NEW YORK (Reuters Health) - Hospital differences in pain management are tied to different patient-reported pain scores after colorectal resection, according to a study from the Michigan Surgical Quality Collaborative (MSQC).

"The best-performing hospitals achieved superior pain control through the use of analgesia regimens that more often used local anesthesia blocks in the operating room,non-steroidal anti-inflammatory drugs, and patient-controlled analgesia rather than intermittent narcotics," said Dr. Scott E. Regenbogen from the University of Michigan, Ann Arbor.

"This suggests that efforts to implement multimodal analgesia regimens may improve pain control in the immediate postoperative period," he told Reuters Health by email.

Despite increasing attention to postoperative pain management, most patients continue to experience severe pain after major surgery, Dr. Regenbogen and colleagues note in Annals of Surgery, online January 7.

The researchers used MSQC data from 52 hospitals to evaluate the extent to which multimodal pain management practices are used after major surgery and how hospitals' perioperative practices might affect patient-reported pain levels in real-world surgical practice. Their study included 7,221 patients who underwent colorectal resection between 2012 and 2014.

Nine hospitals had average adjusted pain scores significantly worse and eight hospitals had average adjusted pain scores significantly better than the overall average. The "best" hospitals were somewhat larger and had higher annual volumes of colorectal resection than the "worst" hospitals.

Patients in hospitals with best pain scores were significantly more likely to receive local anesthesia and epidural anesthesia during the operation and to have patient-controlled analgesia (PCA), nonsteroidal anti-inflammatory drugs (NSAIDs), or a combination of PCA and NSAIDs and significantly less likely to receive intermittent postoperative narcotics, compared with patients in hospitals with worst pain scores.

Hospitals with the lowest pain scores had a significantly higher proportion of operations with a minimally invasive approach than did hospitals with the highest pain scores.

Patients whose operations took place in hospitals in the lowest quartile of pain scores had significantly shorter mean postoperative length of stay and were significantly less likely to have a postoperative complication, emergency department visit, or readmission.

Patient factors contributing to worse pain scores included being younger than 50 (versus age over 75), a woman, black (versus white), a smoker, and uninsured or insured by Medicaid (versus Medicare or privately insured).

"Most likely," the researchers note, "both pain scores and clinical outcomes reflect more global features of the quality of care in hospitals' surgical performance. Thus, hospitals with the most streamlined, high-quality perioperative care pathways experience the best pain scores, as well as improved clinical outcomes."

"Early postoperative analgesia regimens are an essential component of efforts to improve the efficiency and quality of postoperative recovery," Dr. Regenbogen said."Effective pain control, even in the first postoperative day, is associated with reduced postoperative length of stay and fewer major complications and readmissions. Thus, effective multimodal analgesia is an essential component of high-value perioperative care around colorectal surgery."

"This study is hopefully just one example of a growing emphasis on patient-reported outcomes in surgery," Dr.Regenbogen said. "Within a statewide quality collaborative, we have begun to prioritize engagement of patients, in addition to our partnering surgeons, hospitals, and mayors, in efforts to improve surgical care in Michigan. In this study, we used patient-reported pain measures to evaluate quality of care. In the near future, we will elicit patient-reported measures of functional recovery, psychosocial support, and other outcomes to validate the perioperative outcomes we have relied on traditionally. We hope this study will serve as a model for those novel areas of investigation."

Dr. Antoni Sabate from Hospital Universitari de Bellvitge in Barcelona, Spain, who has researched postoperative analgesia told Reuters Health by email, "Pain is largely influenced by magnitude of the surgical procedure, surgical technique (minimally invasive), analgesia protocol (the use of local anesthetic infiltration in open and laparoscopic, the use of epidural in open procedures, implementation of PCA and NSAID in both laparoscopic and open procedures."

NEW YORK (Reuters Health) - Hospital differences in pain management are tied to different patient-reported pain scores after colorectal resection, according to a study from the Michigan Surgical Quality Collaborative (MSQC).

"The best-performing hospitals achieved superior pain control through the use of analgesia regimens that more often used local anesthesia blocks in the operating room,non-steroidal anti-inflammatory drugs, and patient-controlled analgesia rather than intermittent narcotics," said Dr. Scott E. Regenbogen from the University of Michigan, Ann Arbor.

"This suggests that efforts to implement multimodal analgesia regimens may improve pain control in the immediate postoperative period," he told Reuters Health by email.

Despite increasing attention to postoperative pain management, most patients continue to experience severe pain after major surgery, Dr. Regenbogen and colleagues note in Annals of Surgery, online January 7.

The researchers used MSQC data from 52 hospitals to evaluate the extent to which multimodal pain management practices are used after major surgery and how hospitals' perioperative practices might affect patient-reported pain levels in real-world surgical practice. Their study included 7,221 patients who underwent colorectal resection between 2012 and 2014.

Nine hospitals had average adjusted pain scores significantly worse and eight hospitals had average adjusted pain scores significantly better than the overall average. The "best" hospitals were somewhat larger and had higher annual volumes of colorectal resection than the "worst" hospitals.

Patients in hospitals with best pain scores were significantly more likely to receive local anesthesia and epidural anesthesia during the operation and to have patient-controlled analgesia (PCA), nonsteroidal anti-inflammatory drugs (NSAIDs), or a combination of PCA and NSAIDs and significantly less likely to receive intermittent postoperative narcotics, compared with patients in hospitals with worst pain scores.

Hospitals with the lowest pain scores had a significantly higher proportion of operations with a minimally invasive approach than did hospitals with the highest pain scores.

Patients whose operations took place in hospitals in the lowest quartile of pain scores had significantly shorter mean postoperative length of stay and were significantly less likely to have a postoperative complication, emergency department visit, or readmission.

Patient factors contributing to worse pain scores included being younger than 50 (versus age over 75), a woman, black (versus white), a smoker, and uninsured or insured by Medicaid (versus Medicare or privately insured).

"Most likely," the researchers note, "both pain scores and clinical outcomes reflect more global features of the quality of care in hospitals' surgical performance. Thus, hospitals with the most streamlined, high-quality perioperative care pathways experience the best pain scores, as well as improved clinical outcomes."

"Early postoperative analgesia regimens are an essential component of efforts to improve the efficiency and quality of postoperative recovery," Dr. Regenbogen said."Effective pain control, even in the first postoperative day, is associated with reduced postoperative length of stay and fewer major complications and readmissions. Thus, effective multimodal analgesia is an essential component of high-value perioperative care around colorectal surgery."

"This study is hopefully just one example of a growing emphasis on patient-reported outcomes in surgery," Dr.Regenbogen said. "Within a statewide quality collaborative, we have begun to prioritize engagement of patients, in addition to our partnering surgeons, hospitals, and mayors, in efforts to improve surgical care in Michigan. In this study, we used patient-reported pain measures to evaluate quality of care. In the near future, we will elicit patient-reported measures of functional recovery, psychosocial support, and other outcomes to validate the perioperative outcomes we have relied on traditionally. We hope this study will serve as a model for those novel areas of investigation."

Dr. Antoni Sabate from Hospital Universitari de Bellvitge in Barcelona, Spain, who has researched postoperative analgesia told Reuters Health by email, "Pain is largely influenced by magnitude of the surgical procedure, surgical technique (minimally invasive), analgesia protocol (the use of local anesthetic infiltration in open and laparoscopic, the use of epidural in open procedures, implementation of PCA and NSAID in both laparoscopic and open procedures."

NEW YORK (Reuters Health) - Hospital differences in pain management are tied to different patient-reported pain scores after colorectal resection, according to a study from the Michigan Surgical Quality Collaborative (MSQC).

"The best-performing hospitals achieved superior pain control through the use of analgesia regimens that more often used local anesthesia blocks in the operating room,non-steroidal anti-inflammatory drugs, and patient-controlled analgesia rather than intermittent narcotics," said Dr. Scott E. Regenbogen from the University of Michigan, Ann Arbor.

"This suggests that efforts to implement multimodal analgesia regimens may improve pain control in the immediate postoperative period," he told Reuters Health by email.

Despite increasing attention to postoperative pain management, most patients continue to experience severe pain after major surgery, Dr. Regenbogen and colleagues note in Annals of Surgery, online January 7.

The researchers used MSQC data from 52 hospitals to evaluate the extent to which multimodal pain management practices are used after major surgery and how hospitals' perioperative practices might affect patient-reported pain levels in real-world surgical practice. Their study included 7,221 patients who underwent colorectal resection between 2012 and 2014.

Nine hospitals had average adjusted pain scores significantly worse and eight hospitals had average adjusted pain scores significantly better than the overall average. The "best" hospitals were somewhat larger and had higher annual volumes of colorectal resection than the "worst" hospitals.

Patients in hospitals with best pain scores were significantly more likely to receive local anesthesia and epidural anesthesia during the operation and to have patient-controlled analgesia (PCA), nonsteroidal anti-inflammatory drugs (NSAIDs), or a combination of PCA and NSAIDs and significantly less likely to receive intermittent postoperative narcotics, compared with patients in hospitals with worst pain scores.

Hospitals with the lowest pain scores had a significantly higher proportion of operations with a minimally invasive approach than did hospitals with the highest pain scores.

Patients whose operations took place in hospitals in the lowest quartile of pain scores had significantly shorter mean postoperative length of stay and were significantly less likely to have a postoperative complication, emergency department visit, or readmission.

Patient factors contributing to worse pain scores included being younger than 50 (versus age over 75), a woman, black (versus white), a smoker, and uninsured or insured by Medicaid (versus Medicare or privately insured).

"Most likely," the researchers note, "both pain scores and clinical outcomes reflect more global features of the quality of care in hospitals' surgical performance. Thus, hospitals with the most streamlined, high-quality perioperative care pathways experience the best pain scores, as well as improved clinical outcomes."

"Early postoperative analgesia regimens are an essential component of efforts to improve the efficiency and quality of postoperative recovery," Dr. Regenbogen said."Effective pain control, even in the first postoperative day, is associated with reduced postoperative length of stay and fewer major complications and readmissions. Thus, effective multimodal analgesia is an essential component of high-value perioperative care around colorectal surgery."

"This study is hopefully just one example of a growing emphasis on patient-reported outcomes in surgery," Dr.Regenbogen said. "Within a statewide quality collaborative, we have begun to prioritize engagement of patients, in addition to our partnering surgeons, hospitals, and mayors, in efforts to improve surgical care in Michigan. In this study, we used patient-reported pain measures to evaluate quality of care. In the near future, we will elicit patient-reported measures of functional recovery, psychosocial support, and other outcomes to validate the perioperative outcomes we have relied on traditionally. We hope this study will serve as a model for those novel areas of investigation."

Dr. Antoni Sabate from Hospital Universitari de Bellvitge in Barcelona, Spain, who has researched postoperative analgesia told Reuters Health by email, "Pain is largely influenced by magnitude of the surgical procedure, surgical technique (minimally invasive), analgesia protocol (the use of local anesthetic infiltration in open and laparoscopic, the use of epidural in open procedures, implementation of PCA and NSAID in both laparoscopic and open procedures."

Blood sample collection

Photo by Juan D. Alfonso

The National Institute for Health and Care Excellence (NICE) has said there is not enough evidence to recommend the routine use of 3 new tests to help identify the cause of sepsis.

The agency issued a final diagnostics guidance recommending further research on the tests—the LightCycler SeptiFast Test MGRADE (Roche Diagnostics), SepsiTest (Molzym Molecular Diagnostics), and IRIDICA BAC BSI assay (Abbott Laboratories).

All 3 tests analyze whole blood samples to identify bacterial and fungal DNA. The tests aim to identify the causes of infection much quicker than traditional microbiology techniques, which require blood samples to be incubated and cultured before pathogens can be identified.

“Rapid molecular tests that can identify the cause of an infection in hours rather than the days typically needed for traditional microbiology tests could ensure the most appropriate antibiotics are used much earlier,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“This, in turn, could improve outcomes for patients with suspected bloodstream infections, as well as help to reduce the spread of resistant microbes. The independent diagnostics advisory committee [advising NICE on the tests] concluded that, although the tests show promise, there is currently not enough evidence to recommend their routine adoption in the NHS [National Health Service].”

“They felt the tests may offer clinical benefit by providing results more quickly, but there was currently too much uncertainty in their accuracy for clinicians to be able to use them as the basis for clinical decision-making in people with suspected bloodstream infections, who can be acutely unwell.”

“The committee therefore decided that further research should be encouraged to provide robust evidence, particularly around demonstrating the value of using the test results in clinical decision-making.”

The diagnostics guidance on the tests is available on the NICE website.

Blood sample collection

Photo by Juan D. Alfonso

The National Institute for Health and Care Excellence (NICE) has said there is not enough evidence to recommend the routine use of 3 new tests to help identify the cause of sepsis.

The agency issued a final diagnostics guidance recommending further research on the tests—the LightCycler SeptiFast Test MGRADE (Roche Diagnostics), SepsiTest (Molzym Molecular Diagnostics), and IRIDICA BAC BSI assay (Abbott Laboratories).

All 3 tests analyze whole blood samples to identify bacterial and fungal DNA. The tests aim to identify the causes of infection much quicker than traditional microbiology techniques, which require blood samples to be incubated and cultured before pathogens can be identified.

“Rapid molecular tests that can identify the cause of an infection in hours rather than the days typically needed for traditional microbiology tests could ensure the most appropriate antibiotics are used much earlier,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“This, in turn, could improve outcomes for patients with suspected bloodstream infections, as well as help to reduce the spread of resistant microbes. The independent diagnostics advisory committee [advising NICE on the tests] concluded that, although the tests show promise, there is currently not enough evidence to recommend their routine adoption in the NHS [National Health Service].”

“They felt the tests may offer clinical benefit by providing results more quickly, but there was currently too much uncertainty in their accuracy for clinicians to be able to use them as the basis for clinical decision-making in people with suspected bloodstream infections, who can be acutely unwell.”

“The committee therefore decided that further research should be encouraged to provide robust evidence, particularly around demonstrating the value of using the test results in clinical decision-making.”

The diagnostics guidance on the tests is available on the NICE website.

Blood sample collection

Photo by Juan D. Alfonso

The National Institute for Health and Care Excellence (NICE) has said there is not enough evidence to recommend the routine use of 3 new tests to help identify the cause of sepsis.

The agency issued a final diagnostics guidance recommending further research on the tests—the LightCycler SeptiFast Test MGRADE (Roche Diagnostics), SepsiTest (Molzym Molecular Diagnostics), and IRIDICA BAC BSI assay (Abbott Laboratories).

All 3 tests analyze whole blood samples to identify bacterial and fungal DNA. The tests aim to identify the causes of infection much quicker than traditional microbiology techniques, which require blood samples to be incubated and cultured before pathogens can be identified.

“Rapid molecular tests that can identify the cause of an infection in hours rather than the days typically needed for traditional microbiology tests could ensure the most appropriate antibiotics are used much earlier,” said Carole Longson, NICE Health Technology Evaluation Centre Director.

“This, in turn, could improve outcomes for patients with suspected bloodstream infections, as well as help to reduce the spread of resistant microbes. The independent diagnostics advisory committee [advising NICE on the tests] concluded that, although the tests show promise, there is currently not enough evidence to recommend their routine adoption in the NHS [National Health Service].”

“They felt the tests may offer clinical benefit by providing results more quickly, but there was currently too much uncertainty in their accuracy for clinicians to be able to use them as the basis for clinical decision-making in people with suspected bloodstream infections, who can be acutely unwell.”

“The committee therefore decided that further research should be encouraged to provide robust evidence, particularly around demonstrating the value of using the test results in clinical decision-making.”

The diagnostics guidance on the tests is available on the NICE website.

Alopecia areata’s mysterious appearances, regressions, and recurrences frustrate patients and stymie physicians, but new treatments may be around the corner.

Tofacitinib, along with other medications that target the autoimmune etiology of alopecia areata, have shown complete alopecia reversal in case studies, Dr. Maria Hordinsky said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. “There’s a lot of excitement bubbling up in hair disease research because of these new potential topical and oral treatments.”

Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and ruxolitinib, have also been reported to reverse alopecia areata.

“There’s been a surge of enthusiasm for using more aggressive systemic therapies, including not only tobacitinib and ruxolitinib but also methotrexate and interleukin-2,” Dr. Hordinsky said, noting that these are still investigational uses.

The new treatment targets are welcome for physicians treating patients with alopecia areata, since currently there are no FDA-approved treatments, Dr. Hordinsky said.

A review by Dr. Hordinsky and colleague found a total of 29 trials investigating more than a dozen topical and oral treatments. Most trials were of moderate or lower quality, and most had major limitations. Treatments that were effective included topical and oral corticosteroids, as well as the sensitizing agents diphenylcyclopropenone and dinitrochlorobenzene (Am J Clin Dermatol. 2014;15:231-46).

In the absence of high-quality evidence for effective treatments, patient characteristics and preference, as well as disease activity and location, can guide treatment. In some cases, a scalp biopsy can give more information about follicle differentiation, inflammation, and the stage of the hair cycle at the time of assessment, Dr. Hordinsky said.

It’s important to set expectations for patients, so they know that treatments will take time, she said. Providers should be alert to the possibility that hair loss may also be associated with an underlying medical problem, so a thorough workup is indicated.

Patients should be given the opportunity to enroll in clinical trials, where available, and should also be directed to the National Alopecia Areata Foundation (NAAF). Their website provides information and resources for patients and families, information for local support groups, and information on a national registry.

Dr. Hordinsky reported receiving grant or research support from a number of pharmaceutical and consumer product companies in the dermatology space. She serves on the scientific advisory board of the National Alopecia Areata Foundation.

This news organization and SDEF are owned by the same parent company.

koakes@frontlinemedcom.com

On Twitter @karioakes

Alopecia areata’s mysterious appearances, regressions, and recurrences frustrate patients and stymie physicians, but new treatments may be around the corner.

Tofacitinib, along with other medications that target the autoimmune etiology of alopecia areata, have shown complete alopecia reversal in case studies, Dr. Maria Hordinsky said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. “There’s a lot of excitement bubbling up in hair disease research because of these new potential topical and oral treatments.”

Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and ruxolitinib, have also been reported to reverse alopecia areata.

“There’s been a surge of enthusiasm for using more aggressive systemic therapies, including not only tobacitinib and ruxolitinib but also methotrexate and interleukin-2,” Dr. Hordinsky said, noting that these are still investigational uses.

The new treatment targets are welcome for physicians treating patients with alopecia areata, since currently there are no FDA-approved treatments, Dr. Hordinsky said.

A review by Dr. Hordinsky and colleague found a total of 29 trials investigating more than a dozen topical and oral treatments. Most trials were of moderate or lower quality, and most had major limitations. Treatments that were effective included topical and oral corticosteroids, as well as the sensitizing agents diphenylcyclopropenone and dinitrochlorobenzene (Am J Clin Dermatol. 2014;15:231-46).

In the absence of high-quality evidence for effective treatments, patient characteristics and preference, as well as disease activity and location, can guide treatment. In some cases, a scalp biopsy can give more information about follicle differentiation, inflammation, and the stage of the hair cycle at the time of assessment, Dr. Hordinsky said.

It’s important to set expectations for patients, so they know that treatments will take time, she said. Providers should be alert to the possibility that hair loss may also be associated with an underlying medical problem, so a thorough workup is indicated.

Patients should be given the opportunity to enroll in clinical trials, where available, and should also be directed to the National Alopecia Areata Foundation (NAAF). Their website provides information and resources for patients and families, information for local support groups, and information on a national registry.

Dr. Hordinsky reported receiving grant or research support from a number of pharmaceutical and consumer product companies in the dermatology space. She serves on the scientific advisory board of the National Alopecia Areata Foundation.

This news organization and SDEF are owned by the same parent company.

koakes@frontlinemedcom.com

On Twitter @karioakes

Alopecia areata’s mysterious appearances, regressions, and recurrences frustrate patients and stymie physicians, but new treatments may be around the corner.

Tofacitinib, along with other medications that target the autoimmune etiology of alopecia areata, have shown complete alopecia reversal in case studies, Dr. Maria Hordinsky said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation. “There’s a lot of excitement bubbling up in hair disease research because of these new potential topical and oral treatments.”

Janus kinase (JAK) inhibitors, including tofacitinib, baricitinib, and ruxolitinib, have also been reported to reverse alopecia areata.

“There’s been a surge of enthusiasm for using more aggressive systemic therapies, including not only tobacitinib and ruxolitinib but also methotrexate and interleukin-2,” Dr. Hordinsky said, noting that these are still investigational uses.

The new treatment targets are welcome for physicians treating patients with alopecia areata, since currently there are no FDA-approved treatments, Dr. Hordinsky said.

A review by Dr. Hordinsky and colleague found a total of 29 trials investigating more than a dozen topical and oral treatments. Most trials were of moderate or lower quality, and most had major limitations. Treatments that were effective included topical and oral corticosteroids, as well as the sensitizing agents diphenylcyclopropenone and dinitrochlorobenzene (Am J Clin Dermatol. 2014;15:231-46).

In the absence of high-quality evidence for effective treatments, patient characteristics and preference, as well as disease activity and location, can guide treatment. In some cases, a scalp biopsy can give more information about follicle differentiation, inflammation, and the stage of the hair cycle at the time of assessment, Dr. Hordinsky said.

It’s important to set expectations for patients, so they know that treatments will take time, she said. Providers should be alert to the possibility that hair loss may also be associated with an underlying medical problem, so a thorough workup is indicated.

Patients should be given the opportunity to enroll in clinical trials, where available, and should also be directed to the National Alopecia Areata Foundation (NAAF). Their website provides information and resources for patients and families, information for local support groups, and information on a national registry.

Dr. Hordinsky reported receiving grant or research support from a number of pharmaceutical and consumer product companies in the dermatology space. She serves on the scientific advisory board of the National Alopecia Areata Foundation.

This news organization and SDEF are owned by the same parent company.

koakes@frontlinemedcom.com

On Twitter @karioakes

Some kinds of scarring alopecia may also be related to lipid metabolism, pointing the way to novel therapeutic targets for this class of hair diseases, Dr. Maria Hordinsky said at the Hawaii Dermatology Symposium.

While the scarring alopecias are broadly divided into lymphocytic and neutrophilic alopecias, clinically, they are a heterogeneous group, said Dr. Hordinsky, chair of the department of dermatology at the University of Minnesota, Minneapolis.

Two lymphocytic cicatricial alopecias, lichen planopilaris and frontal fibrosing alopecia, have been associated with peroxisome proliferator-activated receptor gamma (PPARG) deficiency. This finding suggests that they may be a type of lipid metabolism disorder; the theory is bolstered by case reports of improvement with the use of pioglitazone, Dr. Hordinsky said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

In both of these cicatricial alopecias, patients may also have significant discomfort including scalp burning, pain, paresthesias, and itching. Patients may even say they feel as though their scalp is on fire.

Dr. Hordinsky and her collaborators are currently conducting a clinical trial of the efficacy of a compounded formulation of 6% topical gabapentin to address the scalp discomfort associated with the cicatricial alopecias. The study is ongoing and recruiting patients. “FFA has been described as an emerging disease, and participation of FFA patients in a national registry focused on improving our understanding of the epidemiology of this disease is highly recommended,” said Dr. Hordinsky.

Currently, stepwise treatment for the lymphocytic cicatricial alopecias can be divided into 3 tiers:

• Tier 1: Topical high potency corticosteroids and/or intralesional steroids, as well as non-steroidal topical anti-inflammatory medications, such as tacrolimus and pemicrolimus.

• Tier 2: Hydroxychloroquine and acetretin, as well as low-dose antibiotics, which are used for anti-inflammatory effect.

• Tier 3: Cyclosporin, mycophenolate mofetil, and prednisone.

Low-level light therapy – approved by the Food and Drug Administration to treat thinning hair in men and women – may also be of benefit for those with inflammatory scalp diseases, Dr. Hordinsky added.

Dr. Hordinsky reported financial relationships with a number of pharmaceutical and consumer product companies in the dermatologic space.

This news organization and SDEF are owned by the same parent company.

koakes@frontlinemedcom.com

On Twitter @karioakes

Some kinds of scarring alopecia may also be related to lipid metabolism, pointing the way to novel therapeutic targets for this class of hair diseases, Dr. Maria Hordinsky said at the Hawaii Dermatology Symposium.

While the scarring alopecias are broadly divided into lymphocytic and neutrophilic alopecias, clinically, they are a heterogeneous group, said Dr. Hordinsky, chair of the department of dermatology at the University of Minnesota, Minneapolis.

Two lymphocytic cicatricial alopecias, lichen planopilaris and frontal fibrosing alopecia, have been associated with peroxisome proliferator-activated receptor gamma (PPARG) deficiency. This finding suggests that they may be a type of lipid metabolism disorder; the theory is bolstered by case reports of improvement with the use of pioglitazone, Dr. Hordinsky said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

In both of these cicatricial alopecias, patients may also have significant discomfort including scalp burning, pain, paresthesias, and itching. Patients may even say they feel as though their scalp is on fire.

Dr. Hordinsky and her collaborators are currently conducting a clinical trial of the efficacy of a compounded formulation of 6% topical gabapentin to address the scalp discomfort associated with the cicatricial alopecias. The study is ongoing and recruiting patients. “FFA has been described as an emerging disease, and participation of FFA patients in a national registry focused on improving our understanding of the epidemiology of this disease is highly recommended,” said Dr. Hordinsky.

Currently, stepwise treatment for the lymphocytic cicatricial alopecias can be divided into 3 tiers:

• Tier 1: Topical high potency corticosteroids and/or intralesional steroids, as well as non-steroidal topical anti-inflammatory medications, such as tacrolimus and pemicrolimus.

• Tier 2: Hydroxychloroquine and acetretin, as well as low-dose antibiotics, which are used for anti-inflammatory effect.

• Tier 3: Cyclosporin, mycophenolate mofetil, and prednisone.

Low-level light therapy – approved by the Food and Drug Administration to treat thinning hair in men and women – may also be of benefit for those with inflammatory scalp diseases, Dr. Hordinsky added.

Dr. Hordinsky reported financial relationships with a number of pharmaceutical and consumer product companies in the dermatologic space.

This news organization and SDEF are owned by the same parent company.

koakes@frontlinemedcom.com

On Twitter @karioakes

Some kinds of scarring alopecia may also be related to lipid metabolism, pointing the way to novel therapeutic targets for this class of hair diseases, Dr. Maria Hordinsky said at the Hawaii Dermatology Symposium.

While the scarring alopecias are broadly divided into lymphocytic and neutrophilic alopecias, clinically, they are a heterogeneous group, said Dr. Hordinsky, chair of the department of dermatology at the University of Minnesota, Minneapolis.

Two lymphocytic cicatricial alopecias, lichen planopilaris and frontal fibrosing alopecia, have been associated with peroxisome proliferator-activated receptor gamma (PPARG) deficiency. This finding suggests that they may be a type of lipid metabolism disorder; the theory is bolstered by case reports of improvement with the use of pioglitazone, Dr. Hordinsky said at the meeting provided by Global Academy for Medical Education/Skin Disease Education Foundation.

In both of these cicatricial alopecias, patients may also have significant discomfort including scalp burning, pain, paresthesias, and itching. Patients may even say they feel as though their scalp is on fire.

Dr. Hordinsky and her collaborators are currently conducting a clinical trial of the efficacy of a compounded formulation of 6% topical gabapentin to address the scalp discomfort associated with the cicatricial alopecias. The study is ongoing and recruiting patients. “FFA has been described as an emerging disease, and participation of FFA patients in a national registry focused on improving our understanding of the epidemiology of this disease is highly recommended,” said Dr. Hordinsky.

Currently, stepwise treatment for the lymphocytic cicatricial alopecias can be divided into 3 tiers:

• Tier 1: Topical high potency corticosteroids and/or intralesional steroids, as well as non-steroidal topical anti-inflammatory medications, such as tacrolimus and pemicrolimus.

• Tier 2: Hydroxychloroquine and acetretin, as well as low-dose antibiotics, which are used for anti-inflammatory effect.

• Tier 3: Cyclosporin, mycophenolate mofetil, and prednisone.

Low-level light therapy – approved by the Food and Drug Administration to treat thinning hair in men and women – may also be of benefit for those with inflammatory scalp diseases, Dr. Hordinsky added.

Dr. Hordinsky reported financial relationships with a number of pharmaceutical and consumer product companies in the dermatologic space.

This news organization and SDEF are owned by the same parent company.

koakes@frontlinemedcom.com

On Twitter @karioakes

Hematopoietic stem cells

in the bone marrow

Nearly 30 years after the discovery of the hematopoietic stem cell (HSC), researchers believe they have found a marker specific to long-term HSCs—the gene Hoxb5.

If confirmed, this finding would help settle long-standing debates about the identity of long-term HSCs and their support cells.

It may also pave the way for understanding how long-term HSCs maintain themselves and provide scientists with the necessary information to grow HSCs in the lab.

Irving Weissman, MD, of Stanford University School of Medicine in California, and his colleagues described this work in a letter to Nature.

In 1988, Dr Weissman and his colleagues isolated the HSC. Since that time, researchers have had mixed success in their attempts to get a detailed picture of how HSCs maintain themselves and grow in the body.

Over the years, it became clear why. HSCs come in 2 forms—short-term HSCs that lose their powers of replication over time and long-term HSCs that can replicate indefinitely.

With the new study, Dr Weissman and his colleagues believe they have found a reliable way to tell the difference between long-term and short-term HSCs. Namely, the presence of Hoxb5.

“In this paper, we have found a single marker that, in the entire bone marrow, is only found in these long-term stem cells,” Dr Weissman said.

The researchers hope this finding will enable them to look at how nearby cells create a niche where the long-term HSCs are supported and maintained.

“For nearly 30 years, people have been trying to grow HSCs outside the body and have not been able to do it; it’s arguably the ‘holy grail’ in this field,” said James Y. Chen, an MD/PhD candidate at Stanford University School of Medicine.

“Now that we have an anchor, a way to look at long-term HSCs, we can look at the cells around them to understand and, ideally, recreate the niche.”

An extensive search

Over the years, scientists have proposed various markers that they felt were unique to long-term HSCs, but the reliability of each proposed marker has been heatedly debated by other research groups, said Masanori Miyanishi, MD, PhD, also of Stanford University School of Medicine.

In an attempt to settle the issue, Chen and Dr Miyanishi examined a list of more than 100 genes that are expressed in the bone marrow and seemed like good candidates to be unique markers of long-term HSCs.

The researchers eliminated genes that are turned on in areas of the bone that don’t involve the creation of new blood and immune cells. That narrowed the field to 45 genes.

The team then performed an analysis to determine how much protein these genes were making in various cells. They found that only 3 proteins were produced at a high enough level to mark HSCs.

Finally, the researchers needed to find if 1 of these 3 was turned on in long-term HSCs and turned off in short-term HSCs.

Although they couldn’t yet identify which cells were long-term HSCs, the team knew that any collection of HSCs should have both long-term and short-term HSCs, so they expected to find the candidate gene turned off in some cells and on in others. Only 1 gene fit that bill—Hoxb5.

The researchers pointed out that there may be other unique markers of long-term HSCs, such as genes that weren’t among the initial group of genes screened. But among the screened genes, only Hoxb5 was a unique identifier of the long-term HSC.

Finding the niche

The researchers were also able to solve another mystery by showing where in the bone marrow long-term HSCs reside.

Satoshi Yamazaki, PhD, and Hiromitsu Nakauchi, MD, PhD, both from the University of Tokyo in Japan, used new technology to prepare bone marrow tissue and do computational analyses that validated the location and architecture of the HSC niche.

“More than 90% of these cells reside on a particular type of blood vessel called venous sinusoids,” Dr Nakauchi said.

The researchers believe the ability to identify long-term HSCs will give scientists a powerful tool for further study.

“This opens the way to observe long-term HSCs and other cells in the niche as they exist in the body, without transplanting them,” Dr Weissman said. “This is how science works, by getting down to the purest irreducible element—in this case, blood stem cells—in order to develop new tools and understandings.”

Hematopoietic stem cells

in the bone marrow

Nearly 30 years after the discovery of the hematopoietic stem cell (HSC), researchers believe they have found a marker specific to long-term HSCs—the gene Hoxb5.

If confirmed, this finding would help settle long-standing debates about the identity of long-term HSCs and their support cells.

It may also pave the way for understanding how long-term HSCs maintain themselves and provide scientists with the necessary information to grow HSCs in the lab.

Irving Weissman, MD, of Stanford University School of Medicine in California, and his colleagues described this work in a letter to Nature.

In 1988, Dr Weissman and his colleagues isolated the HSC. Since that time, researchers have had mixed success in their attempts to get a detailed picture of how HSCs maintain themselves and grow in the body.

Over the years, it became clear why. HSCs come in 2 forms—short-term HSCs that lose their powers of replication over time and long-term HSCs that can replicate indefinitely.

With the new study, Dr Weissman and his colleagues believe they have found a reliable way to tell the difference between long-term and short-term HSCs. Namely, the presence of Hoxb5.

“In this paper, we have found a single marker that, in the entire bone marrow, is only found in these long-term stem cells,” Dr Weissman said.

The researchers hope this finding will enable them to look at how nearby cells create a niche where the long-term HSCs are supported and maintained.

“For nearly 30 years, people have been trying to grow HSCs outside the body and have not been able to do it; it’s arguably the ‘holy grail’ in this field,” said James Y. Chen, an MD/PhD candidate at Stanford University School of Medicine.

“Now that we have an anchor, a way to look at long-term HSCs, we can look at the cells around them to understand and, ideally, recreate the niche.”

An extensive search

Over the years, scientists have proposed various markers that they felt were unique to long-term HSCs, but the reliability of each proposed marker has been heatedly debated by other research groups, said Masanori Miyanishi, MD, PhD, also of Stanford University School of Medicine.

In an attempt to settle the issue, Chen and Dr Miyanishi examined a list of more than 100 genes that are expressed in the bone marrow and seemed like good candidates to be unique markers of long-term HSCs.

The researchers eliminated genes that are turned on in areas of the bone that don’t involve the creation of new blood and immune cells. That narrowed the field to 45 genes.

The team then performed an analysis to determine how much protein these genes were making in various cells. They found that only 3 proteins were produced at a high enough level to mark HSCs.

Finally, the researchers needed to find if 1 of these 3 was turned on in long-term HSCs and turned off in short-term HSCs.

Although they couldn’t yet identify which cells were long-term HSCs, the team knew that any collection of HSCs should have both long-term and short-term HSCs, so they expected to find the candidate gene turned off in some cells and on in others. Only 1 gene fit that bill—Hoxb5.

The researchers pointed out that there may be other unique markers of long-term HSCs, such as genes that weren’t among the initial group of genes screened. But among the screened genes, only Hoxb5 was a unique identifier of the long-term HSC.

Finding the niche

The researchers were also able to solve another mystery by showing where in the bone marrow long-term HSCs reside.

Satoshi Yamazaki, PhD, and Hiromitsu Nakauchi, MD, PhD, both from the University of Tokyo in Japan, used new technology to prepare bone marrow tissue and do computational analyses that validated the location and architecture of the HSC niche.

“More than 90% of these cells reside on a particular type of blood vessel called venous sinusoids,” Dr Nakauchi said.

The researchers believe the ability to identify long-term HSCs will give scientists a powerful tool for further study.

“This opens the way to observe long-term HSCs and other cells in the niche as they exist in the body, without transplanting them,” Dr Weissman said. “This is how science works, by getting down to the purest irreducible element—in this case, blood stem cells—in order to develop new tools and understandings.”

Hematopoietic stem cells

in the bone marrow

Nearly 30 years after the discovery of the hematopoietic stem cell (HSC), researchers believe they have found a marker specific to long-term HSCs—the gene Hoxb5.

If confirmed, this finding would help settle long-standing debates about the identity of long-term HSCs and their support cells.

It may also pave the way for understanding how long-term HSCs maintain themselves and provide scientists with the necessary information to grow HSCs in the lab.

Irving Weissman, MD, of Stanford University School of Medicine in California, and his colleagues described this work in a letter to Nature.

In 1988, Dr Weissman and his colleagues isolated the HSC. Since that time, researchers have had mixed success in their attempts to get a detailed picture of how HSCs maintain themselves and grow in the body.

Over the years, it became clear why. HSCs come in 2 forms—short-term HSCs that lose their powers of replication over time and long-term HSCs that can replicate indefinitely.

With the new study, Dr Weissman and his colleagues believe they have found a reliable way to tell the difference between long-term and short-term HSCs. Namely, the presence of Hoxb5.

“In this paper, we have found a single marker that, in the entire bone marrow, is only found in these long-term stem cells,” Dr Weissman said.

The researchers hope this finding will enable them to look at how nearby cells create a niche where the long-term HSCs are supported and maintained.

“For nearly 30 years, people have been trying to grow HSCs outside the body and have not been able to do it; it’s arguably the ‘holy grail’ in this field,” said James Y. Chen, an MD/PhD candidate at Stanford University School of Medicine.

“Now that we have an anchor, a way to look at long-term HSCs, we can look at the cells around them to understand and, ideally, recreate the niche.”

An extensive search

Over the years, scientists have proposed various markers that they felt were unique to long-term HSCs, but the reliability of each proposed marker has been heatedly debated by other research groups, said Masanori Miyanishi, MD, PhD, also of Stanford University School of Medicine.

In an attempt to settle the issue, Chen and Dr Miyanishi examined a list of more than 100 genes that are expressed in the bone marrow and seemed like good candidates to be unique markers of long-term HSCs.

The researchers eliminated genes that are turned on in areas of the bone that don’t involve the creation of new blood and immune cells. That narrowed the field to 45 genes.

The team then performed an analysis to determine how much protein these genes were making in various cells. They found that only 3 proteins were produced at a high enough level to mark HSCs.

Finally, the researchers needed to find if 1 of these 3 was turned on in long-term HSCs and turned off in short-term HSCs.

Although they couldn’t yet identify which cells were long-term HSCs, the team knew that any collection of HSCs should have both long-term and short-term HSCs, so they expected to find the candidate gene turned off in some cells and on in others. Only 1 gene fit that bill—Hoxb5.

The researchers pointed out that there may be other unique markers of long-term HSCs, such as genes that weren’t among the initial group of genes screened. But among the screened genes, only Hoxb5 was a unique identifier of the long-term HSC.

Finding the niche

The researchers were also able to solve another mystery by showing where in the bone marrow long-term HSCs reside.

Satoshi Yamazaki, PhD, and Hiromitsu Nakauchi, MD, PhD, both from the University of Tokyo in Japan, used new technology to prepare bone marrow tissue and do computational analyses that validated the location and architecture of the HSC niche.

“More than 90% of these cells reside on a particular type of blood vessel called venous sinusoids,” Dr Nakauchi said.

The researchers believe the ability to identify long-term HSCs will give scientists a powerful tool for further study.

“This opens the way to observe long-term HSCs and other cells in the niche as they exist in the body, without transplanting them,” Dr Weissman said. “This is how science works, by getting down to the purest irreducible element—in this case, blood stem cells—in order to develop new tools and understandings.”

Plasmodium sporozoite

Image by Ute Frevert

and Margaret Shear

Researchers say they have designed a compound that kills malaria parasites—even those resistant to current antimalarial therapy—but

avoids harming human cells.

The compound exploits tiny structural differences between the parasitic and human versions of the proteasome.

In preclinical experiments, this proteasome inhibitor was able to kill artemisinin-resistant malaria parasites and further sensitize parasites to artemisinin.

Matthew Bogyo, PhD, of Stanford University School of Medicine in California, and his colleagues conducted this research and recounted the results in a letter to Nature.

Previous research has shown that proteasome inhibitors can be toxic to the malaria parasite Plasmodium falciparum. But the drugs have tended to inhibit the human version of the proteasome too, resulting in toxicity that would be unacceptable in a malaria drug.

Dr Bogyo and his colleagues wanted to overcome this problem, so they produced highly purified preparations of both human and P falciparum proteasomes. The team then “fed” those 2 preparations a set of protein fragments containing a variety of amino-acid linkages to see which amino-acid linkages the proteasomes would cleave.

The researchers identified 113 amino-acid linkages that are readily cleaved by P falciparum proteasomes but not so well by human proteasomes, and 153 amino-acid linkages where the reverse is the case.

The team used this information to design tiny protein snippets that failed to interact with human proteasomes but inhibited parts of the P falciparum proteasomes responsible for cleaving certain amino-acid links.

The researchers investigated the basis for this selectivity by using high-resolution electron microscopy to map the detailed structure of the parasite and human proteasomes. This allowed them to optimize the protein snippets they were using as parasite-selective proteasome inhibitors.

The 3-amino-acid snippet they ultimately focused on, called WLL, was able to inhibit 2 different catalytic regions in P falciparum proteasomes without having any effect on those of cultured human cells. There was a 600-fold difference in WLL’s potency at killing the parasitic cells over the human cells.

In experiments with mice, the researchers saw a nearly complete reduction of malaria parasites with both single and multiple doses of WLL.

Other tests, performed on artemisinin-resistant parasites infecting human red blood cells, suggested the WLL compound was equally effective at killing artemisinin-resistant parasites and artemisinin-sensitive parasites.

Dr Bogyo pointed out that the artemisinin family of drugs work by modifying proteins in the parasite. Resistance occurs when the parasites’ proteasomes are able to recycle those modified proteins. But this means that artemisinin-treated parasites are particularly sensitive to disruption of normal protein function.

“The compounds we’ve derived can kill artemisinin-resistant parasites because those parasites have an increased need for highly efficient proteasomes,” he said.

“So combining the proteasome inhibitor with artemisinin should make it possible to block the onset of resistance. That will, in turn, allow the continued use of that front-line malaria treatment, which has been so effective up until now.”

Clinical trials of compounds derived from this research remain several years away, Dr Bogyo added.

Study author Leann Tilley, PhD, of the University of Melbourne in Victoria, Australia, and her team are working with experts from Takeda Pharmaceutical Company Limited and Medicines for Malaria Venture to identify additional classes of parasite-specific proteasome inhibitors that could be advanced to clinical trials.

“The next step is screening the Takeda libraries to find a similar drug that doesn’t affect the human proteasome,” Dr Tilley said. “The current drug is a good start, but it’s not yet suitable for humans. It needs to be able to be administered orally and needs to last a long time in the blood stream.”

Dr Tilley said if they can find an existing drug in Takeda’s libraries that matches the structure of the new malaria drug, they could move it toward human trials very quickly.

Plasmodium sporozoite

Image by Ute Frevert

and Margaret Shear

Researchers say they have designed a compound that kills malaria parasites—even those resistant to current antimalarial therapy—but

avoids harming human cells.

The compound exploits tiny structural differences between the parasitic and human versions of the proteasome.

In preclinical experiments, this proteasome inhibitor was able to kill artemisinin-resistant malaria parasites and further sensitize parasites to artemisinin.

Matthew Bogyo, PhD, of Stanford University School of Medicine in California, and his colleagues conducted this research and recounted the results in a letter to Nature.

Previous research has shown that proteasome inhibitors can be toxic to the malaria parasite Plasmodium falciparum. But the drugs have tended to inhibit the human version of the proteasome too, resulting in toxicity that would be unacceptable in a malaria drug.

Dr Bogyo and his colleagues wanted to overcome this problem, so they produced highly purified preparations of both human and P falciparum proteasomes. The team then “fed” those 2 preparations a set of protein fragments containing a variety of amino-acid linkages to see which amino-acid linkages the proteasomes would cleave.

The researchers identified 113 amino-acid linkages that are readily cleaved by P falciparum proteasomes but not so well by human proteasomes, and 153 amino-acid linkages where the reverse is the case.

The team used this information to design tiny protein snippets that failed to interact with human proteasomes but inhibited parts of the P falciparum proteasomes responsible for cleaving certain amino-acid links.

The researchers investigated the basis for this selectivity by using high-resolution electron microscopy to map the detailed structure of the parasite and human proteasomes. This allowed them to optimize the protein snippets they were using as parasite-selective proteasome inhibitors.

The 3-amino-acid snippet they ultimately focused on, called WLL, was able to inhibit 2 different catalytic regions in P falciparum proteasomes without having any effect on those of cultured human cells. There was a 600-fold difference in WLL’s potency at killing the parasitic cells over the human cells.

In experiments with mice, the researchers saw a nearly complete reduction of malaria parasites with both single and multiple doses of WLL.

Other tests, performed on artemisinin-resistant parasites infecting human red blood cells, suggested the WLL compound was equally effective at killing artemisinin-resistant parasites and artemisinin-sensitive parasites.

Dr Bogyo pointed out that the artemisinin family of drugs work by modifying proteins in the parasite. Resistance occurs when the parasites’ proteasomes are able to recycle those modified proteins. But this means that artemisinin-treated parasites are particularly sensitive to disruption of normal protein function.

“The compounds we’ve derived can kill artemisinin-resistant parasites because those parasites have an increased need for highly efficient proteasomes,” he said.

“So combining the proteasome inhibitor with artemisinin should make it possible to block the onset of resistance. That will, in turn, allow the continued use of that front-line malaria treatment, which has been so effective up until now.”

Clinical trials of compounds derived from this research remain several years away, Dr Bogyo added.

Study author Leann Tilley, PhD, of the University of Melbourne in Victoria, Australia, and her team are working with experts from Takeda Pharmaceutical Company Limited and Medicines for Malaria Venture to identify additional classes of parasite-specific proteasome inhibitors that could be advanced to clinical trials.

“The next step is screening the Takeda libraries to find a similar drug that doesn’t affect the human proteasome,” Dr Tilley said. “The current drug is a good start, but it’s not yet suitable for humans. It needs to be able to be administered orally and needs to last a long time in the blood stream.”

Dr Tilley said if they can find an existing drug in Takeda’s libraries that matches the structure of the new malaria drug, they could move it toward human trials very quickly.

Plasmodium sporozoite

Image by Ute Frevert

and Margaret Shear

Researchers say they have designed a compound that kills malaria parasites—even those resistant to current antimalarial therapy—but

avoids harming human cells.

The compound exploits tiny structural differences between the parasitic and human versions of the proteasome.

In preclinical experiments, this proteasome inhibitor was able to kill artemisinin-resistant malaria parasites and further sensitize parasites to artemisinin.

Matthew Bogyo, PhD, of Stanford University School of Medicine in California, and his colleagues conducted this research and recounted the results in a letter to Nature.

Previous research has shown that proteasome inhibitors can be toxic to the malaria parasite Plasmodium falciparum. But the drugs have tended to inhibit the human version of the proteasome too, resulting in toxicity that would be unacceptable in a malaria drug.

Dr Bogyo and his colleagues wanted to overcome this problem, so they produced highly purified preparations of both human and P falciparum proteasomes. The team then “fed” those 2 preparations a set of protein fragments containing a variety of amino-acid linkages to see which amino-acid linkages the proteasomes would cleave.

The researchers identified 113 amino-acid linkages that are readily cleaved by P falciparum proteasomes but not so well by human proteasomes, and 153 amino-acid linkages where the reverse is the case.

The team used this information to design tiny protein snippets that failed to interact with human proteasomes but inhibited parts of the P falciparum proteasomes responsible for cleaving certain amino-acid links.

The researchers investigated the basis for this selectivity by using high-resolution electron microscopy to map the detailed structure of the parasite and human proteasomes. This allowed them to optimize the protein snippets they were using as parasite-selective proteasome inhibitors.

The 3-amino-acid snippet they ultimately focused on, called WLL, was able to inhibit 2 different catalytic regions in P falciparum proteasomes without having any effect on those of cultured human cells. There was a 600-fold difference in WLL’s potency at killing the parasitic cells over the human cells.

In experiments with mice, the researchers saw a nearly complete reduction of malaria parasites with both single and multiple doses of WLL.

Other tests, performed on artemisinin-resistant parasites infecting human red blood cells, suggested the WLL compound was equally effective at killing artemisinin-resistant parasites and artemisinin-sensitive parasites.

Dr Bogyo pointed out that the artemisinin family of drugs work by modifying proteins in the parasite. Resistance occurs when the parasites’ proteasomes are able to recycle those modified proteins. But this means that artemisinin-treated parasites are particularly sensitive to disruption of normal protein function.

“The compounds we’ve derived can kill artemisinin-resistant parasites because those parasites have an increased need for highly efficient proteasomes,” he said.

“So combining the proteasome inhibitor with artemisinin should make it possible to block the onset of resistance. That will, in turn, allow the continued use of that front-line malaria treatment, which has been so effective up until now.”

Clinical trials of compounds derived from this research remain several years away, Dr Bogyo added.

Study author Leann Tilley, PhD, of the University of Melbourne in Victoria, Australia, and her team are working with experts from Takeda Pharmaceutical Company Limited and Medicines for Malaria Venture to identify additional classes of parasite-specific proteasome inhibitors that could be advanced to clinical trials.

“The next step is screening the Takeda libraries to find a similar drug that doesn’t affect the human proteasome,” Dr Tilley said. “The current drug is a good start, but it’s not yet suitable for humans. It needs to be able to be administered orally and needs to last a long time in the blood stream.”

Dr Tilley said if they can find an existing drug in Takeda’s libraries that matches the structure of the new malaria drug, they could move it toward human trials very quickly.

A diagnosis of influenza increased the risk of subsequent atrial fibrillation by about 18%, investigators reported online in Heart Rhythm.

Clinicians therefore should consider atrial fibrillation (AF) in patients with influenza-like symptoms who report palpitations or experience an ischemic stroke, said Dr. Ting-Yung Chang of Taipei Veterans General Hospital in Taiwan and his associates. Influenza vaccination might help prevent AF, and high-risk patients should be encouraged to receive the vaccination annually, they said. However, a large prospective study is needed to clarify whether influenza vaccination reduces the risk of AF and subsequent ischemic stroke and systemic thromboembolic events, they added.

©Graça Victoria/Thinkstockphotos.com

Atrial fibrillation increases the risk of stroke about fivefold, triples the risk of heart failure, and doubles the chances of dementia and death, the researchers noted. Mounting evidence implicates inflammation and sympathetic nervous system dysregulation in the pathogenesis of AF, raising questions about whether influenza might underlie or contribute to some cases of AF. To explore relationships among AF, influenza, and influenza vaccination, the investigators analyzed data for 11,374 patients with AF who were enrolled in the Taiwan National Health Insurance Research Database between 2000 and 2010. They matched each patient with AF to four controls based on age, sex, enrollment date, and the Charlson comorbidity index (

Heart Rhythm. 2016 Feb. doi: 10.1016/j.hrthm.2016.01.026

).

Unvaccinated patients with influenza were 18% more likely to develop AF than unvaccinated patients without influenza (odds ratio, 1.18; 95% confidence interval, 1.01-1.38; P = .032), even after adjusting for demographic factors, medical history, and use of relevant health care services, the researchers reported. In contrast, vaccinated patients who later developed influenza were about as likely to develop AF as unvaccinated patients who did not develop influenza, both in the overall analysis and in subgroups stratified by age, sex, and comorbidities. Moreover, vaccinated patients without influenza were even less likely to develop AF than unvaccinated patients without influenza (OR, 0.88; 95% CI, 0.84-0.93; P less than .001).

The registry database excluded relevant data on smoking history, body mass index, and physical activity level, the researchers said. “Influenza infection was diagnosed using ICD-9 codes with concomitant use of antiviral agents, and was not further confirmed based on the results of viral culture with throat swab,” they added. “The diagnostic accuracy of influenza infection cannot be fully ascertained.”

The National Science Council and the Taipei Veterans General Hospital funded the study. The researchers had no disclosures.

A diagnosis of influenza increased the risk of subsequent atrial fibrillation by about 18%, investigators reported online in Heart Rhythm.

Clinicians therefore should consider atrial fibrillation (AF) in patients with influenza-like symptoms who report palpitations or experience an ischemic stroke, said Dr. Ting-Yung Chang of Taipei Veterans General Hospital in Taiwan and his associates. Influenza vaccination might help prevent AF, and high-risk patients should be encouraged to receive the vaccination annually, they said. However, a large prospective study is needed to clarify whether influenza vaccination reduces the risk of AF and subsequent ischemic stroke and systemic thromboembolic events, they added.

©Graça Victoria/Thinkstockphotos.com

Atrial fibrillation increases the risk of stroke about fivefold, triples the risk of heart failure, and doubles the chances of dementia and death, the researchers noted. Mounting evidence implicates inflammation and sympathetic nervous system dysregulation in the pathogenesis of AF, raising questions about whether influenza might underlie or contribute to some cases of AF. To explore relationships among AF, influenza, and influenza vaccination, the investigators analyzed data for 11,374 patients with AF who were enrolled in the Taiwan National Health Insurance Research Database between 2000 and 2010. They matched each patient with AF to four controls based on age, sex, enrollment date, and the Charlson comorbidity index (

Heart Rhythm. 2016 Feb. doi: 10.1016/j.hrthm.2016.01.026

).

Unvaccinated patients with influenza were 18% more likely to develop AF than unvaccinated patients without influenza (odds ratio, 1.18; 95% confidence interval, 1.01-1.38; P = .032), even after adjusting for demographic factors, medical history, and use of relevant health care services, the researchers reported. In contrast, vaccinated patients who later developed influenza were about as likely to develop AF as unvaccinated patients who did not develop influenza, both in the overall analysis and in subgroups stratified by age, sex, and comorbidities. Moreover, vaccinated patients without influenza were even less likely to develop AF than unvaccinated patients without influenza (OR, 0.88; 95% CI, 0.84-0.93; P less than .001).

The registry database excluded relevant data on smoking history, body mass index, and physical activity level, the researchers said. “Influenza infection was diagnosed using ICD-9 codes with concomitant use of antiviral agents, and was not further confirmed based on the results of viral culture with throat swab,” they added. “The diagnostic accuracy of influenza infection cannot be fully ascertained.”

The National Science Council and the Taipei Veterans General Hospital funded the study. The researchers had no disclosures.

A diagnosis of influenza increased the risk of subsequent atrial fibrillation by about 18%, investigators reported online in Heart Rhythm.

Clinicians therefore should consider atrial fibrillation (AF) in patients with influenza-like symptoms who report palpitations or experience an ischemic stroke, said Dr. Ting-Yung Chang of Taipei Veterans General Hospital in Taiwan and his associates. Influenza vaccination might help prevent AF, and high-risk patients should be encouraged to receive the vaccination annually, they said. However, a large prospective study is needed to clarify whether influenza vaccination reduces the risk of AF and subsequent ischemic stroke and systemic thromboembolic events, they added.

©Graça Victoria/Thinkstockphotos.com

Atrial fibrillation increases the risk of stroke about fivefold, triples the risk of heart failure, and doubles the chances of dementia and death, the researchers noted. Mounting evidence implicates inflammation and sympathetic nervous system dysregulation in the pathogenesis of AF, raising questions about whether influenza might underlie or contribute to some cases of AF. To explore relationships among AF, influenza, and influenza vaccination, the investigators analyzed data for 11,374 patients with AF who were enrolled in the Taiwan National Health Insurance Research Database between 2000 and 2010. They matched each patient with AF to four controls based on age, sex, enrollment date, and the Charlson comorbidity index (

Heart Rhythm. 2016 Feb. doi: 10.1016/j.hrthm.2016.01.026

).

Unvaccinated patients with influenza were 18% more likely to develop AF than unvaccinated patients without influenza (odds ratio, 1.18; 95% confidence interval, 1.01-1.38; P = .032), even after adjusting for demographic factors, medical history, and use of relevant health care services, the researchers reported. In contrast, vaccinated patients who later developed influenza were about as likely to develop AF as unvaccinated patients who did not develop influenza, both in the overall analysis and in subgroups stratified by age, sex, and comorbidities. Moreover, vaccinated patients without influenza were even less likely to develop AF than unvaccinated patients without influenza (OR, 0.88; 95% CI, 0.84-0.93; P less than .001).

The registry database excluded relevant data on smoking history, body mass index, and physical activity level, the researchers said. “Influenza infection was diagnosed using ICD-9 codes with concomitant use of antiviral agents, and was not further confirmed based on the results of viral culture with throat swab,” they added. “The diagnostic accuracy of influenza infection cannot be fully ascertained.”

The National Science Council and the Taipei Veterans General Hospital funded the study. The researchers had no disclosures.

LAS VEGAS – People who use spice, bath salts, and other so-called designer drugs may present with symptoms that resemble numerous psychiatric conditions, including schizophrenia, anxiety disorders, and depression.

“Given the recent emergence of designer drugs, the long-term consequences of their use have not been extensively studied and are relatively unknown,” Dr. William M. Sauve said at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Dr. Sauve, medical director of TMS NeuroHealth Centers of Richmond and Charlottesville, both in Virginia, said designer drugs have grown in popularity in recent years because they are perceived as legal alternatives to illicit substances. In addition, their detection by standard drug toxicology screens is limited.

In October 2011, components of designer drugs, including synthetic cannabinoids and the major constituents of bath salts, were categorized as emergency Schedule I substances. In July 2012, President Obama signed the Synthetic Drug Abuse Prevention Act, which doubled the time that a substance may be temporarily assigned to Schedule I, from 18 months to 36 months.

“Under federal law, any chemical that is similar to a classified drug and is meant to be used for the same purposes is considered to be classified,” Dr. Sauve said. However, designer drugs “get labeled ‘not for human consumption’ and can be sold out in the open and camouflaged under names such as ‘stain remover,’ ‘research chemicals,’ and even ‘insect repellent.’ That’s why it’s very difficult for the law to catch up with these things. Active ingredients are also a moving target.”

He discussed three types of these designer drugs: synthetic cannabinoids, bath salts, and krokodil.

Synthetic cannabinoids mimic THC

Also known as spice, K2, and incense, these substances began to appear in the United States in 2008 and are mostly used by males. Primarily inhaled, these substances are meant to mimic the effects of tetrahydrocannabinol (THC). They work by decreasing levels of gamma-aminobutyric acid (GABA) and by increasing levels of glutamate and dopamine. “Serotonin levels can also be affected indirectly by endocannabinoid control of GABA and glutamate release,” he added.

Unlike marijuana, which is a partial agonist at the cannabinoid 1 (CB-1) receptor, synthetics are full agonists at the CB-1 receptor, “so as you use it, it will hit every receptor until you have maximal stimulation, and it may have 800 times greater affinity than THC,” he said. Signs and symptoms of acute intoxication can be wide ranging, from agitation and dysphoria to paranoia and tachycardia, and can last up to 6 hours. While commercial tests are available to detect synthetic cannabinoid metabolites, formulations change so often that “most tests quickly become obsolete,” Dr. Sauve said. He noted that intoxication with spice should be suspected in patients who present with bizarre behavior, anxiety, agitation, and/or psychosis in those with no known psychiatric history. Intravaneous benzodiazepines can be used for agitation and seizures. While knowledge of their long-term impact is lacking, synthetic cannabinoids may increase the risk of subsequent psychosis by threefold, he said, and kidney failure has been reported in several cases.

Bath salts widely available

Also labeled as “plant food,” “pond water cleaner,” “novelty collector’s items,” and “not for human consumption,” these stimulants began to be used in the United States in 2010, and are widely available online and in smoke shops. Users have a median age of 26 years, Dr. Sauve said, and are mostly male.

Bath salts may be comprised of methcathinones, especially synthetic cathinones. Natural cathinones are found in khat, a root from a shrub that is chewed upon primarily by people in North Africa. Bath salts also may contain methamphetamine analogues, which can be synthesized from ephedrine and pseudoephedrine. These include methylone (similar to MDMA, or ecstasy), mephedrone (similar to methamphetamine), and methylenedioxypyrovalerone (similar to cocaine). Bath salts can be inhaled, injected, snorted, swallowed, or inserted into the rectum or vagina, and effects occur in doses of 2-5 mg. Pharmacological effects vary and may include increased plasma norepinephrine, sympathetic effects, serotonin syndrome, and increased dopamine. He also noted that the transition from recreational to addictive use “may occur in a matter of days.”

Signs of toxicity with bath salts, Dr. Sauve continued, include the following: disorientation and agitation; dilated pupils with involuntary eye movements; lockjaw and teeth grinding; rapid, inappropriate, incoherent speech; being emotionally, verbally, or physically abusive, and having elevated liver enzymes and/or liver failure.

Treatment is primarily supportive and may include sedatives for anxiety, agitation, aggression, tremors, seizures, and psychosis. Physical restraints may be necessary.

Krokodil not seen much in U.S.

Formally known as desomorphine, this substance is synthesized from codeine and became popular in Russia after a crackdown on heroin there in 2010, Dr. Sauve said. The ingredients for krokodil synthesis include tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants, and red phosphorus from matchboxes. While desomorphine is believed to be highly addictive, “all the other sequelae of krokodil are generally thought to be a result of phosphorus” and other substances. No good data exist in the prevalence of its use, he said. “We’re not really seeing this much in the United States, because it’s way too easy to get Oxycontin and heroin [here].”

Dr. Sauve reported that he is a consultant to Avanir Pharmaceuticals and Otsuka Pharmaceutical. He also reported being a member of the speakers bureau or receiving honoraria from Avanir Pharmaceuticals, Otsuka Pharmaceutical, and Sunovion Pharmaceuticals.

dbrunk@frontlinemedcom.com

LAS VEGAS – People who use spice, bath salts, and other so-called designer drugs may present with symptoms that resemble numerous psychiatric conditions, including schizophrenia, anxiety disorders, and depression.

“Given the recent emergence of designer drugs, the long-term consequences of their use have not been extensively studied and are relatively unknown,” Dr. William M. Sauve said at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Dr. Sauve, medical director of TMS NeuroHealth Centers of Richmond and Charlottesville, both in Virginia, said designer drugs have grown in popularity in recent years because they are perceived as legal alternatives to illicit substances. In addition, their detection by standard drug toxicology screens is limited.

In October 2011, components of designer drugs, including synthetic cannabinoids and the major constituents of bath salts, were categorized as emergency Schedule I substances. In July 2012, President Obama signed the Synthetic Drug Abuse Prevention Act, which doubled the time that a substance may be temporarily assigned to Schedule I, from 18 months to 36 months.

“Under federal law, any chemical that is similar to a classified drug and is meant to be used for the same purposes is considered to be classified,” Dr. Sauve said. However, designer drugs “get labeled ‘not for human consumption’ and can be sold out in the open and camouflaged under names such as ‘stain remover,’ ‘research chemicals,’ and even ‘insect repellent.’ That’s why it’s very difficult for the law to catch up with these things. Active ingredients are also a moving target.”

He discussed three types of these designer drugs: synthetic cannabinoids, bath salts, and krokodil.

Synthetic cannabinoids mimic THC

Also known as spice, K2, and incense, these substances began to appear in the United States in 2008 and are mostly used by males. Primarily inhaled, these substances are meant to mimic the effects of tetrahydrocannabinol (THC). They work by decreasing levels of gamma-aminobutyric acid (GABA) and by increasing levels of glutamate and dopamine. “Serotonin levels can also be affected indirectly by endocannabinoid control of GABA and glutamate release,” he added.

Unlike marijuana, which is a partial agonist at the cannabinoid 1 (CB-1) receptor, synthetics are full agonists at the CB-1 receptor, “so as you use it, it will hit every receptor until you have maximal stimulation, and it may have 800 times greater affinity than THC,” he said. Signs and symptoms of acute intoxication can be wide ranging, from agitation and dysphoria to paranoia and tachycardia, and can last up to 6 hours. While commercial tests are available to detect synthetic cannabinoid metabolites, formulations change so often that “most tests quickly become obsolete,” Dr. Sauve said. He noted that intoxication with spice should be suspected in patients who present with bizarre behavior, anxiety, agitation, and/or psychosis in those with no known psychiatric history. Intravaneous benzodiazepines can be used for agitation and seizures. While knowledge of their long-term impact is lacking, synthetic cannabinoids may increase the risk of subsequent psychosis by threefold, he said, and kidney failure has been reported in several cases.

Bath salts widely available

Also labeled as “plant food,” “pond water cleaner,” “novelty collector’s items,” and “not for human consumption,” these stimulants began to be used in the United States in 2010, and are widely available online and in smoke shops. Users have a median age of 26 years, Dr. Sauve said, and are mostly male.

Bath salts may be comprised of methcathinones, especially synthetic cathinones. Natural cathinones are found in khat, a root from a shrub that is chewed upon primarily by people in North Africa. Bath salts also may contain methamphetamine analogues, which can be synthesized from ephedrine and pseudoephedrine. These include methylone (similar to MDMA, or ecstasy), mephedrone (similar to methamphetamine), and methylenedioxypyrovalerone (similar to cocaine). Bath salts can be inhaled, injected, snorted, swallowed, or inserted into the rectum or vagina, and effects occur in doses of 2-5 mg. Pharmacological effects vary and may include increased plasma norepinephrine, sympathetic effects, serotonin syndrome, and increased dopamine. He also noted that the transition from recreational to addictive use “may occur in a matter of days.”

Signs of toxicity with bath salts, Dr. Sauve continued, include the following: disorientation and agitation; dilated pupils with involuntary eye movements; lockjaw and teeth grinding; rapid, inappropriate, incoherent speech; being emotionally, verbally, or physically abusive, and having elevated liver enzymes and/or liver failure.

Treatment is primarily supportive and may include sedatives for anxiety, agitation, aggression, tremors, seizures, and psychosis. Physical restraints may be necessary.

Krokodil not seen much in U.S.

Formally known as desomorphine, this substance is synthesized from codeine and became popular in Russia after a crackdown on heroin there in 2010, Dr. Sauve said. The ingredients for krokodil synthesis include tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants, and red phosphorus from matchboxes. While desomorphine is believed to be highly addictive, “all the other sequelae of krokodil are generally thought to be a result of phosphorus” and other substances. No good data exist in the prevalence of its use, he said. “We’re not really seeing this much in the United States, because it’s way too easy to get Oxycontin and heroin [here].”

Dr. Sauve reported that he is a consultant to Avanir Pharmaceuticals and Otsuka Pharmaceutical. He also reported being a member of the speakers bureau or receiving honoraria from Avanir Pharmaceuticals, Otsuka Pharmaceutical, and Sunovion Pharmaceuticals.

dbrunk@frontlinemedcom.com

LAS VEGAS – People who use spice, bath salts, and other so-called designer drugs may present with symptoms that resemble numerous psychiatric conditions, including schizophrenia, anxiety disorders, and depression.

“Given the recent emergence of designer drugs, the long-term consequences of their use have not been extensively studied and are relatively unknown,” Dr. William M. Sauve said at the annual psychopharmacology update held by the Nevada Psychiatric Association.

Dr. Sauve, medical director of TMS NeuroHealth Centers of Richmond and Charlottesville, both in Virginia, said designer drugs have grown in popularity in recent years because they are perceived as legal alternatives to illicit substances. In addition, their detection by standard drug toxicology screens is limited.

In October 2011, components of designer drugs, including synthetic cannabinoids and the major constituents of bath salts, were categorized as emergency Schedule I substances. In July 2012, President Obama signed the Synthetic Drug Abuse Prevention Act, which doubled the time that a substance may be temporarily assigned to Schedule I, from 18 months to 36 months.

“Under federal law, any chemical that is similar to a classified drug and is meant to be used for the same purposes is considered to be classified,” Dr. Sauve said. However, designer drugs “get labeled ‘not for human consumption’ and can be sold out in the open and camouflaged under names such as ‘stain remover,’ ‘research chemicals,’ and even ‘insect repellent.’ That’s why it’s very difficult for the law to catch up with these things. Active ingredients are also a moving target.”

He discussed three types of these designer drugs: synthetic cannabinoids, bath salts, and krokodil.

Synthetic cannabinoids mimic THC

Also known as spice, K2, and incense, these substances began to appear in the United States in 2008 and are mostly used by males. Primarily inhaled, these substances are meant to mimic the effects of tetrahydrocannabinol (THC). They work by decreasing levels of gamma-aminobutyric acid (GABA) and by increasing levels of glutamate and dopamine. “Serotonin levels can also be affected indirectly by endocannabinoid control of GABA and glutamate release,” he added.

Unlike marijuana, which is a partial agonist at the cannabinoid 1 (CB-1) receptor, synthetics are full agonists at the CB-1 receptor, “so as you use it, it will hit every receptor until you have maximal stimulation, and it may have 800 times greater affinity than THC,” he said. Signs and symptoms of acute intoxication can be wide ranging, from agitation and dysphoria to paranoia and tachycardia, and can last up to 6 hours. While commercial tests are available to detect synthetic cannabinoid metabolites, formulations change so often that “most tests quickly become obsolete,” Dr. Sauve said. He noted that intoxication with spice should be suspected in patients who present with bizarre behavior, anxiety, agitation, and/or psychosis in those with no known psychiatric history. Intravaneous benzodiazepines can be used for agitation and seizures. While knowledge of their long-term impact is lacking, synthetic cannabinoids may increase the risk of subsequent psychosis by threefold, he said, and kidney failure has been reported in several cases.

Bath salts widely available

Also labeled as “plant food,” “pond water cleaner,” “novelty collector’s items,” and “not for human consumption,” these stimulants began to be used in the United States in 2010, and are widely available online and in smoke shops. Users have a median age of 26 years, Dr. Sauve said, and are mostly male.

Bath salts may be comprised of methcathinones, especially synthetic cathinones. Natural cathinones are found in khat, a root from a shrub that is chewed upon primarily by people in North Africa. Bath salts also may contain methamphetamine analogues, which can be synthesized from ephedrine and pseudoephedrine. These include methylone (similar to MDMA, or ecstasy), mephedrone (similar to methamphetamine), and methylenedioxypyrovalerone (similar to cocaine). Bath salts can be inhaled, injected, snorted, swallowed, or inserted into the rectum or vagina, and effects occur in doses of 2-5 mg. Pharmacological effects vary and may include increased plasma norepinephrine, sympathetic effects, serotonin syndrome, and increased dopamine. He also noted that the transition from recreational to addictive use “may occur in a matter of days.”

Signs of toxicity with bath salts, Dr. Sauve continued, include the following: disorientation and agitation; dilated pupils with involuntary eye movements; lockjaw and teeth grinding; rapid, inappropriate, incoherent speech; being emotionally, verbally, or physically abusive, and having elevated liver enzymes and/or liver failure.

Treatment is primarily supportive and may include sedatives for anxiety, agitation, aggression, tremors, seizures, and psychosis. Physical restraints may be necessary.

Krokodil not seen much in U.S.

Formally known as desomorphine, this substance is synthesized from codeine and became popular in Russia after a crackdown on heroin there in 2010, Dr. Sauve said. The ingredients for krokodil synthesis include tablets containing codeine, caustic soda, gasoline, hydrochloric acid, iodine from disinfectants, and red phosphorus from matchboxes. While desomorphine is believed to be highly addictive, “all the other sequelae of krokodil are generally thought to be a result of phosphorus” and other substances. No good data exist in the prevalence of its use, he said. “We’re not really seeing this much in the United States, because it’s way too easy to get Oxycontin and heroin [here].”

Dr. Sauve reported that he is a consultant to Avanir Pharmaceuticals and Otsuka Pharmaceutical. He also reported being a member of the speakers bureau or receiving honoraria from Avanir Pharmaceuticals, Otsuka Pharmaceutical, and Sunovion Pharmaceuticals.

dbrunk@frontlinemedcom.com

The way Sarah Verbiest, Dr.P.H., sees it, postpartum care for new moms could use a little more respect.

“We see [childbirth] in movies all the time: It’s so exciting when a woman gives birth, and then the next thing you see is that she’s fitting back into her jeans and she looks fabulous and rested,” said Dr. Verbiest, executive director of the center for maternal and infant health at the University of North Carolina (UNC) at Chapel Hill.

“We perpetuate this myth that you’re supposed to feel great. It’s not true,” she said. “It’s a huge physical event that has been unattended and kind of downplayed for a long time, and I think a lot of women suffer because we don’t have the best advice to give them or we don’t talk about it.”

Dr. Verbiest and her colleagues at UNC are hoping to shake up the postpartum paradigm by better defining the gaps in care that occur in those first 12 weeks after childbirth or as they are calling this time, the “4th trimester.”

Defining postpartum care

The goal of the 4th Trimester Project is to bring together about 100 mothers, clinicians, researchers, and other stakeholders to identify ways to improve outcomes for mothers, infants, and families. Participants will gather in Chapel Hill, following the Breastfeeding and Feminism International Conference in March. There, experts will deliver state-of-the-art talks on what’s currently known about the six domains of postpartum care, and make recommendations for future research projects.

The six domains of postpartum care are:

• Physical recovery from childbirth.

• Mood.

• Infant feeding.

• Medications, substances, and environmental exposures.

• Sexuality, contraception, and birth spacing.

• Sleep and fatigue.

©kdshutterman/Thinkstock

“The first step is connecting moms and researchers, coming to some agreement and enthusiasm about what needs to be studied,” Dr. Verbiest said. “We’re going to have a nice diversity of opinions around the table. It will be interesting to see what clinicians think is important and what moms think is important, and how those match up.”

A national survey of new mothers sheds light on some of the postpartum health issues. In a survey from the Childbirth Connection, released in 2008, more than 15 specific health problems were cited as new problems by 25% or more of the mothers during the first 2 months after delivery. At 6 months, many women continued to experience these issues, including stress (43%), weight control (40%), sleep loss (34%), lack of sexual desire (26%), physical exhaustion (25%), and backache (24%).

Drop-off in care

Although national efforts to promote breastfeeding and increase awareness of the potential for postpartum depression have emerged in recent years, many gaps exist in today’s postpartum care landscape, Dr. Verbiest said, including what she described as a “precipitous drop-off” in basic follow-up care during the first 3 months after giving birth.

New mothers are discharged from the hospital, and they don’t necessarily come back to see anybody for another 6 weeks. “Some women never come back for a visit. So they’ve had all this care, and we care about them so much when they’re carrying a baby, but once they have the baby, the focus is all on that baby, and not on mom,” she said.

Some clinicians and researchers may not view postpartum sleep and fatigue as an important issue to explore, but it’s something that affects quality of life for the mother and the family, as well as overall health and wellness, Dr. Verbiest said.

“It’s exhausting having your body completely change from a hormonal standpoint and being dedicated to this little being that doesn’t sleep very well,” she said. “But have we done a lot of research so we can provide moms with the best coping strategies?”

Dr. Alison Stuebe, who is also part of the interdisciplinary research team working on the 4th Trimester Project, saw this firsthand with one of her friends.

About a year ago, a longtime friend had her first baby, and required a cesarean for arrest of descent. “She said, ‘I cannot believe someone would cut me open and they’re not even going to see me in 6 weeks,’” recalled Dr. Stuebe of the department of obstetrics and gynecology at UNC.

“There’s a sense that it’s customary to see the women at 6 weeks, make sure they have birth control, and their partners are hoping that means they’re cleared to come home and have sex again,” Dr. Stuebe said. “That’s what the extent is for a lot of women, but there are a lot of things moms need in that time period. I do a lot of work with moms who are struggling with breastfeeding. It’s usually not purely an issue of how the baby is attaching.”

Moving research forward

Dr. Stuebe, who is a distinguished scholar of infant and young child feeding in the Gillings School of Global Public Health at UNC, described the 4th Trimester Project as “not a be all and end all,” but rather as an opportunity to “specifically engage moms to tell us what we’re not telling them or what they wish we would tell them in the postpartum period.”

After the first in-person meeting of the project participants in March 2016, the investigators will stage a series of webinars and discussion groups aimed at refining specific research projects before the participants reconvene in person in March 2017.

The project recently got a boost when the Patient-Centered Outcomes Research Institute (PCORI) approved $248,594 in funding for the research.

“This will hopefully launch a whole series of research projects, whether funded through PCORI or through other research mechanisms, to drive the work forward,” Dr. Verbiest said.

One such project, for example, could compare the effectiveness of a postpartum doula coming to a mother’s house versus offering her postpartum support by phone.

“Part of what we hope in the long term from this PCORI work is to ask, ‘If moms felt really supported during the postpartum period, what questions would we need to ask to show that we’re doing it well?’” Dr. Stuebe said. “If there were a quality of postpartum care questionnaire, what would we want moms to check?”

dbrunk@frontlinemedcom.com

The way Sarah Verbiest, Dr.P.H., sees it, postpartum care for new moms could use a little more respect.

“We see [childbirth] in movies all the time: It’s so exciting when a woman gives birth, and then the next thing you see is that she’s fitting back into her jeans and she looks fabulous and rested,” said Dr. Verbiest, executive director of the center for maternal and infant health at the University of North Carolina (UNC) at Chapel Hill.

“We perpetuate this myth that you’re supposed to feel great. It’s not true,” she said. “It’s a huge physical event that has been unattended and kind of downplayed for a long time, and I think a lot of women suffer because we don’t have the best advice to give them or we don’t talk about it.”

Dr. Verbiest and her colleagues at UNC are hoping to shake up the postpartum paradigm by better defining the gaps in care that occur in those first 12 weeks after childbirth or as they are calling this time, the “4th trimester.”

Defining postpartum care

The goal of the 4th Trimester Project is to bring together about 100 mothers, clinicians, researchers, and other stakeholders to identify ways to improve outcomes for mothers, infants, and families. Participants will gather in Chapel Hill, following the Breastfeeding and Feminism International Conference in March. There, experts will deliver state-of-the-art talks on what’s currently known about the six domains of postpartum care, and make recommendations for future research projects.

The six domains of postpartum care are:

• Physical recovery from childbirth.

• Mood.

• Infant feeding.

• Medications, substances, and environmental exposures.

• Sexuality, contraception, and birth spacing.

• Sleep and fatigue.

©kdshutterman/Thinkstock

“The first step is connecting moms and researchers, coming to some agreement and enthusiasm about what needs to be studied,” Dr. Verbiest said. “We’re going to have a nice diversity of opinions around the table. It will be interesting to see what clinicians think is important and what moms think is important, and how those match up.”

A national survey of new mothers sheds light on some of the postpartum health issues. In a survey from the Childbirth Connection, released in 2008, more than 15 specific health problems were cited as new problems by 25% or more of the mothers during the first 2 months after delivery. At 6 months, many women continued to experience these issues, including stress (43%), weight control (40%), sleep loss (34%), lack of sexual desire (26%), physical exhaustion (25%), and backache (24%).

Drop-off in care

Although national efforts to promote breastfeeding and increase awareness of the potential for postpartum depression have emerged in recent years, many gaps exist in today’s postpartum care landscape, Dr. Verbiest said, including what she described as a “precipitous drop-off” in basic follow-up care during the first 3 months after giving birth.

New mothers are discharged from the hospital, and they don’t necessarily come back to see anybody for another 6 weeks. “Some women never come back for a visit. So they’ve had all this care, and we care about them so much when they’re carrying a baby, but once they have the baby, the focus is all on that baby, and not on mom,” she said.

Some clinicians and researchers may not view postpartum sleep and fatigue as an important issue to explore, but it’s something that affects quality of life for the mother and the family, as well as overall health and wellness, Dr. Verbiest said.

“It’s exhausting having your body completely change from a hormonal standpoint and being dedicated to this little being that doesn’t sleep very well,” she said. “But have we done a lot of research so we can provide moms with the best coping strategies?”

Dr. Alison Stuebe, who is also part of the interdisciplinary research team working on the 4th Trimester Project, saw this firsthand with one of her friends.

About a year ago, a longtime friend had her first baby, and required a cesarean for arrest of descent. “She said, ‘I cannot believe someone would cut me open and they’re not even going to see me in 6 weeks,’” recalled Dr. Stuebe of the department of obstetrics and gynecology at UNC.

“There’s a sense that it’s customary to see the women at 6 weeks, make sure they have birth control, and their partners are hoping that means they’re cleared to come home and have sex again,” Dr. Stuebe said. “That’s what the extent is for a lot of women, but there are a lot of things moms need in that time period. I do a lot of work with moms who are struggling with breastfeeding. It’s usually not purely an issue of how the baby is attaching.”

Moving research forward

Dr. Stuebe, who is a distinguished scholar of infant and young child feeding in the Gillings School of Global Public Health at UNC, described the 4th Trimester Project as “not a be all and end all,” but rather as an opportunity to “specifically engage moms to tell us what we’re not telling them or what they wish we would tell them in the postpartum period.”

After the first in-person meeting of the project participants in March 2016, the investigators will stage a series of webinars and discussion groups aimed at refining specific research projects before the participants reconvene in person in March 2017.

The project recently got a boost when the Patient-Centered Outcomes Research Institute (PCORI) approved $248,594 in funding for the research.

“This will hopefully launch a whole series of research projects, whether funded through PCORI or through other research mechanisms, to drive the work forward,” Dr. Verbiest said.

One such project, for example, could compare the effectiveness of a postpartum doula coming to a mother’s house versus offering her postpartum support by phone.

“Part of what we hope in the long term from this PCORI work is to ask, ‘If moms felt really supported during the postpartum period, what questions would we need to ask to show that we’re doing it well?’” Dr. Stuebe said. “If there were a quality of postpartum care questionnaire, what would we want moms to check?”

dbrunk@frontlinemedcom.com

The way Sarah Verbiest, Dr.P.H., sees it, postpartum care for new moms could use a little more respect.

“We see [childbirth] in movies all the time: It’s so exciting when a woman gives birth, and then the next thing you see is that she’s fitting back into her jeans and she looks fabulous and rested,” said Dr. Verbiest, executive director of the center for maternal and infant health at the University of North Carolina (UNC) at Chapel Hill.

“We perpetuate this myth that you’re supposed to feel great. It’s not true,” she said. “It’s a huge physical event that has been unattended and kind of downplayed for a long time, and I think a lot of women suffer because we don’t have the best advice to give them or we don’t talk about it.”

Dr. Verbiest and her colleagues at UNC are hoping to shake up the postpartum paradigm by better defining the gaps in care that occur in those first 12 weeks after childbirth or as they are calling this time, the “4th trimester.”

Defining postpartum care

The goal of the 4th Trimester Project is to bring together about 100 mothers, clinicians, researchers, and other stakeholders to identify ways to improve outcomes for mothers, infants, and families. Participants will gather in Chapel Hill, following the Breastfeeding and Feminism International Conference in March. There, experts will deliver state-of-the-art talks on what’s currently known about the six domains of postpartum care, and make recommendations for future research projects.

The six domains of postpartum care are:

• Physical recovery from childbirth.

• Mood.

• Infant feeding.

• Medications, substances, and environmental exposures.

• Sexuality, contraception, and birth spacing.

• Sleep and fatigue.

©kdshutterman/Thinkstock

“The first step is connecting moms and researchers, coming to some agreement and enthusiasm about what needs to be studied,” Dr. Verbiest said. “We’re going to have a nice diversity of opinions around the table. It will be interesting to see what clinicians think is important and what moms think is important, and how those match up.”

A national survey of new mothers sheds light on some of the postpartum health issues. In a survey from the Childbirth Connection, released in 2008, more than 15 specific health problems were cited as new problems by 25% or more of the mothers during the first 2 months after delivery. At 6 months, many women continued to experience these issues, including stress (43%), weight control (40%), sleep loss (34%), lack of sexual desire (26%), physical exhaustion (25%), and backache (24%).

Drop-off in care

Although national efforts to promote breastfeeding and increase awareness of the potential for postpartum depression have emerged in recent years, many gaps exist in today’s postpartum care landscape, Dr. Verbiest said, including what she described as a “precipitous drop-off” in basic follow-up care during the first 3 months after giving birth.

New mothers are discharged from the hospital, and they don’t necessarily come back to see anybody for another 6 weeks. “Some women never come back for a visit. So they’ve had all this care, and we care about them so much when they’re carrying a baby, but once they have the baby, the focus is all on that baby, and not on mom,” she said.

Some clinicians and researchers may not view postpartum sleep and fatigue as an important issue to explore, but it’s something that affects quality of life for the mother and the family, as well as overall health and wellness, Dr. Verbiest said.

“It’s exhausting having your body completely change from a hormonal standpoint and being dedicated to this little being that doesn’t sleep very well,” she said. “But have we done a lot of research so we can provide moms with the best coping strategies?”

Dr. Alison Stuebe, who is also part of the interdisciplinary research team working on the 4th Trimester Project, saw this firsthand with one of her friends.

About a year ago, a longtime friend had her first baby, and required a cesarean for arrest of descent. “She said, ‘I cannot believe someone would cut me open and they’re not even going to see me in 6 weeks,’” recalled Dr. Stuebe of the department of obstetrics and gynecology at UNC.

“There’s a sense that it’s customary to see the women at 6 weeks, make sure they have birth control, and their partners are hoping that means they’re cleared to come home and have sex again,” Dr. Stuebe said. “That’s what the extent is for a lot of women, but there are a lot of things moms need in that time period. I do a lot of work with moms who are struggling with breastfeeding. It’s usually not purely an issue of how the baby is attaching.”

Moving research forward

Dr. Stuebe, who is a distinguished scholar of infant and young child feeding in the Gillings School of Global Public Health at UNC, described the 4th Trimester Project as “not a be all and end all,” but rather as an opportunity to “specifically engage moms to tell us what we’re not telling them or what they wish we would tell them in the postpartum period.”

After the first in-person meeting of the project participants in March 2016, the investigators will stage a series of webinars and discussion groups aimed at refining specific research projects before the participants reconvene in person in March 2017.

The project recently got a boost when the Patient-Centered Outcomes Research Institute (PCORI) approved $248,594 in funding for the research.

“This will hopefully launch a whole series of research projects, whether funded through PCORI or through other research mechanisms, to drive the work forward,” Dr. Verbiest said.

One such project, for example, could compare the effectiveness of a postpartum doula coming to a mother’s house versus offering her postpartum support by phone.

“Part of what we hope in the long term from this PCORI work is to ask, ‘If moms felt really supported during the postpartum period, what questions would we need to ask to show that we’re doing it well?’” Dr. Stuebe said. “If there were a quality of postpartum care questionnaire, what would we want moms to check?”

dbrunk@frontlinemedcom.com

A consensus study of the scientific underpinnings of human gene editing technologies is underway, and the committee of experts behind the effort will independently review potential applications for those technologies, as well as the clinical, ethical, legal, and social implications of their use.

The multidisciplinary committee met Feb. 11 to receive input from select stakeholders as it launches its review, the results of which will represent the official views of the National Academy of Sciences and the National Academy of Medicine.

©Thinkstock.com

Among those stakeholders were representatives from several companies commercializing gene editing, a representative from the National Institutes of Health, and patient advocacy groups.

With some caveats, participants lobbied to maintain the existing regulatory framework related to gene therapy.

Michael Werner, cofounder and executive director of the Alliance for Regenerative Medicine, which advocates globally for regenerative medicine and advanced therapies, said his organization believes “the existing regulatory framework overall works for these technologies.”

“We don’t believe the [Food and Drug Administration], for example, needs to create a whole separate oversight process in addition to the process we already have now for gene therapy,” he said, adding that “the ultimate goal here is not to have regulatory action or legislative action that will hinder or delay the development of these technologies.”

The consensus study follows an International Summit on Human Gene Editing held in December, and is the next component of the Human Gene Editing Initiative. The committee will study the potential for gene editing in biomedical research and medicine – including human germline editing – although representatives from each of the companies represented at the meeting noted that they are not currently focused on germline applications.

Rather, the commercial focus is on other areas, such as correcting genes in somatic cells.

“We start with medical need. We want to work on things where there is not currently a therapy that addresses adequately the medical need, and we need the ability to generate a differentiated product,” said Vic Myer, Ph.D., of Editas Medicine in Cambridge, Mass.

The company has projects underway for opthalmologic applications, sickle cell anemia, beta-thalassemia, Duchenne muscular dystrophy, cystic fibrosis, alpha₁-antitrypsin deficiency in the liver, and others.

“We are working on a number of different types of edits in a number of different tissues with a number of delivery modalities,” Dr. Myer said, noting that some programs will move quickly, while others will not.

Similarly, Intellia Therapeutics, also of Cambridge, Mass., is “focusing very much on what we hope will be curative products for somatic gene-based disorders,” said Dr. John Leonard, the company’s chief medical officer.

“We limit our work to somatic cells. We thought very carefully about that and that is what we do,” he added, noting that a recently launched division of Intellia is focused on autoimmune oncology opportunities (ex vivo), and on liver disease (in vivo).

The committee of experts conducting the consensus study, which began its information-gathering process in December at the International Summit on Human Gene Editing, will take these and other views expressed at the meeting into consideration during its work over the next year. The study will include a literature review and data gathering via meetings in the United States and abroad. The committee will continue to seek input from researchers, clinicians, policy makers, and the public.

“The committee will also monitor in real time the latest scientific achievements of importance in this rapidly developing field,” according to information from the National Academies.

The field has enormous potential, according to Mr. Werner, who explained that combined, the various types of gene editing technology available are “pretty powerful” in terms of an approach for targeting and changing DNA sequences in human cells.

“We’re talking about the potential to durably treat and potentially even cure diseases that currently represent unmet medical needs,” he said. “We could, in theory, be talking about millions of patients worldwide.”

sworcester@frontlinemedcom.com

A consensus study of the scientific underpinnings of human gene editing technologies is underway, and the committee of experts behind the effort will independently review potential applications for those technologies, as well as the clinical, ethical, legal, and social implications of their use.

The multidisciplinary committee met Feb. 11 to receive input from select stakeholders as it launches its review, the results of which will represent the official views of the National Academy of Sciences and the National Academy of Medicine.

©Thinkstock.com

Among those stakeholders were representatives from several companies commercializing gene editing, a representative from the National Institutes of Health, and patient advocacy groups.

With some caveats, participants lobbied to maintain the existing regulatory framework related to gene therapy.

Michael Werner, cofounder and executive director of the Alliance for Regenerative Medicine, which advocates globally for regenerative medicine and advanced therapies, said his organization believes “the existing regulatory framework overall works for these technologies.”

“We don’t believe the [Food and Drug Administration], for example, needs to create a whole separate oversight process in addition to the process we already have now for gene therapy,” he said, adding that “the ultimate goal here is not to have regulatory action or legislative action that will hinder or delay the development of these technologies.”

The consensus study follows an International Summit on Human Gene Editing held in December, and is the next component of the Human Gene Editing Initiative. The committee will study the potential for gene editing in biomedical research and medicine – including human germline editing – although representatives from each of the companies represented at the meeting noted that they are not currently focused on germline applications.

Rather, the commercial focus is on other areas, such as correcting genes in somatic cells.

“We start with medical need. We want to work on things where there is not currently a therapy that addresses adequately the medical need, and we need the ability to generate a differentiated product,” said Vic Myer, Ph.D., of Editas Medicine in Cambridge, Mass.

The company has projects underway for opthalmologic applications, sickle cell anemia, beta-thalassemia, Duchenne muscular dystrophy, cystic fibrosis, alpha₁-antitrypsin deficiency in the liver, and others.

“We are working on a number of different types of edits in a number of different tissues with a number of delivery modalities,” Dr. Myer said, noting that some programs will move quickly, while others will not.

Similarly, Intellia Therapeutics, also of Cambridge, Mass., is “focusing very much on what we hope will be curative products for somatic gene-based disorders,” said Dr. John Leonard, the company’s chief medical officer.

“We limit our work to somatic cells. We thought very carefully about that and that is what we do,” he added, noting that a recently launched division of Intellia is focused on autoimmune oncology opportunities (ex vivo), and on liver disease (in vivo).

The committee of experts conducting the consensus study, which began its information-gathering process in December at the International Summit on Human Gene Editing, will take these and other views expressed at the meeting into consideration during its work over the next year. The study will include a literature review and data gathering via meetings in the United States and abroad. The committee will continue to seek input from researchers, clinicians, policy makers, and the public.

“The committee will also monitor in real time the latest scientific achievements of importance in this rapidly developing field,” according to information from the National Academies.

The field has enormous potential, according to Mr. Werner, who explained that combined, the various types of gene editing technology available are “pretty powerful” in terms of an approach for targeting and changing DNA sequences in human cells.

“We’re talking about the potential to durably treat and potentially even cure diseases that currently represent unmet medical needs,” he said. “We could, in theory, be talking about millions of patients worldwide.”

sworcester@frontlinemedcom.com

A consensus study of the scientific underpinnings of human gene editing technologies is underway, and the committee of experts behind the effort will independently review potential applications for those technologies, as well as the clinical, ethical, legal, and social implications of their use.

The multidisciplinary committee met Feb. 11 to receive input from select stakeholders as it launches its review, the results of which will represent the official views of the National Academy of Sciences and the National Academy of Medicine.

©Thinkstock.com

Among those stakeholders were representatives from several companies commercializing gene editing, a representative from the National Institutes of Health, and patient advocacy groups.

With some caveats, participants lobbied to maintain the existing regulatory framework related to gene therapy.

Michael Werner, cofounder and executive director of the Alliance for Regenerative Medicine, which advocates globally for regenerative medicine and advanced therapies, said his organization believes “the existing regulatory framework overall works for these technologies.”

“We don’t believe the [Food and Drug Administration], for example, needs to create a whole separate oversight process in addition to the process we already have now for gene therapy,” he said, adding that “the ultimate goal here is not to have regulatory action or legislative action that will hinder or delay the development of these technologies.”

The consensus study follows an International Summit on Human Gene Editing held in December, and is the next component of the Human Gene Editing Initiative. The committee will study the potential for gene editing in biomedical research and medicine – including human germline editing – although representatives from each of the companies represented at the meeting noted that they are not currently focused on germline applications.

Rather, the commercial focus is on other areas, such as correcting genes in somatic cells.

“We start with medical need. We want to work on things where there is not currently a therapy that addresses adequately the medical need, and we need the ability to generate a differentiated product,” said Vic Myer, Ph.D., of Editas Medicine in Cambridge, Mass.

The company has projects underway for opthalmologic applications, sickle cell anemia, beta-thalassemia, Duchenne muscular dystrophy, cystic fibrosis, alpha₁-antitrypsin deficiency in the liver, and others.

“We are working on a number of different types of edits in a number of different tissues with a number of delivery modalities,” Dr. Myer said, noting that some programs will move quickly, while others will not.

Similarly, Intellia Therapeutics, also of Cambridge, Mass., is “focusing very much on what we hope will be curative products for somatic gene-based disorders,” said Dr. John Leonard, the company’s chief medical officer.

“We limit our work to somatic cells. We thought very carefully about that and that is what we do,” he added, noting that a recently launched division of Intellia is focused on autoimmune oncology opportunities (ex vivo), and on liver disease (in vivo).

The committee of experts conducting the consensus study, which began its information-gathering process in December at the International Summit on Human Gene Editing, will take these and other views expressed at the meeting into consideration during its work over the next year. The study will include a literature review and data gathering via meetings in the United States and abroad. The committee will continue to seek input from researchers, clinicians, policy makers, and the public.

“The committee will also monitor in real time the latest scientific achievements of importance in this rapidly developing field,” according to information from the National Academies.

The field has enormous potential, according to Mr. Werner, who explained that combined, the various types of gene editing technology available are “pretty powerful” in terms of an approach for targeting and changing DNA sequences in human cells.

“We’re talking about the potential to durably treat and potentially even cure diseases that currently represent unmet medical needs,” he said. “We could, in theory, be talking about millions of patients worldwide.”

sworcester@frontlinemedcom.com