Light micrograph

of cancellous bone

Patients with acute lymphoblastic leukemia (ALL) may experience significant bone loss much earlier than previously assumed, according to a study published in the journal Bone.

Investigators analyzed a cohort of adolescent and young adult ALL patients before and after their first month of chemotherapy and observed “significant alterations” to cancellous and cortical bone in this short period of time.

Previous studies to determine the changes to bone density during ALL therapy had focused on the cumulative effects of chemotherapy after months or even years of treatment.

“In clinic, we would see patients with fractures and vertebral compression during the very first few weeks of treatment,” said study author Etan Orgel, MD, of Children’s Hospital Los Angeles in California.

“But we were unaware of any study that specifically examined bone before chemotherapy and immediately after the first 30 days of treatment, which would allow us to understand the impact of this early treatment phase.”

So Dr Orgel and his colleagues conducted a prospective study of 38 patients, ages 10 to 21, who were newly diagnosed with ALL.

The team used quantitative computerized tomography (QCT) to assess leukemia-related changes to bone at diagnosis and then the subsequent effects of the induction phase of chemotherapy.

All of the patients received a 28-day induction regimen consisting of vincristine, pegylated L-asparaginase, anthracycline (daunorubicin or doxorubicin), and a glucocorticoid (either prednisone at 60 mg/m²/day for 28 days or dexamethasone at 10 mg/m²/day for 14 days).

The investigators compared the patients to age- and sex-matched controls and found that leukemia did not dramatically alter the properties of bone before chemotherapy.

However, QCT revealed significant changes during the 30-day induction phase in the 35 patients who were well enough to undergo imaging after treatment.

The patients experienced a significant decrease in cancellous volumetric bone mineral density, which was measured in the spine. The median decrease was 27% (P<0.001).

There was no significant change in cortical volumetric bone mineral density, which was measured in the tibia (−0.0%, P=0.860) or femur (−0.7%, P=0.290).

But there was significant cortical thinning in the tibia. The average cortical thickness decreased 1.2% (P<0.001), and the cortical area decreased 0.4% (P=0.014).

The femur was less affected, the investigators said. There was a decrease in average cortical thickness, but this was not significant (-0.3%, P=0.740).

To help clinicians relate to these findings, the investigators also measured bone mineral density using the older but more widely available technique of dual-energy x-ray absorptiometry. They found that it underestimated these changes as compared to QCT measurements.

“Now that we know how soon bone toxicity occurs, we need to re-evaluate our approaches to managing these changes and focus research efforts on new ways to mitigate this common yet significant adverse effect,” said study author Steven Mittelman, MD, PhD, of Children’s Hospital Los Angeles.

Light micrograph

of cancellous bone

Patients with acute lymphoblastic leukemia (ALL) may experience significant bone loss much earlier than previously assumed, according to a study published in the journal Bone.

Investigators analyzed a cohort of adolescent and young adult ALL patients before and after their first month of chemotherapy and observed “significant alterations” to cancellous and cortical bone in this short period of time.

Previous studies to determine the changes to bone density during ALL therapy had focused on the cumulative effects of chemotherapy after months or even years of treatment.

“In clinic, we would see patients with fractures and vertebral compression during the very first few weeks of treatment,” said study author Etan Orgel, MD, of Children’s Hospital Los Angeles in California.

“But we were unaware of any study that specifically examined bone before chemotherapy and immediately after the first 30 days of treatment, which would allow us to understand the impact of this early treatment phase.”

So Dr Orgel and his colleagues conducted a prospective study of 38 patients, ages 10 to 21, who were newly diagnosed with ALL.

The team used quantitative computerized tomography (QCT) to assess leukemia-related changes to bone at diagnosis and then the subsequent effects of the induction phase of chemotherapy.

All of the patients received a 28-day induction regimen consisting of vincristine, pegylated L-asparaginase, anthracycline (daunorubicin or doxorubicin), and a glucocorticoid (either prednisone at 60 mg/m²/day for 28 days or dexamethasone at 10 mg/m²/day for 14 days).

The investigators compared the patients to age- and sex-matched controls and found that leukemia did not dramatically alter the properties of bone before chemotherapy.

However, QCT revealed significant changes during the 30-day induction phase in the 35 patients who were well enough to undergo imaging after treatment.

The patients experienced a significant decrease in cancellous volumetric bone mineral density, which was measured in the spine. The median decrease was 27% (P<0.001).

There was no significant change in cortical volumetric bone mineral density, which was measured in the tibia (−0.0%, P=0.860) or femur (−0.7%, P=0.290).

But there was significant cortical thinning in the tibia. The average cortical thickness decreased 1.2% (P<0.001), and the cortical area decreased 0.4% (P=0.014).

The femur was less affected, the investigators said. There was a decrease in average cortical thickness, but this was not significant (-0.3%, P=0.740).

To help clinicians relate to these findings, the investigators also measured bone mineral density using the older but more widely available technique of dual-energy x-ray absorptiometry. They found that it underestimated these changes as compared to QCT measurements.

“Now that we know how soon bone toxicity occurs, we need to re-evaluate our approaches to managing these changes and focus research efforts on new ways to mitigate this common yet significant adverse effect,” said study author Steven Mittelman, MD, PhD, of Children’s Hospital Los Angeles.

Light micrograph

of cancellous bone

Patients with acute lymphoblastic leukemia (ALL) may experience significant bone loss much earlier than previously assumed, according to a study published in the journal Bone.

Investigators analyzed a cohort of adolescent and young adult ALL patients before and after their first month of chemotherapy and observed “significant alterations” to cancellous and cortical bone in this short period of time.

Previous studies to determine the changes to bone density during ALL therapy had focused on the cumulative effects of chemotherapy after months or even years of treatment.

“In clinic, we would see patients with fractures and vertebral compression during the very first few weeks of treatment,” said study author Etan Orgel, MD, of Children’s Hospital Los Angeles in California.

“But we were unaware of any study that specifically examined bone before chemotherapy and immediately after the first 30 days of treatment, which would allow us to understand the impact of this early treatment phase.”

So Dr Orgel and his colleagues conducted a prospective study of 38 patients, ages 10 to 21, who were newly diagnosed with ALL.

The team used quantitative computerized tomography (QCT) to assess leukemia-related changes to bone at diagnosis and then the subsequent effects of the induction phase of chemotherapy.

All of the patients received a 28-day induction regimen consisting of vincristine, pegylated L-asparaginase, anthracycline (daunorubicin or doxorubicin), and a glucocorticoid (either prednisone at 60 mg/m²/day for 28 days or dexamethasone at 10 mg/m²/day for 14 days).

The investigators compared the patients to age- and sex-matched controls and found that leukemia did not dramatically alter the properties of bone before chemotherapy.

However, QCT revealed significant changes during the 30-day induction phase in the 35 patients who were well enough to undergo imaging after treatment.

The patients experienced a significant decrease in cancellous volumetric bone mineral density, which was measured in the spine. The median decrease was 27% (P<0.001).

There was no significant change in cortical volumetric bone mineral density, which was measured in the tibia (−0.0%, P=0.860) or femur (−0.7%, P=0.290).

But there was significant cortical thinning in the tibia. The average cortical thickness decreased 1.2% (P<0.001), and the cortical area decreased 0.4% (P=0.014).

The femur was less affected, the investigators said. There was a decrease in average cortical thickness, but this was not significant (-0.3%, P=0.740).

To help clinicians relate to these findings, the investigators also measured bone mineral density using the older but more widely available technique of dual-energy x-ray absorptiometry. They found that it underestimated these changes as compared to QCT measurements.

“Now that we know how soon bone toxicity occurs, we need to re-evaluate our approaches to managing these changes and focus research efforts on new ways to mitigate this common yet significant adverse effect,” said study author Steven Mittelman, MD, PhD, of Children’s Hospital Los Angeles.

I have become increasingly dismayed by reports of dermatologists who allow their nurse practitioners and physician assistants to practice independently.

That is, the employing dermatologists only see the patients, new or established, if they are asked to, and often are not even on the premises. In fact, they might be thousands of miles away.

A little background is in order. Physician assistants and nurse practitioners are formally trained in primary care, not in dermatology, although there are currently three 1-year programs to help them specialize in dermatology. When Congress authorized their independent payment in 1997, they envisioned primary care nurses traveling the hills, hollers, and inner cities improving health care. Unfortunately, this hasn’t happened, and instead they have moved into suburban America, and increasingly, are practicing specialty medicine.

It can be argued that decreased access to primary care, which was the reason midlevels were created, is more important than is access to dermatology. In particular, extenders have targeted office-based specialties such as dermatology, but also neurology and pain medicine. These specialties are office based, and credentialing by hospitals is not required to bill insurance plans. Also, these specialties have good-paying, seemingly simple, small procedures. They have accomplished this with the avid help of dermatologists, I might add. There will be an estimated 10,000 “dermatology” nurse practitioners and physician assistants next year.

Let me be clear: I am not opposed to a dermatology extender who works closely with a dermatologist and does intake histories and physicals, then staffs with the physician, assists with surgery, or sees routine follow-ups (think acne, psoriasis, atopy, suture removal, and warts) on an established protocol with the full knowledge of the patient.

This is not what we are seeing. We have nurse practitioners buying retiring dermatologists’ practices, physician assistants independently setting up remote clinics then hiring “supervising” dermatologists to visit once a week to sign and review charts, and independent “dermatology” clinics with a doctor thousands of miles away available, if really needed, by telephone or the Internet. (This is not really telemedicine, is it?) These extenders are listed as dermatologists on the Internet, or they hide behind the name of a dermatologist, and when you call their offices, and ask if you will see a “real” dermatologist, the answer is often “Oh, don’t worry, our nurse or PA specializes in dermatology.”

I think this is grossly unfair to patients, who, when they call the dermatology center listed on the Internet, can’t conceive that their dermatology appointment is not being made with a dermatologist, not even being made with a physician, but with a nurse practitioner or physician assistant! I also think it does a huge disservice to the specialty. The “collaborating” dermatologists enabling these extenders are renting out the good name of our specialty.

Patients seen by these extenders may also be subject to unnecessary biopsies. (If you don’t know what it is, you must biopsy it!) It also results in additional charges for pathology and additional medical misadventures.

In addition, I think it is unfair to the extender who is put in this situation. They may have worked in a dermatologist’s office for a few months or even years but are now being asked to pretend to be something they are not and being expected to perform at the level of a medical professional who has had many years of intense, focused training in dermatology. If they are not uncomfortable being thrust into this situation, then they are delusional.

I think it is unfair to the medical system who pays for the less informed opinion and unnecessary procedures. This is not a “good value” except to the rent-seeking dermatologists, who are the front men for this money-making deception.

This is an elephant in the room of dermatology, and I think we have to confront it. This trivializes our specialty and helps allow other specialties and regulatory agencies to ignore or exclude us from the networks and from the conversation. Unfortunately, many of our members and some of our leadership have been corrupted by the “easy money” or “easy time” afforded by this cheapening of the specialty.

Let me give you some examples. The rent seekers piously claim, “there is a shortage of dermatologists, and we are just trying to help save the world.” They also say “my nurses are special and great.”

The honest ones in private practice, however, say, “Man, I make $200,000 a year off my PA while I am off.” The honest academics say, “Listen, I work in a gulag, and I would never be able to travel if my nurses didn’t see my patients.” Time is money, and the academic who gets an extra 10 hours a week out of clinic is benefiting as much as the guy who makes $200,000 a year.

Of course, this situation is not sustainable and will become less viable because of a coming tsunami of malpractice claims, more focused insurer benchmarks revealing excessive test ordering and minor procedures, and patients getting wise. One obvious solution to this would be to reimburse extenders only for evaluation and management codes, which will take a change in law.

Meanwhile, I encourage all of you who feel the same nausea I do to ask candidates for your state and national dermatology organizations if they employ unsupervised extenders. Then check their website for the names of the extenders they employ. Then go to the Medicare data and look up their extenders and see if they bill independently for dermatologic procedures. I think you will be very disturbed, as I was and am.

I hope this stimulates a little self-examination among dermatologists.

Dr. Coldiron is a past-president of the American Academy of Dermatology. He is currently in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Reach him at dermnews@frontlinemedcom.com.

I have become increasingly dismayed by reports of dermatologists who allow their nurse practitioners and physician assistants to practice independently.

That is, the employing dermatologists only see the patients, new or established, if they are asked to, and often are not even on the premises. In fact, they might be thousands of miles away.

A little background is in order. Physician assistants and nurse practitioners are formally trained in primary care, not in dermatology, although there are currently three 1-year programs to help them specialize in dermatology. When Congress authorized their independent payment in 1997, they envisioned primary care nurses traveling the hills, hollers, and inner cities improving health care. Unfortunately, this hasn’t happened, and instead they have moved into suburban America, and increasingly, are practicing specialty medicine.

It can be argued that decreased access to primary care, which was the reason midlevels were created, is more important than is access to dermatology. In particular, extenders have targeted office-based specialties such as dermatology, but also neurology and pain medicine. These specialties are office based, and credentialing by hospitals is not required to bill insurance plans. Also, these specialties have good-paying, seemingly simple, small procedures. They have accomplished this with the avid help of dermatologists, I might add. There will be an estimated 10,000 “dermatology” nurse practitioners and physician assistants next year.

Let me be clear: I am not opposed to a dermatology extender who works closely with a dermatologist and does intake histories and physicals, then staffs with the physician, assists with surgery, or sees routine follow-ups (think acne, psoriasis, atopy, suture removal, and warts) on an established protocol with the full knowledge of the patient.

This is not what we are seeing. We have nurse practitioners buying retiring dermatologists’ practices, physician assistants independently setting up remote clinics then hiring “supervising” dermatologists to visit once a week to sign and review charts, and independent “dermatology” clinics with a doctor thousands of miles away available, if really needed, by telephone or the Internet. (This is not really telemedicine, is it?) These extenders are listed as dermatologists on the Internet, or they hide behind the name of a dermatologist, and when you call their offices, and ask if you will see a “real” dermatologist, the answer is often “Oh, don’t worry, our nurse or PA specializes in dermatology.”

I think this is grossly unfair to patients, who, when they call the dermatology center listed on the Internet, can’t conceive that their dermatology appointment is not being made with a dermatologist, not even being made with a physician, but with a nurse practitioner or physician assistant! I also think it does a huge disservice to the specialty. The “collaborating” dermatologists enabling these extenders are renting out the good name of our specialty.

Patients seen by these extenders may also be subject to unnecessary biopsies. (If you don’t know what it is, you must biopsy it!) It also results in additional charges for pathology and additional medical misadventures.

In addition, I think it is unfair to the extender who is put in this situation. They may have worked in a dermatologist’s office for a few months or even years but are now being asked to pretend to be something they are not and being expected to perform at the level of a medical professional who has had many years of intense, focused training in dermatology. If they are not uncomfortable being thrust into this situation, then they are delusional.

I think it is unfair to the medical system who pays for the less informed opinion and unnecessary procedures. This is not a “good value” except to the rent-seeking dermatologists, who are the front men for this money-making deception.

This is an elephant in the room of dermatology, and I think we have to confront it. This trivializes our specialty and helps allow other specialties and regulatory agencies to ignore or exclude us from the networks and from the conversation. Unfortunately, many of our members and some of our leadership have been corrupted by the “easy money” or “easy time” afforded by this cheapening of the specialty.

Let me give you some examples. The rent seekers piously claim, “there is a shortage of dermatologists, and we are just trying to help save the world.” They also say “my nurses are special and great.”

The honest ones in private practice, however, say, “Man, I make $200,000 a year off my PA while I am off.” The honest academics say, “Listen, I work in a gulag, and I would never be able to travel if my nurses didn’t see my patients.” Time is money, and the academic who gets an extra 10 hours a week out of clinic is benefiting as much as the guy who makes $200,000 a year.

Of course, this situation is not sustainable and will become less viable because of a coming tsunami of malpractice claims, more focused insurer benchmarks revealing excessive test ordering and minor procedures, and patients getting wise. One obvious solution to this would be to reimburse extenders only for evaluation and management codes, which will take a change in law.

Meanwhile, I encourage all of you who feel the same nausea I do to ask candidates for your state and national dermatology organizations if they employ unsupervised extenders. Then check their website for the names of the extenders they employ. Then go to the Medicare data and look up their extenders and see if they bill independently for dermatologic procedures. I think you will be very disturbed, as I was and am.

I hope this stimulates a little self-examination among dermatologists.

Dr. Coldiron is a past-president of the American Academy of Dermatology. He is currently in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Reach him at dermnews@frontlinemedcom.com.

I have become increasingly dismayed by reports of dermatologists who allow their nurse practitioners and physician assistants to practice independently.

That is, the employing dermatologists only see the patients, new or established, if they are asked to, and often are not even on the premises. In fact, they might be thousands of miles away.

A little background is in order. Physician assistants and nurse practitioners are formally trained in primary care, not in dermatology, although there are currently three 1-year programs to help them specialize in dermatology. When Congress authorized their independent payment in 1997, they envisioned primary care nurses traveling the hills, hollers, and inner cities improving health care. Unfortunately, this hasn’t happened, and instead they have moved into suburban America, and increasingly, are practicing specialty medicine.

It can be argued that decreased access to primary care, which was the reason midlevels were created, is more important than is access to dermatology. In particular, extenders have targeted office-based specialties such as dermatology, but also neurology and pain medicine. These specialties are office based, and credentialing by hospitals is not required to bill insurance plans. Also, these specialties have good-paying, seemingly simple, small procedures. They have accomplished this with the avid help of dermatologists, I might add. There will be an estimated 10,000 “dermatology” nurse practitioners and physician assistants next year.

Let me be clear: I am not opposed to a dermatology extender who works closely with a dermatologist and does intake histories and physicals, then staffs with the physician, assists with surgery, or sees routine follow-ups (think acne, psoriasis, atopy, suture removal, and warts) on an established protocol with the full knowledge of the patient.

This is not what we are seeing. We have nurse practitioners buying retiring dermatologists’ practices, physician assistants independently setting up remote clinics then hiring “supervising” dermatologists to visit once a week to sign and review charts, and independent “dermatology” clinics with a doctor thousands of miles away available, if really needed, by telephone or the Internet. (This is not really telemedicine, is it?) These extenders are listed as dermatologists on the Internet, or they hide behind the name of a dermatologist, and when you call their offices, and ask if you will see a “real” dermatologist, the answer is often “Oh, don’t worry, our nurse or PA specializes in dermatology.”

I think this is grossly unfair to patients, who, when they call the dermatology center listed on the Internet, can’t conceive that their dermatology appointment is not being made with a dermatologist, not even being made with a physician, but with a nurse practitioner or physician assistant! I also think it does a huge disservice to the specialty. The “collaborating” dermatologists enabling these extenders are renting out the good name of our specialty.

Patients seen by these extenders may also be subject to unnecessary biopsies. (If you don’t know what it is, you must biopsy it!) It also results in additional charges for pathology and additional medical misadventures.

In addition, I think it is unfair to the extender who is put in this situation. They may have worked in a dermatologist’s office for a few months or even years but are now being asked to pretend to be something they are not and being expected to perform at the level of a medical professional who has had many years of intense, focused training in dermatology. If they are not uncomfortable being thrust into this situation, then they are delusional.

I think it is unfair to the medical system who pays for the less informed opinion and unnecessary procedures. This is not a “good value” except to the rent-seeking dermatologists, who are the front men for this money-making deception.

This is an elephant in the room of dermatology, and I think we have to confront it. This trivializes our specialty and helps allow other specialties and regulatory agencies to ignore or exclude us from the networks and from the conversation. Unfortunately, many of our members and some of our leadership have been corrupted by the “easy money” or “easy time” afforded by this cheapening of the specialty.

Let me give you some examples. The rent seekers piously claim, “there is a shortage of dermatologists, and we are just trying to help save the world.” They also say “my nurses are special and great.”

The honest ones in private practice, however, say, “Man, I make $200,000 a year off my PA while I am off.” The honest academics say, “Listen, I work in a gulag, and I would never be able to travel if my nurses didn’t see my patients.” Time is money, and the academic who gets an extra 10 hours a week out of clinic is benefiting as much as the guy who makes $200,000 a year.

Of course, this situation is not sustainable and will become less viable because of a coming tsunami of malpractice claims, more focused insurer benchmarks revealing excessive test ordering and minor procedures, and patients getting wise. One obvious solution to this would be to reimburse extenders only for evaluation and management codes, which will take a change in law.

Meanwhile, I encourage all of you who feel the same nausea I do to ask candidates for your state and national dermatology organizations if they employ unsupervised extenders. Then check their website for the names of the extenders they employ. Then go to the Medicare data and look up their extenders and see if they bill independently for dermatologic procedures. I think you will be very disturbed, as I was and am.

I hope this stimulates a little self-examination among dermatologists.

Dr. Coldiron is a past-president of the American Academy of Dermatology. He is currently in private practice but maintains a clinical assistant professorship at the University of Cincinnati. He cares for patients, teaches medical students and residents, and has several active clinical research projects. Dr. Coldiron is the author of more than 80 scientific letters, papers, and several book chapters, and he speaks frequently on a variety of topics. Reach him at dermnews@frontlinemedcom.com.

The world health community has lost ground in its fight to reduce end-stage renal disease in patients with lupus nephritis, a systematic review and meta-analysis concluded.

The risk of end-stage renal disease (ESRD) at 5 years of lupus nephritis decreased substantially from the 1970s, when it was 16%, to the mid-1990s, when it plateaued at 11%.

ESRD risks at 10 years and 15 years declined more sharply in the 1970s and 1980s but also plateaued in the mid-1990s at 17% and 22%, respectively.

This plateau was followed by a notable increase in risk in the late 2000s, particularly in the 10-year and 15-year estimates, Dr. Maria Tektonidou of the University of Athens and her coauthors reported (Arthritis Rheumatol. 2016 Jan 27. doi: 10.1002/art.39594).

“Despite extensive use of immunosuppressive medications through the 2000s, we did not find continued improvement in ESRD risks, but instead a slight increase in risks in the late 2000s,” they wrote.

The increase did not appear to be related to greater representation in recent studies of ethnic minorities, who may be more likely to develop ESRD. In the main analysis involving 148 of the 187 studies, “trends suggest this increase may have been temporary, but further follow-up will be needed to determine if this is sustained,” the investigators added.

Notably, patients with class-IV lupus nephritis had the greatest risk of ESRD during the 2000s, with a 15-year risk of 44%.

The 15-year risk of ESRD also was higher by 10 percentage points in developing countries than in developed countries during the 2000s.

The trends are worrisome because ESRD is a costly complication of lupus nephritis, which affects more than half of all patients with systemic lupus erythematosus (SLE). Patients with lupus nephritis have a 26-fold increased risk of death and estimated annual health care costs between $43,000 and $107,000 per patient, the authors noted.

The systematic review and Bayesian meta-analysis included 187 studies reporting on 18,309 adults with lupus nephritis from 1971 to 2015. The main analysis of ESRD risk included 102 studies from developed countries and 46 studies from developing countries.

Across all studies, 86% of patients were women, 32% had elevated serum creatinine levels at study entry, and proteinuria averaged 3.6 g daily. The average age was 31.2 years and mean duration of lupus nephritis was 2.7 years.

The proportion of patients treated with glucocorticoids alone in the studies declined from 54% in 1966 to 9% in 2010, while use of immunosuppressive therapies increased.

The decrease in ESRD risks early on coincided with increased use of immunosuppressives, particularly cyclophosphamide, and better control of hypertension and proteinuria. As for why those gains have stalled, Dr. Tektonidou and her colleagues said it’s possible that the limits of effectiveness of current treatments have been reached and better outcomes will require new therapies. “It is also possible that the plateau primarily reflects lack of progress in the way currently available and effective treatments are deployed,” they added. “This includes health system factors that result in delays in treatment initiation, and patient and health system factors that result in treatment interruptions and reduced adherence.”

In an accompanying editorial, Dr. Candace Feldman and Dr. Karen Costenbader, both of Brigham and Women’s Hospital in Boston, wrote, “While we have made advances over the past 50 years in our understanding of immunosuppressive medications, there have been few meaningful improvements in other domains that contribute to ESRD and to the persistent and disproportionate burden among vulnerable populations” (Ann Rheum Dis. 2016 Jan 27. doi: 10.1002/art.39593).

Despite the clear importance of medication adherence to SLE care, a recent systematic review of adherence interventions in rheumatic diseases (Ann Rheum Dis. 2015 Feb 9. doi: 10.1136/annrheumdis-2014-206593) found few SLE-specific interventions overall and none that significantly improved adherence outcomes, Dr. Feldman and Dr. Costenbader pointed out.

Dr. Tektonidou and her associates acknowledged that the new systematic review and meta-analysis were limited by the inability to estimate risks beyond 15 years and because the findings were similar only when observational studies were considered. Factors associated with ESRD, such as renal flares and uncontrolled hypertension, were not examined, and few studies were judged to be of high-quality.

Still, the results can be used to counsel patients on risks of ESRD and also will provide benchmarks to judge the effectiveness of future treatments, the authors concluded.

Dr. Feldman and Dr. Costenbader disagreed with this conclusion, citing various study limitations and the many nuanced factors that play into a patient’s risk of developing ESRD.

“This study should rather be used to provide a broad overview of our understanding of changes in SLE ESRD over time, rather than data to counsel an individual patient on his/her risks,” they wrote.

The study was supported by the intramural research program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors reported having no conflicts of interest.

pwendling@frontlinemedcom.com

The world health community has lost ground in its fight to reduce end-stage renal disease in patients with lupus nephritis, a systematic review and meta-analysis concluded.

The risk of end-stage renal disease (ESRD) at 5 years of lupus nephritis decreased substantially from the 1970s, when it was 16%, to the mid-1990s, when it plateaued at 11%.

ESRD risks at 10 years and 15 years declined more sharply in the 1970s and 1980s but also plateaued in the mid-1990s at 17% and 22%, respectively.

This plateau was followed by a notable increase in risk in the late 2000s, particularly in the 10-year and 15-year estimates, Dr. Maria Tektonidou of the University of Athens and her coauthors reported (Arthritis Rheumatol. 2016 Jan 27. doi: 10.1002/art.39594).

“Despite extensive use of immunosuppressive medications through the 2000s, we did not find continued improvement in ESRD risks, but instead a slight increase in risks in the late 2000s,” they wrote.

The increase did not appear to be related to greater representation in recent studies of ethnic minorities, who may be more likely to develop ESRD. In the main analysis involving 148 of the 187 studies, “trends suggest this increase may have been temporary, but further follow-up will be needed to determine if this is sustained,” the investigators added.

Notably, patients with class-IV lupus nephritis had the greatest risk of ESRD during the 2000s, with a 15-year risk of 44%.

The 15-year risk of ESRD also was higher by 10 percentage points in developing countries than in developed countries during the 2000s.

The trends are worrisome because ESRD is a costly complication of lupus nephritis, which affects more than half of all patients with systemic lupus erythematosus (SLE). Patients with lupus nephritis have a 26-fold increased risk of death and estimated annual health care costs between $43,000 and $107,000 per patient, the authors noted.

The systematic review and Bayesian meta-analysis included 187 studies reporting on 18,309 adults with lupus nephritis from 1971 to 2015. The main analysis of ESRD risk included 102 studies from developed countries and 46 studies from developing countries.

Across all studies, 86% of patients were women, 32% had elevated serum creatinine levels at study entry, and proteinuria averaged 3.6 g daily. The average age was 31.2 years and mean duration of lupus nephritis was 2.7 years.

The proportion of patients treated with glucocorticoids alone in the studies declined from 54% in 1966 to 9% in 2010, while use of immunosuppressive therapies increased.

The decrease in ESRD risks early on coincided with increased use of immunosuppressives, particularly cyclophosphamide, and better control of hypertension and proteinuria. As for why those gains have stalled, Dr. Tektonidou and her colleagues said it’s possible that the limits of effectiveness of current treatments have been reached and better outcomes will require new therapies. “It is also possible that the plateau primarily reflects lack of progress in the way currently available and effective treatments are deployed,” they added. “This includes health system factors that result in delays in treatment initiation, and patient and health system factors that result in treatment interruptions and reduced adherence.”

In an accompanying editorial, Dr. Candace Feldman and Dr. Karen Costenbader, both of Brigham and Women’s Hospital in Boston, wrote, “While we have made advances over the past 50 years in our understanding of immunosuppressive medications, there have been few meaningful improvements in other domains that contribute to ESRD and to the persistent and disproportionate burden among vulnerable populations” (Ann Rheum Dis. 2016 Jan 27. doi: 10.1002/art.39593).

Despite the clear importance of medication adherence to SLE care, a recent systematic review of adherence interventions in rheumatic diseases (Ann Rheum Dis. 2015 Feb 9. doi: 10.1136/annrheumdis-2014-206593) found few SLE-specific interventions overall and none that significantly improved adherence outcomes, Dr. Feldman and Dr. Costenbader pointed out.

Dr. Tektonidou and her associates acknowledged that the new systematic review and meta-analysis were limited by the inability to estimate risks beyond 15 years and because the findings were similar only when observational studies were considered. Factors associated with ESRD, such as renal flares and uncontrolled hypertension, were not examined, and few studies were judged to be of high-quality.

Still, the results can be used to counsel patients on risks of ESRD and also will provide benchmarks to judge the effectiveness of future treatments, the authors concluded.

Dr. Feldman and Dr. Costenbader disagreed with this conclusion, citing various study limitations and the many nuanced factors that play into a patient’s risk of developing ESRD.

“This study should rather be used to provide a broad overview of our understanding of changes in SLE ESRD over time, rather than data to counsel an individual patient on his/her risks,” they wrote.

The study was supported by the intramural research program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors reported having no conflicts of interest.

pwendling@frontlinemedcom.com

The world health community has lost ground in its fight to reduce end-stage renal disease in patients with lupus nephritis, a systematic review and meta-analysis concluded.

The risk of end-stage renal disease (ESRD) at 5 years of lupus nephritis decreased substantially from the 1970s, when it was 16%, to the mid-1990s, when it plateaued at 11%.

ESRD risks at 10 years and 15 years declined more sharply in the 1970s and 1980s but also plateaued in the mid-1990s at 17% and 22%, respectively.

This plateau was followed by a notable increase in risk in the late 2000s, particularly in the 10-year and 15-year estimates, Dr. Maria Tektonidou of the University of Athens and her coauthors reported (Arthritis Rheumatol. 2016 Jan 27. doi: 10.1002/art.39594).

“Despite extensive use of immunosuppressive medications through the 2000s, we did not find continued improvement in ESRD risks, but instead a slight increase in risks in the late 2000s,” they wrote.

The increase did not appear to be related to greater representation in recent studies of ethnic minorities, who may be more likely to develop ESRD. In the main analysis involving 148 of the 187 studies, “trends suggest this increase may have been temporary, but further follow-up will be needed to determine if this is sustained,” the investigators added.

Notably, patients with class-IV lupus nephritis had the greatest risk of ESRD during the 2000s, with a 15-year risk of 44%.

The 15-year risk of ESRD also was higher by 10 percentage points in developing countries than in developed countries during the 2000s.

The trends are worrisome because ESRD is a costly complication of lupus nephritis, which affects more than half of all patients with systemic lupus erythematosus (SLE). Patients with lupus nephritis have a 26-fold increased risk of death and estimated annual health care costs between $43,000 and $107,000 per patient, the authors noted.

The systematic review and Bayesian meta-analysis included 187 studies reporting on 18,309 adults with lupus nephritis from 1971 to 2015. The main analysis of ESRD risk included 102 studies from developed countries and 46 studies from developing countries.

Across all studies, 86% of patients were women, 32% had elevated serum creatinine levels at study entry, and proteinuria averaged 3.6 g daily. The average age was 31.2 years and mean duration of lupus nephritis was 2.7 years.

The proportion of patients treated with glucocorticoids alone in the studies declined from 54% in 1966 to 9% in 2010, while use of immunosuppressive therapies increased.

The decrease in ESRD risks early on coincided with increased use of immunosuppressives, particularly cyclophosphamide, and better control of hypertension and proteinuria. As for why those gains have stalled, Dr. Tektonidou and her colleagues said it’s possible that the limits of effectiveness of current treatments have been reached and better outcomes will require new therapies. “It is also possible that the plateau primarily reflects lack of progress in the way currently available and effective treatments are deployed,” they added. “This includes health system factors that result in delays in treatment initiation, and patient and health system factors that result in treatment interruptions and reduced adherence.”

In an accompanying editorial, Dr. Candace Feldman and Dr. Karen Costenbader, both of Brigham and Women’s Hospital in Boston, wrote, “While we have made advances over the past 50 years in our understanding of immunosuppressive medications, there have been few meaningful improvements in other domains that contribute to ESRD and to the persistent and disproportionate burden among vulnerable populations” (Ann Rheum Dis. 2016 Jan 27. doi: 10.1002/art.39593).

Despite the clear importance of medication adherence to SLE care, a recent systematic review of adherence interventions in rheumatic diseases (Ann Rheum Dis. 2015 Feb 9. doi: 10.1136/annrheumdis-2014-206593) found few SLE-specific interventions overall and none that significantly improved adherence outcomes, Dr. Feldman and Dr. Costenbader pointed out.

Dr. Tektonidou and her associates acknowledged that the new systematic review and meta-analysis were limited by the inability to estimate risks beyond 15 years and because the findings were similar only when observational studies were considered. Factors associated with ESRD, such as renal flares and uncontrolled hypertension, were not examined, and few studies were judged to be of high-quality.

Still, the results can be used to counsel patients on risks of ESRD and also will provide benchmarks to judge the effectiveness of future treatments, the authors concluded.

Dr. Feldman and Dr. Costenbader disagreed with this conclusion, citing various study limitations and the many nuanced factors that play into a patient’s risk of developing ESRD.

“This study should rather be used to provide a broad overview of our understanding of changes in SLE ESRD over time, rather than data to counsel an individual patient on his/her risks,” they wrote.

The study was supported by the intramural research program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases. The authors reported having no conflicts of interest.

pwendling@frontlinemedcom.com

A novel DNA-based test may prove useful for identifying which chronic myeloid leukemia patients with undetectable BCR-ABL1 transcripts can safely discontinue tyrosine kinase inhibitor (TKI) therapy, according to Mary Alikian, Ph.D., of Hammersmith Hospital, London, and her colleagues.

The test can quantify very low levels of residual disease in peripheral blood samples from patients with CML in whom BCR-ABL1 transcripts were undetectable using reverse transcription quantitative polymerase chain reaction (RT-qPCR), the researchers reported in a study published online in the Journal of Molecular Diagnostics.

©Jezperklauzen/ThinkStock

Their personalized DNA-based digital PCR method rapidly identifies t(9;22) fusion junctions using targeted next-generation sequencing and generates high-performance DNA-based hydrolysis probe assays that are specific to the unique molecular footprint of each patient’s CML clone. The researchers further enhanced the sensitivity of the DNA-based approach by optimizing the technique for use on a digital PCR (dPCR) platform, which provides absolute molecular quantification without the need for a standard curve. This approach avoids laborious breakpoint mapping and improves sensitivity.

The researchers successfully mapped genomic breakpoints in all samples from 32 patients with early-stage disease. Using DNA-based dPCR, disease was quantified in 46 follow-up samples from 6 of the 32 patients, including 36 samples that were in deep molecular remission.

Digital PCR for BCR-ABL1 DNA detected persistent disease in 81% of the molecular-remission samples, outperforming both RT-dPCR (25%) and DNA-based quantitative PCR (19%), the researchers reported (J Mol Diagn. 2016;18:176e189).

Of CML patients who achieve sustained undetectable BCR-ABL1 transcripts on TKI therapy, about 60% experience the return of detectable disease after stopping TKIs and have to restart treatment. An improved method of identifying patients with the lowest likelihood of relapse would allow safe withdrawal of TKI therapy for the 40% of patients who would remain disease free.

The researchers are currently investigating the impact of residual-disease level as assessed by dPCR at the time of treatment withdrawal on outcome within the UK-based DESTINY clinical trial (Deescalation and Stopping Treatment of Imatinib, Nilotinib or Sprycel in Chronic Myeloid Leukaemia). “If validated in clinical trials of stopping TKI, the technique will permit a more personalized approach to recommendations for dose reduction or drug cessation in individual patients, ensuring that therapy is withdrawn only from patients with the highest likelihood of long-term remission,” they wrote.

Identifying genomic breakpoints as soon as CML is diagnosed would allow for the design and optimization of a patient-specific assay. Patients’ response to therapy would then be monitored via standard RT-qPCR until they have reached molecular response. Thereafter, routine monitoring would be augmented with DNA quantification by dPCR and would benefit from the publication of standardized guidelines, as with RT-qPCR.

In the future, it will therefore be important to explore not only whether the risk of relapse after withdrawal is a feature of the number of residual CML cells but also whether it relates to the degree of transcriptional activity in those cells, the researchers wrote. “We observed that 8% (3 of 36) of the samples were positive by RNA-based but negative by DNA-based methods. Conversely, in samples with detectable BCR-ABL1 DNA, there was heterogeneity in the detectability of transcript by RT-dPCR that appeared to be unrelated to the amount of BCR-ABL1 DNA detected. It should be borne in mind that RT and cDNA synthesis steps remain a potential source of variation affecting cDNA concentration, and therefore these results should be interpreted with caution.”

The researchers had no relevant disclosures. The study was supported by Leading Leukemia Research (LEUKA) charity grant 06/Q0406/47, the National Institute for Health Research Biomedical Research Center Funding Scheme, and the Imperial College High Performance Computing Service.

mdales@frontlinemedcom.com

On Twitter @maryjodales

A novel DNA-based test may prove useful for identifying which chronic myeloid leukemia patients with undetectable BCR-ABL1 transcripts can safely discontinue tyrosine kinase inhibitor (TKI) therapy, according to Mary Alikian, Ph.D., of Hammersmith Hospital, London, and her colleagues.

The test can quantify very low levels of residual disease in peripheral blood samples from patients with CML in whom BCR-ABL1 transcripts were undetectable using reverse transcription quantitative polymerase chain reaction (RT-qPCR), the researchers reported in a study published online in the Journal of Molecular Diagnostics.

©Jezperklauzen/ThinkStock

Their personalized DNA-based digital PCR method rapidly identifies t(9;22) fusion junctions using targeted next-generation sequencing and generates high-performance DNA-based hydrolysis probe assays that are specific to the unique molecular footprint of each patient’s CML clone. The researchers further enhanced the sensitivity of the DNA-based approach by optimizing the technique for use on a digital PCR (dPCR) platform, which provides absolute molecular quantification without the need for a standard curve. This approach avoids laborious breakpoint mapping and improves sensitivity.

The researchers successfully mapped genomic breakpoints in all samples from 32 patients with early-stage disease. Using DNA-based dPCR, disease was quantified in 46 follow-up samples from 6 of the 32 patients, including 36 samples that were in deep molecular remission.

Digital PCR for BCR-ABL1 DNA detected persistent disease in 81% of the molecular-remission samples, outperforming both RT-dPCR (25%) and DNA-based quantitative PCR (19%), the researchers reported (J Mol Diagn. 2016;18:176e189).

Of CML patients who achieve sustained undetectable BCR-ABL1 transcripts on TKI therapy, about 60% experience the return of detectable disease after stopping TKIs and have to restart treatment. An improved method of identifying patients with the lowest likelihood of relapse would allow safe withdrawal of TKI therapy for the 40% of patients who would remain disease free.

The researchers are currently investigating the impact of residual-disease level as assessed by dPCR at the time of treatment withdrawal on outcome within the UK-based DESTINY clinical trial (Deescalation and Stopping Treatment of Imatinib, Nilotinib or Sprycel in Chronic Myeloid Leukaemia). “If validated in clinical trials of stopping TKI, the technique will permit a more personalized approach to recommendations for dose reduction or drug cessation in individual patients, ensuring that therapy is withdrawn only from patients with the highest likelihood of long-term remission,” they wrote.

Identifying genomic breakpoints as soon as CML is diagnosed would allow for the design and optimization of a patient-specific assay. Patients’ response to therapy would then be monitored via standard RT-qPCR until they have reached molecular response. Thereafter, routine monitoring would be augmented with DNA quantification by dPCR and would benefit from the publication of standardized guidelines, as with RT-qPCR.

In the future, it will therefore be important to explore not only whether the risk of relapse after withdrawal is a feature of the number of residual CML cells but also whether it relates to the degree of transcriptional activity in those cells, the researchers wrote. “We observed that 8% (3 of 36) of the samples were positive by RNA-based but negative by DNA-based methods. Conversely, in samples with detectable BCR-ABL1 DNA, there was heterogeneity in the detectability of transcript by RT-dPCR that appeared to be unrelated to the amount of BCR-ABL1 DNA detected. It should be borne in mind that RT and cDNA synthesis steps remain a potential source of variation affecting cDNA concentration, and therefore these results should be interpreted with caution.”

The researchers had no relevant disclosures. The study was supported by Leading Leukemia Research (LEUKA) charity grant 06/Q0406/47, the National Institute for Health Research Biomedical Research Center Funding Scheme, and the Imperial College High Performance Computing Service.

mdales@frontlinemedcom.com

On Twitter @maryjodales

A novel DNA-based test may prove useful for identifying which chronic myeloid leukemia patients with undetectable BCR-ABL1 transcripts can safely discontinue tyrosine kinase inhibitor (TKI) therapy, according to Mary Alikian, Ph.D., of Hammersmith Hospital, London, and her colleagues.

The test can quantify very low levels of residual disease in peripheral blood samples from patients with CML in whom BCR-ABL1 transcripts were undetectable using reverse transcription quantitative polymerase chain reaction (RT-qPCR), the researchers reported in a study published online in the Journal of Molecular Diagnostics.

©Jezperklauzen/ThinkStock

Their personalized DNA-based digital PCR method rapidly identifies t(9;22) fusion junctions using targeted next-generation sequencing and generates high-performance DNA-based hydrolysis probe assays that are specific to the unique molecular footprint of each patient’s CML clone. The researchers further enhanced the sensitivity of the DNA-based approach by optimizing the technique for use on a digital PCR (dPCR) platform, which provides absolute molecular quantification without the need for a standard curve. This approach avoids laborious breakpoint mapping and improves sensitivity.

The researchers successfully mapped genomic breakpoints in all samples from 32 patients with early-stage disease. Using DNA-based dPCR, disease was quantified in 46 follow-up samples from 6 of the 32 patients, including 36 samples that were in deep molecular remission.

Digital PCR for BCR-ABL1 DNA detected persistent disease in 81% of the molecular-remission samples, outperforming both RT-dPCR (25%) and DNA-based quantitative PCR (19%), the researchers reported (J Mol Diagn. 2016;18:176e189).

Of CML patients who achieve sustained undetectable BCR-ABL1 transcripts on TKI therapy, about 60% experience the return of detectable disease after stopping TKIs and have to restart treatment. An improved method of identifying patients with the lowest likelihood of relapse would allow safe withdrawal of TKI therapy for the 40% of patients who would remain disease free.

The researchers are currently investigating the impact of residual-disease level as assessed by dPCR at the time of treatment withdrawal on outcome within the UK-based DESTINY clinical trial (Deescalation and Stopping Treatment of Imatinib, Nilotinib or Sprycel in Chronic Myeloid Leukaemia). “If validated in clinical trials of stopping TKI, the technique will permit a more personalized approach to recommendations for dose reduction or drug cessation in individual patients, ensuring that therapy is withdrawn only from patients with the highest likelihood of long-term remission,” they wrote.

Identifying genomic breakpoints as soon as CML is diagnosed would allow for the design and optimization of a patient-specific assay. Patients’ response to therapy would then be monitored via standard RT-qPCR until they have reached molecular response. Thereafter, routine monitoring would be augmented with DNA quantification by dPCR and would benefit from the publication of standardized guidelines, as with RT-qPCR.

In the future, it will therefore be important to explore not only whether the risk of relapse after withdrawal is a feature of the number of residual CML cells but also whether it relates to the degree of transcriptional activity in those cells, the researchers wrote. “We observed that 8% (3 of 36) of the samples were positive by RNA-based but negative by DNA-based methods. Conversely, in samples with detectable BCR-ABL1 DNA, there was heterogeneity in the detectability of transcript by RT-dPCR that appeared to be unrelated to the amount of BCR-ABL1 DNA detected. It should be borne in mind that RT and cDNA synthesis steps remain a potential source of variation affecting cDNA concentration, and therefore these results should be interpreted with caution.”

The researchers had no relevant disclosures. The study was supported by Leading Leukemia Research (LEUKA) charity grant 06/Q0406/47, the National Institute for Health Research Biomedical Research Center Funding Scheme, and the Imperial College High Performance Computing Service.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Rivaroxaban (Xarelto)

The European Medicines Agency (EMA) has concluded that a defect discovered in a system used to measure international normalized ratios (INRs) in the ROCKET AF study does not change the study’s overall conclusions.

The Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) was recalled in December 2014 after it was found to produce falsely low test results.

A recent investigation by The BMJ suggested this defect may have impacted the results of ROCKET AF, in which researchers compared warfarin to rivaroxaban (Xarelto) in patients with non-valvular atrial fibrillation (NVAF).

However, the EMA said further analyses of the study suggest the issue with the INRatio system did not affect the overall safety or benefit-risk balance of rivaroxaban. So rivaroxaban can continue to be used as before, in line with the current prescribing information.

The ROCKET AF study was the main clinical trial underpinning the use of rivaroxaban in patients with NVAF.

The results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism in these patients. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

The INRatio system was used to measure INRs in study subjects taking warfarin. Because of the defect, there were concerns that the system could have provided lower INR values in some patients in the warfarin group.

The lower values could, in turn, have led investigators to give too high a dose in the warfarin group, increasing their risk of bleeding and therefore giving a false impression of the comparative safety of rivaroxaban.

So the EMA’s Committee for Medicinal Products for Human Use (CHMP) assessed further analyses of the ROCKET AF study data, taking into account the defect of the INRatio system.

The CHMP concluded that any incorrect measurements obtained with the defective system would have had a marginal effect on the study results, and the safety of rivaroxaban remains unchanged.

In addition, the CHMP said data from other large studies confirmed the comparative safety of rivaroxaban and showed similar rates of bleeding in their warfarin groups.

The CHMP therefore concluded that the benefit-risk balance of rivaroxaban in patients with NVAF remains unchanged.

The CHMP’s assessment report, which includes detailed information on the analyses performed, will be published on the EMA’s website soon.

The EMA started investigating this issue as soon as it was informed of the defect of the INRatio system by the marketing authorization holder of rivaroxaban, Bayer Pharma AG, in September 2015.

Bayer said that, although the INRatio system was recalled in December 2014, the company and its development partner, Janssen, did not become aware of the defect until September 2015.

Rivaroxaban (Xarelto)

The European Medicines Agency (EMA) has concluded that a defect discovered in a system used to measure international normalized ratios (INRs) in the ROCKET AF study does not change the study’s overall conclusions.

The Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) was recalled in December 2014 after it was found to produce falsely low test results.

A recent investigation by The BMJ suggested this defect may have impacted the results of ROCKET AF, in which researchers compared warfarin to rivaroxaban (Xarelto) in patients with non-valvular atrial fibrillation (NVAF).

However, the EMA said further analyses of the study suggest the issue with the INRatio system did not affect the overall safety or benefit-risk balance of rivaroxaban. So rivaroxaban can continue to be used as before, in line with the current prescribing information.

The ROCKET AF study was the main clinical trial underpinning the use of rivaroxaban in patients with NVAF.

The results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism in these patients. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

The INRatio system was used to measure INRs in study subjects taking warfarin. Because of the defect, there were concerns that the system could have provided lower INR values in some patients in the warfarin group.

The lower values could, in turn, have led investigators to give too high a dose in the warfarin group, increasing their risk of bleeding and therefore giving a false impression of the comparative safety of rivaroxaban.

So the EMA’s Committee for Medicinal Products for Human Use (CHMP) assessed further analyses of the ROCKET AF study data, taking into account the defect of the INRatio system.

The CHMP concluded that any incorrect measurements obtained with the defective system would have had a marginal effect on the study results, and the safety of rivaroxaban remains unchanged.

In addition, the CHMP said data from other large studies confirmed the comparative safety of rivaroxaban and showed similar rates of bleeding in their warfarin groups.

The CHMP therefore concluded that the benefit-risk balance of rivaroxaban in patients with NVAF remains unchanged.

The CHMP’s assessment report, which includes detailed information on the analyses performed, will be published on the EMA’s website soon.

The EMA started investigating this issue as soon as it was informed of the defect of the INRatio system by the marketing authorization holder of rivaroxaban, Bayer Pharma AG, in September 2015.

Bayer said that, although the INRatio system was recalled in December 2014, the company and its development partner, Janssen, did not become aware of the defect until September 2015.

Rivaroxaban (Xarelto)

The European Medicines Agency (EMA) has concluded that a defect discovered in a system used to measure international normalized ratios (INRs) in the ROCKET AF study does not change the study’s overall conclusions.

The Alere INRatio Monitor System (INRatio Monitor or INRatio2 Monitor and INRatio Test Strips) was recalled in December 2014 after it was found to produce falsely low test results.

A recent investigation by The BMJ suggested this defect may have impacted the results of ROCKET AF, in which researchers compared warfarin to rivaroxaban (Xarelto) in patients with non-valvular atrial fibrillation (NVAF).

However, the EMA said further analyses of the study suggest the issue with the INRatio system did not affect the overall safety or benefit-risk balance of rivaroxaban. So rivaroxaban can continue to be used as before, in line with the current prescribing information.

The ROCKET AF study was the main clinical trial underpinning the use of rivaroxaban in patients with NVAF.

The results suggested rivaroxaban was noninferior to warfarin for preventing stroke or systemic embolism in these patients. And there was no significant difference between the treatment arms with regard to major or nonmajor clinically relevant bleeding.

The INRatio system was used to measure INRs in study subjects taking warfarin. Because of the defect, there were concerns that the system could have provided lower INR values in some patients in the warfarin group.

The lower values could, in turn, have led investigators to give too high a dose in the warfarin group, increasing their risk of bleeding and therefore giving a false impression of the comparative safety of rivaroxaban.

So the EMA’s Committee for Medicinal Products for Human Use (CHMP) assessed further analyses of the ROCKET AF study data, taking into account the defect of the INRatio system.

The CHMP concluded that any incorrect measurements obtained with the defective system would have had a marginal effect on the study results, and the safety of rivaroxaban remains unchanged.

In addition, the CHMP said data from other large studies confirmed the comparative safety of rivaroxaban and showed similar rates of bleeding in their warfarin groups.

The CHMP therefore concluded that the benefit-risk balance of rivaroxaban in patients with NVAF remains unchanged.

The CHMP’s assessment report, which includes detailed information on the analyses performed, will be published on the EMA’s website soon.

The EMA started investigating this issue as soon as it was informed of the defect of the INRatio system by the marketing authorization holder of rivaroxaban, Bayer Pharma AG, in September 2015.

Bayer said that, although the INRatio system was recalled in December 2014, the company and its development partner, Janssen, did not become aware of the defect until September 2015.

I have had a long and circuitous relationship with the radius. When I was 9 years old, I slipped on the wet grass of our front yard in an attempt to make a highlight-reel baseball catch and landed awkwardly on my left arm. After I continued to complain for a day and a half, my mother took me to see our pediatrician, Dr. Blum. After feeling up and down my forearm and asking me to squeeze his fingers, he pronounced me well.

A week and a half later, when I was still favoring what is my dominant arm, we returned to Dr. Blum. Apparently still unimpressed with my physical exam, he begrudgingly ordered an x-ray. Hurrah! I had a fracture! But then he announced that we would treat it with a splint and an ace wrap. Come on! Everyone knows that if you break a bone you get a cast. From then on he was Dr. Bum to me.

For the next 2 weeks, I was forbidden to play sports, meanwhile losing serious credibility points with my peers who suspected that I was a wimp and had fabricated the whole story. And of course, does anyone go around asking their friends to sign his ace wrap ... really? It took me years of overcompensation to regain even a hint of preteen machismo.

During my last year of medical school, I leapt at the opportunity to take an elective in pediatric orthopedics. It was great! With coaching from the residents, I learned when to suspect a buckle fracture of the radius, identify it on x-ray, and best of all, how to apply a cast.

When I finally entered practice here in Brunswick, we were seriously short of specialists, including orthopedists. When it was discovered that I knew how to apply a forearm cast, the orthopedists encouraged me to treat my own patients with simple forearm fractures. They were more than busy enough with really exciting stuff.

As an artist at heart, the chance to mold in plaster and plastic was a special treat. I took great pride in my creations, and making a beautiful crafted cast was sometimes the high point of my day. No splints or wimpy ace wraps for my patients!

Parents loved the one-stop shopping. History, exam, x-ray, casting, and out the door in less than an hour. Because I was the only primary care physician in town who was casting fractures, I occasionally had to remind the emergency room physicians to send me my patients with buckle fractures instead of knee-jerking a referral to an orthopedist.

But then about 10 years ago, some party-pooping orthopedists from who-knows-where looked at a very large series of pediatric patients with buckle fractures of the radius and discovered that those patients treated with splints had at least as good results as those who had been casted. And ... the patients and parents preferred the splints. I had to admit that maybe Dr. Blum wasn’t such a bum after all. Sadly, I had to respond to the evidence by giving up my hobby except when a child’s temperament or past history of injury suggested that he or she might benefit from the extra protection a cast could afford.

A recent study from Toronto published in Pediatrics, “Primary Care Physician Follow-up of Distal Radius Buckle Fractures,” by Koelink et al., makes me wonder whether a splint and ace wrap may even be overtreatment (Pediatrics. 2016 Jan;137[1]:11-9. doi: 10.1542/peds.2015-2262). In this review of 200 pediatric patients with distal radius buckle fractures, the investigators found that regardless of whether the primary care physician discussed how long to use the splint or when to return to activity, more than two-thirds of the patients wore their splints less than 3 weeks. Despite what the authors considered suboptimal primary care physician guidance, 99% of the patients returned to usual activities within 4 weeks.

My mother and Dr. Blum were on the right track from the beginning. They just needed to ignore my complaints a few days longer.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

I have had a long and circuitous relationship with the radius. When I was 9 years old, I slipped on the wet grass of our front yard in an attempt to make a highlight-reel baseball catch and landed awkwardly on my left arm. After I continued to complain for a day and a half, my mother took me to see our pediatrician, Dr. Blum. After feeling up and down my forearm and asking me to squeeze his fingers, he pronounced me well.

A week and a half later, when I was still favoring what is my dominant arm, we returned to Dr. Blum. Apparently still unimpressed with my physical exam, he begrudgingly ordered an x-ray. Hurrah! I had a fracture! But then he announced that we would treat it with a splint and an ace wrap. Come on! Everyone knows that if you break a bone you get a cast. From then on he was Dr. Bum to me.

For the next 2 weeks, I was forbidden to play sports, meanwhile losing serious credibility points with my peers who suspected that I was a wimp and had fabricated the whole story. And of course, does anyone go around asking their friends to sign his ace wrap ... really? It took me years of overcompensation to regain even a hint of preteen machismo.

During my last year of medical school, I leapt at the opportunity to take an elective in pediatric orthopedics. It was great! With coaching from the residents, I learned when to suspect a buckle fracture of the radius, identify it on x-ray, and best of all, how to apply a cast.

When I finally entered practice here in Brunswick, we were seriously short of specialists, including orthopedists. When it was discovered that I knew how to apply a forearm cast, the orthopedists encouraged me to treat my own patients with simple forearm fractures. They were more than busy enough with really exciting stuff.

As an artist at heart, the chance to mold in plaster and plastic was a special treat. I took great pride in my creations, and making a beautiful crafted cast was sometimes the high point of my day. No splints or wimpy ace wraps for my patients!

Parents loved the one-stop shopping. History, exam, x-ray, casting, and out the door in less than an hour. Because I was the only primary care physician in town who was casting fractures, I occasionally had to remind the emergency room physicians to send me my patients with buckle fractures instead of knee-jerking a referral to an orthopedist.

But then about 10 years ago, some party-pooping orthopedists from who-knows-where looked at a very large series of pediatric patients with buckle fractures of the radius and discovered that those patients treated with splints had at least as good results as those who had been casted. And ... the patients and parents preferred the splints. I had to admit that maybe Dr. Blum wasn’t such a bum after all. Sadly, I had to respond to the evidence by giving up my hobby except when a child’s temperament or past history of injury suggested that he or she might benefit from the extra protection a cast could afford.

A recent study from Toronto published in Pediatrics, “Primary Care Physician Follow-up of Distal Radius Buckle Fractures,” by Koelink et al., makes me wonder whether a splint and ace wrap may even be overtreatment (Pediatrics. 2016 Jan;137[1]:11-9. doi: 10.1542/peds.2015-2262). In this review of 200 pediatric patients with distal radius buckle fractures, the investigators found that regardless of whether the primary care physician discussed how long to use the splint or when to return to activity, more than two-thirds of the patients wore their splints less than 3 weeks. Despite what the authors considered suboptimal primary care physician guidance, 99% of the patients returned to usual activities within 4 weeks.

My mother and Dr. Blum were on the right track from the beginning. They just needed to ignore my complaints a few days longer.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

I have had a long and circuitous relationship with the radius. When I was 9 years old, I slipped on the wet grass of our front yard in an attempt to make a highlight-reel baseball catch and landed awkwardly on my left arm. After I continued to complain for a day and a half, my mother took me to see our pediatrician, Dr. Blum. After feeling up and down my forearm and asking me to squeeze his fingers, he pronounced me well.

A week and a half later, when I was still favoring what is my dominant arm, we returned to Dr. Blum. Apparently still unimpressed with my physical exam, he begrudgingly ordered an x-ray. Hurrah! I had a fracture! But then he announced that we would treat it with a splint and an ace wrap. Come on! Everyone knows that if you break a bone you get a cast. From then on he was Dr. Bum to me.

For the next 2 weeks, I was forbidden to play sports, meanwhile losing serious credibility points with my peers who suspected that I was a wimp and had fabricated the whole story. And of course, does anyone go around asking their friends to sign his ace wrap ... really? It took me years of overcompensation to regain even a hint of preteen machismo.

During my last year of medical school, I leapt at the opportunity to take an elective in pediatric orthopedics. It was great! With coaching from the residents, I learned when to suspect a buckle fracture of the radius, identify it on x-ray, and best of all, how to apply a cast.

When I finally entered practice here in Brunswick, we were seriously short of specialists, including orthopedists. When it was discovered that I knew how to apply a forearm cast, the orthopedists encouraged me to treat my own patients with simple forearm fractures. They were more than busy enough with really exciting stuff.

As an artist at heart, the chance to mold in plaster and plastic was a special treat. I took great pride in my creations, and making a beautiful crafted cast was sometimes the high point of my day. No splints or wimpy ace wraps for my patients!

Parents loved the one-stop shopping. History, exam, x-ray, casting, and out the door in less than an hour. Because I was the only primary care physician in town who was casting fractures, I occasionally had to remind the emergency room physicians to send me my patients with buckle fractures instead of knee-jerking a referral to an orthopedist.

But then about 10 years ago, some party-pooping orthopedists from who-knows-where looked at a very large series of pediatric patients with buckle fractures of the radius and discovered that those patients treated with splints had at least as good results as those who had been casted. And ... the patients and parents preferred the splints. I had to admit that maybe Dr. Blum wasn’t such a bum after all. Sadly, I had to respond to the evidence by giving up my hobby except when a child’s temperament or past history of injury suggested that he or she might benefit from the extra protection a cast could afford.

A recent study from Toronto published in Pediatrics, “Primary Care Physician Follow-up of Distal Radius Buckle Fractures,” by Koelink et al., makes me wonder whether a splint and ace wrap may even be overtreatment (Pediatrics. 2016 Jan;137[1]:11-9. doi: 10.1542/peds.2015-2262). In this review of 200 pediatric patients with distal radius buckle fractures, the investigators found that regardless of whether the primary care physician discussed how long to use the splint or when to return to activity, more than two-thirds of the patients wore their splints less than 3 weeks. Despite what the authors considered suboptimal primary care physician guidance, 99% of the patients returned to usual activities within 4 weeks.

My mother and Dr. Blum were on the right track from the beginning. They just needed to ignore my complaints a few days longer.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

Overall influenza-like illness (ILI) activity underwent a small increase in the United States during week 16 of the 2015-2016 flu season, but Puerto Rico took a significant turn for the worse as activity there rose to the highest possible level, the Centers for Disease Control and Prevention reported Feb. 5.

Puerto Rico, which had been at level 8 on the CDC’s 1-10 scale of flu activity for the previous 3 weeks, jumped up to level 10 for the week ending Jan. 30, 2016. Meanwhile, the main measure for national flu activity, the proportion of outpatient visits for ILI, was 2.2% for the second week in a row, just above the national baseline of 2.1%, the CDC said.

The state with the highest level of flu activity (level 7) for the week was Connecticut, with Arkansas the only other state in the “moderate” range at level 6. States in the “low” range were Florida, Hawaii, Illinois, Maryland, Nevada, New Jersey, and Pennsylvania at level 4 and Georgia, Idaho, Louisiana, Massachusetts, Mississippi, New Mexico, and Virginia at level 3. All told, there were 22 states with activity above level 1, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network.

There were two influenza-associated pediatric deaths reported during week 16, although one death actually occurred during the week ending Jan. 16. There have been nine flu-associated pediatric deaths reported so far during the 2015-2016 season.

The hospitalization rate for the season so far is 2.6/100,000 population, up from 2.1/100,000 last week. Adults aged 65 years and older had the highest rate at 8.5/100,000, with children aged 0-4 years next at 3.8/100,000.

rfranki@frontlinemedcom.com

Overall influenza-like illness (ILI) activity underwent a small increase in the United States during week 16 of the 2015-2016 flu season, but Puerto Rico took a significant turn for the worse as activity there rose to the highest possible level, the Centers for Disease Control and Prevention reported Feb. 5.

Puerto Rico, which had been at level 8 on the CDC’s 1-10 scale of flu activity for the previous 3 weeks, jumped up to level 10 for the week ending Jan. 30, 2016. Meanwhile, the main measure for national flu activity, the proportion of outpatient visits for ILI, was 2.2% for the second week in a row, just above the national baseline of 2.1%, the CDC said.

The state with the highest level of flu activity (level 7) for the week was Connecticut, with Arkansas the only other state in the “moderate” range at level 6. States in the “low” range were Florida, Hawaii, Illinois, Maryland, Nevada, New Jersey, and Pennsylvania at level 4 and Georgia, Idaho, Louisiana, Massachusetts, Mississippi, New Mexico, and Virginia at level 3. All told, there were 22 states with activity above level 1, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network.

There were two influenza-associated pediatric deaths reported during week 16, although one death actually occurred during the week ending Jan. 16. There have been nine flu-associated pediatric deaths reported so far during the 2015-2016 season.

The hospitalization rate for the season so far is 2.6/100,000 population, up from 2.1/100,000 last week. Adults aged 65 years and older had the highest rate at 8.5/100,000, with children aged 0-4 years next at 3.8/100,000.

rfranki@frontlinemedcom.com

Overall influenza-like illness (ILI) activity underwent a small increase in the United States during week 16 of the 2015-2016 flu season, but Puerto Rico took a significant turn for the worse as activity there rose to the highest possible level, the Centers for Disease Control and Prevention reported Feb. 5.

Puerto Rico, which had been at level 8 on the CDC’s 1-10 scale of flu activity for the previous 3 weeks, jumped up to level 10 for the week ending Jan. 30, 2016. Meanwhile, the main measure for national flu activity, the proportion of outpatient visits for ILI, was 2.2% for the second week in a row, just above the national baseline of 2.1%, the CDC said.

The state with the highest level of flu activity (level 7) for the week was Connecticut, with Arkansas the only other state in the “moderate” range at level 6. States in the “low” range were Florida, Hawaii, Illinois, Maryland, Nevada, New Jersey, and Pennsylvania at level 4 and Georgia, Idaho, Louisiana, Massachusetts, Mississippi, New Mexico, and Virginia at level 3. All told, there were 22 states with activity above level 1, according to data from the CDC’s Outpatient Influenza-like Illness Surveillance Network.

There were two influenza-associated pediatric deaths reported during week 16, although one death actually occurred during the week ending Jan. 16. There have been nine flu-associated pediatric deaths reported so far during the 2015-2016 season.

The hospitalization rate for the season so far is 2.6/100,000 population, up from 2.1/100,000 last week. Adults aged 65 years and older had the highest rate at 8.5/100,000, with children aged 0-4 years next at 3.8/100,000.

rfranki@frontlinemedcom.com

A wearable pulsed electromagnetic fields device reduced pain intensity and improved physical functioning in patients with painful knee osteoarthritis (OA) in a double-blind, randomized trial.

The commercially available device (ActiPatch, Bioelectronics Corp.) did not improve patients’ mental health, but significantly reduced patients’ intake of NSAIDs and analgesics, compared with placebo.

“Although NSAIDs remain the gold standard for the treatment of pain in OA, there is increasing need to find conservative and alternative approaches, in order to avoid the toxicity associated with the chronic use of the analgesics, mostly in the elderly population,” wrote Dr. Gian Luca Bagnato of the University of Messina (Italy) and his colleagues (Rheumatology [Oxford]. 2015 Dec 24. doi: 10.1093/rheumatology/kev426).

courtesy BioElectronics Corporation

Pulsed electromagnetic fields (PEMF) therapy has been shown to reduce chondrocyte apoptosis and MMP-13 expression of knee cartilage and favorably affect cartilage homeostasis in animal models, but data regarding osteoarthritis (OA) pain and function in humans are mixed.

A recent systematic review found no effect in all 14 trials analyzed, but when only high-quality randomized clinical trials were included, PEMF provided significantly better pain relief at 4 and 8 weeks and better function at 8 weeks than did placebo (Rheumatology [Oxford]. 2013;52[5]:815-24).

Not only has the quality of trials varied, so has the PEMF pulse frequency and duration used in trials, “further limiting the possibility of comparing efficacy and safety,” Dr. Bagnato and associates observed.

The current study evenly randomized 60 patients with radiologic evidence of knee OA and persistent pain to wear the PEMF or a placebo device for a minimum of 12 hours, mainly at night, with the device kept in place with a wrap. The active device emits a form of non-ionizing electromagnetic radiation at a frequency of 27.12 MHz, a pulse rate of 1,000 Hz, and a burst width of 100 microsec.

Persistent pain was defined as a minimal mean score of 40 mm for global pain on the VAS (visual analog scale) and daily pain during the month prior to enrollment despite maximal tolerated doses of conventional medical therapy, including acetaminophen and/or an NSAID. The patients’ mean age was 67.7 years and mean OA duration 12 years.

The primary efficacy endpoint was reduction in pain intensity at 1 month on the VAS and WOMAC (Western Ontario and McMaster Universities Arthritis Index). The mean WOMAC total score at baseline was 132.9.

At 1 month, VAS pain scores were reduced 25.5% with the PEMF device and 3.6% with the placebo device. The standardized treatment effect size induced by PEMF therapy was –0.73 (95% confidence interval, –1.24 to –0.19), the investigators reported.

WOMAC pain subscale and total scores fell 23.4% and 18.4% with the PEMF device versus a 2.3% reduction for both scores with the placebo device. The standardized effect size was –0.61 for WOMAC pain (95% CI, –1.12 to –0.09) and –0.34 for WOMAC total score (95% CI, –0.85 to 0.17).

At 1 month, the mean Short Form-36 physical health score was significantly better in the PEMF group than in the placebo group (55.8 vs. 53.1; P = .024), while SF-36 mental health scores were nearly identical (43.8 vs. 43.6; P = .6).

Patients were allowed per protocol to take prescribed analgesic therapy as needed, but eight patients from the PEMF group stopped these medications, while one patient from the placebo group stopped medication and three started a new therapy for chronic pain. No adverse events were reported during the study.

“Given that our data are limited to a low number of participants and the long-term efficacy of the wearable device is unknown, the generalizability of the results needs to be confirmed in a larger clinical trial with a longer duration of treatment,” Dr. Bagnato and his coauthors concluded. “However, the use of a wearable PEMF therapy in knee OA can be considered as an alternative safe and effective therapy in knee OA, providing the possibility for home-based management of pain, compared with previous studies.”

pwendling@frontlinemedcom.com

A wearable pulsed electromagnetic fields device reduced pain intensity and improved physical functioning in patients with painful knee osteoarthritis (OA) in a double-blind, randomized trial.

The commercially available device (ActiPatch, Bioelectronics Corp.) did not improve patients’ mental health, but significantly reduced patients’ intake of NSAIDs and analgesics, compared with placebo.

“Although NSAIDs remain the gold standard for the treatment of pain in OA, there is increasing need to find conservative and alternative approaches, in order to avoid the toxicity associated with the chronic use of the analgesics, mostly in the elderly population,” wrote Dr. Gian Luca Bagnato of the University of Messina (Italy) and his colleagues (Rheumatology [Oxford]. 2015 Dec 24. doi: 10.1093/rheumatology/kev426).

courtesy BioElectronics Corporation

Pulsed electromagnetic fields (PEMF) therapy has been shown to reduce chondrocyte apoptosis and MMP-13 expression of knee cartilage and favorably affect cartilage homeostasis in animal models, but data regarding osteoarthritis (OA) pain and function in humans are mixed.

A recent systematic review found no effect in all 14 trials analyzed, but when only high-quality randomized clinical trials were included, PEMF provided significantly better pain relief at 4 and 8 weeks and better function at 8 weeks than did placebo (Rheumatology [Oxford]. 2013;52[5]:815-24).

Not only has the quality of trials varied, so has the PEMF pulse frequency and duration used in trials, “further limiting the possibility of comparing efficacy and safety,” Dr. Bagnato and associates observed.

The current study evenly randomized 60 patients with radiologic evidence of knee OA and persistent pain to wear the PEMF or a placebo device for a minimum of 12 hours, mainly at night, with the device kept in place with a wrap. The active device emits a form of non-ionizing electromagnetic radiation at a frequency of 27.12 MHz, a pulse rate of 1,000 Hz, and a burst width of 100 microsec.

Persistent pain was defined as a minimal mean score of 40 mm for global pain on the VAS (visual analog scale) and daily pain during the month prior to enrollment despite maximal tolerated doses of conventional medical therapy, including acetaminophen and/or an NSAID. The patients’ mean age was 67.7 years and mean OA duration 12 years.

The primary efficacy endpoint was reduction in pain intensity at 1 month on the VAS and WOMAC (Western Ontario and McMaster Universities Arthritis Index). The mean WOMAC total score at baseline was 132.9.

At 1 month, VAS pain scores were reduced 25.5% with the PEMF device and 3.6% with the placebo device. The standardized treatment effect size induced by PEMF therapy was –0.73 (95% confidence interval, –1.24 to –0.19), the investigators reported.

WOMAC pain subscale and total scores fell 23.4% and 18.4% with the PEMF device versus a 2.3% reduction for both scores with the placebo device. The standardized effect size was –0.61 for WOMAC pain (95% CI, –1.12 to –0.09) and –0.34 for WOMAC total score (95% CI, –0.85 to 0.17).

At 1 month, the mean Short Form-36 physical health score was significantly better in the PEMF group than in the placebo group (55.8 vs. 53.1; P = .024), while SF-36 mental health scores were nearly identical (43.8 vs. 43.6; P = .6).

Patients were allowed per protocol to take prescribed analgesic therapy as needed, but eight patients from the PEMF group stopped these medications, while one patient from the placebo group stopped medication and three started a new therapy for chronic pain. No adverse events were reported during the study.

“Given that our data are limited to a low number of participants and the long-term efficacy of the wearable device is unknown, the generalizability of the results needs to be confirmed in a larger clinical trial with a longer duration of treatment,” Dr. Bagnato and his coauthors concluded. “However, the use of a wearable PEMF therapy in knee OA can be considered as an alternative safe and effective therapy in knee OA, providing the possibility for home-based management of pain, compared with previous studies.”

pwendling@frontlinemedcom.com

A wearable pulsed electromagnetic fields device reduced pain intensity and improved physical functioning in patients with painful knee osteoarthritis (OA) in a double-blind, randomized trial.

The commercially available device (ActiPatch, Bioelectronics Corp.) did not improve patients’ mental health, but significantly reduced patients’ intake of NSAIDs and analgesics, compared with placebo.

“Although NSAIDs remain the gold standard for the treatment of pain in OA, there is increasing need to find conservative and alternative approaches, in order to avoid the toxicity associated with the chronic use of the analgesics, mostly in the elderly population,” wrote Dr. Gian Luca Bagnato of the University of Messina (Italy) and his colleagues (Rheumatology [Oxford]. 2015 Dec 24. doi: 10.1093/rheumatology/kev426).

courtesy BioElectronics Corporation

Pulsed electromagnetic fields (PEMF) therapy has been shown to reduce chondrocyte apoptosis and MMP-13 expression of knee cartilage and favorably affect cartilage homeostasis in animal models, but data regarding osteoarthritis (OA) pain and function in humans are mixed.

A recent systematic review found no effect in all 14 trials analyzed, but when only high-quality randomized clinical trials were included, PEMF provided significantly better pain relief at 4 and 8 weeks and better function at 8 weeks than did placebo (Rheumatology [Oxford]. 2013;52[5]:815-24).

Not only has the quality of trials varied, so has the PEMF pulse frequency and duration used in trials, “further limiting the possibility of comparing efficacy and safety,” Dr. Bagnato and associates observed.

The current study evenly randomized 60 patients with radiologic evidence of knee OA and persistent pain to wear the PEMF or a placebo device for a minimum of 12 hours, mainly at night, with the device kept in place with a wrap. The active device emits a form of non-ionizing electromagnetic radiation at a frequency of 27.12 MHz, a pulse rate of 1,000 Hz, and a burst width of 100 microsec.

Persistent pain was defined as a minimal mean score of 40 mm for global pain on the VAS (visual analog scale) and daily pain during the month prior to enrollment despite maximal tolerated doses of conventional medical therapy, including acetaminophen and/or an NSAID. The patients’ mean age was 67.7 years and mean OA duration 12 years.

The primary efficacy endpoint was reduction in pain intensity at 1 month on the VAS and WOMAC (Western Ontario and McMaster Universities Arthritis Index). The mean WOMAC total score at baseline was 132.9.

At 1 month, VAS pain scores were reduced 25.5% with the PEMF device and 3.6% with the placebo device. The standardized treatment effect size induced by PEMF therapy was –0.73 (95% confidence interval, –1.24 to –0.19), the investigators reported.

WOMAC pain subscale and total scores fell 23.4% and 18.4% with the PEMF device versus a 2.3% reduction for both scores with the placebo device. The standardized effect size was –0.61 for WOMAC pain (95% CI, –1.12 to –0.09) and –0.34 for WOMAC total score (95% CI, –0.85 to 0.17).

At 1 month, the mean Short Form-36 physical health score was significantly better in the PEMF group than in the placebo group (55.8 vs. 53.1; P = .024), while SF-36 mental health scores were nearly identical (43.8 vs. 43.6; P = .6).

Patients were allowed per protocol to take prescribed analgesic therapy as needed, but eight patients from the PEMF group stopped these medications, while one patient from the placebo group stopped medication and three started a new therapy for chronic pain. No adverse events were reported during the study.

“Given that our data are limited to a low number of participants and the long-term efficacy of the wearable device is unknown, the generalizability of the results needs to be confirmed in a larger clinical trial with a longer duration of treatment,” Dr. Bagnato and his coauthors concluded. “However, the use of a wearable PEMF therapy in knee OA can be considered as an alternative safe and effective therapy in knee OA, providing the possibility for home-based management of pain, compared with previous studies.”

pwendling@frontlinemedcom.com

In her role as the Dowager Countess on Public Broadcasting Service’s Downton Abbey, Maggie Smith has delivered many memorable one-liners, but none as revealing of her character’s social isolation as the clueless query, “What is a weekend?” How could anyone not appreciate the qualitative differences between the first 4 days of the week and the trio of Friday, Saturday, and Sunday?

A recent study by two Stanford University sociologists suggests that one doesn’t even need to have a job to place a higher value on the weekend (“You Don’t Need More Free Time,” by Cristobal Young, New York Times, Jan. 8, 2016). Using data from more than 500,000 respondents to a Gallup Daily Poll, the investigators found that a variety of indicators of well-being were lowest during the beginning of the workweek and then not surprisingly began to climb on Friday, reaching a peak on Saturday and Sunday. However, it turns out that the emotions of the unemployed respondents tracked exactly the same pattern as those of the people who had jobs.

In an effort to explain this unexpected finding, one of the investigators points out that time, particularly free time, is a “network good.” And in sociologist lingo, “Network goods are things that derive their value from being widely shared.” Although someone without a job may have an abundance of free time, the majority of the people with whom he or she could share that time are busy at work.

This study suggests that you may feel that you would be happier if you had more time off from work; part of the problem may be that there is a mismatch between your schedule and the schedules of the people and activities that you value most. You may have done this kind of self-assessment when you were looking for a job, but how successful were you in negotiating your schedule? Have you been able to renegotiate your schedule to match changes in your social situation? Spouse? Children?

How creative have you been in seeking out arrangements with coworkers who don’t share your time-off value profile? Although you might be tempted to say that based on this recent Stanford study, everyone places the same high value on weekend time off, is this really the case? There are a few people out there whose interests, personalities, and social situations make them value time off when you would just as soon work.

For example, I recently encountered a new word as I was scanning the classified advertisements in the back of this month’s Pediatrics. A hospital in California was looking for a “nocturnist.” An Internet search quickly confirmed my suspicion that a nocturnist is a physician, often a hospitalist, who prefers to work the night shift. Now, it may be just for the money, but if I were an avid birdwatcher, I can imagine wanting to maximize my time off when the sun was up.

Of course the trick is finding those coworkers whose lifestyles are as dissimilar from yours as possible ... and who are willing to trade work schedules. While I think that on many campuses, “diversity” has become an overused buzzword, diversity at your workplace might give you the best chance of finding a time-off arrangement that better matches your value profile.

Finally, if you are really unhappy, it may be time to swallow hard and entertain an arrangement in which you worked more and actually had less total free time, but the time you do have off is time you can share with the people you value and the activities you enjoy. It’s all about choosing the right set of compromises and learning to live with them. Good luck!

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

In her role as the Dowager Countess on Public Broadcasting Service’s Downton Abbey, Maggie Smith has delivered many memorable one-liners, but none as revealing of her character’s social isolation as the clueless query, “What is a weekend?” How could anyone not appreciate the qualitative differences between the first 4 days of the week and the trio of Friday, Saturday, and Sunday?

A recent study by two Stanford University sociologists suggests that one doesn’t even need to have a job to place a higher value on the weekend (“You Don’t Need More Free Time,” by Cristobal Young, New York Times, Jan. 8, 2016). Using data from more than 500,000 respondents to a Gallup Daily Poll, the investigators found that a variety of indicators of well-being were lowest during the beginning of the workweek and then not surprisingly began to climb on Friday, reaching a peak on Saturday and Sunday. However, it turns out that the emotions of the unemployed respondents tracked exactly the same pattern as those of the people who had jobs.

In an effort to explain this unexpected finding, one of the investigators points out that time, particularly free time, is a “network good.” And in sociologist lingo, “Network goods are things that derive their value from being widely shared.” Although someone without a job may have an abundance of free time, the majority of the people with whom he or she could share that time are busy at work.

This study suggests that you may feel that you would be happier if you had more time off from work; part of the problem may be that there is a mismatch between your schedule and the schedules of the people and activities that you value most. You may have done this kind of self-assessment when you were looking for a job, but how successful were you in negotiating your schedule? Have you been able to renegotiate your schedule to match changes in your social situation? Spouse? Children?

How creative have you been in seeking out arrangements with coworkers who don’t share your time-off value profile? Although you might be tempted to say that based on this recent Stanford study, everyone places the same high value on weekend time off, is this really the case? There are a few people out there whose interests, personalities, and social situations make them value time off when you would just as soon work.

For example, I recently encountered a new word as I was scanning the classified advertisements in the back of this month’s Pediatrics. A hospital in California was looking for a “nocturnist.” An Internet search quickly confirmed my suspicion that a nocturnist is a physician, often a hospitalist, who prefers to work the night shift. Now, it may be just for the money, but if I were an avid birdwatcher, I can imagine wanting to maximize my time off when the sun was up.

Of course the trick is finding those coworkers whose lifestyles are as dissimilar from yours as possible ... and who are willing to trade work schedules. While I think that on many campuses, “diversity” has become an overused buzzword, diversity at your workplace might give you the best chance of finding a time-off arrangement that better matches your value profile.

Finally, if you are really unhappy, it may be time to swallow hard and entertain an arrangement in which you worked more and actually had less total free time, but the time you do have off is time you can share with the people you value and the activities you enjoy. It’s all about choosing the right set of compromises and learning to live with them. Good luck!

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

In her role as the Dowager Countess on Public Broadcasting Service’s Downton Abbey, Maggie Smith has delivered many memorable one-liners, but none as revealing of her character’s social isolation as the clueless query, “What is a weekend?” How could anyone not appreciate the qualitative differences between the first 4 days of the week and the trio of Friday, Saturday, and Sunday?

A recent study by two Stanford University sociologists suggests that one doesn’t even need to have a job to place a higher value on the weekend (“You Don’t Need More Free Time,” by Cristobal Young, New York Times, Jan. 8, 2016). Using data from more than 500,000 respondents to a Gallup Daily Poll, the investigators found that a variety of indicators of well-being were lowest during the beginning of the workweek and then not surprisingly began to climb on Friday, reaching a peak on Saturday and Sunday. However, it turns out that the emotions of the unemployed respondents tracked exactly the same pattern as those of the people who had jobs.

In an effort to explain this unexpected finding, one of the investigators points out that time, particularly free time, is a “network good.” And in sociologist lingo, “Network goods are things that derive their value from being widely shared.” Although someone without a job may have an abundance of free time, the majority of the people with whom he or she could share that time are busy at work.

This study suggests that you may feel that you would be happier if you had more time off from work; part of the problem may be that there is a mismatch between your schedule and the schedules of the people and activities that you value most. You may have done this kind of self-assessment when you were looking for a job, but how successful were you in negotiating your schedule? Have you been able to renegotiate your schedule to match changes in your social situation? Spouse? Children?

How creative have you been in seeking out arrangements with coworkers who don’t share your time-off value profile? Although you might be tempted to say that based on this recent Stanford study, everyone places the same high value on weekend time off, is this really the case? There are a few people out there whose interests, personalities, and social situations make them value time off when you would just as soon work.

For example, I recently encountered a new word as I was scanning the classified advertisements in the back of this month’s Pediatrics. A hospital in California was looking for a “nocturnist.” An Internet search quickly confirmed my suspicion that a nocturnist is a physician, often a hospitalist, who prefers to work the night shift. Now, it may be just for the money, but if I were an avid birdwatcher, I can imagine wanting to maximize my time off when the sun was up.

Of course the trick is finding those coworkers whose lifestyles are as dissimilar from yours as possible ... and who are willing to trade work schedules. While I think that on many campuses, “diversity” has become an overused buzzword, diversity at your workplace might give you the best chance of finding a time-off arrangement that better matches your value profile.

Finally, if you are really unhappy, it may be time to swallow hard and entertain an arrangement in which you worked more and actually had less total free time, but the time you do have off is time you can share with the people you value and the activities you enjoy. It’s all about choosing the right set of compromises and learning to live with them. Good luck!

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics including “How to Say No to Your Toddler.”

To the Editor:

Infections caused by herpes simplex (HS) and herpes zoster (HZ) usually can be recognized by clinical findings; however, laboratory confirmation sometimes is required. Polymerase chain reaction (PCR) laboratory tests detect HS or HZ in a sensible and specific manner. New PCR systems such as real-time PCR (RT-PCR) give faster and more precise results. We report a case of recurrent concomitant HZ and HS diagnosed by RT-PCR.

A 62-year-old woman presented with recurrent painful cutaneous lesions on the left buttock and thigh of 9 years’ duration. This eruption was preceded by a burning sensation of 1 week’s duration that extended toward the heel. Cutaneous lesions normally were sparse and persisted for a few days. She also had annular erythematous lesions of 3 years’ duration on the upper trunk and shoulders after sun exposure. On physical examination, an atrophic hypopigmented patch was seen with a few vesicles located on the thigh. Whitish atrophic patches also were found in a linear distribution on the left buttock and thigh (Figure).

Laboratory results included the following: antinuclear antibody, 1:400 on a nuclear dotted pattern; extractable nuclear antigens (anti-Ro60 and anti-Ro52) were positive (reference range, >15); and rheumatoid factor was 24.1 U/mL (reference range, 0–15 U/mL). The patient did not meet any other American College of Rheumatology criteria^1,2 of systemic lupus erythematosus apart from photosensitivity. The rest of the analysis—complete blood cell count, liver enzymes, and biochemistry—was normal or negative. Human immunodeficiency virus, herpes simplex virus types 1 and 2 (HHV-1 and HHV-2), and varicella-zoster virus (VZV) IgM serologies were negative, whereas IgG VZV serology was positive.

The microbiological study via swab obtained from the roof and fluid from the vesicles showed an indeterminate result from the rapid direct antigen detection with immunofluorescent antibodies. Viral cultures were HHV-2 positive and VZV negative. Conventional PCR showed positive results, both for HHV-2 and VZV. A second analysis, performed with RT-PCR from a new sample taken 2 months later, showed the same results, which led to the diagnosis of recurrent concomitant HS and HZ with a recurrent HZ clinical pattern. The patient was started on valacyclovir 1 g daily, and the number and intensity of flares diminished in the months following treatment.

Concomitant HS and HZ on the same dermatome has been described in the literature.^3,4 In a retrospective series of 20 immunocompetent patients, HZ was the main presumed diagnosis before laboratory confirmation of diagnosis, and only 1 case corresponded to recurrent HZ.³ Other cases of simultaneous HS and HZ have been described, but they did not occur on the same dermatome. Half of these reported cases were in immunosuppressed patients.^5,6

The recurrent nature of HS is well known; however, recurrent cases of HZ are rare. Nevertheless, in a population-based cohort study of patients with a confirmed prior episode of HZ (N=1669), recurrences were found in 6% of patients.⁷ Recurrence was more common if the patient was immunosuppressed, was female and 50 years or older, and had pain for more than 30 days.⁷

The recurrence rate was high in our case, but no immunosuppressive factor could be found apart from probable subacute cutaneous lupus erythematosus. Systemic lupus erythematosus has been associated with a high risk for developing HZ secondary to cell-mediated immunosuppression. The annual incidence of HZ can reach 32 of 1000 patients with systemic lupus erythematosus, while in the general population the incidence is only 1.5 to 3 of 1000 patients.^8-10

Direct detection of antigens of HS and HZ is a fast and inexpensive technique but lacks the sensitivity of viral cultures. Viral cultures used to be considered the gold standard; however, they are less sensitive than PCR.¹¹ Furthermore, VZV detection is more difficult than HS, leading to a notable percentage of false-negative results.¹² Polymerase chain reaction is a fast, reliable, and sensitive laboratory technique. Real-time PCR permits faster results than conventional PCR, specifically for HHV-1, HHV-2, and HZ detection. It also has minimal risk for contamination.^13,14 In our opinion, PCR should be the gold standard instead of viral cultures. It has proven its superiority as a rapid method for detection, it is the most sensitive test, it is easier to perform, and it is cost effective (Table).^11,15-19 However, viral cultures can allow sensitivity testing and are still an option for determination of susceptibility to antivirals.

In our case, a false-positive was excluded because no sign of possible contamination was found, repeated internal analysis from the same sample confirmed the results, and a new analysis from a new flare showed the same results 2 months later. However, we cannot rule out that the positivity for HZ of the second sample was due to the high sensitivity of the test and a virus latency in nerves.

We propose the use of PCR as a method of choice. Presumably more cases of recurrent HZ and concomitant HS and HZ will be seen with PCR use. In the case of a concomitant infection of HS and HZ, it is reasonable to use an antiviral dosage as in HZ treatment. No literature regarding outcomes from therapy could be found.

To the Editor:

Infections caused by herpes simplex (HS) and herpes zoster (HZ) usually can be recognized by clinical findings; however, laboratory confirmation sometimes is required. Polymerase chain reaction (PCR) laboratory tests detect HS or HZ in a sensible and specific manner. New PCR systems such as real-time PCR (RT-PCR) give faster and more precise results. We report a case of recurrent concomitant HZ and HS diagnosed by RT-PCR.

A 62-year-old woman presented with recurrent painful cutaneous lesions on the left buttock and thigh of 9 years’ duration. This eruption was preceded by a burning sensation of 1 week’s duration that extended toward the heel. Cutaneous lesions normally were sparse and persisted for a few days. She also had annular erythematous lesions of 3 years’ duration on the upper trunk and shoulders after sun exposure. On physical examination, an atrophic hypopigmented patch was seen with a few vesicles located on the thigh. Whitish atrophic patches also were found in a linear distribution on the left buttock and thigh (Figure).

Laboratory results included the following: antinuclear antibody, 1:400 on a nuclear dotted pattern; extractable nuclear antigens (anti-Ro60 and anti-Ro52) were positive (reference range, >15); and rheumatoid factor was 24.1 U/mL (reference range, 0–15 U/mL). The patient did not meet any other American College of Rheumatology criteria^1,2 of systemic lupus erythematosus apart from photosensitivity. The rest of the analysis—complete blood cell count, liver enzymes, and biochemistry—was normal or negative. Human immunodeficiency virus, herpes simplex virus types 1 and 2 (HHV-1 and HHV-2), and varicella-zoster virus (VZV) IgM serologies were negative, whereas IgG VZV serology was positive.

The microbiological study via swab obtained from the roof and fluid from the vesicles showed an indeterminate result from the rapid direct antigen detection with immunofluorescent antibodies. Viral cultures were HHV-2 positive and VZV negative. Conventional PCR showed positive results, both for HHV-2 and VZV. A second analysis, performed with RT-PCR from a new sample taken 2 months later, showed the same results, which led to the diagnosis of recurrent concomitant HS and HZ with a recurrent HZ clinical pattern. The patient was started on valacyclovir 1 g daily, and the number and intensity of flares diminished in the months following treatment.

Concomitant HS and HZ on the same dermatome has been described in the literature.^3,4 In a retrospective series of 20 immunocompetent patients, HZ was the main presumed diagnosis before laboratory confirmation of diagnosis, and only 1 case corresponded to recurrent HZ.³ Other cases of simultaneous HS and HZ have been described, but they did not occur on the same dermatome. Half of these reported cases were in immunosuppressed patients.^5,6

The recurrent nature of HS is well known; however, recurrent cases of HZ are rare. Nevertheless, in a population-based cohort study of patients with a confirmed prior episode of HZ (N=1669), recurrences were found in 6% of patients.⁷ Recurrence was more common if the patient was immunosuppressed, was female and 50 years or older, and had pain for more than 30 days.⁷

The recurrence rate was high in our case, but no immunosuppressive factor could be found apart from probable subacute cutaneous lupus erythematosus. Systemic lupus erythematosus has been associated with a high risk for developing HZ secondary to cell-mediated immunosuppression. The annual incidence of HZ can reach 32 of 1000 patients with systemic lupus erythematosus, while in the general population the incidence is only 1.5 to 3 of 1000 patients.^8-10

Direct detection of antigens of HS and HZ is a fast and inexpensive technique but lacks the sensitivity of viral cultures. Viral cultures used to be considered the gold standard; however, they are less sensitive than PCR.¹¹ Furthermore, VZV detection is more difficult than HS, leading to a notable percentage of false-negative results.¹² Polymerase chain reaction is a fast, reliable, and sensitive laboratory technique. Real-time PCR permits faster results than conventional PCR, specifically for HHV-1, HHV-2, and HZ detection. It also has minimal risk for contamination.^13,14 In our opinion, PCR should be the gold standard instead of viral cultures. It has proven its superiority as a rapid method for detection, it is the most sensitive test, it is easier to perform, and it is cost effective (Table).^11,15-19 However, viral cultures can allow sensitivity testing and are still an option for determination of susceptibility to antivirals.

In our case, a false-positive was excluded because no sign of possible contamination was found, repeated internal analysis from the same sample confirmed the results, and a new analysis from a new flare showed the same results 2 months later. However, we cannot rule out that the positivity for HZ of the second sample was due to the high sensitivity of the test and a virus latency in nerves.

We propose the use of PCR as a method of choice. Presumably more cases of recurrent HZ and concomitant HS and HZ will be seen with PCR use. In the case of a concomitant infection of HS and HZ, it is reasonable to use an antiviral dosage as in HZ treatment. No literature regarding outcomes from therapy could be found.

To the Editor:

Infections caused by herpes simplex (HS) and herpes zoster (HZ) usually can be recognized by clinical findings; however, laboratory confirmation sometimes is required. Polymerase chain reaction (PCR) laboratory tests detect HS or HZ in a sensible and specific manner. New PCR systems such as real-time PCR (RT-PCR) give faster and more precise results. We report a case of recurrent concomitant HZ and HS diagnosed by RT-PCR.

A 62-year-old woman presented with recurrent painful cutaneous lesions on the left buttock and thigh of 9 years’ duration. This eruption was preceded by a burning sensation of 1 week’s duration that extended toward the heel. Cutaneous lesions normally were sparse and persisted for a few days. She also had annular erythematous lesions of 3 years’ duration on the upper trunk and shoulders after sun exposure. On physical examination, an atrophic hypopigmented patch was seen with a few vesicles located on the thigh. Whitish atrophic patches also were found in a linear distribution on the left buttock and thigh (Figure).

Laboratory results included the following: antinuclear antibody, 1:400 on a nuclear dotted pattern; extractable nuclear antigens (anti-Ro60 and anti-Ro52) were positive (reference range, >15); and rheumatoid factor was 24.1 U/mL (reference range, 0–15 U/mL). The patient did not meet any other American College of Rheumatology criteria^1,2 of systemic lupus erythematosus apart from photosensitivity. The rest of the analysis—complete blood cell count, liver enzymes, and biochemistry—was normal or negative. Human immunodeficiency virus, herpes simplex virus types 1 and 2 (HHV-1 and HHV-2), and varicella-zoster virus (VZV) IgM serologies were negative, whereas IgG VZV serology was positive.

The microbiological study via swab obtained from the roof and fluid from the vesicles showed an indeterminate result from the rapid direct antigen detection with immunofluorescent antibodies. Viral cultures were HHV-2 positive and VZV negative. Conventional PCR showed positive results, both for HHV-2 and VZV. A second analysis, performed with RT-PCR from a new sample taken 2 months later, showed the same results, which led to the diagnosis of recurrent concomitant HS and HZ with a recurrent HZ clinical pattern. The patient was started on valacyclovir 1 g daily, and the number and intensity of flares diminished in the months following treatment.

Concomitant HS and HZ on the same dermatome has been described in the literature.^3,4 In a retrospective series of 20 immunocompetent patients, HZ was the main presumed diagnosis before laboratory confirmation of diagnosis, and only 1 case corresponded to recurrent HZ.³ Other cases of simultaneous HS and HZ have been described, but they did not occur on the same dermatome. Half of these reported cases were in immunosuppressed patients.^5,6

The recurrent nature of HS is well known; however, recurrent cases of HZ are rare. Nevertheless, in a population-based cohort study of patients with a confirmed prior episode of HZ (N=1669), recurrences were found in 6% of patients.⁷ Recurrence was more common if the patient was immunosuppressed, was female and 50 years or older, and had pain for more than 30 days.⁷

The recurrence rate was high in our case, but no immunosuppressive factor could be found apart from probable subacute cutaneous lupus erythematosus. Systemic lupus erythematosus has been associated with a high risk for developing HZ secondary to cell-mediated immunosuppression. The annual incidence of HZ can reach 32 of 1000 patients with systemic lupus erythematosus, while in the general population the incidence is only 1.5 to 3 of 1000 patients.^8-10

Direct detection of antigens of HS and HZ is a fast and inexpensive technique but lacks the sensitivity of viral cultures. Viral cultures used to be considered the gold standard; however, they are less sensitive than PCR.¹¹ Furthermore, VZV detection is more difficult than HS, leading to a notable percentage of false-negative results.¹² Polymerase chain reaction is a fast, reliable, and sensitive laboratory technique. Real-time PCR permits faster results than conventional PCR, specifically for HHV-1, HHV-2, and HZ detection. It also has minimal risk for contamination.^13,14 In our opinion, PCR should be the gold standard instead of viral cultures. It has proven its superiority as a rapid method for detection, it is the most sensitive test, it is easier to perform, and it is cost effective (Table).^11,15-19 However, viral cultures can allow sensitivity testing and are still an option for determination of susceptibility to antivirals.

In our case, a false-positive was excluded because no sign of possible contamination was found, repeated internal analysis from the same sample confirmed the results, and a new analysis from a new flare showed the same results 2 months later. However, we cannot rule out that the positivity for HZ of the second sample was due to the high sensitivity of the test and a virus latency in nerves.

We propose the use of PCR as a method of choice. Presumably more cases of recurrent HZ and concomitant HS and HZ will be seen with PCR use. In the case of a concomitant infection of HS and HZ, it is reasonable to use an antiviral dosage as in HZ treatment. No literature regarding outcomes from therapy could be found.