Thrombus

Credit: Andre E.X. Brown

Health Canada has expanded the indication for the oral anticoagulant apixaban (Eliquis).

The direct factor Xa inhibitor can now be used to prevent venous thromboembolism (VTE) in adult patients who have undergone elective total hip surgery or knee replacement surgery.

The drug was already approved in Canada to treat and prevent recurrent VTE and for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

“The development of VTE or pulmonary embolism is an important risk for patients having major orthopedic surgery such as total knee or hip replacement,” said John Eikelboom, MBBS, of McMaster University in Hamilton, Ontario.

“The approval of apixaban gives Canadian surgeons a new option to help prevent VTE in these patients. As an oral option for patients in hospital and once they return home after surgery, where most clotting complications can take place after they are discharged from hospital, apixaban offers patients an alternative to an injected anticoagulant.”

Health Canada’s approval of apixaban is based on results of the ADVANCE clinical trials. In these trials, researchers randomized 11,659 patients and assessed the efficacy and safety of apixaban compared to enoxaparin.

The primary efficacy endpoint of the trials was the composite of asymptomatic and symptomatic deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), and death from any cause during study treatment. The principal safety measure was the composite of major and clinically relevant nonmajor bleeding.

Results of the first ADVANCE study suggested apixaban was roughly as effective as enoxaparin at preventing DVT and PE in patients who had undergone total knee replacement surgery. But apixaban posed a significantly lower risk of major and nonmajor bleeding.

The ADVANCE-2 study, on the other hand, indicated that apixaban was a more effective means of thromboprophylaxis than enoxaparin in this patient population. And there was no significant difference between the treatment arms in the frequency of major or clinically relevant bleeding.

The ADVANCE-3 study suggested apixaban was more effective than enoxaparin in preventing DVT and PE among patients undergoing hip replacement. And there was no significant difference between the groups with regard to major or clinically relevant bleeding.

Apixaban is under development in Canada by Bristol-Myers Squibb and Pfizer Canada Inc. For more details on the drug, see the product monograph.

Thrombus

Credit: Andre E.X. Brown

Health Canada has expanded the indication for the oral anticoagulant apixaban (Eliquis).

The direct factor Xa inhibitor can now be used to prevent venous thromboembolism (VTE) in adult patients who have undergone elective total hip surgery or knee replacement surgery.

The drug was already approved in Canada to treat and prevent recurrent VTE and for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

“The development of VTE or pulmonary embolism is an important risk for patients having major orthopedic surgery such as total knee or hip replacement,” said John Eikelboom, MBBS, of McMaster University in Hamilton, Ontario.

“The approval of apixaban gives Canadian surgeons a new option to help prevent VTE in these patients. As an oral option for patients in hospital and once they return home after surgery, where most clotting complications can take place after they are discharged from hospital, apixaban offers patients an alternative to an injected anticoagulant.”

Health Canada’s approval of apixaban is based on results of the ADVANCE clinical trials. In these trials, researchers randomized 11,659 patients and assessed the efficacy and safety of apixaban compared to enoxaparin.

The primary efficacy endpoint of the trials was the composite of asymptomatic and symptomatic deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), and death from any cause during study treatment. The principal safety measure was the composite of major and clinically relevant nonmajor bleeding.

Results of the first ADVANCE study suggested apixaban was roughly as effective as enoxaparin at preventing DVT and PE in patients who had undergone total knee replacement surgery. But apixaban posed a significantly lower risk of major and nonmajor bleeding.

The ADVANCE-2 study, on the other hand, indicated that apixaban was a more effective means of thromboprophylaxis than enoxaparin in this patient population. And there was no significant difference between the treatment arms in the frequency of major or clinically relevant bleeding.

The ADVANCE-3 study suggested apixaban was more effective than enoxaparin in preventing DVT and PE among patients undergoing hip replacement. And there was no significant difference between the groups with regard to major or clinically relevant bleeding.

Apixaban is under development in Canada by Bristol-Myers Squibb and Pfizer Canada Inc. For more details on the drug, see the product monograph.

Thrombus

Credit: Andre E.X. Brown

Health Canada has expanded the indication for the oral anticoagulant apixaban (Eliquis).

The direct factor Xa inhibitor can now be used to prevent venous thromboembolism (VTE) in adult patients who have undergone elective total hip surgery or knee replacement surgery.

The drug was already approved in Canada to treat and prevent recurrent VTE and for the prevention of stroke and systemic embolism in patients with atrial fibrillation.

“The development of VTE or pulmonary embolism is an important risk for patients having major orthopedic surgery such as total knee or hip replacement,” said John Eikelboom, MBBS, of McMaster University in Hamilton, Ontario.

“The approval of apixaban gives Canadian surgeons a new option to help prevent VTE in these patients. As an oral option for patients in hospital and once they return home after surgery, where most clotting complications can take place after they are discharged from hospital, apixaban offers patients an alternative to an injected anticoagulant.”

Health Canada’s approval of apixaban is based on results of the ADVANCE clinical trials. In these trials, researchers randomized 11,659 patients and assessed the efficacy and safety of apixaban compared to enoxaparin.

The primary efficacy endpoint of the trials was the composite of asymptomatic and symptomatic deep vein thrombosis (DVT), nonfatal pulmonary embolism (PE), and death from any cause during study treatment. The principal safety measure was the composite of major and clinically relevant nonmajor bleeding.

Results of the first ADVANCE study suggested apixaban was roughly as effective as enoxaparin at preventing DVT and PE in patients who had undergone total knee replacement surgery. But apixaban posed a significantly lower risk of major and nonmajor bleeding.

The ADVANCE-2 study, on the other hand, indicated that apixaban was a more effective means of thromboprophylaxis than enoxaparin in this patient population. And there was no significant difference between the treatment arms in the frequency of major or clinically relevant bleeding.

The ADVANCE-3 study suggested apixaban was more effective than enoxaparin in preventing DVT and PE among patients undergoing hip replacement. And there was no significant difference between the groups with regard to major or clinically relevant bleeding.

Apixaban is under development in Canada by Bristol-Myers Squibb and Pfizer Canada Inc. For more details on the drug, see the product monograph.

Anopheles albimanus mosquito

Credit: James Gathany

Two studies comparing mosquito genomes have begun to provide answers to a century-old mystery: why only some Anopheles mosquitoes transmit human malaria.

There are more than 400 species of Anopheles mosquitoes, but only about 60 transmit parasites that cause malaria in humans.

Variation in the ability to transmit malaria, or “vectorial capacity,” is determined by many factors, including feeding and breeding preferences, as well as immune responses to infections.

Much of our understanding of such processes is derived from the sequencing of the Anopheles gambiae genome in 2002, which facilitated large-scale functional studies that have offered insights into how this mosquito became highly specialized to live among and feed upon humans.

The lack of such genomic resources for other Anopheles species limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquitoes’ ability to transmit parasites.

In an attempt to change that, Daniel Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues sequenced the genomes of 16 anopheline mosquito species.

A second team of researchers—Michael Fontaine, PhD, of the University of Notre Dame in Indiana, and his colleagues—leveraged the 16 reference sequences to uncover additional information.

Both groups described their work in Science Express.

The researchers performed comparative genomics analyses among the Anopheles species and Drosophila (one of the most closely related genera for which equivalent genomic resources exist). This revealed significant genetic differences that make certain Anopheles species particularly adept at inflicting life-threatening infections.

Anopheles species had high rates of gene gain and loss, about 5 times higher than in Drosophila. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely related species.

“These dynamic changes may offer clues to understanding the diversification of Anopheles mosquitoes: why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans,” said Nora Besansky, PhD, a professor at the University of Notre Dame and senior author of both studies.

The genome sequences also provided conclusive evidence of the true relations among several species that are very closely related to Anopheles gambiae but show different traits that affect their vectorial capacity.

“The question of the true species phylogeny has been a highly contentious issue in the field,” Dr Besansky said. “Our results show that the most efficient vectors are not necessarily the most closely related species, and that traits enhancing vectorial capacity may be gained by gene flow between species.”

The researchers found that gene flow is much more extensive in anophelines than in Drosophila, largely because of a process called introgression, whereby a gene from one species enters the gene pool of another. The process allows for a much more rapid transfer of genes than would arise simply by waiting for new mutations to crop up.

The high degree of anopheline gene flow provides a source of genetic variation on which natural selection can act—paving the way for traits that make mosquitoes highly effective vectors for malaria (like insecticide resistance or tolerance of more malaria parasites) to be fixed in certain anophelines.

Anopheles albimanus mosquito

Credit: James Gathany

Two studies comparing mosquito genomes have begun to provide answers to a century-old mystery: why only some Anopheles mosquitoes transmit human malaria.

There are more than 400 species of Anopheles mosquitoes, but only about 60 transmit parasites that cause malaria in humans.

Variation in the ability to transmit malaria, or “vectorial capacity,” is determined by many factors, including feeding and breeding preferences, as well as immune responses to infections.

Much of our understanding of such processes is derived from the sequencing of the Anopheles gambiae genome in 2002, which facilitated large-scale functional studies that have offered insights into how this mosquito became highly specialized to live among and feed upon humans.

The lack of such genomic resources for other Anopheles species limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquitoes’ ability to transmit parasites.

In an attempt to change that, Daniel Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues sequenced the genomes of 16 anopheline mosquito species.

A second team of researchers—Michael Fontaine, PhD, of the University of Notre Dame in Indiana, and his colleagues—leveraged the 16 reference sequences to uncover additional information.

Both groups described their work in Science Express.

The researchers performed comparative genomics analyses among the Anopheles species and Drosophila (one of the most closely related genera for which equivalent genomic resources exist). This revealed significant genetic differences that make certain Anopheles species particularly adept at inflicting life-threatening infections.

Anopheles species had high rates of gene gain and loss, about 5 times higher than in Drosophila. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely related species.

“These dynamic changes may offer clues to understanding the diversification of Anopheles mosquitoes: why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans,” said Nora Besansky, PhD, a professor at the University of Notre Dame and senior author of both studies.

The genome sequences also provided conclusive evidence of the true relations among several species that are very closely related to Anopheles gambiae but show different traits that affect their vectorial capacity.

“The question of the true species phylogeny has been a highly contentious issue in the field,” Dr Besansky said. “Our results show that the most efficient vectors are not necessarily the most closely related species, and that traits enhancing vectorial capacity may be gained by gene flow between species.”

The researchers found that gene flow is much more extensive in anophelines than in Drosophila, largely because of a process called introgression, whereby a gene from one species enters the gene pool of another. The process allows for a much more rapid transfer of genes than would arise simply by waiting for new mutations to crop up.

The high degree of anopheline gene flow provides a source of genetic variation on which natural selection can act—paving the way for traits that make mosquitoes highly effective vectors for malaria (like insecticide resistance or tolerance of more malaria parasites) to be fixed in certain anophelines.

Anopheles albimanus mosquito

Credit: James Gathany

Two studies comparing mosquito genomes have begun to provide answers to a century-old mystery: why only some Anopheles mosquitoes transmit human malaria.

There are more than 400 species of Anopheles mosquitoes, but only about 60 transmit parasites that cause malaria in humans.

Variation in the ability to transmit malaria, or “vectorial capacity,” is determined by many factors, including feeding and breeding preferences, as well as immune responses to infections.

Much of our understanding of such processes is derived from the sequencing of the Anopheles gambiae genome in 2002, which facilitated large-scale functional studies that have offered insights into how this mosquito became highly specialized to live among and feed upon humans.

The lack of such genomic resources for other Anopheles species limited comparisons to small-scale studies of individual genes with no genome-wide data to investigate key attributes that impact the mosquitoes’ ability to transmit parasites.

In an attempt to change that, Daniel Neafsey, PhD, of the Broad Institute in Cambridge, Massachusetts, and his colleagues sequenced the genomes of 16 anopheline mosquito species.

A second team of researchers—Michael Fontaine, PhD, of the University of Notre Dame in Indiana, and his colleagues—leveraged the 16 reference sequences to uncover additional information.

Both groups described their work in Science Express.

The researchers performed comparative genomics analyses among the Anopheles species and Drosophila (one of the most closely related genera for which equivalent genomic resources exist). This revealed significant genetic differences that make certain Anopheles species particularly adept at inflicting life-threatening infections.

Anopheles species had high rates of gene gain and loss, about 5 times higher than in Drosophila. Some genes, such as those involved in reproduction or those that encode proteins secreted into the mosquito saliva, have very high rates of sequence evolution and are only found in subsets of the most closely related species.

“These dynamic changes may offer clues to understanding the diversification of Anopheles mosquitoes: why some breed in salty water while others need temporary or permanent pools of fresh water, or why some are attracted to livestock while others will only feed on humans,” said Nora Besansky, PhD, a professor at the University of Notre Dame and senior author of both studies.

The genome sequences also provided conclusive evidence of the true relations among several species that are very closely related to Anopheles gambiae but show different traits that affect their vectorial capacity.

“The question of the true species phylogeny has been a highly contentious issue in the field,” Dr Besansky said. “Our results show that the most efficient vectors are not necessarily the most closely related species, and that traits enhancing vectorial capacity may be gained by gene flow between species.”

The researchers found that gene flow is much more extensive in anophelines than in Drosophila, largely because of a process called introgression, whereby a gene from one species enters the gene pool of another. The process allows for a much more rapid transfer of genes than would arise simply by waiting for new mutations to crop up.

The high degree of anopheline gene flow provides a source of genetic variation on which natural selection can act—paving the way for traits that make mosquitoes highly effective vectors for malaria (like insecticide resistance or tolerance of more malaria parasites) to be fixed in certain anophelines.

University of Delaware

 

A newly developed injectable material can prevent blood loss from serious internal injuries, according to research published in ACS Nano.

This biodegradable hydrogel is embedded with silicate nanoplatelets that aid in coagulation.

Once injected, the material locks into place at the site of the injury and decreases clotting time.

In experiments, the hydrogel decreased clotting time by 77% in vitro and promoted life-saving hemostasis in vivo.

Though it’s still in early testing, the researchers envision the material being preloaded into syringes that soldiers can carry with them into combat situations.

If a soldier experiences a penetrating, incompressible injury, he or she could inject the hydrogel into the wound site, where it would trigger rapid coagulation and, ideally, provide enough time to get to a medical facility for treatment.

“The time to get to a medical facility can take a half hour to an hour, and this hour is crucial; it can decide life and death,” said study author Akhilesh Gaharwar, PhD, of Texas A&M University in College Station, Texas.

“Our material’s combination of injectability, rapid mechanical recovery, physiological stability, and the ability to promote coagulation result in a hemostat for treating incompressible wounds in out-of-hospital, emergency situations.”

Unlike some injectable solutions, which pose the risk of flowing to other parts of the body and forming unintended and potentially harmful clots, the material designed by Dr Gaharwar and his colleagues solidifies at the site of the wound and begins promoting coagulation in the targeted area.

To engineer the material, the researchers inserted 2-dimensional synthetic silicate nanoplatelets into hydrogels. The structure, composition, and arrangement of the nanoplatelets result in both positive and negative charges on each particle.

These charges cause the platelets to interact with the hydrogel in a unique way. The interaction causes the gel to temporarily undergo a change in its viscosity when mechanical force is applied. This allows the hydrogel to be injected and regain its shape once inside the body.

In addition to changing the mechanical properties of the hydrogel, these disc-shaped nanoplatelets interact with blood to promote clotting.

Animal models showed clot formation occurring in about 1 minute as opposed to 5 minutes without the presence of these nanoparticles. Animal models also demonstrated the formation of life-saving clots with the hydrogel.

“These 2D, silicate nanoparticles are unprecedented in the biomedical field,” Dr Gaharwar said. “And their use promises to lead to both conceptual and therapeutic advances in the important and emerging field of tissue engineering, drug delivery, cancer therapies, and immune engineering.”

The researchers plan to further enhance the biomaterial so it can initiate regeneration of damaged tissues through the formation of new blood vessels. The result could be a 2-pronged wound treatment—one that not only aids in damage control but also assists the body’s natural healing process.

University of Delaware

 

A newly developed injectable material can prevent blood loss from serious internal injuries, according to research published in ACS Nano.

This biodegradable hydrogel is embedded with silicate nanoplatelets that aid in coagulation.

Once injected, the material locks into place at the site of the injury and decreases clotting time.

In experiments, the hydrogel decreased clotting time by 77% in vitro and promoted life-saving hemostasis in vivo.

Though it’s still in early testing, the researchers envision the material being preloaded into syringes that soldiers can carry with them into combat situations.

If a soldier experiences a penetrating, incompressible injury, he or she could inject the hydrogel into the wound site, where it would trigger rapid coagulation and, ideally, provide enough time to get to a medical facility for treatment.

“The time to get to a medical facility can take a half hour to an hour, and this hour is crucial; it can decide life and death,” said study author Akhilesh Gaharwar, PhD, of Texas A&M University in College Station, Texas.

“Our material’s combination of injectability, rapid mechanical recovery, physiological stability, and the ability to promote coagulation result in a hemostat for treating incompressible wounds in out-of-hospital, emergency situations.”

Unlike some injectable solutions, which pose the risk of flowing to other parts of the body and forming unintended and potentially harmful clots, the material designed by Dr Gaharwar and his colleagues solidifies at the site of the wound and begins promoting coagulation in the targeted area.

To engineer the material, the researchers inserted 2-dimensional synthetic silicate nanoplatelets into hydrogels. The structure, composition, and arrangement of the nanoplatelets result in both positive and negative charges on each particle.

These charges cause the platelets to interact with the hydrogel in a unique way. The interaction causes the gel to temporarily undergo a change in its viscosity when mechanical force is applied. This allows the hydrogel to be injected and regain its shape once inside the body.

In addition to changing the mechanical properties of the hydrogel, these disc-shaped nanoplatelets interact with blood to promote clotting.

Animal models showed clot formation occurring in about 1 minute as opposed to 5 minutes without the presence of these nanoparticles. Animal models also demonstrated the formation of life-saving clots with the hydrogel.

“These 2D, silicate nanoparticles are unprecedented in the biomedical field,” Dr Gaharwar said. “And their use promises to lead to both conceptual and therapeutic advances in the important and emerging field of tissue engineering, drug delivery, cancer therapies, and immune engineering.”

The researchers plan to further enhance the biomaterial so it can initiate regeneration of damaged tissues through the formation of new blood vessels. The result could be a 2-pronged wound treatment—one that not only aids in damage control but also assists the body’s natural healing process.

University of Delaware

 

A newly developed injectable material can prevent blood loss from serious internal injuries, according to research published in ACS Nano.

This biodegradable hydrogel is embedded with silicate nanoplatelets that aid in coagulation.

Once injected, the material locks into place at the site of the injury and decreases clotting time.

In experiments, the hydrogel decreased clotting time by 77% in vitro and promoted life-saving hemostasis in vivo.

Though it’s still in early testing, the researchers envision the material being preloaded into syringes that soldiers can carry with them into combat situations.

If a soldier experiences a penetrating, incompressible injury, he or she could inject the hydrogel into the wound site, where it would trigger rapid coagulation and, ideally, provide enough time to get to a medical facility for treatment.

“The time to get to a medical facility can take a half hour to an hour, and this hour is crucial; it can decide life and death,” said study author Akhilesh Gaharwar, PhD, of Texas A&M University in College Station, Texas.

“Our material’s combination of injectability, rapid mechanical recovery, physiological stability, and the ability to promote coagulation result in a hemostat for treating incompressible wounds in out-of-hospital, emergency situations.”

Unlike some injectable solutions, which pose the risk of flowing to other parts of the body and forming unintended and potentially harmful clots, the material designed by Dr Gaharwar and his colleagues solidifies at the site of the wound and begins promoting coagulation in the targeted area.

To engineer the material, the researchers inserted 2-dimensional synthetic silicate nanoplatelets into hydrogels. The structure, composition, and arrangement of the nanoplatelets result in both positive and negative charges on each particle.

These charges cause the platelets to interact with the hydrogel in a unique way. The interaction causes the gel to temporarily undergo a change in its viscosity when mechanical force is applied. This allows the hydrogel to be injected and regain its shape once inside the body.

In addition to changing the mechanical properties of the hydrogel, these disc-shaped nanoplatelets interact with blood to promote clotting.

Animal models showed clot formation occurring in about 1 minute as opposed to 5 minutes without the presence of these nanoparticles. Animal models also demonstrated the formation of life-saving clots with the hydrogel.

“These 2D, silicate nanoparticles are unprecedented in the biomedical field,” Dr Gaharwar said. “And their use promises to lead to both conceptual and therapeutic advances in the important and emerging field of tissue engineering, drug delivery, cancer therapies, and immune engineering.”

The researchers plan to further enhance the biomaterial so it can initiate regeneration of damaged tissues through the formation of new blood vessels. The result could be a 2-pronged wound treatment—one that not only aids in damage control but also assists the body’s natural healing process.

Pill production

Credit: FDA

New research suggests that 20% of recent drug approvals occurred without pharmaceutical companies and the US Food and Drug Administration (FDA) meeting to discuss pivotal studies.

When these meetings did occur, companies did not comply with a quarter of FDA recommendations regarding study design or primary outcome.

Steven Woloshin, MD, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire, and his colleagues reported these findings in JAMA.

The researchers noted that federal regulations encourage but do not require meetings between pharmaceutical companies and the FDA during the design phase of pivotal studies assessing drug efficacy and safety for the proposed indication.

These meetings often generate FDA recommendations for improving research, but companies are not bound to follow them.

To evaluate this process, Dr Woloshin and his colleagues reviewed and analyzed approximately 200 FDA documents (memos, meeting minutes, filing checklists, and medical, statistical, and summary reviews) for 35 new drugs approved between February 1, 2011, and February 29, 2012.

The researchers identified all FDA comments and analyzed recommendations about pivotal study design or primary outcomes and characterized the effect of recommendations on study quality.

Of 35 new drug approvals, companies met with the FDA to discuss pivotal studies for 28 (80%). The FDA made 53 recommendations about design (eg, controls, doses, study length) or primary outcome for 21 approvals.

Fifty-one recommendations were judged as increasing study quality (eg, adding controls, blinding, or specific measures and frequency for toxicity assessments, lengthening studies to assess outcome durability) and 2 as having an uncertain effect.

Companies complied with 40 of the 53 recommendations (75%). An example of non-compliance is the FDA recommending randomized trials of brentuximab and crizotinib, with the companies conducting uncontrolled studies.

Other cases included primary outcome choice (eg, progression-free survival instead of overall survival) and drug (active comparator) doses tested.

Companies can also request FDA review of pivotal trial protocols. If the FDA endorses the protocol, it agrees not to object to any study design issues when reviewing the drug for approval.

Companies requested protocol review for 21 of the 35 new drug approvals, and the FDA endorsed the protocol for 12.

The researchers said instituting mandatory FDA review of pivotal trial protocols with the power to issue binding recommendations could be an effective way to optimize study quality.

An FDA-commissioned report suggested that stronger early FDA involvement could prevent deficiencies that delay the approval of effective drugs and more clearly identify drugs that are ineffective or harmful.

Pill production

Credit: FDA

New research suggests that 20% of recent drug approvals occurred without pharmaceutical companies and the US Food and Drug Administration (FDA) meeting to discuss pivotal studies.

When these meetings did occur, companies did not comply with a quarter of FDA recommendations regarding study design or primary outcome.

Steven Woloshin, MD, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire, and his colleagues reported these findings in JAMA.

The researchers noted that federal regulations encourage but do not require meetings between pharmaceutical companies and the FDA during the design phase of pivotal studies assessing drug efficacy and safety for the proposed indication.

These meetings often generate FDA recommendations for improving research, but companies are not bound to follow them.

To evaluate this process, Dr Woloshin and his colleagues reviewed and analyzed approximately 200 FDA documents (memos, meeting minutes, filing checklists, and medical, statistical, and summary reviews) for 35 new drugs approved between February 1, 2011, and February 29, 2012.

The researchers identified all FDA comments and analyzed recommendations about pivotal study design or primary outcomes and characterized the effect of recommendations on study quality.

Of 35 new drug approvals, companies met with the FDA to discuss pivotal studies for 28 (80%). The FDA made 53 recommendations about design (eg, controls, doses, study length) or primary outcome for 21 approvals.

Fifty-one recommendations were judged as increasing study quality (eg, adding controls, blinding, or specific measures and frequency for toxicity assessments, lengthening studies to assess outcome durability) and 2 as having an uncertain effect.

Companies complied with 40 of the 53 recommendations (75%). An example of non-compliance is the FDA recommending randomized trials of brentuximab and crizotinib, with the companies conducting uncontrolled studies.

Other cases included primary outcome choice (eg, progression-free survival instead of overall survival) and drug (active comparator) doses tested.

Companies can also request FDA review of pivotal trial protocols. If the FDA endorses the protocol, it agrees not to object to any study design issues when reviewing the drug for approval.

Companies requested protocol review for 21 of the 35 new drug approvals, and the FDA endorsed the protocol for 12.

The researchers said instituting mandatory FDA review of pivotal trial protocols with the power to issue binding recommendations could be an effective way to optimize study quality.

An FDA-commissioned report suggested that stronger early FDA involvement could prevent deficiencies that delay the approval of effective drugs and more clearly identify drugs that are ineffective or harmful.

Pill production

Credit: FDA

New research suggests that 20% of recent drug approvals occurred without pharmaceutical companies and the US Food and Drug Administration (FDA) meeting to discuss pivotal studies.

When these meetings did occur, companies did not comply with a quarter of FDA recommendations regarding study design or primary outcome.

Steven Woloshin, MD, of the Dartmouth Institute for Health Policy and Clinical Practice in Lebanon, New Hampshire, and his colleagues reported these findings in JAMA.

The researchers noted that federal regulations encourage but do not require meetings between pharmaceutical companies and the FDA during the design phase of pivotal studies assessing drug efficacy and safety for the proposed indication.

These meetings often generate FDA recommendations for improving research, but companies are not bound to follow them.

To evaluate this process, Dr Woloshin and his colleagues reviewed and analyzed approximately 200 FDA documents (memos, meeting minutes, filing checklists, and medical, statistical, and summary reviews) for 35 new drugs approved between February 1, 2011, and February 29, 2012.

The researchers identified all FDA comments and analyzed recommendations about pivotal study design or primary outcomes and characterized the effect of recommendations on study quality.

Of 35 new drug approvals, companies met with the FDA to discuss pivotal studies for 28 (80%). The FDA made 53 recommendations about design (eg, controls, doses, study length) or primary outcome for 21 approvals.

Fifty-one recommendations were judged as increasing study quality (eg, adding controls, blinding, or specific measures and frequency for toxicity assessments, lengthening studies to assess outcome durability) and 2 as having an uncertain effect.

Companies complied with 40 of the 53 recommendations (75%). An example of non-compliance is the FDA recommending randomized trials of brentuximab and crizotinib, with the companies conducting uncontrolled studies.

Other cases included primary outcome choice (eg, progression-free survival instead of overall survival) and drug (active comparator) doses tested.

Companies can also request FDA review of pivotal trial protocols. If the FDA endorses the protocol, it agrees not to object to any study design issues when reviewing the drug for approval.

Companies requested protocol review for 21 of the 35 new drug approvals, and the FDA endorsed the protocol for 12.

The researchers said instituting mandatory FDA review of pivotal trial protocols with the power to issue binding recommendations could be an effective way to optimize study quality.

An FDA-commissioned report suggested that stronger early FDA involvement could prevent deficiencies that delay the approval of effective drugs and more clearly identify drugs that are ineffective or harmful.

VANCOUVER – Morcellation is an effective, lifesaving tool in gynecologic surgery when used appropriately and should not be abandoned despite recent concerns about the dissemination of occult cancers, according to an expert panel that weighed in on this issue at a meeting sponsored by AAGL.

Panelists presented new data to inform the intense debate over this procedure, which has culminated in the Food and Drug Administration (FDA) recommending against the use of power morcellators during fibroid removal by hysterectomy or myomectomy for most women.

Earlier this year, AAGL convened the Tissue Extraction Task Force to study this issue and respond to the controversy. The association presented a statement to the FDA on power morcellation and published the task force findings that morcellation can be done safely and effectively when performed by trained and experienced surgeons in informed, carefully screened premenopausal women (J. Minim. Invasive Gynecol. 2014;21:517-30).

Abandoning it may raise mortality

“The priority of this entire discussion needs to focus on the patient’s welfare,” contended panelist Dr. Jubilee Brown, an associate professor in the department of gynecologic oncology and reproductive medicine, University of Texas M.D. Anderson Cancer Center, Houston. “For every piece of data that we look at, we need to keep that in the back of our minds as we analyze this.”

In a new study, she and her colleagues retrospectively studied outcomes in 808 consecutive patients with planned laparoscopic supracervical hysterectomy with morcellation who had at least 5 years of follow-up. The leading indications for surgery were menorrhagia and leiomyomata.

Only a single woman had a leiomyosarcoma; she was converted to an open procedure without morcellation but nonetheless died from the disease. “What hasn’t shown up in much of the literature is the wisdom of the operating surgeon, who identified that this uterus looked abnormal and called our group in,” commented Dr. Brown, who is also AAGL’s designated spokesperson on tissue extraction. “Unfortunately, what’s also missed in much of the literature is that leiomyosarcoma is an aggressive and often deadly disease. … In her case, as in so many cases, the problem was not the surgery, the problem was the cancer.”

Among the 778 women who underwent the planned laparoscopic hysterectomy with morcellation, 16 were found to have endometrial hyperplasia, two had adenocarcinoma, and one had an endometrial stromal sarcoma – but reassuringly, none had evidence of disease at follow-up.

“I think that what this tells us is that we need to be absolutely meticulous in our preoperative evaluation of patients in whom we are considering morcellation,” Dr. Brown said. The findings “speak to our obligation to educate our membership and everybody performing preoperative sampling on these patients.”

A decision analysis study also reported at the meeting by first author Dr. R. Wendel Naumann, Carolinas Medical Center in Charlotte, N.C., showed that mortality from laparoscopic hysterectomy with power morcellation – even accounting for possible dissemination of undiagnosed leiomyosarcomas – was 0.077%, still less than the 0.085% mortality from abdominal hysterectomy. “Though it is a small difference, it is an absolute difference in favor of laparoscopic hysterectomy with power morcellation. In fact, if all women were converted to an open hysterectomy, 17 more women each year would die of open hysterectomy than of power morcellation,” Dr. Brown commented.

“Power morcellation is an important tool,” she concluded, reiterating AAGL’s position that its use should be improved, not abandoned.

Low risk of leiomyosarcomas

Panelist Dr. Marit Lieng, an associate professor and consultant in the gynecology department of Oslo University Hospital, and her coinvestigators retrospectively studied 4,765 women who underwent surgery at the hospital for uterine fibroids between 2000 and 2013.

There were 26 cases of leiomyosarcoma (the majority in postmenopausal women), for an incidence of 0.54%, or 1 in 183 women.

However, only a single patient with leiomyosarcoma had laparoscopic supracervical hysterectomy with morcellation, because the tumor was identified or suspected preoperatively or intraoperatively in the rest, reported Dr. Lieng, who is also with the Institute of Clinical Medicine at the University of Oslo.

Therefore, the risk of unintended morcellation of an undiagnosed leiomyosarcoma was just 1 in 4,765 women, or 0.02%.

“I think the findings of our study support the conclusions of the AAGL expert group. … You can do power morcellation in selected patients,” Dr. Lieng commented. “Given a thorough preoperative evaluation, including a cervical cytology, endometrial biopsy, and evaluation of the myometrium by ultrasound or MRI, the risk of unintended morcellation of a uterine leiomyosarcoma in premenopausal women appears to be very low.”

Leiomyosarcomas best removed en bloc

“When you are creating public health care policy, decision analysis must begin with scientifically valid evidence,” asserted panelist Dr. Elizabeth Pritts, medical director of the Wisconsin Fertility Institute, Middleton.

She and her colleagues undertook a comprehensive new meta-analysis assessing the prevalence of occult leiomyosarcomas at hysterectomy or myomectomy for presumed uterine fibroids, including 133 original articles describing 30,193 women having explicit pathology.

Analysis of all prospective data showed that the predicted prevalence rate of occult leiomyosarcoma was 0.12 per 1,000 operations for presumed benign fibroids.

The corresponding 1 in 8,300 operations needed to find a leiomyosarcoma in this new meta-analysis differs greatly from the 1 in 498 found in an FDA meta-analysis, mainly because of the differing evidence base, Dr. Pritts maintained. “It really has to do with initial search criteria,” she said, noting, for example, that the FDA’s search strategy missed studies in which no cancer was found and studies in languages other than English.

Dr. Pritts and her colleagues also conducted a new systematic review looking at outcomes after morcellation of an unsuspected leiomyosarcoma, which was recently published (J. Minim. Invasive Gynecol. 2014 Sept. 2 [doi: 10.1016/j.jmig.2014.08.781]).

Main analyses here were based on six papers that compared morcellation with en bloc removal of leiomyosarcomas, most of which found worse survival for women whose tumors were morcellated.

“Now this is not great evidence, but remember, in evidence-based medicine, you’ve got to look at the very best available evidence. This is it,” Dr. Pritts maintained. “En bloc removal confers benefit—don’t cut into these.”

On closer inspection, only 3 of the 81 cases of morcellation reported were confirmed to be power morcellation. Comparisons of outcome with power versus hand morcellation, albeit limited by small numbers, suggested no difference in survival or upstaging.

“There are no data to suggest that any type of morcellation is better or worse than another type, even when including simple tumor biopsies,” Dr. Pritts concluded.

Dr. Brown, Dr. Lieng, and Dr. Pritts disclosed that they had no relevant conflicts of interest.

VANCOUVER – Morcellation is an effective, lifesaving tool in gynecologic surgery when used appropriately and should not be abandoned despite recent concerns about the dissemination of occult cancers, according to an expert panel that weighed in on this issue at a meeting sponsored by AAGL.

Panelists presented new data to inform the intense debate over this procedure, which has culminated in the Food and Drug Administration (FDA) recommending against the use of power morcellators during fibroid removal by hysterectomy or myomectomy for most women.

Earlier this year, AAGL convened the Tissue Extraction Task Force to study this issue and respond to the controversy. The association presented a statement to the FDA on power morcellation and published the task force findings that morcellation can be done safely and effectively when performed by trained and experienced surgeons in informed, carefully screened premenopausal women (J. Minim. Invasive Gynecol. 2014;21:517-30).

Abandoning it may raise mortality

“The priority of this entire discussion needs to focus on the patient’s welfare,” contended panelist Dr. Jubilee Brown, an associate professor in the department of gynecologic oncology and reproductive medicine, University of Texas M.D. Anderson Cancer Center, Houston. “For every piece of data that we look at, we need to keep that in the back of our minds as we analyze this.”

In a new study, she and her colleagues retrospectively studied outcomes in 808 consecutive patients with planned laparoscopic supracervical hysterectomy with morcellation who had at least 5 years of follow-up. The leading indications for surgery were menorrhagia and leiomyomata.

Only a single woman had a leiomyosarcoma; she was converted to an open procedure without morcellation but nonetheless died from the disease. “What hasn’t shown up in much of the literature is the wisdom of the operating surgeon, who identified that this uterus looked abnormal and called our group in,” commented Dr. Brown, who is also AAGL’s designated spokesperson on tissue extraction. “Unfortunately, what’s also missed in much of the literature is that leiomyosarcoma is an aggressive and often deadly disease. … In her case, as in so many cases, the problem was not the surgery, the problem was the cancer.”

Among the 778 women who underwent the planned laparoscopic hysterectomy with morcellation, 16 were found to have endometrial hyperplasia, two had adenocarcinoma, and one had an endometrial stromal sarcoma – but reassuringly, none had evidence of disease at follow-up.

“I think that what this tells us is that we need to be absolutely meticulous in our preoperative evaluation of patients in whom we are considering morcellation,” Dr. Brown said. The findings “speak to our obligation to educate our membership and everybody performing preoperative sampling on these patients.”

A decision analysis study also reported at the meeting by first author Dr. R. Wendel Naumann, Carolinas Medical Center in Charlotte, N.C., showed that mortality from laparoscopic hysterectomy with power morcellation – even accounting for possible dissemination of undiagnosed leiomyosarcomas – was 0.077%, still less than the 0.085% mortality from abdominal hysterectomy. “Though it is a small difference, it is an absolute difference in favor of laparoscopic hysterectomy with power morcellation. In fact, if all women were converted to an open hysterectomy, 17 more women each year would die of open hysterectomy than of power morcellation,” Dr. Brown commented.

“Power morcellation is an important tool,” she concluded, reiterating AAGL’s position that its use should be improved, not abandoned.

Low risk of leiomyosarcomas

Panelist Dr. Marit Lieng, an associate professor and consultant in the gynecology department of Oslo University Hospital, and her coinvestigators retrospectively studied 4,765 women who underwent surgery at the hospital for uterine fibroids between 2000 and 2013.

There were 26 cases of leiomyosarcoma (the majority in postmenopausal women), for an incidence of 0.54%, or 1 in 183 women.

However, only a single patient with leiomyosarcoma had laparoscopic supracervical hysterectomy with morcellation, because the tumor was identified or suspected preoperatively or intraoperatively in the rest, reported Dr. Lieng, who is also with the Institute of Clinical Medicine at the University of Oslo.

Therefore, the risk of unintended morcellation of an undiagnosed leiomyosarcoma was just 1 in 4,765 women, or 0.02%.

“I think the findings of our study support the conclusions of the AAGL expert group. … You can do power morcellation in selected patients,” Dr. Lieng commented. “Given a thorough preoperative evaluation, including a cervical cytology, endometrial biopsy, and evaluation of the myometrium by ultrasound or MRI, the risk of unintended morcellation of a uterine leiomyosarcoma in premenopausal women appears to be very low.”

Leiomyosarcomas best removed en bloc

“When you are creating public health care policy, decision analysis must begin with scientifically valid evidence,” asserted panelist Dr. Elizabeth Pritts, medical director of the Wisconsin Fertility Institute, Middleton.

She and her colleagues undertook a comprehensive new meta-analysis assessing the prevalence of occult leiomyosarcomas at hysterectomy or myomectomy for presumed uterine fibroids, including 133 original articles describing 30,193 women having explicit pathology.

Analysis of all prospective data showed that the predicted prevalence rate of occult leiomyosarcoma was 0.12 per 1,000 operations for presumed benign fibroids.

The corresponding 1 in 8,300 operations needed to find a leiomyosarcoma in this new meta-analysis differs greatly from the 1 in 498 found in an FDA meta-analysis, mainly because of the differing evidence base, Dr. Pritts maintained. “It really has to do with initial search criteria,” she said, noting, for example, that the FDA’s search strategy missed studies in which no cancer was found and studies in languages other than English.

Dr. Pritts and her colleagues also conducted a new systematic review looking at outcomes after morcellation of an unsuspected leiomyosarcoma, which was recently published (J. Minim. Invasive Gynecol. 2014 Sept. 2 [doi: 10.1016/j.jmig.2014.08.781]).

Main analyses here were based on six papers that compared morcellation with en bloc removal of leiomyosarcomas, most of which found worse survival for women whose tumors were morcellated.

“Now this is not great evidence, but remember, in evidence-based medicine, you’ve got to look at the very best available evidence. This is it,” Dr. Pritts maintained. “En bloc removal confers benefit—don’t cut into these.”

On closer inspection, only 3 of the 81 cases of morcellation reported were confirmed to be power morcellation. Comparisons of outcome with power versus hand morcellation, albeit limited by small numbers, suggested no difference in survival or upstaging.

“There are no data to suggest that any type of morcellation is better or worse than another type, even when including simple tumor biopsies,” Dr. Pritts concluded.

Dr. Brown, Dr. Lieng, and Dr. Pritts disclosed that they had no relevant conflicts of interest.

VANCOUVER – Morcellation is an effective, lifesaving tool in gynecologic surgery when used appropriately and should not be abandoned despite recent concerns about the dissemination of occult cancers, according to an expert panel that weighed in on this issue at a meeting sponsored by AAGL.

Panelists presented new data to inform the intense debate over this procedure, which has culminated in the Food and Drug Administration (FDA) recommending against the use of power morcellators during fibroid removal by hysterectomy or myomectomy for most women.

Earlier this year, AAGL convened the Tissue Extraction Task Force to study this issue and respond to the controversy. The association presented a statement to the FDA on power morcellation and published the task force findings that morcellation can be done safely and effectively when performed by trained and experienced surgeons in informed, carefully screened premenopausal women (J. Minim. Invasive Gynecol. 2014;21:517-30).

Abandoning it may raise mortality

“The priority of this entire discussion needs to focus on the patient’s welfare,” contended panelist Dr. Jubilee Brown, an associate professor in the department of gynecologic oncology and reproductive medicine, University of Texas M.D. Anderson Cancer Center, Houston. “For every piece of data that we look at, we need to keep that in the back of our minds as we analyze this.”

In a new study, she and her colleagues retrospectively studied outcomes in 808 consecutive patients with planned laparoscopic supracervical hysterectomy with morcellation who had at least 5 years of follow-up. The leading indications for surgery were menorrhagia and leiomyomata.

Only a single woman had a leiomyosarcoma; she was converted to an open procedure without morcellation but nonetheless died from the disease. “What hasn’t shown up in much of the literature is the wisdom of the operating surgeon, who identified that this uterus looked abnormal and called our group in,” commented Dr. Brown, who is also AAGL’s designated spokesperson on tissue extraction. “Unfortunately, what’s also missed in much of the literature is that leiomyosarcoma is an aggressive and often deadly disease. … In her case, as in so many cases, the problem was not the surgery, the problem was the cancer.”

Among the 778 women who underwent the planned laparoscopic hysterectomy with morcellation, 16 were found to have endometrial hyperplasia, two had adenocarcinoma, and one had an endometrial stromal sarcoma – but reassuringly, none had evidence of disease at follow-up.

“I think that what this tells us is that we need to be absolutely meticulous in our preoperative evaluation of patients in whom we are considering morcellation,” Dr. Brown said. The findings “speak to our obligation to educate our membership and everybody performing preoperative sampling on these patients.”

A decision analysis study also reported at the meeting by first author Dr. R. Wendel Naumann, Carolinas Medical Center in Charlotte, N.C., showed that mortality from laparoscopic hysterectomy with power morcellation – even accounting for possible dissemination of undiagnosed leiomyosarcomas – was 0.077%, still less than the 0.085% mortality from abdominal hysterectomy. “Though it is a small difference, it is an absolute difference in favor of laparoscopic hysterectomy with power morcellation. In fact, if all women were converted to an open hysterectomy, 17 more women each year would die of open hysterectomy than of power morcellation,” Dr. Brown commented.

“Power morcellation is an important tool,” she concluded, reiterating AAGL’s position that its use should be improved, not abandoned.

Low risk of leiomyosarcomas

Panelist Dr. Marit Lieng, an associate professor and consultant in the gynecology department of Oslo University Hospital, and her coinvestigators retrospectively studied 4,765 women who underwent surgery at the hospital for uterine fibroids between 2000 and 2013.

There were 26 cases of leiomyosarcoma (the majority in postmenopausal women), for an incidence of 0.54%, or 1 in 183 women.

However, only a single patient with leiomyosarcoma had laparoscopic supracervical hysterectomy with morcellation, because the tumor was identified or suspected preoperatively or intraoperatively in the rest, reported Dr. Lieng, who is also with the Institute of Clinical Medicine at the University of Oslo.

Therefore, the risk of unintended morcellation of an undiagnosed leiomyosarcoma was just 1 in 4,765 women, or 0.02%.

“I think the findings of our study support the conclusions of the AAGL expert group. … You can do power morcellation in selected patients,” Dr. Lieng commented. “Given a thorough preoperative evaluation, including a cervical cytology, endometrial biopsy, and evaluation of the myometrium by ultrasound or MRI, the risk of unintended morcellation of a uterine leiomyosarcoma in premenopausal women appears to be very low.”

Leiomyosarcomas best removed en bloc

“When you are creating public health care policy, decision analysis must begin with scientifically valid evidence,” asserted panelist Dr. Elizabeth Pritts, medical director of the Wisconsin Fertility Institute, Middleton.

She and her colleagues undertook a comprehensive new meta-analysis assessing the prevalence of occult leiomyosarcomas at hysterectomy or myomectomy for presumed uterine fibroids, including 133 original articles describing 30,193 women having explicit pathology.

Analysis of all prospective data showed that the predicted prevalence rate of occult leiomyosarcoma was 0.12 per 1,000 operations for presumed benign fibroids.

The corresponding 1 in 8,300 operations needed to find a leiomyosarcoma in this new meta-analysis differs greatly from the 1 in 498 found in an FDA meta-analysis, mainly because of the differing evidence base, Dr. Pritts maintained. “It really has to do with initial search criteria,” she said, noting, for example, that the FDA’s search strategy missed studies in which no cancer was found and studies in languages other than English.

Dr. Pritts and her colleagues also conducted a new systematic review looking at outcomes after morcellation of an unsuspected leiomyosarcoma, which was recently published (J. Minim. Invasive Gynecol. 2014 Sept. 2 [doi: 10.1016/j.jmig.2014.08.781]).

Main analyses here were based on six papers that compared morcellation with en bloc removal of leiomyosarcomas, most of which found worse survival for women whose tumors were morcellated.

“Now this is not great evidence, but remember, in evidence-based medicine, you’ve got to look at the very best available evidence. This is it,” Dr. Pritts maintained. “En bloc removal confers benefit—don’t cut into these.”

On closer inspection, only 3 of the 81 cases of morcellation reported were confirmed to be power morcellation. Comparisons of outcome with power versus hand morcellation, albeit limited by small numbers, suggested no difference in survival or upstaging.

“There are no data to suggest that any type of morcellation is better or worse than another type, even when including simple tumor biopsies,” Dr. Pritts concluded.

Dr. Brown, Dr. Lieng, and Dr. Pritts disclosed that they had no relevant conflicts of interest.

Acne vulgaris is a diagnosis common to all primary care physicians, and the No. 1 concern for most adolescents. Referral wait times to a dermatologist can be anywhere from 3 to 6 months; if you’re lucky, dermatologists have a physician assistant or nurse practitioner who can see patients sooner. But the majority of acne cases – even complex ones – can successfully be treated by a primary care physician. Not only would you be improving patient satisfaction because the patient can be treated immediately, you also would increase your revenue.

Acne care is a billion dollar industry. Prescription medications are a $2 billion industry, and nonprescription medications are three to four times that (Semin. Cutan. Med. Surg. 2008;27:170). Yet, the average primary care physician will start treatment, then refer to the dermatologist.

The scope of acne care is not that broad; this should decrease your anxiety about being more aggressive with the treatment. Acne begins when there is follicular hyperproliferation, which leads to the obstruction of the follicle. This is followed by an increase in the sebum, by inflammation, and then by colonization with bacteria. Topical retinoids (tretinoin, adapalene, and tazarotene) normalize the follicular hyperproliferation and decrease inflammation. Antibiotics kill the bacteria. So, with implementation of topical retinoids, antibiotics, and a good home regimen, the vast majority of acne cases can be successfully treated without a referral.

When a patient presents with either concerns about acne or obvious full-blown acne, an assessment of the condition should be done. Realizing that there is gender gap in the treatment of acne is crucial. Males are much less likely to admit that they are bothered by their acne or adhere to treatment because they think it’s “girly” to use products on the face or follow a cleansing regimen. But, it is well documented that acne is associated with lower self-esteem, being bullied, depression, and anxiety. The patient assessment should identify acne type (comedonal, inflammatory, nodular), severity, scarring, menstrual history in girls, and the psychological impact on the patient.

Also review past treatments and what worked, what didn’t work, and why. Most patients upon presentation have used the over-the-counter preparations, which usually consist of benzoyl peroxide and salicylic acid.

Managing patients’ expectations is another key component to successful treatment. Most of the topical treatments have undesirable side effects like drying and reddening and hyperpigmentation of the skin. Informing them that irritations will lessen and will improve over time can aid in adherence to the regimen.

If a patient has dry skin, cream formulations will be less irritating; more oily skin will respond better to gels that tend to be more drying. The percentage of benzoyl peroxide also contributes to the discomfort. One study showed that the 2.5% was as effective as the 10% formulation, but resulted in less irritation (Br. J. Dermatol .2014;170:557). Salicylic acid is a good alternative if benzoyl peroxide is not tolerated.

Antibiotics are an essential part of acne treatment. Topicals such as erythromycin, clindamycin, and dapsone reduce Propionibacterium acnes, which also reduces inflammation. Oral antibiotics have similar efficacy, but are associated with more rapid clinical improvement. Another consideration in using oral antibiotics is the side effects. Photosensitivity and gastrointestinal upset are significant issues that arise with their use. Doxycycline monohydrate tends to have fewer GI side effects and is preferred over doxycycline hyclate. Minocycline has fewer GI effects and less photosensitivity, but tends to be more expensive and is associated with vertigo and serum sickness (Arch. Dermatol. 1982;118:989-92). Prolonged use of either topical or oral antibiotics increases the risk of resistant strains of P. acnes. Other antibiotics are available for use, such as trimethoprim-sulfamethoxazole, clindamycin, and erythromycin, but all have either significant side effects associated with them or higher levels of resistance.

Combination therapy is superior to monotherapy. Whether combining benzoyl peroxide with a topical retinoid, antibiotic, or both, improved outcomes have been shown. Studies also confirm that use of benzoyl peroxide with antibiotics lowers the risk of P. acne’s resistance (Dermatol. Clin. 2009;27:25-31).

Now, how do you make acne care work for your business model? It’s easier than you may think. Other highly effective, inexpensive, and efficient treatments can be implemented with little investment.

Establishing and marketing an acne program and dedicating a few hours a week to an acne clinic can add significant revenue to your practice. Educate the patient on cleansing and diet; information can be found at www.acne.com. Beyond using the traditional acne treatments, consider adding peels and a light-based therapy to the regimen. Salicylic acid peels are easy to apply and give great results. Treatments are done monthly for five to six treatments at a cost of $140-$250 per treatment. The application process takes 15-20 minutes.

Light therapy is also easy to implement. With the purchase of a lamp that costs less than $1,000, you can offer this treatment. Patients can come twice a week for 15-minute sessions for a total of eight sessions. The average cost for these treatments is $50-$75 per treatment. Combinations of peels and light therapy have great results with minimal risk and prevent families from having to wait the 3-6 months it takes to get to see the dermatologist.

Lastly, consider cosmeceuticals. There is no great mystery as to what is in the acne medications. You can create your own line using a compounding pharmacy such as MasterPharm or University Compounding Pharmacy . Or use a cosmeceuticals company that will provide you quality products at wholesale prices. Many of them don’t require you to stock the product. SkinMedica and SkinCeuticals ( are popular ones, but there are several more. As opposed to your patient going to the local pharmacy and guessing at which product is best, you can provide a full line of products that will give the best results.

Without compromising care, you can provide complete skin care to your patients and increase your revenue and your patient’s satisfaction.

Dr. Pearce is a pediatrician in Frankfort, Ill. Dr. Pearce had no relevant financial disclosures. E-mail her at [email protected].

Acne vulgaris is a diagnosis common to all primary care physicians, and the No. 1 concern for most adolescents. Referral wait times to a dermatologist can be anywhere from 3 to 6 months; if you’re lucky, dermatologists have a physician assistant or nurse practitioner who can see patients sooner. But the majority of acne cases – even complex ones – can successfully be treated by a primary care physician. Not only would you be improving patient satisfaction because the patient can be treated immediately, you also would increase your revenue.

Acne care is a billion dollar industry. Prescription medications are a $2 billion industry, and nonprescription medications are three to four times that (Semin. Cutan. Med. Surg. 2008;27:170). Yet, the average primary care physician will start treatment, then refer to the dermatologist.

The scope of acne care is not that broad; this should decrease your anxiety about being more aggressive with the treatment. Acne begins when there is follicular hyperproliferation, which leads to the obstruction of the follicle. This is followed by an increase in the sebum, by inflammation, and then by colonization with bacteria. Topical retinoids (tretinoin, adapalene, and tazarotene) normalize the follicular hyperproliferation and decrease inflammation. Antibiotics kill the bacteria. So, with implementation of topical retinoids, antibiotics, and a good home regimen, the vast majority of acne cases can be successfully treated without a referral.

When a patient presents with either concerns about acne or obvious full-blown acne, an assessment of the condition should be done. Realizing that there is gender gap in the treatment of acne is crucial. Males are much less likely to admit that they are bothered by their acne or adhere to treatment because they think it’s “girly” to use products on the face or follow a cleansing regimen. But, it is well documented that acne is associated with lower self-esteem, being bullied, depression, and anxiety. The patient assessment should identify acne type (comedonal, inflammatory, nodular), severity, scarring, menstrual history in girls, and the psychological impact on the patient.

Also review past treatments and what worked, what didn’t work, and why. Most patients upon presentation have used the over-the-counter preparations, which usually consist of benzoyl peroxide and salicylic acid.

Managing patients’ expectations is another key component to successful treatment. Most of the topical treatments have undesirable side effects like drying and reddening and hyperpigmentation of the skin. Informing them that irritations will lessen and will improve over time can aid in adherence to the regimen.

If a patient has dry skin, cream formulations will be less irritating; more oily skin will respond better to gels that tend to be more drying. The percentage of benzoyl peroxide also contributes to the discomfort. One study showed that the 2.5% was as effective as the 10% formulation, but resulted in less irritation (Br. J. Dermatol .2014;170:557). Salicylic acid is a good alternative if benzoyl peroxide is not tolerated.

Antibiotics are an essential part of acne treatment. Topicals such as erythromycin, clindamycin, and dapsone reduce Propionibacterium acnes, which also reduces inflammation. Oral antibiotics have similar efficacy, but are associated with more rapid clinical improvement. Another consideration in using oral antibiotics is the side effects. Photosensitivity and gastrointestinal upset are significant issues that arise with their use. Doxycycline monohydrate tends to have fewer GI side effects and is preferred over doxycycline hyclate. Minocycline has fewer GI effects and less photosensitivity, but tends to be more expensive and is associated with vertigo and serum sickness (Arch. Dermatol. 1982;118:989-92). Prolonged use of either topical or oral antibiotics increases the risk of resistant strains of P. acnes. Other antibiotics are available for use, such as trimethoprim-sulfamethoxazole, clindamycin, and erythromycin, but all have either significant side effects associated with them or higher levels of resistance.

Combination therapy is superior to monotherapy. Whether combining benzoyl peroxide with a topical retinoid, antibiotic, or both, improved outcomes have been shown. Studies also confirm that use of benzoyl peroxide with antibiotics lowers the risk of P. acne’s resistance (Dermatol. Clin. 2009;27:25-31).

Now, how do you make acne care work for your business model? It’s easier than you may think. Other highly effective, inexpensive, and efficient treatments can be implemented with little investment.

Establishing and marketing an acne program and dedicating a few hours a week to an acne clinic can add significant revenue to your practice. Educate the patient on cleansing and diet; information can be found at www.acne.com. Beyond using the traditional acne treatments, consider adding peels and a light-based therapy to the regimen. Salicylic acid peels are easy to apply and give great results. Treatments are done monthly for five to six treatments at a cost of $140-$250 per treatment. The application process takes 15-20 minutes.

Light therapy is also easy to implement. With the purchase of a lamp that costs less than $1,000, you can offer this treatment. Patients can come twice a week for 15-minute sessions for a total of eight sessions. The average cost for these treatments is $50-$75 per treatment. Combinations of peels and light therapy have great results with minimal risk and prevent families from having to wait the 3-6 months it takes to get to see the dermatologist.

Lastly, consider cosmeceuticals. There is no great mystery as to what is in the acne medications. You can create your own line using a compounding pharmacy such as MasterPharm or University Compounding Pharmacy . Or use a cosmeceuticals company that will provide you quality products at wholesale prices. Many of them don’t require you to stock the product. SkinMedica and SkinCeuticals ( are popular ones, but there are several more. As opposed to your patient going to the local pharmacy and guessing at which product is best, you can provide a full line of products that will give the best results.

Without compromising care, you can provide complete skin care to your patients and increase your revenue and your patient’s satisfaction.

Dr. Pearce is a pediatrician in Frankfort, Ill. Dr. Pearce had no relevant financial disclosures. E-mail her at [email protected].

Acne vulgaris is a diagnosis common to all primary care physicians, and the No. 1 concern for most adolescents. Referral wait times to a dermatologist can be anywhere from 3 to 6 months; if you’re lucky, dermatologists have a physician assistant or nurse practitioner who can see patients sooner. But the majority of acne cases – even complex ones – can successfully be treated by a primary care physician. Not only would you be improving patient satisfaction because the patient can be treated immediately, you also would increase your revenue.

Acne care is a billion dollar industry. Prescription medications are a $2 billion industry, and nonprescription medications are three to four times that (Semin. Cutan. Med. Surg. 2008;27:170). Yet, the average primary care physician will start treatment, then refer to the dermatologist.

The scope of acne care is not that broad; this should decrease your anxiety about being more aggressive with the treatment. Acne begins when there is follicular hyperproliferation, which leads to the obstruction of the follicle. This is followed by an increase in the sebum, by inflammation, and then by colonization with bacteria. Topical retinoids (tretinoin, adapalene, and tazarotene) normalize the follicular hyperproliferation and decrease inflammation. Antibiotics kill the bacteria. So, with implementation of topical retinoids, antibiotics, and a good home regimen, the vast majority of acne cases can be successfully treated without a referral.

When a patient presents with either concerns about acne or obvious full-blown acne, an assessment of the condition should be done. Realizing that there is gender gap in the treatment of acne is crucial. Males are much less likely to admit that they are bothered by their acne or adhere to treatment because they think it’s “girly” to use products on the face or follow a cleansing regimen. But, it is well documented that acne is associated with lower self-esteem, being bullied, depression, and anxiety. The patient assessment should identify acne type (comedonal, inflammatory, nodular), severity, scarring, menstrual history in girls, and the psychological impact on the patient.

Also review past treatments and what worked, what didn’t work, and why. Most patients upon presentation have used the over-the-counter preparations, which usually consist of benzoyl peroxide and salicylic acid.

Managing patients’ expectations is another key component to successful treatment. Most of the topical treatments have undesirable side effects like drying and reddening and hyperpigmentation of the skin. Informing them that irritations will lessen and will improve over time can aid in adherence to the regimen.

If a patient has dry skin, cream formulations will be less irritating; more oily skin will respond better to gels that tend to be more drying. The percentage of benzoyl peroxide also contributes to the discomfort. One study showed that the 2.5% was as effective as the 10% formulation, but resulted in less irritation (Br. J. Dermatol .2014;170:557). Salicylic acid is a good alternative if benzoyl peroxide is not tolerated.

Antibiotics are an essential part of acne treatment. Topicals such as erythromycin, clindamycin, and dapsone reduce Propionibacterium acnes, which also reduces inflammation. Oral antibiotics have similar efficacy, but are associated with more rapid clinical improvement. Another consideration in using oral antibiotics is the side effects. Photosensitivity and gastrointestinal upset are significant issues that arise with their use. Doxycycline monohydrate tends to have fewer GI side effects and is preferred over doxycycline hyclate. Minocycline has fewer GI effects and less photosensitivity, but tends to be more expensive and is associated with vertigo and serum sickness (Arch. Dermatol. 1982;118:989-92). Prolonged use of either topical or oral antibiotics increases the risk of resistant strains of P. acnes. Other antibiotics are available for use, such as trimethoprim-sulfamethoxazole, clindamycin, and erythromycin, but all have either significant side effects associated with them or higher levels of resistance.

Combination therapy is superior to monotherapy. Whether combining benzoyl peroxide with a topical retinoid, antibiotic, or both, improved outcomes have been shown. Studies also confirm that use of benzoyl peroxide with antibiotics lowers the risk of P. acne’s resistance (Dermatol. Clin. 2009;27:25-31).

Now, how do you make acne care work for your business model? It’s easier than you may think. Other highly effective, inexpensive, and efficient treatments can be implemented with little investment.

Establishing and marketing an acne program and dedicating a few hours a week to an acne clinic can add significant revenue to your practice. Educate the patient on cleansing and diet; information can be found at www.acne.com. Beyond using the traditional acne treatments, consider adding peels and a light-based therapy to the regimen. Salicylic acid peels are easy to apply and give great results. Treatments are done monthly for five to six treatments at a cost of $140-$250 per treatment. The application process takes 15-20 minutes.

Light therapy is also easy to implement. With the purchase of a lamp that costs less than $1,000, you can offer this treatment. Patients can come twice a week for 15-minute sessions for a total of eight sessions. The average cost for these treatments is $50-$75 per treatment. Combinations of peels and light therapy have great results with minimal risk and prevent families from having to wait the 3-6 months it takes to get to see the dermatologist.

Lastly, consider cosmeceuticals. There is no great mystery as to what is in the acne medications. You can create your own line using a compounding pharmacy such as MasterPharm or University Compounding Pharmacy . Or use a cosmeceuticals company that will provide you quality products at wholesale prices. Many of them don’t require you to stock the product. SkinMedica and SkinCeuticals ( are popular ones, but there are several more. As opposed to your patient going to the local pharmacy and guessing at which product is best, you can provide a full line of products that will give the best results.

Without compromising care, you can provide complete skin care to your patients and increase your revenue and your patient’s satisfaction.

Dr. Pearce is a pediatrician in Frankfort, Ill. Dr. Pearce had no relevant financial disclosures. E-mail her at [email protected].

The rate of cigarette smoking among adults in the United States dropped from 20.9% in 2005 to 17.8% in 2013, the lowest it has been since the Centers for Disease Control and Prevention began recording such data in 1965.

The numbers come from the Nov. 28 issue of the CDC’s Morbidity and Mortality Weekly Report (MMWR 2014;63:1108-12), which also states that the percentage of daily smokers who went through 20-29 cigarettes per day dropped from 34.9% in 2005 to 29.3% in 2013. Conversely, the rate of daily smokers who consumed 10 or fewer cigarettes per day increased from 16.4% in 2005 to 23.3% in 2013.

©thinkstockphotos.com

“Though smokers are smoking fewer cigarettes, cutting back by a few cigarettes a day rather than quitting completely does not produce significant health benefits,” Brian King, Ph.D., a senior scientific advisor with the CDC’s Office on Smoking and Health, said in a statement. “Smokers who quit before they’re 40 years old can get back almost all of the 10 years of life expectancy smoking takes away.”

Despite the strides in cutting down overall smoking among American adults, certain demographics continue to struggle. A total of 42.1 million adults remained smokers in 2013. Smoking rates remain especially high among males, younger individuals, those who are multiracial or American Indian/Alaska Native, have less education, live below the federal poverty level, live in the South or Midwest, have a disability or other limitation, and those who are lesbian, gay, or bisexual.

“There is encouraging news in this study, but we still have much more work to do to help people quit,” Dr. Tim McAfee, director of the CDC’s Office on Smoking and Health, noted in the statement. “We can bring down cigarette smoking rates much further, much faster, if strategies proven to work are put in place like funding tobacco control programs at the CDC-recommended levels, increasing prices of tobacco products, implementing and enforcing comprehensive smoke-free laws, and sustaining hard-hitting media campaigns.”

According to the CDC, cigarette smoking is the leading preventable cause of disease and death in the United States, claiming over 480,000 lives annually. Its impact can also be felt economically, with cigarette smoking costing the United States at least $133 billion in direct medical care for adults and more than $156 billion in lost productivity. Meanwhile, the rates of other forms of tobacco consumption, such as cigars and hookahs, are not declining.

Surveys cited by the CDC estimate that 70% of smokers want to quit.

[email protected]

The rate of cigarette smoking among adults in the United States dropped from 20.9% in 2005 to 17.8% in 2013, the lowest it has been since the Centers for Disease Control and Prevention began recording such data in 1965.

The numbers come from the Nov. 28 issue of the CDC’s Morbidity and Mortality Weekly Report (MMWR 2014;63:1108-12), which also states that the percentage of daily smokers who went through 20-29 cigarettes per day dropped from 34.9% in 2005 to 29.3% in 2013. Conversely, the rate of daily smokers who consumed 10 or fewer cigarettes per day increased from 16.4% in 2005 to 23.3% in 2013.

©thinkstockphotos.com

“Though smokers are smoking fewer cigarettes, cutting back by a few cigarettes a day rather than quitting completely does not produce significant health benefits,” Brian King, Ph.D., a senior scientific advisor with the CDC’s Office on Smoking and Health, said in a statement. “Smokers who quit before they’re 40 years old can get back almost all of the 10 years of life expectancy smoking takes away.”

Despite the strides in cutting down overall smoking among American adults, certain demographics continue to struggle. A total of 42.1 million adults remained smokers in 2013. Smoking rates remain especially high among males, younger individuals, those who are multiracial or American Indian/Alaska Native, have less education, live below the federal poverty level, live in the South or Midwest, have a disability or other limitation, and those who are lesbian, gay, or bisexual.

“There is encouraging news in this study, but we still have much more work to do to help people quit,” Dr. Tim McAfee, director of the CDC’s Office on Smoking and Health, noted in the statement. “We can bring down cigarette smoking rates much further, much faster, if strategies proven to work are put in place like funding tobacco control programs at the CDC-recommended levels, increasing prices of tobacco products, implementing and enforcing comprehensive smoke-free laws, and sustaining hard-hitting media campaigns.”

According to the CDC, cigarette smoking is the leading preventable cause of disease and death in the United States, claiming over 480,000 lives annually. Its impact can also be felt economically, with cigarette smoking costing the United States at least $133 billion in direct medical care for adults and more than $156 billion in lost productivity. Meanwhile, the rates of other forms of tobacco consumption, such as cigars and hookahs, are not declining.

Surveys cited by the CDC estimate that 70% of smokers want to quit.

[email protected]

The rate of cigarette smoking among adults in the United States dropped from 20.9% in 2005 to 17.8% in 2013, the lowest it has been since the Centers for Disease Control and Prevention began recording such data in 1965.

The numbers come from the Nov. 28 issue of the CDC’s Morbidity and Mortality Weekly Report (MMWR 2014;63:1108-12), which also states that the percentage of daily smokers who went through 20-29 cigarettes per day dropped from 34.9% in 2005 to 29.3% in 2013. Conversely, the rate of daily smokers who consumed 10 or fewer cigarettes per day increased from 16.4% in 2005 to 23.3% in 2013.

©thinkstockphotos.com

“Though smokers are smoking fewer cigarettes, cutting back by a few cigarettes a day rather than quitting completely does not produce significant health benefits,” Brian King, Ph.D., a senior scientific advisor with the CDC’s Office on Smoking and Health, said in a statement. “Smokers who quit before they’re 40 years old can get back almost all of the 10 years of life expectancy smoking takes away.”

Despite the strides in cutting down overall smoking among American adults, certain demographics continue to struggle. A total of 42.1 million adults remained smokers in 2013. Smoking rates remain especially high among males, younger individuals, those who are multiracial or American Indian/Alaska Native, have less education, live below the federal poverty level, live in the South or Midwest, have a disability or other limitation, and those who are lesbian, gay, or bisexual.

“There is encouraging news in this study, but we still have much more work to do to help people quit,” Dr. Tim McAfee, director of the CDC’s Office on Smoking and Health, noted in the statement. “We can bring down cigarette smoking rates much further, much faster, if strategies proven to work are put in place like funding tobacco control programs at the CDC-recommended levels, increasing prices of tobacco products, implementing and enforcing comprehensive smoke-free laws, and sustaining hard-hitting media campaigns.”

According to the CDC, cigarette smoking is the leading preventable cause of disease and death in the United States, claiming over 480,000 lives annually. Its impact can also be felt economically, with cigarette smoking costing the United States at least $133 billion in direct medical care for adults and more than $156 billion in lost productivity. Meanwhile, the rates of other forms of tobacco consumption, such as cigars and hookahs, are not declining.

Surveys cited by the CDC estimate that 70% of smokers want to quit.

[email protected]

Introduction

Parents sometimes come to clinicians with concerns about their children’s moods and behaviors, hoping for a rapid fix of the problem. Most child psychiatric issues can’t be fixed with just medication and respond better with psychotherapy or a combination of psychotherapy and medication. In the past 30 years, tremendous strides have been made in studying the effectiveness of psychotherapeutic interventions among youth.

Case Summary

Katy is a 10-year-old girl who gets into arguments with her mother every day after school because she wants to walk to her grandmother’s house not far away. She was exposed to severe domestic violence by her father against her mother when she was 5 years old, and she has nightmares that cause her to wake up often at night, a fear of men, and rapid mood shifts into sudden rage as well as oppositional behavior with her mother. Her mother also has significant fears and views the world as a very unsafe place. She is worried that Katy has bipolar disorder because of her daughter’s rapid mood changes.

Discussion

While Katy has angry outbursts at times, she does not present with clear-cut episodes of elevated mood along with other symptoms of bipolar disorder, particularly grandiosity. Instead her presentation raises the possibility of post-traumatic stress disorder (PTSD) with nightmares, a fear of men who likely trigger past memories, and sudden mood shifts. Her mother also may have some elements of PTSD, which may be complicating Katy’s presentation. No medication interventions so far have demonstrated significant benefit in youth with PTSD. If further evaluation confirms PTSD, what sort of therapy should be sought for Katy?

A large number of websites now list evidence-based treatments, although many of those require that the creators of the treatment apply for inclusion, and do not address the issue of varying levels of evidence. The American Psychological Association has a website entitled Effective Child Therapy, which discusses psychotherapeutic interventions for various diagnostic areas in youth and the varying levels of evidence for such treatments based on the types and numbers of studies that support them. The website also has an excellent video resource library.

Trauma-focused cognitive-behavioral therapy has numerous studies supporting its efficacy for a wide range of traumas and includes work with both the parent and the child to address the ways the trauma can affect their interaction. This would be an excellent choice for Katy and her mother. Other therapies that have supporting research include child-parent psychotherapy, eye movement desensitization and reprocessing therapy, resilient peer treatment, child-centered therapy, and family therapy for PTSD. Treatments have usually been designed for specific ages, so it is important to consider whether the intervention fits the age of the child.

The extent to which evidence-based treatments are available in the community is variable. However, pediatricians can play a significant role in the availability of these interventions by being aware of which ones are most strongly supported, asking the therapists to whom they refer what their experience is with such interventions, and encouraging training in their offices and communities. Therapists should be comfortable describing exactly how much training they have had in a certain area, for instance, extensive training through their professional education or one or several postgraduate trainings, preferably with follow-up consultation with an experienced practitioner while they are seeing their first cases with a particular intervention.

There is controversy about evidence-based treatment among some psychotherapists who argue that the strict requirements of the research setting make the results inapplicable to the complexity of patients seen in typical clinical settings. In fact, many of the treatments, including trauma-focused cognitive-behavioral therapy, work very well in complex families. Certainly there is much more to learn about how to help patients who don’t respond to certain types of therapy or how to engage families who are reluctant to participate in treatment, but the treatments that we know work are clearly what we should choose first.

Dr. Hall is an assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. Dr. Hall said she had no relevant financial disclosures. To comment, e-mail her at [email protected].

Introduction

Parents sometimes come to clinicians with concerns about their children’s moods and behaviors, hoping for a rapid fix of the problem. Most child psychiatric issues can’t be fixed with just medication and respond better with psychotherapy or a combination of psychotherapy and medication. In the past 30 years, tremendous strides have been made in studying the effectiveness of psychotherapeutic interventions among youth.

Case Summary

Katy is a 10-year-old girl who gets into arguments with her mother every day after school because she wants to walk to her grandmother’s house not far away. She was exposed to severe domestic violence by her father against her mother when she was 5 years old, and she has nightmares that cause her to wake up often at night, a fear of men, and rapid mood shifts into sudden rage as well as oppositional behavior with her mother. Her mother also has significant fears and views the world as a very unsafe place. She is worried that Katy has bipolar disorder because of her daughter’s rapid mood changes.

Discussion

While Katy has angry outbursts at times, she does not present with clear-cut episodes of elevated mood along with other symptoms of bipolar disorder, particularly grandiosity. Instead her presentation raises the possibility of post-traumatic stress disorder (PTSD) with nightmares, a fear of men who likely trigger past memories, and sudden mood shifts. Her mother also may have some elements of PTSD, which may be complicating Katy’s presentation. No medication interventions so far have demonstrated significant benefit in youth with PTSD. If further evaluation confirms PTSD, what sort of therapy should be sought for Katy?

A large number of websites now list evidence-based treatments, although many of those require that the creators of the treatment apply for inclusion, and do not address the issue of varying levels of evidence. The American Psychological Association has a website entitled Effective Child Therapy, which discusses psychotherapeutic interventions for various diagnostic areas in youth and the varying levels of evidence for such treatments based on the types and numbers of studies that support them. The website also has an excellent video resource library.

Trauma-focused cognitive-behavioral therapy has numerous studies supporting its efficacy for a wide range of traumas and includes work with both the parent and the child to address the ways the trauma can affect their interaction. This would be an excellent choice for Katy and her mother. Other therapies that have supporting research include child-parent psychotherapy, eye movement desensitization and reprocessing therapy, resilient peer treatment, child-centered therapy, and family therapy for PTSD. Treatments have usually been designed for specific ages, so it is important to consider whether the intervention fits the age of the child.

The extent to which evidence-based treatments are available in the community is variable. However, pediatricians can play a significant role in the availability of these interventions by being aware of which ones are most strongly supported, asking the therapists to whom they refer what their experience is with such interventions, and encouraging training in their offices and communities. Therapists should be comfortable describing exactly how much training they have had in a certain area, for instance, extensive training through their professional education or one or several postgraduate trainings, preferably with follow-up consultation with an experienced practitioner while they are seeing their first cases with a particular intervention.

There is controversy about evidence-based treatment among some psychotherapists who argue that the strict requirements of the research setting make the results inapplicable to the complexity of patients seen in typical clinical settings. In fact, many of the treatments, including trauma-focused cognitive-behavioral therapy, work very well in complex families. Certainly there is much more to learn about how to help patients who don’t respond to certain types of therapy or how to engage families who are reluctant to participate in treatment, but the treatments that we know work are clearly what we should choose first.

Dr. Hall is an assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. Dr. Hall said she had no relevant financial disclosures. To comment, e-mail her at [email protected].

Introduction

Parents sometimes come to clinicians with concerns about their children’s moods and behaviors, hoping for a rapid fix of the problem. Most child psychiatric issues can’t be fixed with just medication and respond better with psychotherapy or a combination of psychotherapy and medication. In the past 30 years, tremendous strides have been made in studying the effectiveness of psychotherapeutic interventions among youth.

Case Summary

Katy is a 10-year-old girl who gets into arguments with her mother every day after school because she wants to walk to her grandmother’s house not far away. She was exposed to severe domestic violence by her father against her mother when she was 5 years old, and she has nightmares that cause her to wake up often at night, a fear of men, and rapid mood shifts into sudden rage as well as oppositional behavior with her mother. Her mother also has significant fears and views the world as a very unsafe place. She is worried that Katy has bipolar disorder because of her daughter’s rapid mood changes.

Discussion

While Katy has angry outbursts at times, she does not present with clear-cut episodes of elevated mood along with other symptoms of bipolar disorder, particularly grandiosity. Instead her presentation raises the possibility of post-traumatic stress disorder (PTSD) with nightmares, a fear of men who likely trigger past memories, and sudden mood shifts. Her mother also may have some elements of PTSD, which may be complicating Katy’s presentation. No medication interventions so far have demonstrated significant benefit in youth with PTSD. If further evaluation confirms PTSD, what sort of therapy should be sought for Katy?

A large number of websites now list evidence-based treatments, although many of those require that the creators of the treatment apply for inclusion, and do not address the issue of varying levels of evidence. The American Psychological Association has a website entitled Effective Child Therapy, which discusses psychotherapeutic interventions for various diagnostic areas in youth and the varying levels of evidence for such treatments based on the types and numbers of studies that support them. The website also has an excellent video resource library.

Trauma-focused cognitive-behavioral therapy has numerous studies supporting its efficacy for a wide range of traumas and includes work with both the parent and the child to address the ways the trauma can affect their interaction. This would be an excellent choice for Katy and her mother. Other therapies that have supporting research include child-parent psychotherapy, eye movement desensitization and reprocessing therapy, resilient peer treatment, child-centered therapy, and family therapy for PTSD. Treatments have usually been designed for specific ages, so it is important to consider whether the intervention fits the age of the child.

The extent to which evidence-based treatments are available in the community is variable. However, pediatricians can play a significant role in the availability of these interventions by being aware of which ones are most strongly supported, asking the therapists to whom they refer what their experience is with such interventions, and encouraging training in their offices and communities. Therapists should be comfortable describing exactly how much training they have had in a certain area, for instance, extensive training through their professional education or one or several postgraduate trainings, preferably with follow-up consultation with an experienced practitioner while they are seeing their first cases with a particular intervention.

There is controversy about evidence-based treatment among some psychotherapists who argue that the strict requirements of the research setting make the results inapplicable to the complexity of patients seen in typical clinical settings. In fact, many of the treatments, including trauma-focused cognitive-behavioral therapy, work very well in complex families. Certainly there is much more to learn about how to help patients who don’t respond to certain types of therapy or how to engage families who are reluctant to participate in treatment, but the treatments that we know work are clearly what we should choose first.

Dr. Hall is an assistant professor of psychiatry and pediatrics at the University of Vermont, Burlington. Dr. Hall said she had no relevant financial disclosures. To comment, e-mail her at [email protected].

The development of language in children is like the canary in the coal mine – problems of genetics, medical conditions, and environment all can cause it to go awry. Whatever the cause, it is very important to make sure a child with a problem in this area gets prompt assistance, because how speech and language progress also affects many aspects of the child’s success in life and what it is like to parent them.

Some of the factors known to put a child at risk for delays or deviations in speech and language development include prematurity and low birth weight; genetic conditions such as Down syndrome; physical problems such as cerebral palsy or seizure disorders; hearing impairment; and, as usual, being a boy. The most common reason for delayed language is general delay or intellectual disability. A family history of speech and language disorders also adds to the risk, and one single gene defect has even been found for a few of these. Eight percent of young children have been estimated to have a delay in speech or language. The vast majority of them have no specific risk factors.

The “language environment” of the home is critical to language learning. Compared with high-income families, parents on welfare say one-third as many words to their children and working-class parents say one-half as many in the first 3 years. Because over 85% of a child’s words at age 3 years come from words heard from their parents, this is estimated to create a 30-million-word difference between children of high- versus low-income families by age 4 years! In addition, low-income parents provide two discouragements for each one encouragement, in contrast to one correction to six encouragements in high-income homes, with the additional psychological implications.

These sad facts contributed to the creation of the Reach Out and Read program, which I hope you have joined. A free book from the doctor at every checkup visit, some modeling of how to read to the child, and information about the importance of talking with the child are things you can do to emphasize the importance of language stimulation to development and academic success.

Most parents are very motivated by the promise of better school success from better language, but it can seem far away when the child is only 1 year old! A more immediate motivator is the threat of more temper tantrums and noncompliance in children with delayed language. Almost all children with language problems understand more than they can express. When the gap between understanding and speaking is greater, so is the child’s frustration. While a large percentage of children with expressive language problems will “outgrow” them, the pattern of angry reactivity and difficult parent child interactions may continue. This is a good reason to discuss promoting language but to also suggest Baby Signs (www.babysignstoo.com) starting in the first year, especially if communication frustration starts to emerge.

School is where the big impact from language impairments appears. And it is not just the significant association between early language disorders and persistent reading disability and even written language disability that you should worry about and monitor. Children with speech and language disorders, even simply dysarticulation, can be teased, bullied, and rejected socially. As a result, children with speech and language deficits experience lower self-esteem, greater discouragement, and sometimes reactive aggression. In addition to identifying these problems and getting treatment for the issues of language, learning, and socio-emotional adjustment, it is important to find nonverbal strengths in the child such as sports or music to give them a social group where they can find success.

Language problems in older children may be subtle and not noticed or complained about by their parents, who may have the same weakness. Even teachers may not connect the student’s poor academic performance to language difficulties because they seem to have “the basics.” If you notice a schoolaged child unable to understand or answer your questions with some sentence complexity, it is important to refer to a speech pathologist for assessment. Although there should be free evaluation and treatment services at the school, the speech pathologist may not be expert at assessing more complex language disorders. In addition, the child’s difficulties may not measure up as “impairing enough” to receive those services, and private services may be needed.

But if you do not feel like a child language expert, you are not alone! Not only were you lucky if you heard one lecture on language development during training, but the younger the child, the less language you are likely to hear from him or her during brief health supervision visits. The parent is probably dominating the conversation (if you are a good listener) trying to have their agenda addressed, and the child is either excited or terrified by your office environment.

The broadband developmental screening now recommended by the American Academy of Pediatrics for all children at 9, 18, and 30 months includes language milestones or parental concern, but these have not been shown to have adequate sensitivity or specificity and will miss many affected children.

Many young children with language disorders are now or will later be on the autism spectrum. The recommended autism-specific screens at 18 and 24-30 months will detect many, but not all, of these children. It is important to realize that the most common reason for a false positive autism screen is language delay, and it deserves follow-up and treatment even though not representing autism.

What should you do given these gaps between need, tools, and knowledge? Of course, collect the general and autism screens as recommended, but also use them when you or the parent have a concern. For children under 2 years, the parent’s report is generally accurate, as expected language is fairly simple. Infants should have different cries and reactions to caregivers in the first 3 months; babble and laugh by 6 months; and imitate sounds as well as recognize a few words by 1 year. While infants typically have 1-2 words by 12 months and two-word combinations by 18 months, as a cutoff they should show 1-2 words by 18 months and either 50 words or 2 words together by 24 months. Listening to a child’s spontaneous language is the best gauge of articulation. By age 2 years, we – a stranger to the child – can only expect to understand about 25% of what they say, but by 3 years it should be 66%, and by age 4 years almost 100%.

Gestures are an important aspect of communication. Use of gestures such as raising arms to be picked up or waving bye-bye by 1 year are typical. Between 1 and 2 years, children should follow your pointing and share their interests by pointing in addition to indicating named pictures and body parts. Deficits in use of gestures should spur a language evaluation and also are part of diagnosing autism, a much more serious and specific condition defined by communication deficits. Most autism screening tools include tapping gestures as well as spoken language.

After 2 years, language assessment has to include more elements than many parents can report easily or you can observe. There is now no formal additional language screening recommendation beyond surveillance, and the general developmental and autism screens. Every state has free child development services that can assess and provide intervention for children 0-3 years if you or the parent has concerns. But you may want to do more to either reassure or clarify the need for and type of referral by using a language-specific tool. The most accurate and practical tools applicable to children 8-35 months are the MacArthur-Bates Communicative Development Inventories (CDI) and the Language Development Survey (LDS), both parent completed. The LDS assesses based on a list of vocabulary words and examples of phrases, and the CDI has three different forms using vocabulary, gestures, and sentences.

After age 3 years, language is so complex that direct testing of the child is needed. A draft report from the U.S. Preventive Services Task Force in November 2014 presents a review of all available measures.

The good news is that a variety of approaches to therapy for speech and language disorders in young children are effective in reducing impairment. The most effective ones involve the parents in learning what communication skills to observe, stimulate, and reinforce, and have an adequate number of total hours of intervention spread over several months.

As for all children and youth with special health care needs, we have the responsibility to detect, monitor, refer, track, and support families of children with speech and language disorders to assure their best outcomes. Whatever the cause, improving the communication abilities of the child can make a big difference to many aspects of their lives.

Dr. Howard is an assistant professor of pediatrics at the Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at [email protected].

The development of language in children is like the canary in the coal mine – problems of genetics, medical conditions, and environment all can cause it to go awry. Whatever the cause, it is very important to make sure a child with a problem in this area gets prompt assistance, because how speech and language progress also affects many aspects of the child’s success in life and what it is like to parent them.

Some of the factors known to put a child at risk for delays or deviations in speech and language development include prematurity and low birth weight; genetic conditions such as Down syndrome; physical problems such as cerebral palsy or seizure disorders; hearing impairment; and, as usual, being a boy. The most common reason for delayed language is general delay or intellectual disability. A family history of speech and language disorders also adds to the risk, and one single gene defect has even been found for a few of these. Eight percent of young children have been estimated to have a delay in speech or language. The vast majority of them have no specific risk factors.

The “language environment” of the home is critical to language learning. Compared with high-income families, parents on welfare say one-third as many words to their children and working-class parents say one-half as many in the first 3 years. Because over 85% of a child’s words at age 3 years come from words heard from their parents, this is estimated to create a 30-million-word difference between children of high- versus low-income families by age 4 years! In addition, low-income parents provide two discouragements for each one encouragement, in contrast to one correction to six encouragements in high-income homes, with the additional psychological implications.

These sad facts contributed to the creation of the Reach Out and Read program, which I hope you have joined. A free book from the doctor at every checkup visit, some modeling of how to read to the child, and information about the importance of talking with the child are things you can do to emphasize the importance of language stimulation to development and academic success.

Most parents are very motivated by the promise of better school success from better language, but it can seem far away when the child is only 1 year old! A more immediate motivator is the threat of more temper tantrums and noncompliance in children with delayed language. Almost all children with language problems understand more than they can express. When the gap between understanding and speaking is greater, so is the child’s frustration. While a large percentage of children with expressive language problems will “outgrow” them, the pattern of angry reactivity and difficult parent child interactions may continue. This is a good reason to discuss promoting language but to also suggest Baby Signs (www.babysignstoo.com) starting in the first year, especially if communication frustration starts to emerge.

School is where the big impact from language impairments appears. And it is not just the significant association between early language disorders and persistent reading disability and even written language disability that you should worry about and monitor. Children with speech and language disorders, even simply dysarticulation, can be teased, bullied, and rejected socially. As a result, children with speech and language deficits experience lower self-esteem, greater discouragement, and sometimes reactive aggression. In addition to identifying these problems and getting treatment for the issues of language, learning, and socio-emotional adjustment, it is important to find nonverbal strengths in the child such as sports or music to give them a social group where they can find success.

Language problems in older children may be subtle and not noticed or complained about by their parents, who may have the same weakness. Even teachers may not connect the student’s poor academic performance to language difficulties because they seem to have “the basics.” If you notice a schoolaged child unable to understand or answer your questions with some sentence complexity, it is important to refer to a speech pathologist for assessment. Although there should be free evaluation and treatment services at the school, the speech pathologist may not be expert at assessing more complex language disorders. In addition, the child’s difficulties may not measure up as “impairing enough” to receive those services, and private services may be needed.

But if you do not feel like a child language expert, you are not alone! Not only were you lucky if you heard one lecture on language development during training, but the younger the child, the less language you are likely to hear from him or her during brief health supervision visits. The parent is probably dominating the conversation (if you are a good listener) trying to have their agenda addressed, and the child is either excited or terrified by your office environment.

The broadband developmental screening now recommended by the American Academy of Pediatrics for all children at 9, 18, and 30 months includes language milestones or parental concern, but these have not been shown to have adequate sensitivity or specificity and will miss many affected children.

Many young children with language disorders are now or will later be on the autism spectrum. The recommended autism-specific screens at 18 and 24-30 months will detect many, but not all, of these children. It is important to realize that the most common reason for a false positive autism screen is language delay, and it deserves follow-up and treatment even though not representing autism.

What should you do given these gaps between need, tools, and knowledge? Of course, collect the general and autism screens as recommended, but also use them when you or the parent have a concern. For children under 2 years, the parent’s report is generally accurate, as expected language is fairly simple. Infants should have different cries and reactions to caregivers in the first 3 months; babble and laugh by 6 months; and imitate sounds as well as recognize a few words by 1 year. While infants typically have 1-2 words by 12 months and two-word combinations by 18 months, as a cutoff they should show 1-2 words by 18 months and either 50 words or 2 words together by 24 months. Listening to a child’s spontaneous language is the best gauge of articulation. By age 2 years, we – a stranger to the child – can only expect to understand about 25% of what they say, but by 3 years it should be 66%, and by age 4 years almost 100%.

Gestures are an important aspect of communication. Use of gestures such as raising arms to be picked up or waving bye-bye by 1 year are typical. Between 1 and 2 years, children should follow your pointing and share their interests by pointing in addition to indicating named pictures and body parts. Deficits in use of gestures should spur a language evaluation and also are part of diagnosing autism, a much more serious and specific condition defined by communication deficits. Most autism screening tools include tapping gestures as well as spoken language.

After 2 years, language assessment has to include more elements than many parents can report easily or you can observe. There is now no formal additional language screening recommendation beyond surveillance, and the general developmental and autism screens. Every state has free child development services that can assess and provide intervention for children 0-3 years if you or the parent has concerns. But you may want to do more to either reassure or clarify the need for and type of referral by using a language-specific tool. The most accurate and practical tools applicable to children 8-35 months are the MacArthur-Bates Communicative Development Inventories (CDI) and the Language Development Survey (LDS), both parent completed. The LDS assesses based on a list of vocabulary words and examples of phrases, and the CDI has three different forms using vocabulary, gestures, and sentences.

After age 3 years, language is so complex that direct testing of the child is needed. A draft report from the U.S. Preventive Services Task Force in November 2014 presents a review of all available measures.

The good news is that a variety of approaches to therapy for speech and language disorders in young children are effective in reducing impairment. The most effective ones involve the parents in learning what communication skills to observe, stimulate, and reinforce, and have an adequate number of total hours of intervention spread over several months.

As for all children and youth with special health care needs, we have the responsibility to detect, monitor, refer, track, and support families of children with speech and language disorders to assure their best outcomes. Whatever the cause, improving the communication abilities of the child can make a big difference to many aspects of their lives.

Dr. Howard is an assistant professor of pediatrics at the Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at [email protected].

The development of language in children is like the canary in the coal mine – problems of genetics, medical conditions, and environment all can cause it to go awry. Whatever the cause, it is very important to make sure a child with a problem in this area gets prompt assistance, because how speech and language progress also affects many aspects of the child’s success in life and what it is like to parent them.

Some of the factors known to put a child at risk for delays or deviations in speech and language development include prematurity and low birth weight; genetic conditions such as Down syndrome; physical problems such as cerebral palsy or seizure disorders; hearing impairment; and, as usual, being a boy. The most common reason for delayed language is general delay or intellectual disability. A family history of speech and language disorders also adds to the risk, and one single gene defect has even been found for a few of these. Eight percent of young children have been estimated to have a delay in speech or language. The vast majority of them have no specific risk factors.

The “language environment” of the home is critical to language learning. Compared with high-income families, parents on welfare say one-third as many words to their children and working-class parents say one-half as many in the first 3 years. Because over 85% of a child’s words at age 3 years come from words heard from their parents, this is estimated to create a 30-million-word difference between children of high- versus low-income families by age 4 years! In addition, low-income parents provide two discouragements for each one encouragement, in contrast to one correction to six encouragements in high-income homes, with the additional psychological implications.

These sad facts contributed to the creation of the Reach Out and Read program, which I hope you have joined. A free book from the doctor at every checkup visit, some modeling of how to read to the child, and information about the importance of talking with the child are things you can do to emphasize the importance of language stimulation to development and academic success.

Most parents are very motivated by the promise of better school success from better language, but it can seem far away when the child is only 1 year old! A more immediate motivator is the threat of more temper tantrums and noncompliance in children with delayed language. Almost all children with language problems understand more than they can express. When the gap between understanding and speaking is greater, so is the child’s frustration. While a large percentage of children with expressive language problems will “outgrow” them, the pattern of angry reactivity and difficult parent child interactions may continue. This is a good reason to discuss promoting language but to also suggest Baby Signs (www.babysignstoo.com) starting in the first year, especially if communication frustration starts to emerge.

School is where the big impact from language impairments appears. And it is not just the significant association between early language disorders and persistent reading disability and even written language disability that you should worry about and monitor. Children with speech and language disorders, even simply dysarticulation, can be teased, bullied, and rejected socially. As a result, children with speech and language deficits experience lower self-esteem, greater discouragement, and sometimes reactive aggression. In addition to identifying these problems and getting treatment for the issues of language, learning, and socio-emotional adjustment, it is important to find nonverbal strengths in the child such as sports or music to give them a social group where they can find success.

Language problems in older children may be subtle and not noticed or complained about by their parents, who may have the same weakness. Even teachers may not connect the student’s poor academic performance to language difficulties because they seem to have “the basics.” If you notice a schoolaged child unable to understand or answer your questions with some sentence complexity, it is important to refer to a speech pathologist for assessment. Although there should be free evaluation and treatment services at the school, the speech pathologist may not be expert at assessing more complex language disorders. In addition, the child’s difficulties may not measure up as “impairing enough” to receive those services, and private services may be needed.

But if you do not feel like a child language expert, you are not alone! Not only were you lucky if you heard one lecture on language development during training, but the younger the child, the less language you are likely to hear from him or her during brief health supervision visits. The parent is probably dominating the conversation (if you are a good listener) trying to have their agenda addressed, and the child is either excited or terrified by your office environment.

The broadband developmental screening now recommended by the American Academy of Pediatrics for all children at 9, 18, and 30 months includes language milestones or parental concern, but these have not been shown to have adequate sensitivity or specificity and will miss many affected children.

Many young children with language disorders are now or will later be on the autism spectrum. The recommended autism-specific screens at 18 and 24-30 months will detect many, but not all, of these children. It is important to realize that the most common reason for a false positive autism screen is language delay, and it deserves follow-up and treatment even though not representing autism.

What should you do given these gaps between need, tools, and knowledge? Of course, collect the general and autism screens as recommended, but also use them when you or the parent have a concern. For children under 2 years, the parent’s report is generally accurate, as expected language is fairly simple. Infants should have different cries and reactions to caregivers in the first 3 months; babble and laugh by 6 months; and imitate sounds as well as recognize a few words by 1 year. While infants typically have 1-2 words by 12 months and two-word combinations by 18 months, as a cutoff they should show 1-2 words by 18 months and either 50 words or 2 words together by 24 months. Listening to a child’s spontaneous language is the best gauge of articulation. By age 2 years, we – a stranger to the child – can only expect to understand about 25% of what they say, but by 3 years it should be 66%, and by age 4 years almost 100%.

Gestures are an important aspect of communication. Use of gestures such as raising arms to be picked up or waving bye-bye by 1 year are typical. Between 1 and 2 years, children should follow your pointing and share their interests by pointing in addition to indicating named pictures and body parts. Deficits in use of gestures should spur a language evaluation and also are part of diagnosing autism, a much more serious and specific condition defined by communication deficits. Most autism screening tools include tapping gestures as well as spoken language.

After 2 years, language assessment has to include more elements than many parents can report easily or you can observe. There is now no formal additional language screening recommendation beyond surveillance, and the general developmental and autism screens. Every state has free child development services that can assess and provide intervention for children 0-3 years if you or the parent has concerns. But you may want to do more to either reassure or clarify the need for and type of referral by using a language-specific tool. The most accurate and practical tools applicable to children 8-35 months are the MacArthur-Bates Communicative Development Inventories (CDI) and the Language Development Survey (LDS), both parent completed. The LDS assesses based on a list of vocabulary words and examples of phrases, and the CDI has three different forms using vocabulary, gestures, and sentences.

After age 3 years, language is so complex that direct testing of the child is needed. A draft report from the U.S. Preventive Services Task Force in November 2014 presents a review of all available measures.

The good news is that a variety of approaches to therapy for speech and language disorders in young children are effective in reducing impairment. The most effective ones involve the parents in learning what communication skills to observe, stimulate, and reinforce, and have an adequate number of total hours of intervention spread over several months.

As for all children and youth with special health care needs, we have the responsibility to detect, monitor, refer, track, and support families of children with speech and language disorders to assure their best outcomes. Whatever the cause, improving the communication abilities of the child can make a big difference to many aspects of their lives.

Dr. Howard is an assistant professor of pediatrics at the Johns Hopkins University School of Medicine, Baltimore, and creator of CHADIS (www.CHADIS.com). She has no other relevant disclosures. Dr. Howard’s contribution to this publication was as a paid expert to Frontline. E-mail her at [email protected].