Mary Ann Moon

Current evidence is insufficient to ascertain the benefits and harms of primary care interventions aimed at preventing or reducing drug use in the pediatric population, according to an updated guideline published March 10 online in the Annals of Internal Medicine.

© Stockphoto4u/ iStockphoto.com

The U.S. Preventive Services Task Force, a voluntary organization that is independent of government and industry, and funded by the Agency for Healthcare Research and Quality, reviews medical evidence and makes recommendations about specific preventive care services. For this guideline, the USPSTF found only six fair- or good-quality studies of four different primary care interventions to prevent children and adolescents from using illicit drugs or misusing prescription drugs, said Dr. Virginia A. Moyer, chair of the writing committee and a vice president of the American Board of Pediatrics, and her associates.

The four interventions were face-to-face counseling, videos, print materials, and interactive computer-based tools, and were "substantially varied in their intensity, components, [target] populations, and sample sizes." But the six studies yielded "almost no evidence of significant improvements in health outcomes," Dr. Moyer and her colleagues reported (Ann. Intern. Med. 2014 March 10).

Drug use is a significant contributor to three of the leading causes of death among adolescents – vehicular accidents, homicide, and suicide – and increases risk-taking behaviors while the youths are under the influence, including driving while impaired, unsafe sexual activity, and violence. It also is associated with low educational achievement. More adolescents use illicit drugs or intentionally misuse prescription drugs than use tobacco, the USPSTF noted.

Currently, the American Academy of Pediatrics recommends that clinicians screen all adolescents for alcohol and drug use, and based on those results, "provide guidance and brief counseling interventions, and, if appropriate, refer for treatment." The screening tool recommended by the AAP, called the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble), takes less than 2 minutes to administer and was designed to be delivered "as an interview or paper- or computer-based self-report," according to the USPSTF.

The American Academy of Family Physicians is in the process of reviewing its recommendation on addressing drug use among children and adolescents.

The USPSTF is an independent, voluntary body supported by the Agency for Healthcare Research and Quality. Dr. Moyer and her associates reported no potential conflicts of interest.

Current evidence is insufficient to ascertain the benefits and harms of primary care interventions aimed at preventing or reducing drug use in the pediatric population, according to an updated guideline published March 10 online in the Annals of Internal Medicine.

© Stockphoto4u/ iStockphoto.com

The U.S. Preventive Services Task Force, a voluntary organization that is independent of government and industry, and funded by the Agency for Healthcare Research and Quality, reviews medical evidence and makes recommendations about specific preventive care services. For this guideline, the USPSTF found only six fair- or good-quality studies of four different primary care interventions to prevent children and adolescents from using illicit drugs or misusing prescription drugs, said Dr. Virginia A. Moyer, chair of the writing committee and a vice president of the American Board of Pediatrics, and her associates.

The four interventions were face-to-face counseling, videos, print materials, and interactive computer-based tools, and were "substantially varied in their intensity, components, [target] populations, and sample sizes." But the six studies yielded "almost no evidence of significant improvements in health outcomes," Dr. Moyer and her colleagues reported (Ann. Intern. Med. 2014 March 10).

Drug use is a significant contributor to three of the leading causes of death among adolescents – vehicular accidents, homicide, and suicide – and increases risk-taking behaviors while the youths are under the influence, including driving while impaired, unsafe sexual activity, and violence. It also is associated with low educational achievement. More adolescents use illicit drugs or intentionally misuse prescription drugs than use tobacco, the USPSTF noted.

Currently, the American Academy of Pediatrics recommends that clinicians screen all adolescents for alcohol and drug use, and based on those results, "provide guidance and brief counseling interventions, and, if appropriate, refer for treatment." The screening tool recommended by the AAP, called the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble), takes less than 2 minutes to administer and was designed to be delivered "as an interview or paper- or computer-based self-report," according to the USPSTF.

The American Academy of Family Physicians is in the process of reviewing its recommendation on addressing drug use among children and adolescents.

The USPSTF is an independent, voluntary body supported by the Agency for Healthcare Research and Quality. Dr. Moyer and her associates reported no potential conflicts of interest.

Current evidence is insufficient to ascertain the benefits and harms of primary care interventions aimed at preventing or reducing drug use in the pediatric population, according to an updated guideline published March 10 online in the Annals of Internal Medicine.

© Stockphoto4u/ iStockphoto.com

The U.S. Preventive Services Task Force, a voluntary organization that is independent of government and industry, and funded by the Agency for Healthcare Research and Quality, reviews medical evidence and makes recommendations about specific preventive care services. For this guideline, the USPSTF found only six fair- or good-quality studies of four different primary care interventions to prevent children and adolescents from using illicit drugs or misusing prescription drugs, said Dr. Virginia A. Moyer, chair of the writing committee and a vice president of the American Board of Pediatrics, and her associates.

The four interventions were face-to-face counseling, videos, print materials, and interactive computer-based tools, and were "substantially varied in their intensity, components, [target] populations, and sample sizes." But the six studies yielded "almost no evidence of significant improvements in health outcomes," Dr. Moyer and her colleagues reported (Ann. Intern. Med. 2014 March 10).

Drug use is a significant contributor to three of the leading causes of death among adolescents – vehicular accidents, homicide, and suicide – and increases risk-taking behaviors while the youths are under the influence, including driving while impaired, unsafe sexual activity, and violence. It also is associated with low educational achievement. More adolescents use illicit drugs or intentionally misuse prescription drugs than use tobacco, the USPSTF noted.

Currently, the American Academy of Pediatrics recommends that clinicians screen all adolescents for alcohol and drug use, and based on those results, "provide guidance and brief counseling interventions, and, if appropriate, refer for treatment." The screening tool recommended by the AAP, called the CRAFFT (Car, Relax, Alone, Forget, Friends, Trouble), takes less than 2 minutes to administer and was designed to be delivered "as an interview or paper- or computer-based self-report," according to the USPSTF.

The American Academy of Family Physicians is in the process of reviewing its recommendation on addressing drug use among children and adolescents.

The USPSTF is an independent, voluntary body supported by the Agency for Healthcare Research and Quality. Dr. Moyer and her associates reported no potential conflicts of interest.

Severe hypoglycemia related to overly "tight" insulin control for type 2 diabetes prompts nearly 100,000 emergency department visits and 30,000 hospitalizations each year and is particularly common among older patients, according to a report published online March 10 in JAMA Internal Medicine.

In an analysis of data from a nationally representative sample of hospitals in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, researchers estimated that 97,648 ED visits occurred annually during a 5-year period among adults with type 2 diabetes who presented with hypoglycemia-related shock, loss of consciousness, seizure, injury or fall, or altered mental status. Most cases involved blood glucose levels of 50 mg/dL or less, said Dr. Andrew I. Geller of the division of healthcare quality promotion at the Centers for Disease Control and Prevention, Atlanta, and his associates.

The case rate was 34.9 per 1,000 insulin-treated patients among those aged 80 years and older. In comparison, the rate was only 13.7 per 1,000 among those aged 45-64 years. Older patients were more than twice as likely as younger ones to require an ED visit and nearly five times as likely to require hospitalization, Dr. Geller and his associates said (JAMA Intern. Med. 2014 March 10 [doi:10.1001/jamainternmed.2014.136]).

The most common precipitating factor was "meal-related misadventure" – failing to eat shortly after taking rapid-acting insulin or failing to adjust the insulin regimen to account for a missed meal or a very small meal. Hypoglycemia also was frequently preceded by the patient taking the wrong dose of insulin or the wrong insulin product, usually taking rapid-acting insulin instead of long-acting insulin.

"These data probably underestimate the total burden of hypoglycemic events because hypoglycemia, although a frequent cause of [emergency medical services] calls, is most often cared for outside the ED setting. Patients who have hypoglycemia unawareness and whose episodes do not result in EMS or ED care [were] not counted, nor [were] those who died en route to the ED," they added.

No financial conflicts of interest were reported.

Severe hypoglycemia related to overly "tight" insulin control for type 2 diabetes prompts nearly 100,000 emergency department visits and 30,000 hospitalizations each year and is particularly common among older patients, according to a report published online March 10 in JAMA Internal Medicine.

In an analysis of data from a nationally representative sample of hospitals in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, researchers estimated that 97,648 ED visits occurred annually during a 5-year period among adults with type 2 diabetes who presented with hypoglycemia-related shock, loss of consciousness, seizure, injury or fall, or altered mental status. Most cases involved blood glucose levels of 50 mg/dL or less, said Dr. Andrew I. Geller of the division of healthcare quality promotion at the Centers for Disease Control and Prevention, Atlanta, and his associates.

The case rate was 34.9 per 1,000 insulin-treated patients among those aged 80 years and older. In comparison, the rate was only 13.7 per 1,000 among those aged 45-64 years. Older patients were more than twice as likely as younger ones to require an ED visit and nearly five times as likely to require hospitalization, Dr. Geller and his associates said (JAMA Intern. Med. 2014 March 10 [doi:10.1001/jamainternmed.2014.136]).

The most common precipitating factor was "meal-related misadventure" – failing to eat shortly after taking rapid-acting insulin or failing to adjust the insulin regimen to account for a missed meal or a very small meal. Hypoglycemia also was frequently preceded by the patient taking the wrong dose of insulin or the wrong insulin product, usually taking rapid-acting insulin instead of long-acting insulin.

"These data probably underestimate the total burden of hypoglycemic events because hypoglycemia, although a frequent cause of [emergency medical services] calls, is most often cared for outside the ED setting. Patients who have hypoglycemia unawareness and whose episodes do not result in EMS or ED care [were] not counted, nor [were] those who died en route to the ED," they added.

No financial conflicts of interest were reported.

Severe hypoglycemia related to overly "tight" insulin control for type 2 diabetes prompts nearly 100,000 emergency department visits and 30,000 hospitalizations each year and is particularly common among older patients, according to a report published online March 10 in JAMA Internal Medicine.

In an analysis of data from a nationally representative sample of hospitals in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, researchers estimated that 97,648 ED visits occurred annually during a 5-year period among adults with type 2 diabetes who presented with hypoglycemia-related shock, loss of consciousness, seizure, injury or fall, or altered mental status. Most cases involved blood glucose levels of 50 mg/dL or less, said Dr. Andrew I. Geller of the division of healthcare quality promotion at the Centers for Disease Control and Prevention, Atlanta, and his associates.

The case rate was 34.9 per 1,000 insulin-treated patients among those aged 80 years and older. In comparison, the rate was only 13.7 per 1,000 among those aged 45-64 years. Older patients were more than twice as likely as younger ones to require an ED visit and nearly five times as likely to require hospitalization, Dr. Geller and his associates said (JAMA Intern. Med. 2014 March 10 [doi:10.1001/jamainternmed.2014.136]).

The most common precipitating factor was "meal-related misadventure" – failing to eat shortly after taking rapid-acting insulin or failing to adjust the insulin regimen to account for a missed meal or a very small meal. Hypoglycemia also was frequently preceded by the patient taking the wrong dose of insulin or the wrong insulin product, usually taking rapid-acting insulin instead of long-acting insulin.

"These data probably underestimate the total burden of hypoglycemic events because hypoglycemia, although a frequent cause of [emergency medical services] calls, is most often cared for outside the ED setting. Patients who have hypoglycemia unawareness and whose episodes do not result in EMS or ED care [were] not counted, nor [were] those who died en route to the ED," they added.

No financial conflicts of interest were reported.

Severe hypoglycemia related to overly "tight" insulin control for type 2 diabetes prompts nearly 100,000 emergency department visits and 30,000 hospitalizations each year and is particularly common among older patients, according to a report published online March 10 in JAMA Internal Medicine.

In an analysis of data from a nationally representative sample of hospitals in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, researchers estimated that 97,648 ED visits occurred annually during a 5-year period among adults with type 2 diabetes who presented with hypoglycemia-related shock, loss of consciousness, seizure, injury or fall, or altered mental status. Most cases involved blood glucose levels of 50 mg/dL or less, said Dr. Andrew I. Geller of the division of healthcare quality promotion at the Centers for Disease Control and Prevention, Atlanta, and his associates.

The case rate was 34.9 per 1,000 insulin-treated patients among those aged 80 years and older. In comparison, the rate was only 13.7 per 1,000 among those aged 45-64 years. Older patients were more than twice as likely as younger ones to require an ED visit and nearly five times as likely to require hospitalization, Dr. Geller and his associates said (JAMA Intern. Med. 2014 March 10 [doi:10.1001/jamainternmed.2014.136]).

The most common precipitating factor was "meal-related misadventure" – failing to eat shortly after taking rapid-acting insulin or failing to adjust the insulin regimen to account for a missed meal or a very small meal. Hypoglycemia also was frequently preceded by the patient taking the wrong dose of insulin or the wrong insulin product, usually taking rapid-acting insulin instead of long-acting insulin.

"These data probably underestimate the total burden of hypoglycemic events because hypoglycemia, although a frequent cause of [emergency medical services] calls, is most often cared for outside the ED setting. Patients who have hypoglycemia unawareness and whose episodes do not result in EMS or ED care [were] not counted, nor [were] those who died en route to the ED," they added.

No financial conflicts of interest were reported.

Severe hypoglycemia related to overly "tight" insulin control for type 2 diabetes prompts nearly 100,000 emergency department visits and 30,000 hospitalizations each year and is particularly common among older patients, according to a report published online March 10 in JAMA Internal Medicine.

In an analysis of data from a nationally representative sample of hospitals in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, researchers estimated that 97,648 ED visits occurred annually during a 5-year period among adults with type 2 diabetes who presented with hypoglycemia-related shock, loss of consciousness, seizure, injury or fall, or altered mental status. Most cases involved blood glucose levels of 50 mg/dL or less, said Dr. Andrew I. Geller of the division of healthcare quality promotion at the Centers for Disease Control and Prevention, Atlanta, and his associates.

The case rate was 34.9 per 1,000 insulin-treated patients among those aged 80 years and older. In comparison, the rate was only 13.7 per 1,000 among those aged 45-64 years. Older patients were more than twice as likely as younger ones to require an ED visit and nearly five times as likely to require hospitalization, Dr. Geller and his associates said (JAMA Intern. Med. 2014 March 10 [doi:10.1001/jamainternmed.2014.136]).

The most common precipitating factor was "meal-related misadventure" – failing to eat shortly after taking rapid-acting insulin or failing to adjust the insulin regimen to account for a missed meal or a very small meal. Hypoglycemia also was frequently preceded by the patient taking the wrong dose of insulin or the wrong insulin product, usually taking rapid-acting insulin instead of long-acting insulin.

"These data probably underestimate the total burden of hypoglycemic events because hypoglycemia, although a frequent cause of [emergency medical services] calls, is most often cared for outside the ED setting. Patients who have hypoglycemia unawareness and whose episodes do not result in EMS or ED care [were] not counted, nor [were] those who died en route to the ED," they added.

No financial conflicts of interest were reported.

Severe hypoglycemia related to overly "tight" insulin control for type 2 diabetes prompts nearly 100,000 emergency department visits and 30,000 hospitalizations each year and is particularly common among older patients, according to a report published online March 10 in JAMA Internal Medicine.

In an analysis of data from a nationally representative sample of hospitals in the National Electronic Injury Surveillance System-Cooperative Adverse Drug Event Surveillance project, researchers estimated that 97,648 ED visits occurred annually during a 5-year period among adults with type 2 diabetes who presented with hypoglycemia-related shock, loss of consciousness, seizure, injury or fall, or altered mental status. Most cases involved blood glucose levels of 50 mg/dL or less, said Dr. Andrew I. Geller of the division of healthcare quality promotion at the Centers for Disease Control and Prevention, Atlanta, and his associates.

The case rate was 34.9 per 1,000 insulin-treated patients among those aged 80 years and older. In comparison, the rate was only 13.7 per 1,000 among those aged 45-64 years. Older patients were more than twice as likely as younger ones to require an ED visit and nearly five times as likely to require hospitalization, Dr. Geller and his associates said (JAMA Intern. Med. 2014 March 10 [doi:10.1001/jamainternmed.2014.136]).

The most common precipitating factor was "meal-related misadventure" – failing to eat shortly after taking rapid-acting insulin or failing to adjust the insulin regimen to account for a missed meal or a very small meal. Hypoglycemia also was frequently preceded by the patient taking the wrong dose of insulin or the wrong insulin product, usually taking rapid-acting insulin instead of long-acting insulin.

"These data probably underestimate the total burden of hypoglycemic events because hypoglycemia, although a frequent cause of [emergency medical services] calls, is most often cared for outside the ED setting. Patients who have hypoglycemia unawareness and whose episodes do not result in EMS or ED care [were] not counted, nor [were] those who died en route to the ED," they added.

No financial conflicts of interest were reported.

Among patients with chronic hepatitis C virus infection, viral factors such as viral load and HCV genotype "did not play any significant role in the causation of acute kidney dysfunction events" but known nonviral risk factors did, according to a report published online in the Journal of Clinical and Experimental Hepatology.

In a retrospective cohort study involving 468 patients with chronic HCV (mean age, 50 years) enrolled during a 1-year period at a single hepatology clinic and followed for 3 months to 6 years*, 124 episodes of acute kidney dysfunction developed in 63 patients.

Such dysfunction was significantly more likely to develop in those who had comorbid diabetes (47.6% prevalence, compared with 16.5% prevalence in nondiabetic participants), hypertension (69.8% prevalence, compared with 38.8% prevalence in nonhypertensive participants), or a history of IV drug use (44.4% prevalence, compared with 29.4% prevalence in nonusers), said Dr. Sanjaya Kumar Satapathy, who was with the division of gastroenterology at New York Medical College during the study, and his associates.

"Acute volume depletion secondary to nausea, vomiting, diarrhea, and large-volume paracentesis accounted for the major bulk of patients with acute kidney dysfunction. ... In addition, infections (n = 23) and GI bleeding (n = 9), the majority of which occurred in patients with advanced liver disease, appeared to play a significant role in developing acute kidney dysfunction," the investigators wrote (J. Clin. Exp. Hepatol. 2014 [doi:10.1016/j.jceh.2014.01.004]).

In contrast, the prevalence of acute kidney dysfunction showed no relation to baseline viral load; viral genotype; or the patient’s sex, race, body mass index, HIV status, or history regarding alcohol abuse. A total of 68 of the 124 acute kidney dysfunction events (54.8%) resolved completely, with serum creatinine returning to baseline levels; there was partial recovery in another 34.7% of the events, and the remaining 10.5% of cases progressed to either chronic kidney disease or end-stage renal disease.

Although acute kidney dysfunction is a well-known complication of cirrhosis and liver failure, most cases in this study (76%) developed in patients who did not have decompensated or advanced liver disease, noted Dr. Satapathy, who is now with the University of Tennessee, Memphis, and his associates.

No funding sources or potential conflicts of interest were disclosed.

*Correction, 4/1/2014: An earlier version of the article misstated the length of time patients were monitored.

Among patients with chronic hepatitis C virus infection, viral factors such as viral load and HCV genotype "did not play any significant role in the causation of acute kidney dysfunction events" but known nonviral risk factors did, according to a report published online in the Journal of Clinical and Experimental Hepatology.

In a retrospective cohort study involving 468 patients with chronic HCV (mean age, 50 years) enrolled during a 1-year period at a single hepatology clinic and followed for 3 months to 6 years*, 124 episodes of acute kidney dysfunction developed in 63 patients.

Such dysfunction was significantly more likely to develop in those who had comorbid diabetes (47.6% prevalence, compared with 16.5% prevalence in nondiabetic participants), hypertension (69.8% prevalence, compared with 38.8% prevalence in nonhypertensive participants), or a history of IV drug use (44.4% prevalence, compared with 29.4% prevalence in nonusers), said Dr. Sanjaya Kumar Satapathy, who was with the division of gastroenterology at New York Medical College during the study, and his associates.

"Acute volume depletion secondary to nausea, vomiting, diarrhea, and large-volume paracentesis accounted for the major bulk of patients with acute kidney dysfunction. ... In addition, infections (n = 23) and GI bleeding (n = 9), the majority of which occurred in patients with advanced liver disease, appeared to play a significant role in developing acute kidney dysfunction," the investigators wrote (J. Clin. Exp. Hepatol. 2014 [doi:10.1016/j.jceh.2014.01.004]).

In contrast, the prevalence of acute kidney dysfunction showed no relation to baseline viral load; viral genotype; or the patient’s sex, race, body mass index, HIV status, or history regarding alcohol abuse. A total of 68 of the 124 acute kidney dysfunction events (54.8%) resolved completely, with serum creatinine returning to baseline levels; there was partial recovery in another 34.7% of the events, and the remaining 10.5% of cases progressed to either chronic kidney disease or end-stage renal disease.

Although acute kidney dysfunction is a well-known complication of cirrhosis and liver failure, most cases in this study (76%) developed in patients who did not have decompensated or advanced liver disease, noted Dr. Satapathy, who is now with the University of Tennessee, Memphis, and his associates.

No funding sources or potential conflicts of interest were disclosed.

*Correction, 4/1/2014: An earlier version of the article misstated the length of time patients were monitored.

Among patients with chronic hepatitis C virus infection, viral factors such as viral load and HCV genotype "did not play any significant role in the causation of acute kidney dysfunction events" but known nonviral risk factors did, according to a report published online in the Journal of Clinical and Experimental Hepatology.

In a retrospective cohort study involving 468 patients with chronic HCV (mean age, 50 years) enrolled during a 1-year period at a single hepatology clinic and followed for 3 months to 6 years*, 124 episodes of acute kidney dysfunction developed in 63 patients.

Such dysfunction was significantly more likely to develop in those who had comorbid diabetes (47.6% prevalence, compared with 16.5% prevalence in nondiabetic participants), hypertension (69.8% prevalence, compared with 38.8% prevalence in nonhypertensive participants), or a history of IV drug use (44.4% prevalence, compared with 29.4% prevalence in nonusers), said Dr. Sanjaya Kumar Satapathy, who was with the division of gastroenterology at New York Medical College during the study, and his associates.

"Acute volume depletion secondary to nausea, vomiting, diarrhea, and large-volume paracentesis accounted for the major bulk of patients with acute kidney dysfunction. ... In addition, infections (n = 23) and GI bleeding (n = 9), the majority of which occurred in patients with advanced liver disease, appeared to play a significant role in developing acute kidney dysfunction," the investigators wrote (J. Clin. Exp. Hepatol. 2014 [doi:10.1016/j.jceh.2014.01.004]).

In contrast, the prevalence of acute kidney dysfunction showed no relation to baseline viral load; viral genotype; or the patient’s sex, race, body mass index, HIV status, or history regarding alcohol abuse. A total of 68 of the 124 acute kidney dysfunction events (54.8%) resolved completely, with serum creatinine returning to baseline levels; there was partial recovery in another 34.7% of the events, and the remaining 10.5% of cases progressed to either chronic kidney disease or end-stage renal disease.

Although acute kidney dysfunction is a well-known complication of cirrhosis and liver failure, most cases in this study (76%) developed in patients who did not have decompensated or advanced liver disease, noted Dr. Satapathy, who is now with the University of Tennessee, Memphis, and his associates.

No funding sources or potential conflicts of interest were disclosed.

*Correction, 4/1/2014: An earlier version of the article misstated the length of time patients were monitored.

Preimplant biopsy of donor kidneys doesn’t accurately predict the organs’ viability and leads to many acceptable kidneys being discarded, according to two separate reports published online in the Clinical Journal of the American Society of Nephrology.

Biopsies are obtained routinely from donor kidneys in the United States, and unfavorable biopsy findings are the most frequently cited reason for discarding donor kidneys as unacceptable. Ideally, such samples would be obtained by core needle biopsy, would not be frozen, would be thoroughly examined by a pathologist with special training in reading kidney biopsies, and would be assessed meticulously for chronic tubular atrophy, arteriolar hyalinosis, interstitial inflammation, interstitial fibrosis, and the presence and severity of acute tubular necrosis.

In actual practice, however, these samples are almost always obtained by wedge biopsy, are frozen, and are rushed through a perfunctory examination by whatever pathologist is available so that the organ can be transplanted as quickly as possible if it is found to be acceptable. So many clinicians have questioned whether the results of such biopsies actually assess the organs’ viability and predict graft failure, both groups of researchers noted.

In what they described as the largest cohort study to date on this issue, one team analyzed data regarding 651 consecutive kidney transplants performed during a 2-year period, for which four organ procurement organizations obtained the kidneys from 369 deceased donors. The four organizations performed wedge biopsies immediately after procurement, and different pathology services evaluated frozen sections from these organs and reported their findings to potential transplant centers.

Patient outcomes were tracked using information in the United Network for Organ Sharing (UNOS) database, said Dr. Isaac E. Hall of the section of nephrology and the program of applied translational research, Yale University, New Haven, Conn., and his associates.

They assessed whether a biopsy finding of acute tubular necrosis correlated with the graft’s performance after transplantation. Acute tubular necrosis was reported in 110 biopsies (17%) overall. The four procurement organizations varied widely in their reported rates of the abnormality, from a low of zero cases to a high of 25% of cases. This variation suggests that the process of obtaining and interpreting these biopsies is, at best, not uniform among procurement groups, according to the investigators.

During a median follow-up of 1 year, the primary outcome of interest – delayed graft function – occurred in 45% of kidneys that were reported to have tubular necrosis and in 39% of those reportedly free of such necrosis. This is a nonsignificant difference. There also was no significant difference in the secondary outcome of graft failure between recipients of organs with acute tubular necrosis, compared with recipients of organs without it.

In summary, there was no significant association between biopsy reports of acute tubular necrosis and graft viability. "It is reasonable to question whether acute tubular necrosis, or acute kidney injury in general for that matter, truly causes important allograft outcomes," Dr. Hall and his colleagues wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.08270813]).

In the second study, Dr. Bertram L. Kasiske of the Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, and his associates assessed the records for 83 kidneys that were discarded because of unfavorable biopsy findings (cases) and 83 contralateral kidneys from the same donors that were transplanted (contralateral controls). They compared these findings with those for 151 transplanted kidneys from 83 deceased donors who were matched for the index cases’ donor profiles.

"Ours is the first controlled study to compare biopsy findings between discarded kidneys and matched transplanted kidneys," Dr. Kasiske and his colleagues noted.

They found that most of the biopsy reports were of low quality, and very few indicated the amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, or acute tubular necrosis. The percentage of glomerulosclerosis was often the only finding upon which to base the decision of whether to use or discard the allograft.

But the percentage of glomerulosclerosis overlapped substantially between cases (discarded kidneys) and controls (transplanted kidneys). This suggests that "information obtained from procurement biopsies is of low quality and may lead to unnecessary discard of transplantable kidneys," Dr. Kasiske and his associates wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.07610713]).

"A reasonable conclusion from this and other studies is that the widespread practice of routinely obtaining procurement biopsies should be abandoned, as has been successfully done in Europe," they noted.

Dr. Hall’s study was supported by the American Heart Association, the Roche Organ Transplantation Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and the U.S. Health Resources and Services Administration. Dr. Kasiske’s study was supported by the Minneapolis Medical Research Foundation, the Organ Procurement and Transplantation Network, the Scientific Registry of Transplant Recipients, and the United Network for Organ Sharing. Both research groups reported no potential financial conflicts of interest.

Preimplant biopsy of donor kidneys doesn’t accurately predict the organs’ viability and leads to many acceptable kidneys being discarded, according to two separate reports published online in the Clinical Journal of the American Society of Nephrology.

Biopsies are obtained routinely from donor kidneys in the United States, and unfavorable biopsy findings are the most frequently cited reason for discarding donor kidneys as unacceptable. Ideally, such samples would be obtained by core needle biopsy, would not be frozen, would be thoroughly examined by a pathologist with special training in reading kidney biopsies, and would be assessed meticulously for chronic tubular atrophy, arteriolar hyalinosis, interstitial inflammation, interstitial fibrosis, and the presence and severity of acute tubular necrosis.

In actual practice, however, these samples are almost always obtained by wedge biopsy, are frozen, and are rushed through a perfunctory examination by whatever pathologist is available so that the organ can be transplanted as quickly as possible if it is found to be acceptable. So many clinicians have questioned whether the results of such biopsies actually assess the organs’ viability and predict graft failure, both groups of researchers noted.

In what they described as the largest cohort study to date on this issue, one team analyzed data regarding 651 consecutive kidney transplants performed during a 2-year period, for which four organ procurement organizations obtained the kidneys from 369 deceased donors. The four organizations performed wedge biopsies immediately after procurement, and different pathology services evaluated frozen sections from these organs and reported their findings to potential transplant centers.

Patient outcomes were tracked using information in the United Network for Organ Sharing (UNOS) database, said Dr. Isaac E. Hall of the section of nephrology and the program of applied translational research, Yale University, New Haven, Conn., and his associates.

They assessed whether a biopsy finding of acute tubular necrosis correlated with the graft’s performance after transplantation. Acute tubular necrosis was reported in 110 biopsies (17%) overall. The four procurement organizations varied widely in their reported rates of the abnormality, from a low of zero cases to a high of 25% of cases. This variation suggests that the process of obtaining and interpreting these biopsies is, at best, not uniform among procurement groups, according to the investigators.

During a median follow-up of 1 year, the primary outcome of interest – delayed graft function – occurred in 45% of kidneys that were reported to have tubular necrosis and in 39% of those reportedly free of such necrosis. This is a nonsignificant difference. There also was no significant difference in the secondary outcome of graft failure between recipients of organs with acute tubular necrosis, compared with recipients of organs without it.

In summary, there was no significant association between biopsy reports of acute tubular necrosis and graft viability. "It is reasonable to question whether acute tubular necrosis, or acute kidney injury in general for that matter, truly causes important allograft outcomes," Dr. Hall and his colleagues wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.08270813]).

In the second study, Dr. Bertram L. Kasiske of the Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, and his associates assessed the records for 83 kidneys that were discarded because of unfavorable biopsy findings (cases) and 83 contralateral kidneys from the same donors that were transplanted (contralateral controls). They compared these findings with those for 151 transplanted kidneys from 83 deceased donors who were matched for the index cases’ donor profiles.

"Ours is the first controlled study to compare biopsy findings between discarded kidneys and matched transplanted kidneys," Dr. Kasiske and his colleagues noted.

They found that most of the biopsy reports were of low quality, and very few indicated the amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, or acute tubular necrosis. The percentage of glomerulosclerosis was often the only finding upon which to base the decision of whether to use or discard the allograft.

But the percentage of glomerulosclerosis overlapped substantially between cases (discarded kidneys) and controls (transplanted kidneys). This suggests that "information obtained from procurement biopsies is of low quality and may lead to unnecessary discard of transplantable kidneys," Dr. Kasiske and his associates wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.07610713]).

"A reasonable conclusion from this and other studies is that the widespread practice of routinely obtaining procurement biopsies should be abandoned, as has been successfully done in Europe," they noted.

Dr. Hall’s study was supported by the American Heart Association, the Roche Organ Transplantation Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and the U.S. Health Resources and Services Administration. Dr. Kasiske’s study was supported by the Minneapolis Medical Research Foundation, the Organ Procurement and Transplantation Network, the Scientific Registry of Transplant Recipients, and the United Network for Organ Sharing. Both research groups reported no potential financial conflicts of interest.

Preimplant biopsy of donor kidneys doesn’t accurately predict the organs’ viability and leads to many acceptable kidneys being discarded, according to two separate reports published online in the Clinical Journal of the American Society of Nephrology.

Biopsies are obtained routinely from donor kidneys in the United States, and unfavorable biopsy findings are the most frequently cited reason for discarding donor kidneys as unacceptable. Ideally, such samples would be obtained by core needle biopsy, would not be frozen, would be thoroughly examined by a pathologist with special training in reading kidney biopsies, and would be assessed meticulously for chronic tubular atrophy, arteriolar hyalinosis, interstitial inflammation, interstitial fibrosis, and the presence and severity of acute tubular necrosis.

In actual practice, however, these samples are almost always obtained by wedge biopsy, are frozen, and are rushed through a perfunctory examination by whatever pathologist is available so that the organ can be transplanted as quickly as possible if it is found to be acceptable. So many clinicians have questioned whether the results of such biopsies actually assess the organs’ viability and predict graft failure, both groups of researchers noted.

In what they described as the largest cohort study to date on this issue, one team analyzed data regarding 651 consecutive kidney transplants performed during a 2-year period, for which four organ procurement organizations obtained the kidneys from 369 deceased donors. The four organizations performed wedge biopsies immediately after procurement, and different pathology services evaluated frozen sections from these organs and reported their findings to potential transplant centers.

Patient outcomes were tracked using information in the United Network for Organ Sharing (UNOS) database, said Dr. Isaac E. Hall of the section of nephrology and the program of applied translational research, Yale University, New Haven, Conn., and his associates.

They assessed whether a biopsy finding of acute tubular necrosis correlated with the graft’s performance after transplantation. Acute tubular necrosis was reported in 110 biopsies (17%) overall. The four procurement organizations varied widely in their reported rates of the abnormality, from a low of zero cases to a high of 25% of cases. This variation suggests that the process of obtaining and interpreting these biopsies is, at best, not uniform among procurement groups, according to the investigators.

During a median follow-up of 1 year, the primary outcome of interest – delayed graft function – occurred in 45% of kidneys that were reported to have tubular necrosis and in 39% of those reportedly free of such necrosis. This is a nonsignificant difference. There also was no significant difference in the secondary outcome of graft failure between recipients of organs with acute tubular necrosis, compared with recipients of organs without it.

In summary, there was no significant association between biopsy reports of acute tubular necrosis and graft viability. "It is reasonable to question whether acute tubular necrosis, or acute kidney injury in general for that matter, truly causes important allograft outcomes," Dr. Hall and his colleagues wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.08270813]).

In the second study, Dr. Bertram L. Kasiske of the Scientific Registry of Transplant Recipients, Minneapolis Medical Research Foundation, and his associates assessed the records for 83 kidneys that were discarded because of unfavorable biopsy findings (cases) and 83 contralateral kidneys from the same donors that were transplanted (contralateral controls). They compared these findings with those for 151 transplanted kidneys from 83 deceased donors who were matched for the index cases’ donor profiles.

"Ours is the first controlled study to compare biopsy findings between discarded kidneys and matched transplanted kidneys," Dr. Kasiske and his colleagues noted.

They found that most of the biopsy reports were of low quality, and very few indicated the amounts of tubular atrophy, interstitial inflammation, arteriolar hyalinosis, or acute tubular necrosis. The percentage of glomerulosclerosis was often the only finding upon which to base the decision of whether to use or discard the allograft.

But the percentage of glomerulosclerosis overlapped substantially between cases (discarded kidneys) and controls (transplanted kidneys). This suggests that "information obtained from procurement biopsies is of low quality and may lead to unnecessary discard of transplantable kidneys," Dr. Kasiske and his associates wrote (Clin. J. Am. Soc. Nephrol. 2014 [doi:10.2215/CJN.07610713]).

"A reasonable conclusion from this and other studies is that the widespread practice of routinely obtaining procurement biopsies should be abandoned, as has been successfully done in Europe," they noted.

Dr. Hall’s study was supported by the American Heart Association, the Roche Organ Transplantation Research Foundation, the National Institute of Diabetes and Digestive and Kidney Diseases, and the U.S. Health Resources and Services Administration. Dr. Kasiske’s study was supported by the Minneapolis Medical Research Foundation, the Organ Procurement and Transplantation Network, the Scientific Registry of Transplant Recipients, and the United Network for Organ Sharing. Both research groups reported no potential financial conflicts of interest.

Extended follow-up confirms that radical prostatectomy continues to substantially reduce mortality from any cause, mortality from prostate cancer, and the risk of developing metastases over the long term, compared with watchful waiting, investigators reported March 5 in the New England Journal of Medicine.

These protective effects were most pronounced in men who were under age 65 at diagnosis, but older men had the additional benefit from radical prostatectomy of improved quality of life, because of a significantly lower risk of palliative care, including androgen-deprivation therapy. "The life experience after the diagnosis of prostate cancer differs substantially between the two study groups and evolves over decades," said Dr. Anna Bill-Axelson of Uppsala (Sweden) University Hospital and her associates.

Between 1989 and 1999, men with localized prostate cancer who were under age 75 and had life expectancies beyond 10 years, were randomly assigned to undergo radical prostatectomy (347 patients) or watchful waiting (348 patients) at 14 medical centers in Sweden, Finland, and Iceland. A total of 447 men (64%) died during extended follow-up lasting until 2012 (median follow-up, 13.4 years).

All-cause mortality was 56.1% in the prostatectomy group, significantly lower than the 68.9% all-cause mortality in the watchful waiting group; the number needed to treat to prevent 1 death at 18 years of follow-up was 8. Similarly, prostate cancer–specific mortality was 17.7% with prostatectomy vs. 28.7% with watchful waiting, and the difference between the two study groups continued to increase over time, the investigators reported (N. Engl. J. Med. 2014 March 5 [doi: 10.1056/NEMoa1311593]).

Among men under age 65 at diagnosis, all-cause mortality was 25.5 percentage points lower, prostate cancer–specific mortality was 15.8 percentage points lower, and risk of metastases was 15.8 percentage points lower with prostatectomy than with watchful waiting. "In this age group, the number needed to treat to prevent 1 death from prostate cancer was 4," Dr. Bill-Axelson and her associates said.

This study was supported by the Swedish Cancer Society, the National Institutes of Health, the Karolinska Institute, the Prostate Cancer Foundation, and the Percy Falk Foundation. The authors reported that they had no financial conflicts of interest.

Extended follow-up confirms that radical prostatectomy continues to substantially reduce mortality from any cause, mortality from prostate cancer, and the risk of developing metastases over the long term, compared with watchful waiting, investigators reported March 5 in the New England Journal of Medicine.

These protective effects were most pronounced in men who were under age 65 at diagnosis, but older men had the additional benefit from radical prostatectomy of improved quality of life, because of a significantly lower risk of palliative care, including androgen-deprivation therapy. "The life experience after the diagnosis of prostate cancer differs substantially between the two study groups and evolves over decades," said Dr. Anna Bill-Axelson of Uppsala (Sweden) University Hospital and her associates.

Between 1989 and 1999, men with localized prostate cancer who were under age 75 and had life expectancies beyond 10 years, were randomly assigned to undergo radical prostatectomy (347 patients) or watchful waiting (348 patients) at 14 medical centers in Sweden, Finland, and Iceland. A total of 447 men (64%) died during extended follow-up lasting until 2012 (median follow-up, 13.4 years).

All-cause mortality was 56.1% in the prostatectomy group, significantly lower than the 68.9% all-cause mortality in the watchful waiting group; the number needed to treat to prevent 1 death at 18 years of follow-up was 8. Similarly, prostate cancer–specific mortality was 17.7% with prostatectomy vs. 28.7% with watchful waiting, and the difference between the two study groups continued to increase over time, the investigators reported (N. Engl. J. Med. 2014 March 5 [doi: 10.1056/NEMoa1311593]).

Among men under age 65 at diagnosis, all-cause mortality was 25.5 percentage points lower, prostate cancer–specific mortality was 15.8 percentage points lower, and risk of metastases was 15.8 percentage points lower with prostatectomy than with watchful waiting. "In this age group, the number needed to treat to prevent 1 death from prostate cancer was 4," Dr. Bill-Axelson and her associates said.

This study was supported by the Swedish Cancer Society, the National Institutes of Health, the Karolinska Institute, the Prostate Cancer Foundation, and the Percy Falk Foundation. The authors reported that they had no financial conflicts of interest.

Extended follow-up confirms that radical prostatectomy continues to substantially reduce mortality from any cause, mortality from prostate cancer, and the risk of developing metastases over the long term, compared with watchful waiting, investigators reported March 5 in the New England Journal of Medicine.

These protective effects were most pronounced in men who were under age 65 at diagnosis, but older men had the additional benefit from radical prostatectomy of improved quality of life, because of a significantly lower risk of palliative care, including androgen-deprivation therapy. "The life experience after the diagnosis of prostate cancer differs substantially between the two study groups and evolves over decades," said Dr. Anna Bill-Axelson of Uppsala (Sweden) University Hospital and her associates.

Between 1989 and 1999, men with localized prostate cancer who were under age 75 and had life expectancies beyond 10 years, were randomly assigned to undergo radical prostatectomy (347 patients) or watchful waiting (348 patients) at 14 medical centers in Sweden, Finland, and Iceland. A total of 447 men (64%) died during extended follow-up lasting until 2012 (median follow-up, 13.4 years).

All-cause mortality was 56.1% in the prostatectomy group, significantly lower than the 68.9% all-cause mortality in the watchful waiting group; the number needed to treat to prevent 1 death at 18 years of follow-up was 8. Similarly, prostate cancer–specific mortality was 17.7% with prostatectomy vs. 28.7% with watchful waiting, and the difference between the two study groups continued to increase over time, the investigators reported (N. Engl. J. Med. 2014 March 5 [doi: 10.1056/NEMoa1311593]).

Among men under age 65 at diagnosis, all-cause mortality was 25.5 percentage points lower, prostate cancer–specific mortality was 15.8 percentage points lower, and risk of metastases was 15.8 percentage points lower with prostatectomy than with watchful waiting. "In this age group, the number needed to treat to prevent 1 death from prostate cancer was 4," Dr. Bill-Axelson and her associates said.

This study was supported by the Swedish Cancer Society, the National Institutes of Health, the Karolinska Institute, the Prostate Cancer Foundation, and the Percy Falk Foundation. The authors reported that they had no financial conflicts of interest.

Warfarin therapy decreased the composite endpoint of death, recurrent myocardial infarction, and ischemic stroke after an incident acute MI with atrial fibrillation among patients who had chronic kidney disease of all severities, according to a report published online March 4 in JAMA.

In a prospective nationwide cohort study involving 24,317 such patients in Sweden, warfarin provided this benefit without raising the risk of bleeding during 1 year of follow-up. Approximately half of the study participants had CKD of stage 3 or higher. Only 22% were given warfarin at hospital discharge, said Juan Jesus Carrero, Ph.D., of the Center for Molecular Medicine, Karolinska Institutet, Stockholm, and his associates.

During follow-up, there were 9,002 composite endpoint events: 3,551 deaths, 4,573 recurrent MIs, and 878 ischemic strokes. Across all categories of CKD severity, patients taking warfarin had 5.8% fewer deaths, 2.2% fewer MIs, and 1.8% fewer ischemic strokes than those not taking warfarin. Yet the relative risk of bleeding events was not significantly higher with warfarin, regardless of the severity of CKD, the investigators said (JAMA 2014 March 4 [doi:10.1001/jama.2014.1334]).

These findings refute the results of some earlier observational studies in which warfarin therapy raised the risk of death or stroke in severe CKD, which prompted a modification of treatment guidelines. Ironically, patients with CKD potentially have the most to gain from using prophylactic warfarin, since their renal dysfunction puts them at additional risk of stroke and death, Dr. Carrero and his colleagues noted.

This study was supported by the Swedish Foundation for Strategic Research. Dr. Carrero reported no potential financial conflicts of interest; his associates reported ties to numerous industry sources.

Warfarin therapy decreased the composite endpoint of death, recurrent myocardial infarction, and ischemic stroke after an incident acute MI with atrial fibrillation among patients who had chronic kidney disease of all severities, according to a report published online March 4 in JAMA.

In a prospective nationwide cohort study involving 24,317 such patients in Sweden, warfarin provided this benefit without raising the risk of bleeding during 1 year of follow-up. Approximately half of the study participants had CKD of stage 3 or higher. Only 22% were given warfarin at hospital discharge, said Juan Jesus Carrero, Ph.D., of the Center for Molecular Medicine, Karolinska Institutet, Stockholm, and his associates.

During follow-up, there were 9,002 composite endpoint events: 3,551 deaths, 4,573 recurrent MIs, and 878 ischemic strokes. Across all categories of CKD severity, patients taking warfarin had 5.8% fewer deaths, 2.2% fewer MIs, and 1.8% fewer ischemic strokes than those not taking warfarin. Yet the relative risk of bleeding events was not significantly higher with warfarin, regardless of the severity of CKD, the investigators said (JAMA 2014 March 4 [doi:10.1001/jama.2014.1334]).

These findings refute the results of some earlier observational studies in which warfarin therapy raised the risk of death or stroke in severe CKD, which prompted a modification of treatment guidelines. Ironically, patients with CKD potentially have the most to gain from using prophylactic warfarin, since their renal dysfunction puts them at additional risk of stroke and death, Dr. Carrero and his colleagues noted.

This study was supported by the Swedish Foundation for Strategic Research. Dr. Carrero reported no potential financial conflicts of interest; his associates reported ties to numerous industry sources.

Warfarin therapy decreased the composite endpoint of death, recurrent myocardial infarction, and ischemic stroke after an incident acute MI with atrial fibrillation among patients who had chronic kidney disease of all severities, according to a report published online March 4 in JAMA.

In a prospective nationwide cohort study involving 24,317 such patients in Sweden, warfarin provided this benefit without raising the risk of bleeding during 1 year of follow-up. Approximately half of the study participants had CKD of stage 3 or higher. Only 22% were given warfarin at hospital discharge, said Juan Jesus Carrero, Ph.D., of the Center for Molecular Medicine, Karolinska Institutet, Stockholm, and his associates.

During follow-up, there were 9,002 composite endpoint events: 3,551 deaths, 4,573 recurrent MIs, and 878 ischemic strokes. Across all categories of CKD severity, patients taking warfarin had 5.8% fewer deaths, 2.2% fewer MIs, and 1.8% fewer ischemic strokes than those not taking warfarin. Yet the relative risk of bleeding events was not significantly higher with warfarin, regardless of the severity of CKD, the investigators said (JAMA 2014 March 4 [doi:10.1001/jama.2014.1334]).

These findings refute the results of some earlier observational studies in which warfarin therapy raised the risk of death or stroke in severe CKD, which prompted a modification of treatment guidelines. Ironically, patients with CKD potentially have the most to gain from using prophylactic warfarin, since their renal dysfunction puts them at additional risk of stroke and death, Dr. Carrero and his colleagues noted.

This study was supported by the Swedish Foundation for Strategic Research. Dr. Carrero reported no potential financial conflicts of interest; his associates reported ties to numerous industry sources.

Most people who misuse opioid pain relievers cite friends and relatives as their sources for the drugs, but more of the people who misuse these agents most often – those who take them from 200 to 365 days of the year – obtain their opioids from physicians’ prescriptions than from any other single source, according to a report published online March 3 in JAMA Internal Medicine.

"These results underscore the need for interventions targeting prescribing behaviors, in addition to those targeting medication sharing, selling, and diversion," the report’s authors warned.

©PhotoDisk

It is a commonly cited statistic that most people who misuse opioid pain relievers obtain the drugs from family and friends for free, so many interventions to stop such misuse focus on patients. But few studies have examined whether the source of these drugs, and thus an appropriate target for interventions, might differ according to the frequency of misuse.

To study this issue, researchers analyzed data from the National Survey on Drug Use and Health, an annual survey that provides information on drug use among U.S. residents aged 12 years and older.

Survey data from 2008 through 2011 identified 11,018,735 respondents who said they misused an opioid pain reliever either by obtaining the drug without a prescription or by getting a prescription but taking the drug strictly because of the feeling or experience it provided. The source of the drug differed according to the frequency of use: As the days of use increased, the likelihood that the user obtained the drug from a friend or family member decreased, and the likelihood that he or she obtained the drug from a physician rose, said Christopher M. Jones, Pharm.D., and his associates at the National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta.

Among people who misused opioids only 1-29 days of the year, 54.4% said they got them from a friend or relative for free – the most popular source. In contrast, only 18% of this patient group said the opioids were prescribed by one or more physicians.

But the percentage of patients who obtained misused opioids through physician prescriptions steadily rose with increasing use.

Among those who misused the drugs 200-365 days a year, the top source was physician prescriptions, 27.3% of users, followed by opioids obtained for free from friends or relatives, 26.4%. A total of 23.2% of users said they bought their opioids from friends or relatives, while another 15% of frequent users bought their drugs from dealers or strangers.

"This pattern is similar to that of patients in opioid treatment programs, who cite dealers and physicians as frequent sources," Dr. Jones and his associates said in a Research Letter to the Editor (JAMA Intern. Med. 2014 March 3 [doi:10.1001/jamainternmed.2013.12809]).

"Many abusers of opioid pain relievers are going directly to doctors for their drugs," CDC Director Tom Frieden commented in a statement. "Health care providers need to screen for abuse risk and prescribe judiciously by checking past records in state prescription drug monitoring programs. It’s time we stop the source and treat the troubled."

"The essential steps health care providers can take to curb this serious health problem include more judicious prescribing, use of prescription-drug–monitoring programs, and screening patients for abuse before prescribing opioids," the study authors noted.

The federal government is encouraging the development of abuse-deterrent opioid formulations, the CDC noted, and requiring companies that make extended-release and long-acting opioids to offer prescribers educational programs about the understanding the risks of opioid therapy; choosing, managing, and monitoring patients; and counseling patients on safe use of opioids.

The Centers for Disease Control and Prevention supported the study. No financial conflicts of interest were reported.

Most people who misuse opioid pain relievers cite friends and relatives as their sources for the drugs, but more of the people who misuse these agents most often – those who take them from 200 to 365 days of the year – obtain their opioids from physicians’ prescriptions than from any other single source, according to a report published online March 3 in JAMA Internal Medicine.

"These results underscore the need for interventions targeting prescribing behaviors, in addition to those targeting medication sharing, selling, and diversion," the report’s authors warned.

©PhotoDisk

It is a commonly cited statistic that most people who misuse opioid pain relievers obtain the drugs from family and friends for free, so many interventions to stop such misuse focus on patients. But few studies have examined whether the source of these drugs, and thus an appropriate target for interventions, might differ according to the frequency of misuse.

To study this issue, researchers analyzed data from the National Survey on Drug Use and Health, an annual survey that provides information on drug use among U.S. residents aged 12 years and older.

Survey data from 2008 through 2011 identified 11,018,735 respondents who said they misused an opioid pain reliever either by obtaining the drug without a prescription or by getting a prescription but taking the drug strictly because of the feeling or experience it provided. The source of the drug differed according to the frequency of use: As the days of use increased, the likelihood that the user obtained the drug from a friend or family member decreased, and the likelihood that he or she obtained the drug from a physician rose, said Christopher M. Jones, Pharm.D., and his associates at the National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta.

Among people who misused opioids only 1-29 days of the year, 54.4% said they got them from a friend or relative for free – the most popular source. In contrast, only 18% of this patient group said the opioids were prescribed by one or more physicians.

But the percentage of patients who obtained misused opioids through physician prescriptions steadily rose with increasing use.

Among those who misused the drugs 200-365 days a year, the top source was physician prescriptions, 27.3% of users, followed by opioids obtained for free from friends or relatives, 26.4%. A total of 23.2% of users said they bought their opioids from friends or relatives, while another 15% of frequent users bought their drugs from dealers or strangers.

"This pattern is similar to that of patients in opioid treatment programs, who cite dealers and physicians as frequent sources," Dr. Jones and his associates said in a Research Letter to the Editor (JAMA Intern. Med. 2014 March 3 [doi:10.1001/jamainternmed.2013.12809]).

"Many abusers of opioid pain relievers are going directly to doctors for their drugs," CDC Director Tom Frieden commented in a statement. "Health care providers need to screen for abuse risk and prescribe judiciously by checking past records in state prescription drug monitoring programs. It’s time we stop the source and treat the troubled."

"The essential steps health care providers can take to curb this serious health problem include more judicious prescribing, use of prescription-drug–monitoring programs, and screening patients for abuse before prescribing opioids," the study authors noted.

The federal government is encouraging the development of abuse-deterrent opioid formulations, the CDC noted, and requiring companies that make extended-release and long-acting opioids to offer prescribers educational programs about the understanding the risks of opioid therapy; choosing, managing, and monitoring patients; and counseling patients on safe use of opioids.

The Centers for Disease Control and Prevention supported the study. No financial conflicts of interest were reported.

Most people who misuse opioid pain relievers cite friends and relatives as their sources for the drugs, but more of the people who misuse these agents most often – those who take them from 200 to 365 days of the year – obtain their opioids from physicians’ prescriptions than from any other single source, according to a report published online March 3 in JAMA Internal Medicine.

"These results underscore the need for interventions targeting prescribing behaviors, in addition to those targeting medication sharing, selling, and diversion," the report’s authors warned.

©PhotoDisk

It is a commonly cited statistic that most people who misuse opioid pain relievers obtain the drugs from family and friends for free, so many interventions to stop such misuse focus on patients. But few studies have examined whether the source of these drugs, and thus an appropriate target for interventions, might differ according to the frequency of misuse.

To study this issue, researchers analyzed data from the National Survey on Drug Use and Health, an annual survey that provides information on drug use among U.S. residents aged 12 years and older.

Survey data from 2008 through 2011 identified 11,018,735 respondents who said they misused an opioid pain reliever either by obtaining the drug without a prescription or by getting a prescription but taking the drug strictly because of the feeling or experience it provided. The source of the drug differed according to the frequency of use: As the days of use increased, the likelihood that the user obtained the drug from a friend or family member decreased, and the likelihood that he or she obtained the drug from a physician rose, said Christopher M. Jones, Pharm.D., and his associates at the National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Atlanta.

Among people who misused opioids only 1-29 days of the year, 54.4% said they got them from a friend or relative for free – the most popular source. In contrast, only 18% of this patient group said the opioids were prescribed by one or more physicians.

But the percentage of patients who obtained misused opioids through physician prescriptions steadily rose with increasing use.

Among those who misused the drugs 200-365 days a year, the top source was physician prescriptions, 27.3% of users, followed by opioids obtained for free from friends or relatives, 26.4%. A total of 23.2% of users said they bought their opioids from friends or relatives, while another 15% of frequent users bought their drugs from dealers or strangers.

"This pattern is similar to that of patients in opioid treatment programs, who cite dealers and physicians as frequent sources," Dr. Jones and his associates said in a Research Letter to the Editor (JAMA Intern. Med. 2014 March 3 [doi:10.1001/jamainternmed.2013.12809]).

"Many abusers of opioid pain relievers are going directly to doctors for their drugs," CDC Director Tom Frieden commented in a statement. "Health care providers need to screen for abuse risk and prescribe judiciously by checking past records in state prescription drug monitoring programs. It’s time we stop the source and treat the troubled."

"The essential steps health care providers can take to curb this serious health problem include more judicious prescribing, use of prescription-drug–monitoring programs, and screening patients for abuse before prescribing opioids," the study authors noted.

The federal government is encouraging the development of abuse-deterrent opioid formulations, the CDC noted, and requiring companies that make extended-release and long-acting opioids to offer prescribers educational programs about the understanding the risks of opioid therapy; choosing, managing, and monitoring patients; and counseling patients on safe use of opioids.

The Centers for Disease Control and Prevention supported the study. No financial conflicts of interest were reported.

Undergoing prophylactic oophorectomy reduces all-cause mortality by 77% among women who carry a deleterious BRCA1 or BRCA2 genetic mutation, according to a report published online Feb. 24 in the Journal of Clinical Oncology.

The surgery’s protective effect stems largely from a reduction in the incidence of ovarian, tubal, and peritoneal cancers, "but there is an important component from reducing breast cancer incidence and mortality as well," reported Dr. Amy P.M. Finch of the University of Toronto and her associates in the Hereditary Ovarian Cancer Clinical Study Group.

©Kativ/iStockphoto

In addition, the results of this prospective cohort study support the recommendation that these women should undergo prophylactic oophorectomy by age 35, because their risk of developing cancer rises markedly after that, the investigators said.

Noting that the effect of oophorectomy on mortality has not been well studied and that the optimal age for undergoing the procedure hasn’t yet been determined, Dr. Finch and her colleagues analyzed data in an international registry of carriers of deleterious BRCA1 and BRCA2 mutations. Their study cohort included 5,783 women followed at 43 medical centers in Canada, the United States, Austria, France, Italy, Norway, and Poland, who were enrolled in 1995-2011.

Just under half of these women had a history of breast cancer, and the mean age at enrollment was 46 years (range, 30-88 years). They were followed for an average of 5.6 years for the development of cancer.

A total of 2,270 women did not undergo prophylactic oophorectomy, while 2,123 had already undergone the surgery at baseline and another 1,390 had it during the study period.

A total of 186 new ovarian, fallopian, and peritoneal cancers were diagnosed during follow-up. These included cases in 108 women with intact ovaries who were diagnosed clinically, 46 cases of occult cancer diagnosed at oophorectomy, and 32 cases of peritoneal cancer that developed after oophorectomy.

Of the 507 women who died during follow-up, 329 died from breast cancer; 67 died from ovarian, fallopian, or peritoneal cancer; 49 died from other cancers; 44 died of noncancer causes; and 18 died from unknown causes.

Oophorectomy had a profound protective effect on all-cause mortality and cancer-specific mortality, both for BRCA1 carriers and for BRCA2 carriers. Those who were cancer free at baseline and underwent the surgery showed a 77% reduction in all-cause mortality to age 70. Women who had a history of breast cancer at enrollment – including those whose mutation-carrier status was discovered when their breast cancer was diagnosed – showed a similar reduction in all-cause mortality after undergoing oophorectomy, the investigators reported (J. Clin. Oncol. 2014 Feb. 24 [doi: 10.1200/jco.2013.53.2820]).

The findings also support the current recommendation to undergo oophorectomy at age 35. "If a woman with a BRCA1 mutation chooses to delay salpingo-oophorectomy until age 40 years, we estimate that she will have a 4.0% chance of being diagnosed with ovarian cancer, either clinically before or at the time of salpingo-oophorectomy. If she chooses to wait until age 50 years, the probability rises to 14.2%," Dr. Finch and her associates said.

In view of this recommendation, "it is important that we ascertain the long-term effects of salpingo-oophorectomy and design effective treatments and preventive strategies for these," they added.

The researchers noted that their study began in 1995, before it was recommended that removal and detailed pathological evaluation of the fallopian tubes be included at oophorectomy. Eighteen of the 46 occult cancers discovered at surgery in this cohort were classified as primary fallopian tube cancers, which reinforces that the standard of care should now include removal of the tubes, they said.

This study was supported by the Canadian Breast Cancer Research Alliance, the National Institutes of Health, and the Ontario Ministry of Research and Innovation. Dr. Finch and her associates reported no financial conflicts of interest.

Undergoing prophylactic oophorectomy reduces all-cause mortality by 77% among women who carry a deleterious BRCA1 or BRCA2 genetic mutation, according to a report published online Feb. 24 in the Journal of Clinical Oncology.

The surgery’s protective effect stems largely from a reduction in the incidence of ovarian, tubal, and peritoneal cancers, "but there is an important component from reducing breast cancer incidence and mortality as well," reported Dr. Amy P.M. Finch of the University of Toronto and her associates in the Hereditary Ovarian Cancer Clinical Study Group.

©Kativ/iStockphoto

In addition, the results of this prospective cohort study support the recommendation that these women should undergo prophylactic oophorectomy by age 35, because their risk of developing cancer rises markedly after that, the investigators said.

Noting that the effect of oophorectomy on mortality has not been well studied and that the optimal age for undergoing the procedure hasn’t yet been determined, Dr. Finch and her colleagues analyzed data in an international registry of carriers of deleterious BRCA1 and BRCA2 mutations. Their study cohort included 5,783 women followed at 43 medical centers in Canada, the United States, Austria, France, Italy, Norway, and Poland, who were enrolled in 1995-2011.

Just under half of these women had a history of breast cancer, and the mean age at enrollment was 46 years (range, 30-88 years). They were followed for an average of 5.6 years for the development of cancer.

A total of 2,270 women did not undergo prophylactic oophorectomy, while 2,123 had already undergone the surgery at baseline and another 1,390 had it during the study period.

A total of 186 new ovarian, fallopian, and peritoneal cancers were diagnosed during follow-up. These included cases in 108 women with intact ovaries who were diagnosed clinically, 46 cases of occult cancer diagnosed at oophorectomy, and 32 cases of peritoneal cancer that developed after oophorectomy.

Of the 507 women who died during follow-up, 329 died from breast cancer; 67 died from ovarian, fallopian, or peritoneal cancer; 49 died from other cancers; 44 died of noncancer causes; and 18 died from unknown causes.

Oophorectomy had a profound protective effect on all-cause mortality and cancer-specific mortality, both for BRCA1 carriers and for BRCA2 carriers. Those who were cancer free at baseline and underwent the surgery showed a 77% reduction in all-cause mortality to age 70. Women who had a history of breast cancer at enrollment – including those whose mutation-carrier status was discovered when their breast cancer was diagnosed – showed a similar reduction in all-cause mortality after undergoing oophorectomy, the investigators reported (J. Clin. Oncol. 2014 Feb. 24 [doi: 10.1200/jco.2013.53.2820]).

The findings also support the current recommendation to undergo oophorectomy at age 35. "If a woman with a BRCA1 mutation chooses to delay salpingo-oophorectomy until age 40 years, we estimate that she will have a 4.0% chance of being diagnosed with ovarian cancer, either clinically before or at the time of salpingo-oophorectomy. If she chooses to wait until age 50 years, the probability rises to 14.2%," Dr. Finch and her associates said.

In view of this recommendation, "it is important that we ascertain the long-term effects of salpingo-oophorectomy and design effective treatments and preventive strategies for these," they added.

The researchers noted that their study began in 1995, before it was recommended that removal and detailed pathological evaluation of the fallopian tubes be included at oophorectomy. Eighteen of the 46 occult cancers discovered at surgery in this cohort were classified as primary fallopian tube cancers, which reinforces that the standard of care should now include removal of the tubes, they said.

This study was supported by the Canadian Breast Cancer Research Alliance, the National Institutes of Health, and the Ontario Ministry of Research and Innovation. Dr. Finch and her associates reported no financial conflicts of interest.

Undergoing prophylactic oophorectomy reduces all-cause mortality by 77% among women who carry a deleterious BRCA1 or BRCA2 genetic mutation, according to a report published online Feb. 24 in the Journal of Clinical Oncology.

The surgery’s protective effect stems largely from a reduction in the incidence of ovarian, tubal, and peritoneal cancers, "but there is an important component from reducing breast cancer incidence and mortality as well," reported Dr. Amy P.M. Finch of the University of Toronto and her associates in the Hereditary Ovarian Cancer Clinical Study Group.

©Kativ/iStockphoto

In addition, the results of this prospective cohort study support the recommendation that these women should undergo prophylactic oophorectomy by age 35, because their risk of developing cancer rises markedly after that, the investigators said.

Noting that the effect of oophorectomy on mortality has not been well studied and that the optimal age for undergoing the procedure hasn’t yet been determined, Dr. Finch and her colleagues analyzed data in an international registry of carriers of deleterious BRCA1 and BRCA2 mutations. Their study cohort included 5,783 women followed at 43 medical centers in Canada, the United States, Austria, France, Italy, Norway, and Poland, who were enrolled in 1995-2011.

Just under half of these women had a history of breast cancer, and the mean age at enrollment was 46 years (range, 30-88 years). They were followed for an average of 5.6 years for the development of cancer.

A total of 2,270 women did not undergo prophylactic oophorectomy, while 2,123 had already undergone the surgery at baseline and another 1,390 had it during the study period.

A total of 186 new ovarian, fallopian, and peritoneal cancers were diagnosed during follow-up. These included cases in 108 women with intact ovaries who were diagnosed clinically, 46 cases of occult cancer diagnosed at oophorectomy, and 32 cases of peritoneal cancer that developed after oophorectomy.

Of the 507 women who died during follow-up, 329 died from breast cancer; 67 died from ovarian, fallopian, or peritoneal cancer; 49 died from other cancers; 44 died of noncancer causes; and 18 died from unknown causes.

Oophorectomy had a profound protective effect on all-cause mortality and cancer-specific mortality, both for BRCA1 carriers and for BRCA2 carriers. Those who were cancer free at baseline and underwent the surgery showed a 77% reduction in all-cause mortality to age 70. Women who had a history of breast cancer at enrollment – including those whose mutation-carrier status was discovered when their breast cancer was diagnosed – showed a similar reduction in all-cause mortality after undergoing oophorectomy, the investigators reported (J. Clin. Oncol. 2014 Feb. 24 [doi: 10.1200/jco.2013.53.2820]).

The findings also support the current recommendation to undergo oophorectomy at age 35. "If a woman with a BRCA1 mutation chooses to delay salpingo-oophorectomy until age 40 years, we estimate that she will have a 4.0% chance of being diagnosed with ovarian cancer, either clinically before or at the time of salpingo-oophorectomy. If she chooses to wait until age 50 years, the probability rises to 14.2%," Dr. Finch and her associates said.

In view of this recommendation, "it is important that we ascertain the long-term effects of salpingo-oophorectomy and design effective treatments and preventive strategies for these," they added.

The researchers noted that their study began in 1995, before it was recommended that removal and detailed pathological evaluation of the fallopian tubes be included at oophorectomy. Eighteen of the 46 occult cancers discovered at surgery in this cohort were classified as primary fallopian tube cancers, which reinforces that the standard of care should now include removal of the tubes, they said.

This study was supported by the Canadian Breast Cancer Research Alliance, the National Institutes of Health, and the Ontario Ministry of Research and Innovation. Dr. Finch and her associates reported no financial conflicts of interest.

The human monoclonal antibody MOR103, which targets granulocyte-macrophage colony-stimulating factor, was well tolerated and exhibited a satisfactory safety profile in the first human study assessing it for the treatment of active, moderate rheumatoid arthritis.

The phase I/II clinical trial was designed to determine the safety of multiple doses of MOR103, but the findings also "provided suggestive evidence for the efficacy of this agent," said Dr. Frank Behrens of the division of rheumatology, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany, and his associates. In exploratory analyses, they found that MOR103 produced significant improvement across all efficacy variables and had a rapid onset of action, compared with placebo.

Their results establish proof of concept for the use of antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the treatment of RA, and "suggest that MOR103 has the potential to become a novel and valuable therapeutic option," the investigators said.

The GM-CSF molecule is thought to play a critical role in both initiating and exacerbating RA, and MOR103, a high-affinity recombinant human IgG1 antibody, blocks its receptors by binding to the GM-CSF epitope. In this industry-sponsored double-blind study of three doses of MOR103, 96 patients with active, moderate RA were treated and followed at 26 medical centers in Europe.

A total of 24 patients received 0.3 mg/kg MOR103; 22 received 1.0 mg/kg MOR103; 23 received 1.5 mg/kg MOR103; and 27 received matching placebo infusions every week for 4 weeks. All were followed for a further 16 weeks.

Adverse effects occurred more often during the study period in patients who received active treatment (42 of 69; 60.9%) than in those who received placebo (12 of 27; 44.4%). However, none of the adverse effects were considered to be definitely or even probably related to treatment, and all were of mild or moderate intensity.

Three adverse effects occurred more frequently in the active-treatment groups than in the placebo group: fatigue, cough, and RA exacerbations. However, the disease flares occurred after treatment ended and were considered to be related to drug withdrawal. There were no infusion reactions, but one case of rash and one case of fatigue were thought to be possibly related MOR103.

All of these differences "should be interpreted with caution because they are based on small subject numbers," Dr. Behrens and his associates said (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-204816]).

High levels of GM-CSF autoantibodies are known to be associated with idiopathic pulmonary alveolar proteinosis, so the study participants’ serum surfactant D levels were monitored and pulmonary function tests were performed at frequent intervals. There were no clinically important changes in these measures or in any other laboratory values between active treatment and placebo.

In an exploratory analysis, scores regarding swollen and tender joints on the Disease Activity Score-28 joints (DAS-28) improved rapidly and robustly with the two higher doses of MOR103, compared with placebo. Improvements also were seen on the European League Against Rheumatism response criteria, American College of Rheumatology improvement criteria, patients’ self-assessments of pain, the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Functional Assessment of Chronic Illness Therapy (FACIT).

Serial MRIs were performed to assess synovitis and bone edema and erosions. No significant differences were observed between active treatment and placebo groups.

Larger clinical trials are warranted to further assess the safety and efficacy of MOR103 for RA, the researchers said.

This study was funded by MorphoSys AG. Many of the investigators reported receiving grants and/or fees from MorphoSys AG. Two authors are employees of the company. No other conflicts of interest were reported.

The human monoclonal antibody MOR103, which targets granulocyte-macrophage colony-stimulating factor, was well tolerated and exhibited a satisfactory safety profile in the first human study assessing it for the treatment of active, moderate rheumatoid arthritis.

The phase I/II clinical trial was designed to determine the safety of multiple doses of MOR103, but the findings also "provided suggestive evidence for the efficacy of this agent," said Dr. Frank Behrens of the division of rheumatology, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany, and his associates. In exploratory analyses, they found that MOR103 produced significant improvement across all efficacy variables and had a rapid onset of action, compared with placebo.

Their results establish proof of concept for the use of antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the treatment of RA, and "suggest that MOR103 has the potential to become a novel and valuable therapeutic option," the investigators said.

The GM-CSF molecule is thought to play a critical role in both initiating and exacerbating RA, and MOR103, a high-affinity recombinant human IgG1 antibody, blocks its receptors by binding to the GM-CSF epitope. In this industry-sponsored double-blind study of three doses of MOR103, 96 patients with active, moderate RA were treated and followed at 26 medical centers in Europe.

A total of 24 patients received 0.3 mg/kg MOR103; 22 received 1.0 mg/kg MOR103; 23 received 1.5 mg/kg MOR103; and 27 received matching placebo infusions every week for 4 weeks. All were followed for a further 16 weeks.

Adverse effects occurred more often during the study period in patients who received active treatment (42 of 69; 60.9%) than in those who received placebo (12 of 27; 44.4%). However, none of the adverse effects were considered to be definitely or even probably related to treatment, and all were of mild or moderate intensity.

Three adverse effects occurred more frequently in the active-treatment groups than in the placebo group: fatigue, cough, and RA exacerbations. However, the disease flares occurred after treatment ended and were considered to be related to drug withdrawal. There were no infusion reactions, but one case of rash and one case of fatigue were thought to be possibly related MOR103.

All of these differences "should be interpreted with caution because they are based on small subject numbers," Dr. Behrens and his associates said (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-204816]).

High levels of GM-CSF autoantibodies are known to be associated with idiopathic pulmonary alveolar proteinosis, so the study participants’ serum surfactant D levels were monitored and pulmonary function tests were performed at frequent intervals. There were no clinically important changes in these measures or in any other laboratory values between active treatment and placebo.

In an exploratory analysis, scores regarding swollen and tender joints on the Disease Activity Score-28 joints (DAS-28) improved rapidly and robustly with the two higher doses of MOR103, compared with placebo. Improvements also were seen on the European League Against Rheumatism response criteria, American College of Rheumatology improvement criteria, patients’ self-assessments of pain, the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Functional Assessment of Chronic Illness Therapy (FACIT).

Serial MRIs were performed to assess synovitis and bone edema and erosions. No significant differences were observed between active treatment and placebo groups.

Larger clinical trials are warranted to further assess the safety and efficacy of MOR103 for RA, the researchers said.

This study was funded by MorphoSys AG. Many of the investigators reported receiving grants and/or fees from MorphoSys AG. Two authors are employees of the company. No other conflicts of interest were reported.

The human monoclonal antibody MOR103, which targets granulocyte-macrophage colony-stimulating factor, was well tolerated and exhibited a satisfactory safety profile in the first human study assessing it for the treatment of active, moderate rheumatoid arthritis.

The phase I/II clinical trial was designed to determine the safety of multiple doses of MOR103, but the findings also "provided suggestive evidence for the efficacy of this agent," said Dr. Frank Behrens of the division of rheumatology, Johann Wolfgang Goethe-Universität, Frankfurt am Main, Germany, and his associates. In exploratory analyses, they found that MOR103 produced significant improvement across all efficacy variables and had a rapid onset of action, compared with placebo.

Their results establish proof of concept for the use of antibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the treatment of RA, and "suggest that MOR103 has the potential to become a novel and valuable therapeutic option," the investigators said.

The GM-CSF molecule is thought to play a critical role in both initiating and exacerbating RA, and MOR103, a high-affinity recombinant human IgG1 antibody, blocks its receptors by binding to the GM-CSF epitope. In this industry-sponsored double-blind study of three doses of MOR103, 96 patients with active, moderate RA were treated and followed at 26 medical centers in Europe.

A total of 24 patients received 0.3 mg/kg MOR103; 22 received 1.0 mg/kg MOR103; 23 received 1.5 mg/kg MOR103; and 27 received matching placebo infusions every week for 4 weeks. All were followed for a further 16 weeks.

Adverse effects occurred more often during the study period in patients who received active treatment (42 of 69; 60.9%) than in those who received placebo (12 of 27; 44.4%). However, none of the adverse effects were considered to be definitely or even probably related to treatment, and all were of mild or moderate intensity.

Three adverse effects occurred more frequently in the active-treatment groups than in the placebo group: fatigue, cough, and RA exacerbations. However, the disease flares occurred after treatment ended and were considered to be related to drug withdrawal. There were no infusion reactions, but one case of rash and one case of fatigue were thought to be possibly related MOR103.

All of these differences "should be interpreted with caution because they are based on small subject numbers," Dr. Behrens and his associates said (Ann. Rheum. Dis. 2014 [doi:10.1136/annrheumdis-2013-204816]).

High levels of GM-CSF autoantibodies are known to be associated with idiopathic pulmonary alveolar proteinosis, so the study participants’ serum surfactant D levels were monitored and pulmonary function tests were performed at frequent intervals. There were no clinically important changes in these measures or in any other laboratory values between active treatment and placebo.

In an exploratory analysis, scores regarding swollen and tender joints on the Disease Activity Score-28 joints (DAS-28) improved rapidly and robustly with the two higher doses of MOR103, compared with placebo. Improvements also were seen on the European League Against Rheumatism response criteria, American College of Rheumatology improvement criteria, patients’ self-assessments of pain, the Health Assessment Questionnaire-Disability Index (HAQ-DI), and the Functional Assessment of Chronic Illness Therapy (FACIT).

Serial MRIs were performed to assess synovitis and bone edema and erosions. No significant differences were observed between active treatment and placebo groups.

Larger clinical trials are warranted to further assess the safety and efficacy of MOR103 for RA, the researchers said.

This study was funded by MorphoSys AG. Many of the investigators reported receiving grants and/or fees from MorphoSys AG. Two authors are employees of the company. No other conflicts of interest were reported.