Prescription medications

Photo courtesy of the CDC

New research has revealed inherited genetic variations that may predispose patients to severe toxicity from thiopurines, a class of medications used as anticancer and immunosuppressive drugs.

Investigators identified 4 variations in the NUDT15 gene that alter thiopurine metabolism, leaving patients particularly sensitive to the drugs and at risk for toxicity.

One in 3 Japanese patients in this study carried the variations.

And evidence suggests the variations are common in other populations across Asia and in individuals of Hispanic ethnicity.

Jun J. Yang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these findings in Nature Genetics.

In 2015, Dr Yang and his colleagues published evidence linking a NUDT15 variant to reduced tolerance of mercaptopurine and reported the variant was more common in patients of East Asian ancestry.

With the current study, the investigators identified 3 additional NUDT15 variants and found that all 4 variants—p.Arg139Cys, p.Arg139His, p.Val18Ile, and p.Val18_Val19insGlyVal—were associated with lower levels of enzymatic activity and imbalance of thiopurine metabolism.

In a group of 270 children with acute lymphoblastic leukemia (ALL), the variants caused a 74.4% to 100% loss of NUDT15 function. They also predicted enzyme activity and mercaptopurine tolerance. In Singapore and Japan, for example, patients with the 2 highest risk variants had the lowest level of enzyme activity.

“These patients had excessive levels of the active drug metabolites per mercaptopurine dose, which suggests we may reduce the drug dose to achieve the level necessary to kill leukemia cells without causing toxicity,” Dr Yang said, adding that the NUDT15 variants have no other known health consequences.

The investigators also checked leukemic cells from 285 children newly diagnosed with ALL and found that patients with NUDT15 variants were more sensitive to thiopurines.

“That suggests we can screen for NUDT15 variants and potentially plan mercaptopurine doses according to each patient’s genotype before the therapy starts,” Dr Yang said. “This way, we hope to avoid toxicity without compromising treatment effectiveness.”

The investigators noted that future studies are needed to determine optimal thiopurine doses for patients with different NUDT15 variants.

Meanwhile, the search continues for variants in NUDT15 or other genes that influence chemotherapy effectiveness and safety. The NUDT15 variants and previously identified TPMT variants could not fully explain why Guatemalan patients in this study tolerated the lowest doses of mercaptopurine.

Prescription medications

Photo courtesy of the CDC

New research has revealed inherited genetic variations that may predispose patients to severe toxicity from thiopurines, a class of medications used as anticancer and immunosuppressive drugs.

Investigators identified 4 variations in the NUDT15 gene that alter thiopurine metabolism, leaving patients particularly sensitive to the drugs and at risk for toxicity.

One in 3 Japanese patients in this study carried the variations.

And evidence suggests the variations are common in other populations across Asia and in individuals of Hispanic ethnicity.

Jun J. Yang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these findings in Nature Genetics.

In 2015, Dr Yang and his colleagues published evidence linking a NUDT15 variant to reduced tolerance of mercaptopurine and reported the variant was more common in patients of East Asian ancestry.

With the current study, the investigators identified 3 additional NUDT15 variants and found that all 4 variants—p.Arg139Cys, p.Arg139His, p.Val18Ile, and p.Val18_Val19insGlyVal—were associated with lower levels of enzymatic activity and imbalance of thiopurine metabolism.

In a group of 270 children with acute lymphoblastic leukemia (ALL), the variants caused a 74.4% to 100% loss of NUDT15 function. They also predicted enzyme activity and mercaptopurine tolerance. In Singapore and Japan, for example, patients with the 2 highest risk variants had the lowest level of enzyme activity.

“These patients had excessive levels of the active drug metabolites per mercaptopurine dose, which suggests we may reduce the drug dose to achieve the level necessary to kill leukemia cells without causing toxicity,” Dr Yang said, adding that the NUDT15 variants have no other known health consequences.

The investigators also checked leukemic cells from 285 children newly diagnosed with ALL and found that patients with NUDT15 variants were more sensitive to thiopurines.

“That suggests we can screen for NUDT15 variants and potentially plan mercaptopurine doses according to each patient’s genotype before the therapy starts,” Dr Yang said. “This way, we hope to avoid toxicity without compromising treatment effectiveness.”

The investigators noted that future studies are needed to determine optimal thiopurine doses for patients with different NUDT15 variants.

Meanwhile, the search continues for variants in NUDT15 or other genes that influence chemotherapy effectiveness and safety. The NUDT15 variants and previously identified TPMT variants could not fully explain why Guatemalan patients in this study tolerated the lowest doses of mercaptopurine.

Prescription medications

Photo courtesy of the CDC

New research has revealed inherited genetic variations that may predispose patients to severe toxicity from thiopurines, a class of medications used as anticancer and immunosuppressive drugs.

Investigators identified 4 variations in the NUDT15 gene that alter thiopurine metabolism, leaving patients particularly sensitive to the drugs and at risk for toxicity.

One in 3 Japanese patients in this study carried the variations.

And evidence suggests the variations are common in other populations across Asia and in individuals of Hispanic ethnicity.

Jun J. Yang, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee, and his colleagues reported these findings in Nature Genetics.

In 2015, Dr Yang and his colleagues published evidence linking a NUDT15 variant to reduced tolerance of mercaptopurine and reported the variant was more common in patients of East Asian ancestry.

With the current study, the investigators identified 3 additional NUDT15 variants and found that all 4 variants—p.Arg139Cys, p.Arg139His, p.Val18Ile, and p.Val18_Val19insGlyVal—were associated with lower levels of enzymatic activity and imbalance of thiopurine metabolism.

In a group of 270 children with acute lymphoblastic leukemia (ALL), the variants caused a 74.4% to 100% loss of NUDT15 function. They also predicted enzyme activity and mercaptopurine tolerance. In Singapore and Japan, for example, patients with the 2 highest risk variants had the lowest level of enzyme activity.

“These patients had excessive levels of the active drug metabolites per mercaptopurine dose, which suggests we may reduce the drug dose to achieve the level necessary to kill leukemia cells without causing toxicity,” Dr Yang said, adding that the NUDT15 variants have no other known health consequences.

The investigators also checked leukemic cells from 285 children newly diagnosed with ALL and found that patients with NUDT15 variants were more sensitive to thiopurines.

“That suggests we can screen for NUDT15 variants and potentially plan mercaptopurine doses according to each patient’s genotype before the therapy starts,” Dr Yang said. “This way, we hope to avoid toxicity without compromising treatment effectiveness.”

The investigators noted that future studies are needed to determine optimal thiopurine doses for patients with different NUDT15 variants.

Meanwhile, the search continues for variants in NUDT15 or other genes that influence chemotherapy effectiveness and safety. The NUDT15 variants and previously identified TPMT variants could not fully explain why Guatemalan patients in this study tolerated the lowest doses of mercaptopurine.

As part of its Next Accreditation System, the Accreditation Council for Graduate Medical Education (ACGME) has introduced the Clinical Learning Environment Review (CLER) program, designed to assess the learning environment of institutions that have ACGME residency and fellowship programs.¹ The CLER program emphasizes the responsibility of these hospitals, multispecialty groups, and other organizations to focus on quality and safety in the health care environment of resident learning and patient care. The expectation is that emphasis on quality of care in a residency training program will influence these physicians’ approach to quality of care after graduation.^2,3 The Department of Dermatology at the University of Mississippi Medical Center (UMMC)(Jackson, Mississippi) saw CLER as an opportunity to demonstrate leadership in the patient safety movement.

CLER Program at UMMC

As a model CLER program at our institution, our project at the outset concentrated resident efforts on the focus areas specified by the ACGME (Table 1). We also were aware that our ACGME committee would need to answer questions during CLER site visits (Table 2). Because the data generated would not be used for accreditation decisions, there was no concern that exposing errors would jeopardize our postgraduate training certification.

The first 15 minutes of monthly faculty meetings were devoted to the presentation of a resident project, called a QA/QI (quality assurance/quality improvement) moment, that addressed ACGME focus areas 1, 2, 3, or 6 (Table 1). (Transitions in care [focus area 4] and work hours and fatigue [focus area 5] generally are less important issues in a predominantly outpatient specialty such as dermatology.) The residents were encouraged to identify areas where patient harm could occur due to poorly designed systems and to report situations in which patients actually were harmed.

Each project had to be approved by the department chairperson based on the following 4 requirements: First, the initiative must have the potential to notably impact patient safety and reduce harm. Second, residents with faculty support had to design methods to assess the identified problem. Third, participants had to design (to the best of their abilities) cost-effective and achievable interventions in a manner that would not produce unintended consequences. Fourth, residents were asked to devise a system to close the loop, ensuring that the effort put into the process was not wasted.

Findings From the CLER Program

The CLER program generates data on program and institutional attributes that have a salutatory effect on quality and safety, specifically involving 6 focus areas highlighted in Table 1. Putting residents at the center of efforts to improve the quality of care in our department proved critical to improving patient safety.

Involving residents in a series of QA/QI initiatives was logical because they rotate with faculty members. They also are in a position to view inconsistencies and to work to establish consistent patterns of patient care. In addition, our busy faculty members are charged with a variety of other clinical, educational, and administrative duties complicated by requirements in the design of a new residency training program. Faculty and residents working together were able to find problem areas in our department and devise solutions to improve those problems.

The CLER program involved a series of steps. Residents were charged with identifying errors (QA) and then devising a system to prevent similar errors from being repeated (QI)(Table 3). Efforts focused on preventing needless harm in our department. Initiatives developed by residents, who are closest to patients, have advantages over safety programs developed by the hospital’s administration. Residents became passionate about error prevention when they determined that their efforts could make a difference to patients.

Forward Thinking for Dermatology Practices

Perhaps there are lessons here that could apply to safety promotion in the practicing dermatologist’s office. The American Board of Dermatology, within the framework established by the American Board of Medical Specialties, requires physicians seeking recertification to participate in preapproved practice assessment QI exercises twice every 10 years.¹⁷ Six programs sponsored by the American Academy of Dermatology have now been approved in the areas of melanoma, biopsy follow-up measure, psoriasis, chronic urticaria, venous insufficiency, and laser- and light-based therapy for rejuvenation.¹⁸ An additional program has been approved for dermatopathologists through the American Society of Dermatopathology.¹⁹ None of these programs match the topics chosen by our residents in consultation with faculty to meet safety gaps identified in clinics at UMMC. Perhaps the next generation of performance improvement continuing medical education programs could include a pilot program for part 4 of Maintenance of Certification credit that is nonpunitive, patient focused, and allows dermatologists to design specific error-prevention solutions tailored to their individual practice in the same way residency programs are taking up this task.

As part of its Next Accreditation System, the Accreditation Council for Graduate Medical Education (ACGME) has introduced the Clinical Learning Environment Review (CLER) program, designed to assess the learning environment of institutions that have ACGME residency and fellowship programs.¹ The CLER program emphasizes the responsibility of these hospitals, multispecialty groups, and other organizations to focus on quality and safety in the health care environment of resident learning and patient care. The expectation is that emphasis on quality of care in a residency training program will influence these physicians’ approach to quality of care after graduation.^2,3 The Department of Dermatology at the University of Mississippi Medical Center (UMMC)(Jackson, Mississippi) saw CLER as an opportunity to demonstrate leadership in the patient safety movement.

CLER Program at UMMC

As a model CLER program at our institution, our project at the outset concentrated resident efforts on the focus areas specified by the ACGME (Table 1). We also were aware that our ACGME committee would need to answer questions during CLER site visits (Table 2). Because the data generated would not be used for accreditation decisions, there was no concern that exposing errors would jeopardize our postgraduate training certification.

The first 15 minutes of monthly faculty meetings were devoted to the presentation of a resident project, called a QA/QI (quality assurance/quality improvement) moment, that addressed ACGME focus areas 1, 2, 3, or 6 (Table 1). (Transitions in care [focus area 4] and work hours and fatigue [focus area 5] generally are less important issues in a predominantly outpatient specialty such as dermatology.) The residents were encouraged to identify areas where patient harm could occur due to poorly designed systems and to report situations in which patients actually were harmed.

Each project had to be approved by the department chairperson based on the following 4 requirements: First, the initiative must have the potential to notably impact patient safety and reduce harm. Second, residents with faculty support had to design methods to assess the identified problem. Third, participants had to design (to the best of their abilities) cost-effective and achievable interventions in a manner that would not produce unintended consequences. Fourth, residents were asked to devise a system to close the loop, ensuring that the effort put into the process was not wasted.

Findings From the CLER Program

The CLER program generates data on program and institutional attributes that have a salutatory effect on quality and safety, specifically involving 6 focus areas highlighted in Table 1. Putting residents at the center of efforts to improve the quality of care in our department proved critical to improving patient safety.

Involving residents in a series of QA/QI initiatives was logical because they rotate with faculty members. They also are in a position to view inconsistencies and to work to establish consistent patterns of patient care. In addition, our busy faculty members are charged with a variety of other clinical, educational, and administrative duties complicated by requirements in the design of a new residency training program. Faculty and residents working together were able to find problem areas in our department and devise solutions to improve those problems.

The CLER program involved a series of steps. Residents were charged with identifying errors (QA) and then devising a system to prevent similar errors from being repeated (QI)(Table 3). Efforts focused on preventing needless harm in our department. Initiatives developed by residents, who are closest to patients, have advantages over safety programs developed by the hospital’s administration. Residents became passionate about error prevention when they determined that their efforts could make a difference to patients.

Forward Thinking for Dermatology Practices

Perhaps there are lessons here that could apply to safety promotion in the practicing dermatologist’s office. The American Board of Dermatology, within the framework established by the American Board of Medical Specialties, requires physicians seeking recertification to participate in preapproved practice assessment QI exercises twice every 10 years.¹⁷ Six programs sponsored by the American Academy of Dermatology have now been approved in the areas of melanoma, biopsy follow-up measure, psoriasis, chronic urticaria, venous insufficiency, and laser- and light-based therapy for rejuvenation.¹⁸ An additional program has been approved for dermatopathologists through the American Society of Dermatopathology.¹⁹ None of these programs match the topics chosen by our residents in consultation with faculty to meet safety gaps identified in clinics at UMMC. Perhaps the next generation of performance improvement continuing medical education programs could include a pilot program for part 4 of Maintenance of Certification credit that is nonpunitive, patient focused, and allows dermatologists to design specific error-prevention solutions tailored to their individual practice in the same way residency programs are taking up this task.

As part of its Next Accreditation System, the Accreditation Council for Graduate Medical Education (ACGME) has introduced the Clinical Learning Environment Review (CLER) program, designed to assess the learning environment of institutions that have ACGME residency and fellowship programs.¹ The CLER program emphasizes the responsibility of these hospitals, multispecialty groups, and other organizations to focus on quality and safety in the health care environment of resident learning and patient care. The expectation is that emphasis on quality of care in a residency training program will influence these physicians’ approach to quality of care after graduation.^2,3 The Department of Dermatology at the University of Mississippi Medical Center (UMMC)(Jackson, Mississippi) saw CLER as an opportunity to demonstrate leadership in the patient safety movement.

CLER Program at UMMC

As a model CLER program at our institution, our project at the outset concentrated resident efforts on the focus areas specified by the ACGME (Table 1). We also were aware that our ACGME committee would need to answer questions during CLER site visits (Table 2). Because the data generated would not be used for accreditation decisions, there was no concern that exposing errors would jeopardize our postgraduate training certification.

The first 15 minutes of monthly faculty meetings were devoted to the presentation of a resident project, called a QA/QI (quality assurance/quality improvement) moment, that addressed ACGME focus areas 1, 2, 3, or 6 (Table 1). (Transitions in care [focus area 4] and work hours and fatigue [focus area 5] generally are less important issues in a predominantly outpatient specialty such as dermatology.) The residents were encouraged to identify areas where patient harm could occur due to poorly designed systems and to report situations in which patients actually were harmed.

Each project had to be approved by the department chairperson based on the following 4 requirements: First, the initiative must have the potential to notably impact patient safety and reduce harm. Second, residents with faculty support had to design methods to assess the identified problem. Third, participants had to design (to the best of their abilities) cost-effective and achievable interventions in a manner that would not produce unintended consequences. Fourth, residents were asked to devise a system to close the loop, ensuring that the effort put into the process was not wasted.

Findings From the CLER Program

The CLER program generates data on program and institutional attributes that have a salutatory effect on quality and safety, specifically involving 6 focus areas highlighted in Table 1. Putting residents at the center of efforts to improve the quality of care in our department proved critical to improving patient safety.

Involving residents in a series of QA/QI initiatives was logical because they rotate with faculty members. They also are in a position to view inconsistencies and to work to establish consistent patterns of patient care. In addition, our busy faculty members are charged with a variety of other clinical, educational, and administrative duties complicated by requirements in the design of a new residency training program. Faculty and residents working together were able to find problem areas in our department and devise solutions to improve those problems.

The CLER program involved a series of steps. Residents were charged with identifying errors (QA) and then devising a system to prevent similar errors from being repeated (QI)(Table 3). Efforts focused on preventing needless harm in our department. Initiatives developed by residents, who are closest to patients, have advantages over safety programs developed by the hospital’s administration. Residents became passionate about error prevention when they determined that their efforts could make a difference to patients.

Forward Thinking for Dermatology Practices

Perhaps there are lessons here that could apply to safety promotion in the practicing dermatologist’s office. The American Board of Dermatology, within the framework established by the American Board of Medical Specialties, requires physicians seeking recertification to participate in preapproved practice assessment QI exercises twice every 10 years.¹⁷ Six programs sponsored by the American Academy of Dermatology have now been approved in the areas of melanoma, biopsy follow-up measure, psoriasis, chronic urticaria, venous insufficiency, and laser- and light-based therapy for rejuvenation.¹⁸ An additional program has been approved for dermatopathologists through the American Society of Dermatopathology.¹⁹ None of these programs match the topics chosen by our residents in consultation with faculty to meet safety gaps identified in clinics at UMMC. Perhaps the next generation of performance improvement continuing medical education programs could include a pilot program for part 4 of Maintenance of Certification credit that is nonpunitive, patient focused, and allows dermatologists to design specific error-prevention solutions tailored to their individual practice in the same way residency programs are taking up this task.

A convenient, once-daily fixed combination of 0.3% adapalene plus 2.5% benzoyl peroxide gel significantly improved lesion counts over the course of 12 weeks in patients aged 12 years and older with moderate or severe acne.

Investigators enrolled just over 500 patients from 31 sites in the United States and Canada. About half of patients were rated as having severe acne and half as having moderate acne on the investigator’s global assessment (IGA) scale, Dr. Linda F. Stein Gold said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Patients were randomized to three treatment groups: adapalene 0.3%/benzoyl peroxide 2.5% gel (A-BPO-0.3%), adapalene 0.1%/benzoyl peroxide 2.5% (A-BPO-0.1%), or vehicle. Patients in each group had approximately the same total lesion count, and about half in each group had truncal acne lesions, said Dr. Stein Gold, director of clinical research in the department of dermatology at Henry Ford Hospital, Detroit.

Patients were instructed to use their study medications once daily at night after washing with a provided cleanser. They were provided with a standardized moisturizer and cleaners.

Treatment with A-BPO-0.3% was judged as successful (IGA of 1 or almost clear) at 12 weeks in 31% of patients with severe acne. By contrast, 13.3% of patients with severe acne were judged as almost clear. In patients with severe acne, A-BPO-1% was not statistically superior to vehicle (J Drugs Dermatol. 2015 Dec 1;14[12]:1427-35).

“Topical treatment is still the cornerstone of acne therapy, and it is great to have additional options, especially for our more severe acne patients,” Dr. Stein Gold said.

Patients noted dryness, scaling, erythema, and stinging/burning with A-BPO-0.3%, especially between weeks 1 and 2.

Dr. Stein Gold disclosed that she serves as a consultant and scientific advisory board member to Galderma, which markets A-BPO-0.3% as Epiduo Forte.

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

[email protected]

On Twitter @denisefulton

A convenient, once-daily fixed combination of 0.3% adapalene plus 2.5% benzoyl peroxide gel significantly improved lesion counts over the course of 12 weeks in patients aged 12 years and older with moderate or severe acne.

Investigators enrolled just over 500 patients from 31 sites in the United States and Canada. About half of patients were rated as having severe acne and half as having moderate acne on the investigator’s global assessment (IGA) scale, Dr. Linda F. Stein Gold said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Patients were randomized to three treatment groups: adapalene 0.3%/benzoyl peroxide 2.5% gel (A-BPO-0.3%), adapalene 0.1%/benzoyl peroxide 2.5% (A-BPO-0.1%), or vehicle. Patients in each group had approximately the same total lesion count, and about half in each group had truncal acne lesions, said Dr. Stein Gold, director of clinical research in the department of dermatology at Henry Ford Hospital, Detroit.

Patients were instructed to use their study medications once daily at night after washing with a provided cleanser. They were provided with a standardized moisturizer and cleaners.

Treatment with A-BPO-0.3% was judged as successful (IGA of 1 or almost clear) at 12 weeks in 31% of patients with severe acne. By contrast, 13.3% of patients with severe acne were judged as almost clear. In patients with severe acne, A-BPO-1% was not statistically superior to vehicle (J Drugs Dermatol. 2015 Dec 1;14[12]:1427-35).

“Topical treatment is still the cornerstone of acne therapy, and it is great to have additional options, especially for our more severe acne patients,” Dr. Stein Gold said.

Patients noted dryness, scaling, erythema, and stinging/burning with A-BPO-0.3%, especially between weeks 1 and 2.

Dr. Stein Gold disclosed that she serves as a consultant and scientific advisory board member to Galderma, which markets A-BPO-0.3% as Epiduo Forte.

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

[email protected]

On Twitter @denisefulton

A convenient, once-daily fixed combination of 0.3% adapalene plus 2.5% benzoyl peroxide gel significantly improved lesion counts over the course of 12 weeks in patients aged 12 years and older with moderate or severe acne.

Investigators enrolled just over 500 patients from 31 sites in the United States and Canada. About half of patients were rated as having severe acne and half as having moderate acne on the investigator’s global assessment (IGA) scale, Dr. Linda F. Stein Gold said at the Hawaii Dermatology Seminar provided by Global Academy for Medical Education/Skin Disease Education Foundation.

Patients were randomized to three treatment groups: adapalene 0.3%/benzoyl peroxide 2.5% gel (A-BPO-0.3%), adapalene 0.1%/benzoyl peroxide 2.5% (A-BPO-0.1%), or vehicle. Patients in each group had approximately the same total lesion count, and about half in each group had truncal acne lesions, said Dr. Stein Gold, director of clinical research in the department of dermatology at Henry Ford Hospital, Detroit.

Patients were instructed to use their study medications once daily at night after washing with a provided cleanser. They were provided with a standardized moisturizer and cleaners.

Treatment with A-BPO-0.3% was judged as successful (IGA of 1 or almost clear) at 12 weeks in 31% of patients with severe acne. By contrast, 13.3% of patients with severe acne were judged as almost clear. In patients with severe acne, A-BPO-1% was not statistically superior to vehicle (J Drugs Dermatol. 2015 Dec 1;14[12]:1427-35).

“Topical treatment is still the cornerstone of acne therapy, and it is great to have additional options, especially for our more severe acne patients,” Dr. Stein Gold said.

Patients noted dryness, scaling, erythema, and stinging/burning with A-BPO-0.3%, especially between weeks 1 and 2.

Dr. Stein Gold disclosed that she serves as a consultant and scientific advisory board member to Galderma, which markets A-BPO-0.3% as Epiduo Forte.

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

[email protected]

On Twitter @denisefulton

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.

[email protected]

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.