blockers than were the statin responders. Other patient characteristics were similar between the two groups. A variety of agents were used, including atorvastatin, rosuvastatin, simvastatin, and pravastatin. Concurrent administration of other antiatherosclerotic agents was permitted and was similar between the groups. Atheroma burden at baseline was also similar between the two groups.

Measuring serial changes in atheroma burden showed a significant difference between statin responders and hyporesponders. The adjusted change in atheroma volume was –0.21% for the responders, compared with +0.83% for the hyporesponders (P = .006). Lumen volume decreased 11.64 mm³ for the responders, while the reduction was 16.54 mm³ for the hyporesponders (P = .006). Of those who responded to lipid therapy with LDL-C lowering, 29.8% had substantial atheroma regression, while 25.9% had substantial plaque progression; among hyporesponders, however, just 13.8% experienced significant plaque regression, while 37.7% had significant atheroma progression, both significant differences.

Dr. Kataoka and his colleagues emphasized that the factors contributing to poor statin response are not well understood. They noted that for this study, the pooled trials all showed adherence rates over 90%, eliminating patient compliance as a variable. Rigorous statistical techniques were used to control for comorbidities and coadministered medications. There are known genetic polymorphisms and phenotypic variations in statin metabolism, though these were not reported here. Although the results were not statistically significant, C-reactive protein levels were higher for the hyporesponse group, suggesting that another factor may be individual response to the anti-inflammatory effect that is among the known pleiotropic effects of this drug class.

In an interview, lead author Stephen Nicholls noted that many clinicians are still reluctant to treat to full effect. Citing the concept of “clinical inertia,” Dr. Nicholls pointed out that “Even when statins are prescribed, they are often at lower doses than ideal. That translated to more plaque growth, which leads directly to more heart attacks and more revascularization procedures.”

Study limitations included the potential residual confounding effects of pooling data from seven discrete clinical trials, though mixed modeling techniques attempted to correct for this effect. The present study also reported atheroma burden, but not actual clinical events. The study authors noted, however, that they had previously reported a direct relationship between atheroma progression and the occurrence of cardiovascular events.

Dr. Nicholls has received speaking honoraria and research support from many pharmaceutical companies, and from Infraredx. Dr. Steven E. Nissen of the Cleveland Clinic was a coinvestigator and has received research support from and is a consultant/adviser to numerous pharmaceutical companies; all honoraria or consulting fees go directly to charity so that he receives neither income nor a tax deduction. The other authors report no conflicts.

For about one in five patients with known atherosclerotic coronary artery disease, standard-dose therapy with statins did not result in significant lowering of LDL cholesterol.

Furthermore, the results of this large pooled data sample showed that for statin hyporesponders, statin therapy did not prevent progression of intravascular plaque volume as measured by grayscale intravascular ultrasound.

Patients exhibit a wide range of response to standard statin dosing, and the effect of minimal LDL-C lowering on atherosclerotic disease progression had not previously been determined, according to Dr. Yu Kataoka of the University of Adelaide, Australia, and his colleagues (Arterioscler. Thromb. Vasc. Biol. 2015 [doi:10.1161/ATVBAHA.114.304477]).

Investigators pooled data from seven clinical trials that examined 647 total patients with angiographically confirmed CAD who were initiated on statins and followed by serial intravascular ultrasound. The present study analyzed baseline characteristics, serial lipid profile, and atheroma burden for the group.

In all, 130 patients of the 647 (20%) had minimal LDL-C lowering with statin therapy, showing nonsignificant lowering or even an increase in LDL-C levels during the study period. This group of hyporesponders differed in being slightly younger, more obese, less likely to have hypertension and dyslipidemia, and less likely to be receiving beta-blockers than were the statin responders. Other patient characteristics were similar between the two groups. A variety of agents were used, including atorvastatin, rosuvastatin, simvastatin, and pravastatin. Concurrent administration of other antiatherosclerotic agents was permitted and was similar between the groups. Atheroma burden at baseline was also similar between the two groups.

Measuring serial changes in atheroma burden showed a significant difference between statin responders and hyporesponders. The adjusted change in atheroma volume was –0.21% for the responders, compared with +0.83% for the hyporesponders (P = .006). Lumen volume decreased 11.64 mm³ for the responders, while the reduction was 16.54 mm³ for the hyporesponders (P = .006). Of those who responded to lipid therapy with LDL-C lowering, 29.8% had substantial atheroma regression, while 25.9% had substantial plaque progression; among hyporesponders, however, just 13.8% experienced significant plaque regression, while 37.7% had significant atheroma progression, both significant differences.

Dr. Kataoka and his colleagues emphasized that the factors contributing to poor statin response are not well understood. They noted that for this study, the pooled trials all showed adherence rates over 90%, eliminating patient compliance as a variable. Rigorous statistical techniques were used to control for comorbidities and coadministered medications. There are known genetic polymorphisms and phenotypic variations in statin metabolism, though these were not reported here. Although the results were not statistically significant, C-reactive protein levels were higher for the hyporesponse group, suggesting that another factor may be individual response to the anti-inflammatory effect that is among the known pleiotropic effects of this drug class.

In an interview, lead author Stephen Nicholls noted that many clinicians are still reluctant to treat to full effect. Citing the concept of “clinical inertia,” Dr. Nicholls pointed out that “Even when statins are prescribed, they are often at lower doses than ideal. That translated to more plaque growth, which leads directly to more heart attacks and more revascularization procedures.”

Study limitations included the potential residual confounding effects of pooling data from seven discrete clinical trials, though mixed modeling techniques attempted to correct for this effect. The present study also reported atheroma burden, but not actual clinical events. The study authors noted, however, that they had previously reported a direct relationship between atheroma progression and the occurrence of cardiovascular events.

Dr. Nicholls has received speaking honoraria and research support from many pharmaceutical companies, and from Infraredx. Dr. Steven E. Nissen of the Cleveland Clinic was a coinvestigator and has received research support from and is a consultant/adviser to numerous pharmaceutical companies; all honoraria or consulting fees go directly to charity so that he receives neither income nor a tax deduction. The other authors report no conflicts.

EVIDENCE SUMMARY

A 2012 Cochrane review of 22 multinational RCTs with a total of 15,288 patients investigated the effect of continuous support in labor on several outcomes, including C-section.¹ All trials included pregnant women in labor. The study populations were heterogenous in terms of parity; most included only nulliparous women, but some included multiparous women. At least one study incorporated higher-risk groups such as mothers of twins, but several trials limited the study group to low-risk pregnancies.

The review found a small but significant decrease in risk of C-section in women receiving continuous support (absolute risk reduction [ARR]=2%; number needed to treat [NNT]=50; P=.0017).¹ The average cost of trained childbirth support in 3 US metropolitan areas in October 2014 was about $875, according to a Web search of established businesses.

The effect only works in the absence of companions and epidurals…

A subgroup analysis of 22 studies investigated several variables to determine circumstances under which a support person decreased the risk of C-section.¹ The support person’s presence was significant only when hospital policy prevented companions (such as the woman’s spouse) in the labor room and when epidurals were not routinely available. Eleven of the 22 studies (11,326 patients) permitted a companion; 11 studies (3849 patients) didn’t.

When policy allowed companions, the presence of a support person didn’t decrease C-section rates significantly (12.7% without support compared with 11.9% with support; P=.20).¹ When the woman wasn’t permitted to have a companion, however, the presence of a support person significantly decreased C-section (ARR=5.4%; NNT=19; P<.01).

In 14 studies, with a total of 13,064 patients, epidurals were routinely available. In the other 8, with 2077 patients, epidurals weren’t available.¹ These were older studies or studies conducted in developing countries. When epidurals were routinely available, the presence of a support person didn’t affect the C-section rate (13.8% rate without support, 12.9% with support; P=.12). But if epidural anesthesia wasn’t available, a support person decreased C-section (ARR=8.6%; NNT=12; P<.00001).

…And when the support person isn’t a hospital staffer or known to the patient

The Cochrane Review also evaluated different types of labor supporters: companions of the patient’s choice from her social network, hospital employees, and people who were neither. The support person conferred significant benefit only when that person was neither hospital staff nor a member of the woman’s social network.

Hospital staff members who provided support didn’t effectively decrease the C-section rate (12% rate in control group vs 11.3% in supported group; P=.28). Support people chosen by the patient likewise didn’t successfully reduce C-sections (19.4% control rate vs 15.5% supported rate; P=.062). When the support person was neither hospital staff nor someone well-known to the patient, the risk of C-section was significantly lower (ARR=6%; NNT=17; P=.0003).

RECOMMENDATIONS

In a Comparative Effectiveness Review published in October 2012, the Agency for Healthcare Research and Quality investigated 18 strategies to reduce C-section, one of which was psychosocial support from doulas and other providers. A trained support person was the only intervention that showed evidence of benefit in decreasing C-section, but the strength of evidence was low.²

An American College of Obstetricians and Gynecologists Practice Bulletin recommends continuous labor support, noting “the continuous presence of a support person may reduce the likelihood of…operative delivery” with no apparent harmful effects.³

EVIDENCE SUMMARY

A 2012 Cochrane review of 22 multinational RCTs with a total of 15,288 patients investigated the effect of continuous support in labor on several outcomes, including C-section.¹ All trials included pregnant women in labor. The study populations were heterogenous in terms of parity; most included only nulliparous women, but some included multiparous women. At least one study incorporated higher-risk groups such as mothers of twins, but several trials limited the study group to low-risk pregnancies.

The review found a small but significant decrease in risk of C-section in women receiving continuous support (absolute risk reduction [ARR]=2%; number needed to treat [NNT]=50; P=.0017).¹ The average cost of trained childbirth support in 3 US metropolitan areas in October 2014 was about $875, according to a Web search of established businesses.

The effect only works in the absence of companions and epidurals…

A subgroup analysis of 22 studies investigated several variables to determine circumstances under which a support person decreased the risk of C-section.¹ The support person’s presence was significant only when hospital policy prevented companions (such as the woman’s spouse) in the labor room and when epidurals were not routinely available. Eleven of the 22 studies (11,326 patients) permitted a companion; 11 studies (3849 patients) didn’t.

When policy allowed companions, the presence of a support person didn’t decrease C-section rates significantly (12.7% without support compared with 11.9% with support; P=.20).¹ When the woman wasn’t permitted to have a companion, however, the presence of a support person significantly decreased C-section (ARR=5.4%; NNT=19; P<.01).

In 14 studies, with a total of 13,064 patients, epidurals were routinely available. In the other 8, with 2077 patients, epidurals weren’t available.¹ These were older studies or studies conducted in developing countries. When epidurals were routinely available, the presence of a support person didn’t affect the C-section rate (13.8% rate without support, 12.9% with support; P=.12). But if epidural anesthesia wasn’t available, a support person decreased C-section (ARR=8.6%; NNT=12; P<.00001).

…And when the support person isn’t a hospital staffer or known to the patient

The Cochrane Review also evaluated different types of labor supporters: companions of the patient’s choice from her social network, hospital employees, and people who were neither. The support person conferred significant benefit only when that person was neither hospital staff nor a member of the woman’s social network.

Hospital staff members who provided support didn’t effectively decrease the C-section rate (12% rate in control group vs 11.3% in supported group; P=.28). Support people chosen by the patient likewise didn’t successfully reduce C-sections (19.4% control rate vs 15.5% supported rate; P=.062). When the support person was neither hospital staff nor someone well-known to the patient, the risk of C-section was significantly lower (ARR=6%; NNT=17; P=.0003).

RECOMMENDATIONS

In a Comparative Effectiveness Review published in October 2012, the Agency for Healthcare Research and Quality investigated 18 strategies to reduce C-section, one of which was psychosocial support from doulas and other providers. A trained support person was the only intervention that showed evidence of benefit in decreasing C-section, but the strength of evidence was low.²

An American College of Obstetricians and Gynecologists Practice Bulletin recommends continuous labor support, noting “the continuous presence of a support person may reduce the likelihood of…operative delivery” with no apparent harmful effects.³

EVIDENCE SUMMARY

A 2012 Cochrane review of 22 multinational RCTs with a total of 15,288 patients investigated the effect of continuous support in labor on several outcomes, including C-section.¹ All trials included pregnant women in labor. The study populations were heterogenous in terms of parity; most included only nulliparous women, but some included multiparous women. At least one study incorporated higher-risk groups such as mothers of twins, but several trials limited the study group to low-risk pregnancies.

The review found a small but significant decrease in risk of C-section in women receiving continuous support (absolute risk reduction [ARR]=2%; number needed to treat [NNT]=50; P=.0017).¹ The average cost of trained childbirth support in 3 US metropolitan areas in October 2014 was about $875, according to a Web search of established businesses.

The effect only works in the absence of companions and epidurals…

A subgroup analysis of 22 studies investigated several variables to determine circumstances under which a support person decreased the risk of C-section.¹ The support person’s presence was significant only when hospital policy prevented companions (such as the woman’s spouse) in the labor room and when epidurals were not routinely available. Eleven of the 22 studies (11,326 patients) permitted a companion; 11 studies (3849 patients) didn’t.

When policy allowed companions, the presence of a support person didn’t decrease C-section rates significantly (12.7% without support compared with 11.9% with support; P=.20).¹ When the woman wasn’t permitted to have a companion, however, the presence of a support person significantly decreased C-section (ARR=5.4%; NNT=19; P<.01).

In 14 studies, with a total of 13,064 patients, epidurals were routinely available. In the other 8, with 2077 patients, epidurals weren’t available.¹ These were older studies or studies conducted in developing countries. When epidurals were routinely available, the presence of a support person didn’t affect the C-section rate (13.8% rate without support, 12.9% with support; P=.12). But if epidural anesthesia wasn’t available, a support person decreased C-section (ARR=8.6%; NNT=12; P<.00001).

…And when the support person isn’t a hospital staffer or known to the patient

The Cochrane Review also evaluated different types of labor supporters: companions of the patient’s choice from her social network, hospital employees, and people who were neither. The support person conferred significant benefit only when that person was neither hospital staff nor a member of the woman’s social network.

Hospital staff members who provided support didn’t effectively decrease the C-section rate (12% rate in control group vs 11.3% in supported group; P=.28). Support people chosen by the patient likewise didn’t successfully reduce C-sections (19.4% control rate vs 15.5% supported rate; P=.062). When the support person was neither hospital staff nor someone well-known to the patient, the risk of C-section was significantly lower (ARR=6%; NNT=17; P=.0003).

RECOMMENDATIONS

In a Comparative Effectiveness Review published in October 2012, the Agency for Healthcare Research and Quality investigated 18 strategies to reduce C-section, one of which was psychosocial support from doulas and other providers. A trained support person was the only intervention that showed evidence of benefit in decreasing C-section, but the strength of evidence was low.²

An American College of Obstetricians and Gynecologists Practice Bulletin recommends continuous labor support, noting “the continuous presence of a support person may reduce the likelihood of…operative delivery” with no apparent harmful effects.³

It’s spring. Have you started your Meaningful Use reporting yet? More important, have you begun reporting at all?

“Say the words Meaningful Use to most orthopedists, and they usually roll their eyes or shake their heads,” says Cheyenne Brinson, MBA, CPA, a KarenZupko & Associates consultant who has been advising surgical practices on Meaningful Use since the program’s inception. Although many orthopedists are successfully using certified electronic health records (EHRs) to e-prescribe and enter radiology and laboratory orders, Brinson says many other requirements are misunderstood and perceived as overly complex. In many cases, practices are doing more work than they need to in order to attest.

“It’s actually not that complicated to meet Meaningful Use requirements,” she says. “The trick is to zero in on what’s relevant only for surgeons. This isn’t crystal clear in the CMS [Centers for Medicare & Medicaid Services] documents, and it’s not the forte of most EHR vendors or trainers either.” In fact, in Brinson’s experience, most EHR trainers present Meaningful Use to every practice as if it were primary care. Yet, the requirements for surgeons are different for primary care and are, frankly, less involved.

That’s good news. Because if you didn’t attest for Meaningful Use in 2014, the first year that reporting was required, you’re automatically getting dinged 2% on your Medicare payments in 2015. So, it’s time to get organized and get moving to avoid further penalties.

Avoid These Four Common Faux Pas

Brinson says the Clinical Quality Measures (CQMs) are hands down the most misunderstood component of Meaningful Use. “When I explain Meaningful Use to surgeons, I can’t jump up and down and wave my hands in the air enough to call attention to this,” she quips.

At issue: There are 64 CQMs, but very few are applicable to surgeons. Yet, many surgeons think they have to perform them for Meaningful Use. Not so, says Brinson. “Surgeons have to report a CQM only if it’s clinically relevant. If none of the CQMs are clinically relevant in your practice, it’s okay to report a zero value if you have not actually performed it.”

Here’s how this plays out. In Stage 2, physicians must report 9 CQMs across 3 domains; Population/Public Health, Patient Safety, and Efficient Use of Healthcare Resources are examples of domains that are most applicable to orthopedists. “If you choose Low Back Pain: Use of Imaging Studies as one of these, it’s possible an orthopedist would have a numeric value to report,” Brinson says. “But if you also choose Use of High-Risk Medications in the Elderly, an orthopedist will probably report a zero value. And that’s totally acceptable. You will not be penalized for reporting zero.”

Another common misconception is around the Vital Signs and Smoking Status measures. “We have worked with surgical practices that think Meaningful Use is requiring them to collect vital signs and smoking status at every visit, even though they may not be clinically relevant,” says Brinson. Again, not true.

“Height and/or weight and blood pressure, as well as smoking status measures, need to be reported only once per patient during the reporting period,” Brinson clarifies. “So from a practical standpoint, most orthopedic practices can collect this data from new patients and then again as clinically necessary,” adding there are even exclusions for physicians who attest that either height and weight and/or blood pressure has no relevance to their scope of practice at all.

Brinson also sees practices do more work than they need to when it comes to Patient Care Reminders. She recently worked with a surgery practice that sent reminders for colonoscopies. “Not exactly clinically relevant,” she says, “and an unnecessary step for staff.” That’s because physicians aren’t required to send reminders that aren’t relevant to their specialty.

The Federal Register states, “An eligible provider (EP) should use clinically relevant information stored within the [EHR] to identify patients who should receive reminders…. The EP is best positioned to decide which information is clinically relevant for this purpose.”

“In orthopedics, clinically relevant reminders could be for an outside referral, a follow-up on an MRI or other test, or a reminder to schedule a postoperative appointment,” Brinson explains. “Work with your EHR vendor to create the reminders that are most appropriate for your patient base.”

The final faux pas that Brinson finds: “Meaningful Use requires you to report data for all patients, not just Medicare patients. That seems to be a point of confusion for many.”

Three Cheers for the Patient Portal Requirement

Stage 2 saw the addition of the Patient Portal Requirement, and Brinson suggests that the benefits of this tool go far beyond Meaningful Use. “Patient portals are essential to a modern practice,” she says. “Patients use them to complete a health history prior to their appointment, pay their bill, schedule follow-up appointments, and more.” Further, the patient portal facilitates another Meaningful Use Stage 2 requirement: secure electronic messaging with patients. For both Meaningful Use and risk management, moving away from e-mail and texting and toward secure/encrypted messaging is a must. The patient portal has this feature already built in, and all messages are stored securely and archived—which meets the HIPAA (Health Insurance Portability and Accountability Act) Omnibus requirements, too.

So if you’ve implemented a patient portal, that’s good for your practice and your patients on many levels. But there is a caveat about meeting the Meaningful Use requirement. “For this requirement, 5% of the unique patients seen during the reporting period must ‘view, download, or transmit to a third party their health information,’” Brinson explains. “So the onus is on your practice to ‘sell’ the benefits of the patient portal and get patients to use it so you can achieve the 5% threshold.”

Clinical Decision Support and Summaries

The requirements of Clinical Decision Support Interventions and Clinical Summaries may seem daunting, but, if you think beyond Meaningful Use for a moment, both facilitate better care.

Take Clinical Decision Support Interventions. What would be helpful for you to know about a patient before surgery? What information would enable you to deliver better care?

“One surgeon told me that a family history of malignant hyperthermia would mean the difference between performing the case in the operating room versus the ambulatory surgery center,” Brinson says. “This is a good example of an intervention that a surgeon would work with their EHR vendor to set up.”

The objective states that each intervention is to be an evidence-based decision-support intervention based on each one and at least one combination of the following data: problem list, medication list, medication allergy list, demographics, laboratory tests and values/results, and vital signs. “Stage 1 requires physicians to implement 1 Clinical Decision Support Intervention, and Stage 2 requires 5,” reminds Brinson.

And here’s all you need to know about Clinical Summaries. Although there are 20 specific required elements of a clinical summary, physicians themselves need to provide details only for clinical instructions and the care plan, including goals and instructions. Ancillary staff can populate the other elements.

Brinson points out that surgeons are not expected to provide a copy of the patient’s note, or to complete the note, before the patient checks out. The requirement under Stage 2 is that the clinical summary is provided to the patient within 1 business day. “From a practical standpoint, practices can print the clinical summary for patients at checkout. A well-done clinical summary is a practice efficiency tool as much as a clinical document. It can reduce phone calls from patients asking, ‘Now what did the doctor tell me to do?’”

Often Overlooked

There are requirements that, Brinson says, surgeons often gloss over: Protect Electronic Health Information and Text-Searchable Progress Notes.

“Stage 2 requires physicians to conduct a privacy risk analysis to protect electronic health information,” she explains. “Most EHR vendors don’t offer this as part of their product, so it’s frequently overlooked.” Such an analysis typically requires an outside vendor, but there are free, do-it-yourself tools available, such as the Privacy and Security Toolkit for Small Provider Organizations,^* from the Healthcare Information and Management Systems Society (HIMSS).

The analysis should follow HIPAA guidelines, and the most intensive part of this requirement is to conduct or review a privacy risk analysis of the clinical technology. “You’ve also got to address data encryption and security in the EHR, and ensure HIPAA policies and procedures are in place,” Brinson states.

Text-Searchable Progress Notes are also a new requirement in Stage 2. All progress notes must be text searchable—practices can no longer include progress notes as scanned attachments. “That means no more PDFs,” Brinson says. “Surgeons can still dictate, but the dictation must be entered into the EHR in such a way that it’s searchable. In Stage 2, 30% of unique patients must have a minimum of 1 text-searchable electronic progress note created, edited, and signed in the EHR.”

Conclusion

Meaningful Use does not have to be cumbersome. Focus on what surgical practices need to know, and attestation won’t be as complicated as you think.

It’s spring. Have you started your Meaningful Use reporting yet? More important, have you begun reporting at all?

“Say the words Meaningful Use to most orthopedists, and they usually roll their eyes or shake their heads,” says Cheyenne Brinson, MBA, CPA, a KarenZupko & Associates consultant who has been advising surgical practices on Meaningful Use since the program’s inception. Although many orthopedists are successfully using certified electronic health records (EHRs) to e-prescribe and enter radiology and laboratory orders, Brinson says many other requirements are misunderstood and perceived as overly complex. In many cases, practices are doing more work than they need to in order to attest.

“It’s actually not that complicated to meet Meaningful Use requirements,” she says. “The trick is to zero in on what’s relevant only for surgeons. This isn’t crystal clear in the CMS [Centers for Medicare & Medicaid Services] documents, and it’s not the forte of most EHR vendors or trainers either.” In fact, in Brinson’s experience, most EHR trainers present Meaningful Use to every practice as if it were primary care. Yet, the requirements for surgeons are different for primary care and are, frankly, less involved.

That’s good news. Because if you didn’t attest for Meaningful Use in 2014, the first year that reporting was required, you’re automatically getting dinged 2% on your Medicare payments in 2015. So, it’s time to get organized and get moving to avoid further penalties.

Avoid These Four Common Faux Pas

Brinson says the Clinical Quality Measures (CQMs) are hands down the most misunderstood component of Meaningful Use. “When I explain Meaningful Use to surgeons, I can’t jump up and down and wave my hands in the air enough to call attention to this,” she quips.

At issue: There are 64 CQMs, but very few are applicable to surgeons. Yet, many surgeons think they have to perform them for Meaningful Use. Not so, says Brinson. “Surgeons have to report a CQM only if it’s clinically relevant. If none of the CQMs are clinically relevant in your practice, it’s okay to report a zero value if you have not actually performed it.”

Here’s how this plays out. In Stage 2, physicians must report 9 CQMs across 3 domains; Population/Public Health, Patient Safety, and Efficient Use of Healthcare Resources are examples of domains that are most applicable to orthopedists. “If you choose Low Back Pain: Use of Imaging Studies as one of these, it’s possible an orthopedist would have a numeric value to report,” Brinson says. “But if you also choose Use of High-Risk Medications in the Elderly, an orthopedist will probably report a zero value. And that’s totally acceptable. You will not be penalized for reporting zero.”

Another common misconception is around the Vital Signs and Smoking Status measures. “We have worked with surgical practices that think Meaningful Use is requiring them to collect vital signs and smoking status at every visit, even though they may not be clinically relevant,” says Brinson. Again, not true.

“Height and/or weight and blood pressure, as well as smoking status measures, need to be reported only once per patient during the reporting period,” Brinson clarifies. “So from a practical standpoint, most orthopedic practices can collect this data from new patients and then again as clinically necessary,” adding there are even exclusions for physicians who attest that either height and weight and/or blood pressure has no relevance to their scope of practice at all.

Brinson also sees practices do more work than they need to when it comes to Patient Care Reminders. She recently worked with a surgery practice that sent reminders for colonoscopies. “Not exactly clinically relevant,” she says, “and an unnecessary step for staff.” That’s because physicians aren’t required to send reminders that aren’t relevant to their specialty.

The Federal Register states, “An eligible provider (EP) should use clinically relevant information stored within the [EHR] to identify patients who should receive reminders…. The EP is best positioned to decide which information is clinically relevant for this purpose.”

“In orthopedics, clinically relevant reminders could be for an outside referral, a follow-up on an MRI or other test, or a reminder to schedule a postoperative appointment,” Brinson explains. “Work with your EHR vendor to create the reminders that are most appropriate for your patient base.”

The final faux pas that Brinson finds: “Meaningful Use requires you to report data for all patients, not just Medicare patients. That seems to be a point of confusion for many.”

Three Cheers for the Patient Portal Requirement

Stage 2 saw the addition of the Patient Portal Requirement, and Brinson suggests that the benefits of this tool go far beyond Meaningful Use. “Patient portals are essential to a modern practice,” she says. “Patients use them to complete a health history prior to their appointment, pay their bill, schedule follow-up appointments, and more.” Further, the patient portal facilitates another Meaningful Use Stage 2 requirement: secure electronic messaging with patients. For both Meaningful Use and risk management, moving away from e-mail and texting and toward secure/encrypted messaging is a must. The patient portal has this feature already built in, and all messages are stored securely and archived—which meets the HIPAA (Health Insurance Portability and Accountability Act) Omnibus requirements, too.

So if you’ve implemented a patient portal, that’s good for your practice and your patients on many levels. But there is a caveat about meeting the Meaningful Use requirement. “For this requirement, 5% of the unique patients seen during the reporting period must ‘view, download, or transmit to a third party their health information,’” Brinson explains. “So the onus is on your practice to ‘sell’ the benefits of the patient portal and get patients to use it so you can achieve the 5% threshold.”

Clinical Decision Support and Summaries

The requirements of Clinical Decision Support Interventions and Clinical Summaries may seem daunting, but, if you think beyond Meaningful Use for a moment, both facilitate better care.

Take Clinical Decision Support Interventions. What would be helpful for you to know about a patient before surgery? What information would enable you to deliver better care?

“One surgeon told me that a family history of malignant hyperthermia would mean the difference between performing the case in the operating room versus the ambulatory surgery center,” Brinson says. “This is a good example of an intervention that a surgeon would work with their EHR vendor to set up.”

The objective states that each intervention is to be an evidence-based decision-support intervention based on each one and at least one combination of the following data: problem list, medication list, medication allergy list, demographics, laboratory tests and values/results, and vital signs. “Stage 1 requires physicians to implement 1 Clinical Decision Support Intervention, and Stage 2 requires 5,” reminds Brinson.

And here’s all you need to know about Clinical Summaries. Although there are 20 specific required elements of a clinical summary, physicians themselves need to provide details only for clinical instructions and the care plan, including goals and instructions. Ancillary staff can populate the other elements.

Brinson points out that surgeons are not expected to provide a copy of the patient’s note, or to complete the note, before the patient checks out. The requirement under Stage 2 is that the clinical summary is provided to the patient within 1 business day. “From a practical standpoint, practices can print the clinical summary for patients at checkout. A well-done clinical summary is a practice efficiency tool as much as a clinical document. It can reduce phone calls from patients asking, ‘Now what did the doctor tell me to do?’”

Often Overlooked

There are requirements that, Brinson says, surgeons often gloss over: Protect Electronic Health Information and Text-Searchable Progress Notes.

“Stage 2 requires physicians to conduct a privacy risk analysis to protect electronic health information,” she explains. “Most EHR vendors don’t offer this as part of their product, so it’s frequently overlooked.” Such an analysis typically requires an outside vendor, but there are free, do-it-yourself tools available, such as the Privacy and Security Toolkit for Small Provider Organizations,^* from the Healthcare Information and Management Systems Society (HIMSS).

The analysis should follow HIPAA guidelines, and the most intensive part of this requirement is to conduct or review a privacy risk analysis of the clinical technology. “You’ve also got to address data encryption and security in the EHR, and ensure HIPAA policies and procedures are in place,” Brinson states.

Text-Searchable Progress Notes are also a new requirement in Stage 2. All progress notes must be text searchable—practices can no longer include progress notes as scanned attachments. “That means no more PDFs,” Brinson says. “Surgeons can still dictate, but the dictation must be entered into the EHR in such a way that it’s searchable. In Stage 2, 30% of unique patients must have a minimum of 1 text-searchable electronic progress note created, edited, and signed in the EHR.”

Conclusion

Meaningful Use does not have to be cumbersome. Focus on what surgical practices need to know, and attestation won’t be as complicated as you think.

It’s spring. Have you started your Meaningful Use reporting yet? More important, have you begun reporting at all?

“Say the words Meaningful Use to most orthopedists, and they usually roll their eyes or shake their heads,” says Cheyenne Brinson, MBA, CPA, a KarenZupko & Associates consultant who has been advising surgical practices on Meaningful Use since the program’s inception. Although many orthopedists are successfully using certified electronic health records (EHRs) to e-prescribe and enter radiology and laboratory orders, Brinson says many other requirements are misunderstood and perceived as overly complex. In many cases, practices are doing more work than they need to in order to attest.

“It’s actually not that complicated to meet Meaningful Use requirements,” she says. “The trick is to zero in on what’s relevant only for surgeons. This isn’t crystal clear in the CMS [Centers for Medicare & Medicaid Services] documents, and it’s not the forte of most EHR vendors or trainers either.” In fact, in Brinson’s experience, most EHR trainers present Meaningful Use to every practice as if it were primary care. Yet, the requirements for surgeons are different for primary care and are, frankly, less involved.

That’s good news. Because if you didn’t attest for Meaningful Use in 2014, the first year that reporting was required, you’re automatically getting dinged 2% on your Medicare payments in 2015. So, it’s time to get organized and get moving to avoid further penalties.

Avoid These Four Common Faux Pas

Brinson says the Clinical Quality Measures (CQMs) are hands down the most misunderstood component of Meaningful Use. “When I explain Meaningful Use to surgeons, I can’t jump up and down and wave my hands in the air enough to call attention to this,” she quips.

At issue: There are 64 CQMs, but very few are applicable to surgeons. Yet, many surgeons think they have to perform them for Meaningful Use. Not so, says Brinson. “Surgeons have to report a CQM only if it’s clinically relevant. If none of the CQMs are clinically relevant in your practice, it’s okay to report a zero value if you have not actually performed it.”

Here’s how this plays out. In Stage 2, physicians must report 9 CQMs across 3 domains; Population/Public Health, Patient Safety, and Efficient Use of Healthcare Resources are examples of domains that are most applicable to orthopedists. “If you choose Low Back Pain: Use of Imaging Studies as one of these, it’s possible an orthopedist would have a numeric value to report,” Brinson says. “But if you also choose Use of High-Risk Medications in the Elderly, an orthopedist will probably report a zero value. And that’s totally acceptable. You will not be penalized for reporting zero.”

Another common misconception is around the Vital Signs and Smoking Status measures. “We have worked with surgical practices that think Meaningful Use is requiring them to collect vital signs and smoking status at every visit, even though they may not be clinically relevant,” says Brinson. Again, not true.

“Height and/or weight and blood pressure, as well as smoking status measures, need to be reported only once per patient during the reporting period,” Brinson clarifies. “So from a practical standpoint, most orthopedic practices can collect this data from new patients and then again as clinically necessary,” adding there are even exclusions for physicians who attest that either height and weight and/or blood pressure has no relevance to their scope of practice at all.

Brinson also sees practices do more work than they need to when it comes to Patient Care Reminders. She recently worked with a surgery practice that sent reminders for colonoscopies. “Not exactly clinically relevant,” she says, “and an unnecessary step for staff.” That’s because physicians aren’t required to send reminders that aren’t relevant to their specialty.

The Federal Register states, “An eligible provider (EP) should use clinically relevant information stored within the [EHR] to identify patients who should receive reminders…. The EP is best positioned to decide which information is clinically relevant for this purpose.”

“In orthopedics, clinically relevant reminders could be for an outside referral, a follow-up on an MRI or other test, or a reminder to schedule a postoperative appointment,” Brinson explains. “Work with your EHR vendor to create the reminders that are most appropriate for your patient base.”

The final faux pas that Brinson finds: “Meaningful Use requires you to report data for all patients, not just Medicare patients. That seems to be a point of confusion for many.”

Three Cheers for the Patient Portal Requirement

Stage 2 saw the addition of the Patient Portal Requirement, and Brinson suggests that the benefits of this tool go far beyond Meaningful Use. “Patient portals are essential to a modern practice,” she says. “Patients use them to complete a health history prior to their appointment, pay their bill, schedule follow-up appointments, and more.” Further, the patient portal facilitates another Meaningful Use Stage 2 requirement: secure electronic messaging with patients. For both Meaningful Use and risk management, moving away from e-mail and texting and toward secure/encrypted messaging is a must. The patient portal has this feature already built in, and all messages are stored securely and archived—which meets the HIPAA (Health Insurance Portability and Accountability Act) Omnibus requirements, too.

So if you’ve implemented a patient portal, that’s good for your practice and your patients on many levels. But there is a caveat about meeting the Meaningful Use requirement. “For this requirement, 5% of the unique patients seen during the reporting period must ‘view, download, or transmit to a third party their health information,’” Brinson explains. “So the onus is on your practice to ‘sell’ the benefits of the patient portal and get patients to use it so you can achieve the 5% threshold.”

Clinical Decision Support and Summaries

The requirements of Clinical Decision Support Interventions and Clinical Summaries may seem daunting, but, if you think beyond Meaningful Use for a moment, both facilitate better care.

Take Clinical Decision Support Interventions. What would be helpful for you to know about a patient before surgery? What information would enable you to deliver better care?

“One surgeon told me that a family history of malignant hyperthermia would mean the difference between performing the case in the operating room versus the ambulatory surgery center,” Brinson says. “This is a good example of an intervention that a surgeon would work with their EHR vendor to set up.”

The objective states that each intervention is to be an evidence-based decision-support intervention based on each one and at least one combination of the following data: problem list, medication list, medication allergy list, demographics, laboratory tests and values/results, and vital signs. “Stage 1 requires physicians to implement 1 Clinical Decision Support Intervention, and Stage 2 requires 5,” reminds Brinson.

And here’s all you need to know about Clinical Summaries. Although there are 20 specific required elements of a clinical summary, physicians themselves need to provide details only for clinical instructions and the care plan, including goals and instructions. Ancillary staff can populate the other elements.

Brinson points out that surgeons are not expected to provide a copy of the patient’s note, or to complete the note, before the patient checks out. The requirement under Stage 2 is that the clinical summary is provided to the patient within 1 business day. “From a practical standpoint, practices can print the clinical summary for patients at checkout. A well-done clinical summary is a practice efficiency tool as much as a clinical document. It can reduce phone calls from patients asking, ‘Now what did the doctor tell me to do?’”

Often Overlooked

There are requirements that, Brinson says, surgeons often gloss over: Protect Electronic Health Information and Text-Searchable Progress Notes.

“Stage 2 requires physicians to conduct a privacy risk analysis to protect electronic health information,” she explains. “Most EHR vendors don’t offer this as part of their product, so it’s frequently overlooked.” Such an analysis typically requires an outside vendor, but there are free, do-it-yourself tools available, such as the Privacy and Security Toolkit for Small Provider Organizations,^* from the Healthcare Information and Management Systems Society (HIMSS).

The analysis should follow HIPAA guidelines, and the most intensive part of this requirement is to conduct or review a privacy risk analysis of the clinical technology. “You’ve also got to address data encryption and security in the EHR, and ensure HIPAA policies and procedures are in place,” Brinson states.

Text-Searchable Progress Notes are also a new requirement in Stage 2. All progress notes must be text searchable—practices can no longer include progress notes as scanned attachments. “That means no more PDFs,” Brinson says. “Surgeons can still dictate, but the dictation must be entered into the EHR in such a way that it’s searchable. In Stage 2, 30% of unique patients must have a minimum of 1 text-searchable electronic progress note created, edited, and signed in the EHR.”

Conclusion

Meaningful Use does not have to be cumbersome. Focus on what surgical practices need to know, and attestation won’t be as complicated as you think.