SVS members have plenty of chances to learn by doing at hands-on workshops at the Vascular Annual Meeting. Twelve topics will be offered in four separate 90-minute sessions on Wednesday, June 8.

The workshops are $100 each (preregistration is required) and are not included in the VAM registration fee. Simply add the desired workshops when registering. Already registered? Just return to the registration page and add the workshops separately. The workshops are not eligible for CME credit.

Visit the VAM website for more information.

SVS members have plenty of chances to learn by doing at hands-on workshops at the Vascular Annual Meeting. Twelve topics will be offered in four separate 90-minute sessions on Wednesday, June 8.

The workshops are $100 each (preregistration is required) and are not included in the VAM registration fee. Simply add the desired workshops when registering. Already registered? Just return to the registration page and add the workshops separately. The workshops are not eligible for CME credit.

Visit the VAM website for more information.

SVS members have plenty of chances to learn by doing at hands-on workshops at the Vascular Annual Meeting. Twelve topics will be offered in four separate 90-minute sessions on Wednesday, June 8.

The workshops are $100 each (preregistration is required) and are not included in the VAM registration fee. Simply add the desired workshops when registering. Already registered? Just return to the registration page and add the workshops separately. The workshops are not eligible for CME credit.

Visit the VAM website for more information.

NEW YORK (Reuters Health) - Edoxaban (Savaysa, Daiichi-Sankyo) shows advantages over warfarin in long-term treatment of patients with venous thromboembolism (VTE), according to a post-hoc analysis of multinational trial data.

As Dr. Gary Raskob told Reuters Health by email, "Our results indicate that once-daily edoxaban provides an effective

and more convenient alternative to warfarin, with lower major bleeding risk, for patients who require extended treatment

beyond three months to prevent recurrent venous thromboembolism."

In a March 22 online paper in the Lancet Haematology, Dr.Raskob, of the University of Oklahoma, Oklahoma City, and colleagues note that guidelines recommend anticoagulant treatment for at least three months. However, "The risk of recurrence is substantial for patients with unprovoked venous thromboembolism or continuing risk factors and many of these

patients need extended anticoagulation therapy beyond three months."

To shed more light on longer term effects, the team examined outcome after three to 12 months in 3,633 patients treated with heparin and edoxaban and 3,594 treated with heparin and warfarin who took part in a randomized, double-blind trial. Median treatment duration was close to 9 months.

At three months, recurrent VTE was seen in 1.1% of the edoxaban group and 1.2% of the warfarin patients. At three to six months, the corresponding proportions were 0.7% and 0.5%. At more than six but less than 12 months, they were 0.2% and 0.8%.

Among other findings was that the cumulative incidence of major bleeding was 0.3% in the edoxaban-treated group and 0.7%

in the warfarin-treated patients. Intention-to-treat analysis gave similar results to these per-protocol findings.

Use of edoxaban, Dr. Raskob concluded, "may enable more patients to stay on extended anticoagulant treatment and help reduce the burden from recurrent venous thromboembolism."

Commenting on the findings by email, Dr. Jerrold H. Levy, coauthor of an accompanying editorial, told Reuters Health, "This post-hoc analysis reports that edoxaban is an alternative to warfarin for extended use in the secondary prevention of venous thromboembolism."

Dr. Levy, of Duke University Hospital, Durham, North Carolina, concluded, "The only other study where a direct oral anticoagulant was compared with warfarin for extended use in this setting was the RE-MEDY trial that compared dabigatran with warfarin in patients for six to 36 months and found dabigatran was similar to warfarin for efficacy with a lower incidence of clinically relevant major bleeding."

This study was funded by Daiichi-Sankyo.  Dr. Raskob received fees from the company during the study. Other coauthors

also have ties to the company and a number are employees of Daiichi-Sankyo.

NEW YORK (Reuters Health) - Edoxaban (Savaysa, Daiichi-Sankyo) shows advantages over warfarin in long-term treatment of patients with venous thromboembolism (VTE), according to a post-hoc analysis of multinational trial data.

As Dr. Gary Raskob told Reuters Health by email, "Our results indicate that once-daily edoxaban provides an effective

and more convenient alternative to warfarin, with lower major bleeding risk, for patients who require extended treatment

beyond three months to prevent recurrent venous thromboembolism."

In a March 22 online paper in the Lancet Haematology, Dr.Raskob, of the University of Oklahoma, Oklahoma City, and colleagues note that guidelines recommend anticoagulant treatment for at least three months. However, "The risk of recurrence is substantial for patients with unprovoked venous thromboembolism or continuing risk factors and many of these

patients need extended anticoagulation therapy beyond three months."

To shed more light on longer term effects, the team examined outcome after three to 12 months in 3,633 patients treated with heparin and edoxaban and 3,594 treated with heparin and warfarin who took part in a randomized, double-blind trial. Median treatment duration was close to 9 months.

At three months, recurrent VTE was seen in 1.1% of the edoxaban group and 1.2% of the warfarin patients. At three to six months, the corresponding proportions were 0.7% and 0.5%. At more than six but less than 12 months, they were 0.2% and 0.8%.

Among other findings was that the cumulative incidence of major bleeding was 0.3% in the edoxaban-treated group and 0.7%

in the warfarin-treated patients. Intention-to-treat analysis gave similar results to these per-protocol findings.

Use of edoxaban, Dr. Raskob concluded, "may enable more patients to stay on extended anticoagulant treatment and help reduce the burden from recurrent venous thromboembolism."

Commenting on the findings by email, Dr. Jerrold H. Levy, coauthor of an accompanying editorial, told Reuters Health, "This post-hoc analysis reports that edoxaban is an alternative to warfarin for extended use in the secondary prevention of venous thromboembolism."

Dr. Levy, of Duke University Hospital, Durham, North Carolina, concluded, "The only other study where a direct oral anticoagulant was compared with warfarin for extended use in this setting was the RE-MEDY trial that compared dabigatran with warfarin in patients for six to 36 months and found dabigatran was similar to warfarin for efficacy with a lower incidence of clinically relevant major bleeding."

This study was funded by Daiichi-Sankyo.  Dr. Raskob received fees from the company during the study. Other coauthors

also have ties to the company and a number are employees of Daiichi-Sankyo.

NEW YORK (Reuters Health) - Edoxaban (Savaysa, Daiichi-Sankyo) shows advantages over warfarin in long-term treatment of patients with venous thromboembolism (VTE), according to a post-hoc analysis of multinational trial data.

As Dr. Gary Raskob told Reuters Health by email, "Our results indicate that once-daily edoxaban provides an effective

and more convenient alternative to warfarin, with lower major bleeding risk, for patients who require extended treatment

beyond three months to prevent recurrent venous thromboembolism."

In a March 22 online paper in the Lancet Haematology, Dr.Raskob, of the University of Oklahoma, Oklahoma City, and colleagues note that guidelines recommend anticoagulant treatment for at least three months. However, "The risk of recurrence is substantial for patients with unprovoked venous thromboembolism or continuing risk factors and many of these

patients need extended anticoagulation therapy beyond three months."

To shed more light on longer term effects, the team examined outcome after three to 12 months in 3,633 patients treated with heparin and edoxaban and 3,594 treated with heparin and warfarin who took part in a randomized, double-blind trial. Median treatment duration was close to 9 months.

At three months, recurrent VTE was seen in 1.1% of the edoxaban group and 1.2% of the warfarin patients. At three to six months, the corresponding proportions were 0.7% and 0.5%. At more than six but less than 12 months, they were 0.2% and 0.8%.

Among other findings was that the cumulative incidence of major bleeding was 0.3% in the edoxaban-treated group and 0.7%

in the warfarin-treated patients. Intention-to-treat analysis gave similar results to these per-protocol findings.

Use of edoxaban, Dr. Raskob concluded, "may enable more patients to stay on extended anticoagulant treatment and help reduce the burden from recurrent venous thromboembolism."

Commenting on the findings by email, Dr. Jerrold H. Levy, coauthor of an accompanying editorial, told Reuters Health, "This post-hoc analysis reports that edoxaban is an alternative to warfarin for extended use in the secondary prevention of venous thromboembolism."

Dr. Levy, of Duke University Hospital, Durham, North Carolina, concluded, "The only other study where a direct oral anticoagulant was compared with warfarin for extended use in this setting was the RE-MEDY trial that compared dabigatran with warfarin in patients for six to 36 months and found dabigatran was similar to warfarin for efficacy with a lower incidence of clinically relevant major bleeding."

This study was funded by Daiichi-Sankyo.  Dr. Raskob received fees from the company during the study. Other coauthors

also have ties to the company and a number are employees of Daiichi-Sankyo.

Malaria-carrying mosquito

Photo by James Gathany

A newly developed hybrid drug can treat malaria that is resistant to other therapies, according to preclinical research.

With previous work, researchers found that chemoreversal agents can re-sensitize resistant malaria parasites to the antimalarial agent chloroquine.

For the current study, the team created hybrid compounds that combine chloroquine and a chemoreversal agent.

One of these compounds, 35, proved particularly active, killing malaria parasites that were resistant to chloroquine and/or artemisinin.

Compound 35 was significantly more effective than chloroquine at killing these resistant strains, which included Hb3 (P<0.001), Dd2 (P<0.001), ARS-233 (P<0.001), ARS-272 (P<0.01), NHP-04559 (P<0.01), NHP04773 (P<0.001), and 7G8 (P<0.01).

In addition, the researchers said compound 35 has a “good therapeutic window” and “favorable drug-like properties,” but they are continuing to refine the compound to make it more effective.

The team noted that malaria drugs and chemoreversal agents have been used to treat drug-resistant malaria before. But this is the first time a hybrid of chloroquine and a newly discovered chemoreversal factor has been used in a single novel molecule for this purpose.

The researchers said a single therapy has several advantages over combination therapy. Besides being more convenient to take, it has less risk of drug-drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.

Kevin S. W. Tan, PhD, of the National University of Singapore, and his colleagues described this research in Antimicrobial Agents and Chemotherapy.

Malaria-carrying mosquito

Photo by James Gathany

A newly developed hybrid drug can treat malaria that is resistant to other therapies, according to preclinical research.

With previous work, researchers found that chemoreversal agents can re-sensitize resistant malaria parasites to the antimalarial agent chloroquine.

For the current study, the team created hybrid compounds that combine chloroquine and a chemoreversal agent.

One of these compounds, 35, proved particularly active, killing malaria parasites that were resistant to chloroquine and/or artemisinin.

Compound 35 was significantly more effective than chloroquine at killing these resistant strains, which included Hb3 (P<0.001), Dd2 (P<0.001), ARS-233 (P<0.001), ARS-272 (P<0.01), NHP-04559 (P<0.01), NHP04773 (P<0.001), and 7G8 (P<0.01).

In addition, the researchers said compound 35 has a “good therapeutic window” and “favorable drug-like properties,” but they are continuing to refine the compound to make it more effective.

The team noted that malaria drugs and chemoreversal agents have been used to treat drug-resistant malaria before. But this is the first time a hybrid of chloroquine and a newly discovered chemoreversal factor has been used in a single novel molecule for this purpose.

The researchers said a single therapy has several advantages over combination therapy. Besides being more convenient to take, it has less risk of drug-drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.

Kevin S. W. Tan, PhD, of the National University of Singapore, and his colleagues described this research in Antimicrobial Agents and Chemotherapy.

Malaria-carrying mosquito

Photo by James Gathany

A newly developed hybrid drug can treat malaria that is resistant to other therapies, according to preclinical research.

With previous work, researchers found that chemoreversal agents can re-sensitize resistant malaria parasites to the antimalarial agent chloroquine.

For the current study, the team created hybrid compounds that combine chloroquine and a chemoreversal agent.

One of these compounds, 35, proved particularly active, killing malaria parasites that were resistant to chloroquine and/or artemisinin.

Compound 35 was significantly more effective than chloroquine at killing these resistant strains, which included Hb3 (P<0.001), Dd2 (P<0.001), ARS-233 (P<0.001), ARS-272 (P<0.01), NHP-04559 (P<0.01), NHP04773 (P<0.001), and 7G8 (P<0.01).

In addition, the researchers said compound 35 has a “good therapeutic window” and “favorable drug-like properties,” but they are continuing to refine the compound to make it more effective.

The team noted that malaria drugs and chemoreversal agents have been used to treat drug-resistant malaria before. But this is the first time a hybrid of chloroquine and a newly discovered chemoreversal factor has been used in a single novel molecule for this purpose.

The researchers said a single therapy has several advantages over combination therapy. Besides being more convenient to take, it has less risk of drug-drug interactions, may be better absorbed and distributed in the body, and could result in slower development of new resistant strains of malaria.

Kevin S. W. Tan, PhD, of the National University of Singapore, and his colleagues described this research in Antimicrobial Agents and Chemotherapy.

Warfarin tablets

ATHENS—A study of patients taking warfarin suggests many do not fully understand the risks associated with the drug.

Researchers asked patients to complete a questionnaire on warfarin use and found that, on average, patients answered 64% of the questions correctly.

The patients tended to be the least informed about food and drug interactions and which side effects necessitate a call or visit to the doctor.

Kjersti Oterhals, RN, PhD, of Haukeland University Hospital in Bergen, Norway, and her colleagues presented these findings at EuroHeartCare 2016 (abstract 36).

“The stroke and bleeding complications from warfarin can be fatal,” Dr Oterhals noted. “Worldwide, warfarin causes the most deaths from drug-related side effects. Patients need to know what foods and drugs have an impact on how warfarin works and what to do if they have symptoms of an overdose or underdose.”

Dr Oterhals and her colleagues evaluated warfarin knowledge in 404 patients with aortic stenosis. The patients’ mean age was 68, and 70% were male.

Nearly two-thirds of the patients (63%) were taking warfarin because they had a mechanical valve, and 24% were taking the drug because they had atrial fibrillation. The remaining patients were taking the drug for unknown reasons (6%) or “other” reasons (7%).

The patients received a postal questionnaire with 28 multiple-choice questions about warfarin. On average, patients answered 18 of the 28 questions correctly. However, 22% of patients answered less than half of the questions correctly.

The questions that were most often answered incorrectly were those concerning food and drug interactions and when to call or see a doctor.

For example, patients were asked which of the following foods would interfere with warfarin: celery, carrots, coleslaw, or green beans. Only 25% correctly said coleslaw. Most patients answered green beans.

“Patients often think green vegetables have the most vitamin K, but that’s not true,” Dr Oterhals said. “Brassica vegetables such as cabbage, broccoli, and cauliflower are rich sources.”

“Patients do not have to avoid these foods, but they should eat an equal amount every week because the vitamin K will decrease their INR and put them at increased risk of thrombosis or embolism. Patients who like to eat a lot of vitamin K-containing foods can take a higher warfarin dosage, but they need to be consistent.”

Dr Oterhals and her colleagues also found that 80% of patients knew they should go directly to the emergency room if they had nose bleeding that would not stop. However, only 45% of patients correctly said diarrhea for more than one day necessitates a visit to the doctor.

The study also showed that increased age was associated with a decrease in correct answers.

“We can only speculate why,” Dr Oterhals said. “Younger people tend to seek out information about how to manage their disease, while the older generation wants the doctor to tell them what to do.”

“Motivated patients should be offered an INR testing kit so that they can monitor their levels and adjust the warfarin dose themselves, just as patients with diabetes who use insulin do. It enables patients to travel and try new foods without having to find a clinic to get tested. Patients tell me that hot weather increases their INR, while another found out while in Asia that nori decreased his INR.”

“Warfarin is a life-saving drug but can be deadly if not used carefully. Health professionals have a responsibility to educate patients, but, unfortunately, even cardiac nurses do not know enough. There is an urgent need to improve health professionals’ warfarin knowledge so they can educate patients.”

Warfarin tablets

ATHENS—A study of patients taking warfarin suggests many do not fully understand the risks associated with the drug.

Researchers asked patients to complete a questionnaire on warfarin use and found that, on average, patients answered 64% of the questions correctly.

The patients tended to be the least informed about food and drug interactions and which side effects necessitate a call or visit to the doctor.

Kjersti Oterhals, RN, PhD, of Haukeland University Hospital in Bergen, Norway, and her colleagues presented these findings at EuroHeartCare 2016 (abstract 36).

“The stroke and bleeding complications from warfarin can be fatal,” Dr Oterhals noted. “Worldwide, warfarin causes the most deaths from drug-related side effects. Patients need to know what foods and drugs have an impact on how warfarin works and what to do if they have symptoms of an overdose or underdose.”

Dr Oterhals and her colleagues evaluated warfarin knowledge in 404 patients with aortic stenosis. The patients’ mean age was 68, and 70% were male.

Nearly two-thirds of the patients (63%) were taking warfarin because they had a mechanical valve, and 24% were taking the drug because they had atrial fibrillation. The remaining patients were taking the drug for unknown reasons (6%) or “other” reasons (7%).

The patients received a postal questionnaire with 28 multiple-choice questions about warfarin. On average, patients answered 18 of the 28 questions correctly. However, 22% of patients answered less than half of the questions correctly.

The questions that were most often answered incorrectly were those concerning food and drug interactions and when to call or see a doctor.

For example, patients were asked which of the following foods would interfere with warfarin: celery, carrots, coleslaw, or green beans. Only 25% correctly said coleslaw. Most patients answered green beans.

“Patients often think green vegetables have the most vitamin K, but that’s not true,” Dr Oterhals said. “Brassica vegetables such as cabbage, broccoli, and cauliflower are rich sources.”

“Patients do not have to avoid these foods, but they should eat an equal amount every week because the vitamin K will decrease their INR and put them at increased risk of thrombosis or embolism. Patients who like to eat a lot of vitamin K-containing foods can take a higher warfarin dosage, but they need to be consistent.”

Dr Oterhals and her colleagues also found that 80% of patients knew they should go directly to the emergency room if they had nose bleeding that would not stop. However, only 45% of patients correctly said diarrhea for more than one day necessitates a visit to the doctor.

The study also showed that increased age was associated with a decrease in correct answers.

“We can only speculate why,” Dr Oterhals said. “Younger people tend to seek out information about how to manage their disease, while the older generation wants the doctor to tell them what to do.”

“Motivated patients should be offered an INR testing kit so that they can monitor their levels and adjust the warfarin dose themselves, just as patients with diabetes who use insulin do. It enables patients to travel and try new foods without having to find a clinic to get tested. Patients tell me that hot weather increases their INR, while another found out while in Asia that nori decreased his INR.”

“Warfarin is a life-saving drug but can be deadly if not used carefully. Health professionals have a responsibility to educate patients, but, unfortunately, even cardiac nurses do not know enough. There is an urgent need to improve health professionals’ warfarin knowledge so they can educate patients.”

Warfarin tablets

ATHENS—A study of patients taking warfarin suggests many do not fully understand the risks associated with the drug.

Researchers asked patients to complete a questionnaire on warfarin use and found that, on average, patients answered 64% of the questions correctly.

The patients tended to be the least informed about food and drug interactions and which side effects necessitate a call or visit to the doctor.

Kjersti Oterhals, RN, PhD, of Haukeland University Hospital in Bergen, Norway, and her colleagues presented these findings at EuroHeartCare 2016 (abstract 36).

“The stroke and bleeding complications from warfarin can be fatal,” Dr Oterhals noted. “Worldwide, warfarin causes the most deaths from drug-related side effects. Patients need to know what foods and drugs have an impact on how warfarin works and what to do if they have symptoms of an overdose or underdose.”

Dr Oterhals and her colleagues evaluated warfarin knowledge in 404 patients with aortic stenosis. The patients’ mean age was 68, and 70% were male.

Nearly two-thirds of the patients (63%) were taking warfarin because they had a mechanical valve, and 24% were taking the drug because they had atrial fibrillation. The remaining patients were taking the drug for unknown reasons (6%) or “other” reasons (7%).

The patients received a postal questionnaire with 28 multiple-choice questions about warfarin. On average, patients answered 18 of the 28 questions correctly. However, 22% of patients answered less than half of the questions correctly.

The questions that were most often answered incorrectly were those concerning food and drug interactions and when to call or see a doctor.

For example, patients were asked which of the following foods would interfere with warfarin: celery, carrots, coleslaw, or green beans. Only 25% correctly said coleslaw. Most patients answered green beans.

“Patients often think green vegetables have the most vitamin K, but that’s not true,” Dr Oterhals said. “Brassica vegetables such as cabbage, broccoli, and cauliflower are rich sources.”

“Patients do not have to avoid these foods, but they should eat an equal amount every week because the vitamin K will decrease their INR and put them at increased risk of thrombosis or embolism. Patients who like to eat a lot of vitamin K-containing foods can take a higher warfarin dosage, but they need to be consistent.”

Dr Oterhals and her colleagues also found that 80% of patients knew they should go directly to the emergency room if they had nose bleeding that would not stop. However, only 45% of patients correctly said diarrhea for more than one day necessitates a visit to the doctor.

The study also showed that increased age was associated with a decrease in correct answers.

“We can only speculate why,” Dr Oterhals said. “Younger people tend to seek out information about how to manage their disease, while the older generation wants the doctor to tell them what to do.”

“Motivated patients should be offered an INR testing kit so that they can monitor their levels and adjust the warfarin dose themselves, just as patients with diabetes who use insulin do. It enables patients to travel and try new foods without having to find a clinic to get tested. Patients tell me that hot weather increases their INR, while another found out while in Asia that nori decreased his INR.”

“Warfarin is a life-saving drug but can be deadly if not used carefully. Health professionals have a responsibility to educate patients, but, unfortunately, even cardiac nurses do not know enough. There is an urgent need to improve health professionals’ warfarin knowledge so they can educate patients.”

Patients with atopic dermatitis are at an increased risk of Staphylococcus aureus colonization of both their lesional and nonlesional skin, as well as their nose, compared with healthy controls, according to a report in the British Journal of Dermatology.

Dr. J.E.E. Totté of the department of dermatology at the Erasmus MC University Medical Centre, Rotterdam, and associates conducted a systematic literature review and meta-analysis to derive pooled estimates of the prevalence and odds of colonization with S. aureus in patients with atopic dermatitis. They focused on original, human experimental, and observational studies including patients of any age with a confirmed diagnosis of atopic dermatitis (Br J Dermatol. 2016 Mar 19. doi: 10.1111/bjd.14566).

Dr. Totté and colleagues identified a total of 4,909 articles, of which 95 were found to meet the study inclusion criteria. All of the included studies were observational, with 30 comparing atopic dermatitis patients with healthy controls.

Almost three-quarters (70%) of patients had S. aureus colonization of lesional skin, while 39% had colonization of nonlesional skin, based on 81 studies including 5,231 patients and 30 studies including 1,496 patients, respectively. Nasal colonization was found in 62% of patients, based on analysis of 43 studies including 2,476 patients.

S. aureus colonization is an important factor in the pathogenesis of atopic dermatitis and should lead to evaluations of targeted antistaphylococcal therapy for the skin and nose, the investigators advised.

The authors reported that the department of dermatology of the Erasmus MC University Medical Centre Rotterdam received an unrestricted grant from Micreos Human Health. Two coauthors disclosed ties to industry sources.

Patients with atopic dermatitis are at an increased risk of Staphylococcus aureus colonization of both their lesional and nonlesional skin, as well as their nose, compared with healthy controls, according to a report in the British Journal of Dermatology.

Dr. J.E.E. Totté of the department of dermatology at the Erasmus MC University Medical Centre, Rotterdam, and associates conducted a systematic literature review and meta-analysis to derive pooled estimates of the prevalence and odds of colonization with S. aureus in patients with atopic dermatitis. They focused on original, human experimental, and observational studies including patients of any age with a confirmed diagnosis of atopic dermatitis (Br J Dermatol. 2016 Mar 19. doi: 10.1111/bjd.14566).

Dr. Totté and colleagues identified a total of 4,909 articles, of which 95 were found to meet the study inclusion criteria. All of the included studies were observational, with 30 comparing atopic dermatitis patients with healthy controls.

Almost three-quarters (70%) of patients had S. aureus colonization of lesional skin, while 39% had colonization of nonlesional skin, based on 81 studies including 5,231 patients and 30 studies including 1,496 patients, respectively. Nasal colonization was found in 62% of patients, based on analysis of 43 studies including 2,476 patients.

S. aureus colonization is an important factor in the pathogenesis of atopic dermatitis and should lead to evaluations of targeted antistaphylococcal therapy for the skin and nose, the investigators advised.

The authors reported that the department of dermatology of the Erasmus MC University Medical Centre Rotterdam received an unrestricted grant from Micreos Human Health. Two coauthors disclosed ties to industry sources.

Patients with atopic dermatitis are at an increased risk of Staphylococcus aureus colonization of both their lesional and nonlesional skin, as well as their nose, compared with healthy controls, according to a report in the British Journal of Dermatology.

Dr. J.E.E. Totté of the department of dermatology at the Erasmus MC University Medical Centre, Rotterdam, and associates conducted a systematic literature review and meta-analysis to derive pooled estimates of the prevalence and odds of colonization with S. aureus in patients with atopic dermatitis. They focused on original, human experimental, and observational studies including patients of any age with a confirmed diagnosis of atopic dermatitis (Br J Dermatol. 2016 Mar 19. doi: 10.1111/bjd.14566).

Dr. Totté and colleagues identified a total of 4,909 articles, of which 95 were found to meet the study inclusion criteria. All of the included studies were observational, with 30 comparing atopic dermatitis patients with healthy controls.

Almost three-quarters (70%) of patients had S. aureus colonization of lesional skin, while 39% had colonization of nonlesional skin, based on 81 studies including 5,231 patients and 30 studies including 1,496 patients, respectively. Nasal colonization was found in 62% of patients, based on analysis of 43 studies including 2,476 patients.

S. aureus colonization is an important factor in the pathogenesis of atopic dermatitis and should lead to evaluations of targeted antistaphylococcal therapy for the skin and nose, the investigators advised.

The authors reported that the department of dermatology of the Erasmus MC University Medical Centre Rotterdam received an unrestricted grant from Micreos Human Health. Two coauthors disclosed ties to industry sources.

The basic premise of the physician-patient relationship is simple: Patients are ill and we want to make them better. But the true nature of the relationship is not so monochromatic. Patients and physicians can differ, either on what ails the patient or on what will make the patient better, and it can be challenging to navigate that divide.

One common source of conflict for me is test ordering. I tend to be somewhat conservative when it comes to ordering tests, but patients will often feel shortchanged if they are not subjected to needlesticks and radiation. One of the most common requests I get, being in New England, is for Lyme testing. Patients have gotten so sophisticated now that they expect a Western blot. “My primary care doc just refuses to order a Western blot for me,” one lady complained.

Settling on a mutually acceptable diagnosis can be tricky as well. Of course, “mutually acceptable” is not the issue: a patient either has a diagnosis or does not. But in order for the patient to accept your recommended therapy, they have to believe that you have the right diagnosis. And some diagnoses are hard to accept and even harder to prove than others. A few patients refuse to believe that they have rheumatoid arthritis, particularly if they test negative. And how many of your patients refuse to believe that they have fibromyalgia? How many insist that they have that catch-all, “autoimmune disease,” despite evidence to the contrary?

On the matter of treatment, there are disagreements, too. The most obvious example, and one of the biggest challenges, is narcotic prescription. Patients with chronic pain often rely on narcotics to feel better, but narcotic use is not recommended in such patients. Physicians and patients can expect to be in a perennial tension over who prevails.

Mental health issues are the most challenging for me. For example, I have a young patient who has a polysubstance use disorder and gets admitted repeatedly for alcohol-induced pancreatitis, yet refuses to get mental health therapy for it despite multiple inpatient psychiatric consultations exhorting her to do so. “It doesn’t do anything for me,” she says. She lies about everything, from medication compliance to where she gets medications to how much she drinks, yet I do not feel equipped to handle these problems.

If any of the above scenarios were board exam questions, choosing the proverbial next best step would be simple. But when does life really operate so neatly? The old paradigm of doctoring was that the physician rendered an opinion informed by his or her education. Today, our exam-room interactions often take the shape of a democracy, one in which an overworked, bandwidth-depleted physician might butt heads with a strong-willed patient, armed with all the wisdom of anecdotes and the Internet. If I were fresh out of med school, I might have had more energy to explain to you why you don’t need that Lyme test or that narcotic prescription. These days though, I find myself waving the white flag far more than I should.

Dr. Chan practices rheumatology in Pawtucket, R.I.

The basic premise of the physician-patient relationship is simple: Patients are ill and we want to make them better. But the true nature of the relationship is not so monochromatic. Patients and physicians can differ, either on what ails the patient or on what will make the patient better, and it can be challenging to navigate that divide.

One common source of conflict for me is test ordering. I tend to be somewhat conservative when it comes to ordering tests, but patients will often feel shortchanged if they are not subjected to needlesticks and radiation. One of the most common requests I get, being in New England, is for Lyme testing. Patients have gotten so sophisticated now that they expect a Western blot. “My primary care doc just refuses to order a Western blot for me,” one lady complained.

Settling on a mutually acceptable diagnosis can be tricky as well. Of course, “mutually acceptable” is not the issue: a patient either has a diagnosis or does not. But in order for the patient to accept your recommended therapy, they have to believe that you have the right diagnosis. And some diagnoses are hard to accept and even harder to prove than others. A few patients refuse to believe that they have rheumatoid arthritis, particularly if they test negative. And how many of your patients refuse to believe that they have fibromyalgia? How many insist that they have that catch-all, “autoimmune disease,” despite evidence to the contrary?

On the matter of treatment, there are disagreements, too. The most obvious example, and one of the biggest challenges, is narcotic prescription. Patients with chronic pain often rely on narcotics to feel better, but narcotic use is not recommended in such patients. Physicians and patients can expect to be in a perennial tension over who prevails.

Mental health issues are the most challenging for me. For example, I have a young patient who has a polysubstance use disorder and gets admitted repeatedly for alcohol-induced pancreatitis, yet refuses to get mental health therapy for it despite multiple inpatient psychiatric consultations exhorting her to do so. “It doesn’t do anything for me,” she says. She lies about everything, from medication compliance to where she gets medications to how much she drinks, yet I do not feel equipped to handle these problems.

If any of the above scenarios were board exam questions, choosing the proverbial next best step would be simple. But when does life really operate so neatly? The old paradigm of doctoring was that the physician rendered an opinion informed by his or her education. Today, our exam-room interactions often take the shape of a democracy, one in which an overworked, bandwidth-depleted physician might butt heads with a strong-willed patient, armed with all the wisdom of anecdotes and the Internet. If I were fresh out of med school, I might have had more energy to explain to you why you don’t need that Lyme test or that narcotic prescription. These days though, I find myself waving the white flag far more than I should.

Dr. Chan practices rheumatology in Pawtucket, R.I.

The basic premise of the physician-patient relationship is simple: Patients are ill and we want to make them better. But the true nature of the relationship is not so monochromatic. Patients and physicians can differ, either on what ails the patient or on what will make the patient better, and it can be challenging to navigate that divide.

One common source of conflict for me is test ordering. I tend to be somewhat conservative when it comes to ordering tests, but patients will often feel shortchanged if they are not subjected to needlesticks and radiation. One of the most common requests I get, being in New England, is for Lyme testing. Patients have gotten so sophisticated now that they expect a Western blot. “My primary care doc just refuses to order a Western blot for me,” one lady complained.

Settling on a mutually acceptable diagnosis can be tricky as well. Of course, “mutually acceptable” is not the issue: a patient either has a diagnosis or does not. But in order for the patient to accept your recommended therapy, they have to believe that you have the right diagnosis. And some diagnoses are hard to accept and even harder to prove than others. A few patients refuse to believe that they have rheumatoid arthritis, particularly if they test negative. And how many of your patients refuse to believe that they have fibromyalgia? How many insist that they have that catch-all, “autoimmune disease,” despite evidence to the contrary?

On the matter of treatment, there are disagreements, too. The most obvious example, and one of the biggest challenges, is narcotic prescription. Patients with chronic pain often rely on narcotics to feel better, but narcotic use is not recommended in such patients. Physicians and patients can expect to be in a perennial tension over who prevails.

Mental health issues are the most challenging for me. For example, I have a young patient who has a polysubstance use disorder and gets admitted repeatedly for alcohol-induced pancreatitis, yet refuses to get mental health therapy for it despite multiple inpatient psychiatric consultations exhorting her to do so. “It doesn’t do anything for me,” she says. She lies about everything, from medication compliance to where she gets medications to how much she drinks, yet I do not feel equipped to handle these problems.

If any of the above scenarios were board exam questions, choosing the proverbial next best step would be simple. But when does life really operate so neatly? The old paradigm of doctoring was that the physician rendered an opinion informed by his or her education. Today, our exam-room interactions often take the shape of a democracy, one in which an overworked, bandwidth-depleted physician might butt heads with a strong-willed patient, armed with all the wisdom of anecdotes and the Internet. If I were fresh out of med school, I might have had more energy to explain to you why you don’t need that Lyme test or that narcotic prescription. These days though, I find myself waving the white flag far more than I should.

Dr. Chan practices rheumatology in Pawtucket, R.I.

Investigator in the lab

Photo by Darren Baker

New research suggests that patients diagnosed with an autism spectrum disorder (ASD) have a higher burden of mutations in oncogenes but lower rates of cancer than the rest of the population.

Investigators analyzed large, publicly available genomic databases of patients with ASD and found that, compared to a set of control subjects, ASD patients had significantly higher rates of DNA variation in oncogenes.

The team followed up this result with an analysis of the University of Iowa Hospitals and Clinics’ electronic medical record and discovered that ASD patients were also significantly less likely to have a co-occurring diagnosis of cancer.

“It’s a very provocative result that makes sense on one level and is extremely perplexing on another,” said Benjamin Darbro, MD, PhD, of the University of Iowa Carver College of Medicine in Iowa City.

Dr Darbro and his colleagues discussed the result, and the research that led to it, in a paper published in PLOS ONE.

The investigators used exome sequencing data from the ARRA Autism Sequencing Collaboration and compared that data to a control cohort from the Exome Variant Server database.

This revealed that rare, coding variants within oncogenes were greatly enriched in the ARRA ASD cohort. By comparison, variants were not significantly enriched in tumor suppressor genes.

To ensure the genetic differences were not technical artifacts but actually bona fide differences in genetic architecture in ASD, the investigators ran numerous controls.

As expected, they found that individuals with ASD had many more DNA variations in genes previously associated with autism, epilepsy, and intellectual disability compared to control individuals.

However, there was no difference between the ASD and control groups when it came to genes involved in other, unrelated conditions such as skeletal dysplasia, retinitis pigmentosa, dilated cardiomyopathy, and non-syndromic hearing loss.

The investigators then turned their attention to the electronic medical record at the University of Iowa Hospitals and Clinics and conducted a retrospective case-control analysis comparing 1837 patients with ASD to 9336 patients with any other diagnosis, and determined what proportion of each group carried a cancer diagnosis.

The team found that, for children and adults with ASD, there appeared to be a protective effect against cancer. The cancer incidence was 1.3% for patients with ASD and 3.9% for controls.

The protective effect was evident in both males and females with ASD, but it was strongest for the youngest group of patients and decreased with age. For ASD patients who were under 14 years of age, the odds of having cancer were reduced by 94% compared to controls.

When the investigators determined the rates of other systemic diseases—such as high blood pressure and diabetes—in the ASD population, they found no relationship.

Furthermore, the team found no relationship with cancer when they examined the rates of other common conditions such as esophageal reflux, allergic rhinitis, atopic dermatitis, and short stature. They said this demonstrated that the inverse relationship observed between ASD and cancer is not due to a technical artifact.

Investigator in the lab

Photo by Darren Baker

New research suggests that patients diagnosed with an autism spectrum disorder (ASD) have a higher burden of mutations in oncogenes but lower rates of cancer than the rest of the population.

Investigators analyzed large, publicly available genomic databases of patients with ASD and found that, compared to a set of control subjects, ASD patients had significantly higher rates of DNA variation in oncogenes.

The team followed up this result with an analysis of the University of Iowa Hospitals and Clinics’ electronic medical record and discovered that ASD patients were also significantly less likely to have a co-occurring diagnosis of cancer.

“It’s a very provocative result that makes sense on one level and is extremely perplexing on another,” said Benjamin Darbro, MD, PhD, of the University of Iowa Carver College of Medicine in Iowa City.

Dr Darbro and his colleagues discussed the result, and the research that led to it, in a paper published in PLOS ONE.

The investigators used exome sequencing data from the ARRA Autism Sequencing Collaboration and compared that data to a control cohort from the Exome Variant Server database.

This revealed that rare, coding variants within oncogenes were greatly enriched in the ARRA ASD cohort. By comparison, variants were not significantly enriched in tumor suppressor genes.

To ensure the genetic differences were not technical artifacts but actually bona fide differences in genetic architecture in ASD, the investigators ran numerous controls.

As expected, they found that individuals with ASD had many more DNA variations in genes previously associated with autism, epilepsy, and intellectual disability compared to control individuals.

However, there was no difference between the ASD and control groups when it came to genes involved in other, unrelated conditions such as skeletal dysplasia, retinitis pigmentosa, dilated cardiomyopathy, and non-syndromic hearing loss.

The investigators then turned their attention to the electronic medical record at the University of Iowa Hospitals and Clinics and conducted a retrospective case-control analysis comparing 1837 patients with ASD to 9336 patients with any other diagnosis, and determined what proportion of each group carried a cancer diagnosis.

The team found that, for children and adults with ASD, there appeared to be a protective effect against cancer. The cancer incidence was 1.3% for patients with ASD and 3.9% for controls.

The protective effect was evident in both males and females with ASD, but it was strongest for the youngest group of patients and decreased with age. For ASD patients who were under 14 years of age, the odds of having cancer were reduced by 94% compared to controls.

When the investigators determined the rates of other systemic diseases—such as high blood pressure and diabetes—in the ASD population, they found no relationship.

Furthermore, the team found no relationship with cancer when they examined the rates of other common conditions such as esophageal reflux, allergic rhinitis, atopic dermatitis, and short stature. They said this demonstrated that the inverse relationship observed between ASD and cancer is not due to a technical artifact.

Investigator in the lab

Photo by Darren Baker

New research suggests that patients diagnosed with an autism spectrum disorder (ASD) have a higher burden of mutations in oncogenes but lower rates of cancer than the rest of the population.

Investigators analyzed large, publicly available genomic databases of patients with ASD and found that, compared to a set of control subjects, ASD patients had significantly higher rates of DNA variation in oncogenes.

The team followed up this result with an analysis of the University of Iowa Hospitals and Clinics’ electronic medical record and discovered that ASD patients were also significantly less likely to have a co-occurring diagnosis of cancer.

“It’s a very provocative result that makes sense on one level and is extremely perplexing on another,” said Benjamin Darbro, MD, PhD, of the University of Iowa Carver College of Medicine in Iowa City.

Dr Darbro and his colleagues discussed the result, and the research that led to it, in a paper published in PLOS ONE.

The investigators used exome sequencing data from the ARRA Autism Sequencing Collaboration and compared that data to a control cohort from the Exome Variant Server database.

This revealed that rare, coding variants within oncogenes were greatly enriched in the ARRA ASD cohort. By comparison, variants were not significantly enriched in tumor suppressor genes.

To ensure the genetic differences were not technical artifacts but actually bona fide differences in genetic architecture in ASD, the investigators ran numerous controls.

As expected, they found that individuals with ASD had many more DNA variations in genes previously associated with autism, epilepsy, and intellectual disability compared to control individuals.

However, there was no difference between the ASD and control groups when it came to genes involved in other, unrelated conditions such as skeletal dysplasia, retinitis pigmentosa, dilated cardiomyopathy, and non-syndromic hearing loss.

The investigators then turned their attention to the electronic medical record at the University of Iowa Hospitals and Clinics and conducted a retrospective case-control analysis comparing 1837 patients with ASD to 9336 patients with any other diagnosis, and determined what proportion of each group carried a cancer diagnosis.

The team found that, for children and adults with ASD, there appeared to be a protective effect against cancer. The cancer incidence was 1.3% for patients with ASD and 3.9% for controls.

The protective effect was evident in both males and females with ASD, but it was strongest for the youngest group of patients and decreased with age. For ASD patients who were under 14 years of age, the odds of having cancer were reduced by 94% compared to controls.

When the investigators determined the rates of other systemic diseases—such as high blood pressure and diabetes—in the ASD population, they found no relationship.

Furthermore, the team found no relationship with cancer when they examined the rates of other common conditions such as esophageal reflux, allergic rhinitis, atopic dermatitis, and short stature. They said this demonstrated that the inverse relationship observed between ASD and cancer is not due to a technical artifact.

Blood for transfusion

Photo courtesy of UAB Hospital

Even a short delay in the administration of packed red blood cells (pRBCs) can increase the risk of death for some traumatically injured patients, according to research published in the Journal of Trauma and Acute Care Surgery.

The study showed that a delay of 10 minutes was associated with a higher risk of death among patients who required pRBCs early.

However, a 10-minute delay did not increase the risk of death for the entire study cohort.

For this study, researchers tracked trauma patients taken from the scene of their injury to the University of Cincinnati Medical Center by a helicopter service known as Air Care. The service carries 2 units of pRBCs for protocol-driven prehospital transfusion.

“Air Care is the only helicopter in the area to carry blood (and plasma), so we had the research platform to study how early blood transfusions impact outcomes,” said study author Elizabeth Powell, MD, of the University of Cincinnati Medical Center in Ohio.

Dr Powell and her colleagues studied 94 patients who had received at least 1 unit of pRBCs within 24 hours of arriving at the hospital. Ninety-three percent of patients (n=87) were Caucasian, 70% (n=66) were male, and they had a mean age of 43.

Ninety-four percent of patients (n=88) had sustained blunt force injuries, and 33% (n=31) died within 30 days of hospital arrival.

Thirty-three percent of patients (n=31) received a transfusion during transport, 54% (n=51) were transfused within an hour of hospital arrival, and 13% (n=12) were transfused after the first hour but within 24 hours of hospital arrival.

When considering all 94 patients together, the researchers found that a 10-minute increase in time to pRBC administration did not significantly affect the odds of death, even when adjusting for injury severity. The odds ratio was 1.00 (P=0.575).

However, among the 82 patients who received their first pRBC transfusion during transport or within an hour of hospital arrival, each 10 minute increase in time to transfusion increased the odds of death. When the researchers controlled for Trauma Injury Severity Score, the odds ratio was 1.27 (P=0.044).

“Delays in the time to blood transfusion are associated with increased chances of dying,” Dr Powell said. “Shortening the time to transfusion, including having blood available in the prehospital setting, may improve outcomes.”

Blood for transfusion

Photo courtesy of UAB Hospital

Even a short delay in the administration of packed red blood cells (pRBCs) can increase the risk of death for some traumatically injured patients, according to research published in the Journal of Trauma and Acute Care Surgery.

The study showed that a delay of 10 minutes was associated with a higher risk of death among patients who required pRBCs early.

However, a 10-minute delay did not increase the risk of death for the entire study cohort.

For this study, researchers tracked trauma patients taken from the scene of their injury to the University of Cincinnati Medical Center by a helicopter service known as Air Care. The service carries 2 units of pRBCs for protocol-driven prehospital transfusion.

“Air Care is the only helicopter in the area to carry blood (and plasma), so we had the research platform to study how early blood transfusions impact outcomes,” said study author Elizabeth Powell, MD, of the University of Cincinnati Medical Center in Ohio.

Dr Powell and her colleagues studied 94 patients who had received at least 1 unit of pRBCs within 24 hours of arriving at the hospital. Ninety-three percent of patients (n=87) were Caucasian, 70% (n=66) were male, and they had a mean age of 43.

Ninety-four percent of patients (n=88) had sustained blunt force injuries, and 33% (n=31) died within 30 days of hospital arrival.

Thirty-three percent of patients (n=31) received a transfusion during transport, 54% (n=51) were transfused within an hour of hospital arrival, and 13% (n=12) were transfused after the first hour but within 24 hours of hospital arrival.

When considering all 94 patients together, the researchers found that a 10-minute increase in time to pRBC administration did not significantly affect the odds of death, even when adjusting for injury severity. The odds ratio was 1.00 (P=0.575).

However, among the 82 patients who received their first pRBC transfusion during transport or within an hour of hospital arrival, each 10 minute increase in time to transfusion increased the odds of death. When the researchers controlled for Trauma Injury Severity Score, the odds ratio was 1.27 (P=0.044).

“Delays in the time to blood transfusion are associated with increased chances of dying,” Dr Powell said. “Shortening the time to transfusion, including having blood available in the prehospital setting, may improve outcomes.”

Blood for transfusion

Photo courtesy of UAB Hospital

Even a short delay in the administration of packed red blood cells (pRBCs) can increase the risk of death for some traumatically injured patients, according to research published in the Journal of Trauma and Acute Care Surgery.

The study showed that a delay of 10 minutes was associated with a higher risk of death among patients who required pRBCs early.

However, a 10-minute delay did not increase the risk of death for the entire study cohort.

For this study, researchers tracked trauma patients taken from the scene of their injury to the University of Cincinnati Medical Center by a helicopter service known as Air Care. The service carries 2 units of pRBCs for protocol-driven prehospital transfusion.

“Air Care is the only helicopter in the area to carry blood (and plasma), so we had the research platform to study how early blood transfusions impact outcomes,” said study author Elizabeth Powell, MD, of the University of Cincinnati Medical Center in Ohio.

Dr Powell and her colleagues studied 94 patients who had received at least 1 unit of pRBCs within 24 hours of arriving at the hospital. Ninety-three percent of patients (n=87) were Caucasian, 70% (n=66) were male, and they had a mean age of 43.

Ninety-four percent of patients (n=88) had sustained blunt force injuries, and 33% (n=31) died within 30 days of hospital arrival.

Thirty-three percent of patients (n=31) received a transfusion during transport, 54% (n=51) were transfused within an hour of hospital arrival, and 13% (n=12) were transfused after the first hour but within 24 hours of hospital arrival.

When considering all 94 patients together, the researchers found that a 10-minute increase in time to pRBC administration did not significantly affect the odds of death, even when adjusting for injury severity. The odds ratio was 1.00 (P=0.575).

However, among the 82 patients who received their first pRBC transfusion during transport or within an hour of hospital arrival, each 10 minute increase in time to transfusion increased the odds of death. When the researchers controlled for Trauma Injury Severity Score, the odds ratio was 1.27 (P=0.044).

“Delays in the time to blood transfusion are associated with increased chances of dying,” Dr Powell said. “Shortening the time to transfusion, including having blood available in the prehospital setting, may improve outcomes.”

A description of two bipolar I disorder cases presents examples of the phenomenon of transient neutrophilia that occurred during admission into a state psychiatric hospital. A brief review of the mechanisms that may explain this hematologic response is included.

Background

In 1889, the U.S. territory of New Mexico established the New Mexico Insane Asylum, and it was known as such until 1955, when it became the State Hospital. In 1970, it became the Las Vegas Medical Center but changed its name in 2005 to the New Mexico Behavioral Health Institute (NMBHI), which services the entire state for inpatient and long-term care patients. On average, it accepts two admissions per day, of which two patients per month present with neutrophilia (white blood cell [WBC] count greater than 11,000), which resolves after 1-4 days in the hospital.

Case presentations

Case one. A 21-year-old Native American man presented with multiple psychiatric admissions for bipolar I disorder and major depression with suicidal ideation. He was brought into the local emergency department by police, who found him walking down the interstate highway trying to hitch a ride back to his native pueblo after a disagreement with a fellow resident at a local boarding home. He had discontinued his Seroquel and lithium 2 weeks earlier because he felt he no longer needed them and required medical clearance for admission.¹ His presenting hemogram in the ED was normal except for an elevated WBC count of 20,000. His vital signs were normal except for tachycardia of 110 beats per minute. On exam the patient demonstrated a flat affect and anxiety but other than mild ingrown toenails and tachycardia, there were no abnormal findings.

He received a chest x-ray and abdominal computed tomography scan that were both normal, and the patient was cleared for admission. He was cooperative with staff and restarted his lithium. A repeat WBC at day 5 was 9,700.

Case two. A 24-year-old white man with a history of bipolar I disorder and dependency on benzodiazepines and Ritalin was transferred from a distant county jail after 10 days of incarceration. He started screaming in his cell, praying, and perseverating that he “needed to kill himself,” which triggered his transfer to the NMBHI. His aggressive behavior upon arrival necessitated a transfer to the local ED for sedation and four-point restraints. He received Versed and Ativan IVP before allowing a blood collection, which revealed dehydration and a WBC count of 17,100. After 4 L of normal saline, his labs normalized with a WBC of 10,100, and he was admitted for a 7-day committal.

Discussion

Neutrophilia can result from granulocytes moving from pericapillary tissue margins into the circulating pool.² It may occur in association with vigorous exercise, seizures, paroxysmal tachycardia, and adrenergic stress.³ The duration is fewer than 30 minutes and usually results in WBC counts of 15,000-20,000.⁴ Beta receptors on endothelial cells may mediate neutrophil adherence and release from marginal sites. A left shift is absent, because there is no change of the inflow of cells from the marrow.

In these two cases, a transient neutrophilia and tachycardia were observed. Neither case was febrile, and the platelet count remained normal. Both patients voluntarily stopped taking their lithium about 2 weeks before decompensating from bipolar I disorders. Stress was evident in both cases, one from walking on a cold December night after a disagreement, while the other patient in case two was highly agitated and aggressive requiring four-point restraints and intravenous sedation in the ED before admission to NMBHI. Past histories of psychiatric admissions were noted in both cases, and neither subject smoked tobacco – which can increase WBC by 25%-50% with the use of one-two packs per day, respectively.⁵

These two cases show that clinicians should consider stress in its many permutations to the long list of causes to explain elevated WBC, particularly in the ED. They also illustrate the power of antianxiety medications for some patients with acute mania who present to the ED.

References

1. J Emerg Med. 2012;43(5):866-70.

2. “Wintrobe’s Clinical Hematology,” Philadelphia: Lea & Febiger, 1981, p.1292.

3. “Diagnostic Hematology,” London: Springer, 2009, p. 324.

4. Gen Hosp Psychiatry. 2005;27(6):454-56.

5. Euro Heart J. 2003 Jul;24(14)1365-72.

Dr. Taylor is a staff physician affiliated with the New Mexico Behavioral Health Institute, New Mexico Department of Health, Santa Fe. He reports no financial disclosures or conflicts of interest. The author wishes to thank Dr. Dan Collins from the NMBHI for recommending that he research and write about this topic. In addition, document access was greatly aided by Lisa Apodaca and Mary Bunker, CNP, from the NMBHI, and Karen Ebler and Dr. Irwin Hoffman from Christus St. Vincent Hospital in Santa Fe. Finally, the following colleagues helped by proofreading the manuscript: Dr. Wendy Dimmette, Dr. Richard Nail, and Dr. Matt Streicherz. Eva Romero and Dr. Troy Jones provided useful historical documentation.

A description of two bipolar I disorder cases presents examples of the phenomenon of transient neutrophilia that occurred during admission into a state psychiatric hospital. A brief review of the mechanisms that may explain this hematologic response is included.

Background

In 1889, the U.S. territory of New Mexico established the New Mexico Insane Asylum, and it was known as such until 1955, when it became the State Hospital. In 1970, it became the Las Vegas Medical Center but changed its name in 2005 to the New Mexico Behavioral Health Institute (NMBHI), which services the entire state for inpatient and long-term care patients. On average, it accepts two admissions per day, of which two patients per month present with neutrophilia (white blood cell [WBC] count greater than 11,000), which resolves after 1-4 days in the hospital.

Case presentations

Case one. A 21-year-old Native American man presented with multiple psychiatric admissions for bipolar I disorder and major depression with suicidal ideation. He was brought into the local emergency department by police, who found him walking down the interstate highway trying to hitch a ride back to his native pueblo after a disagreement with a fellow resident at a local boarding home. He had discontinued his Seroquel and lithium 2 weeks earlier because he felt he no longer needed them and required medical clearance for admission.¹ His presenting hemogram in the ED was normal except for an elevated WBC count of 20,000. His vital signs were normal except for tachycardia of 110 beats per minute. On exam the patient demonstrated a flat affect and anxiety but other than mild ingrown toenails and tachycardia, there were no abnormal findings.

He received a chest x-ray and abdominal computed tomography scan that were both normal, and the patient was cleared for admission. He was cooperative with staff and restarted his lithium. A repeat WBC at day 5 was 9,700.

Case two. A 24-year-old white man with a history of bipolar I disorder and dependency on benzodiazepines and Ritalin was transferred from a distant county jail after 10 days of incarceration. He started screaming in his cell, praying, and perseverating that he “needed to kill himself,” which triggered his transfer to the NMBHI. His aggressive behavior upon arrival necessitated a transfer to the local ED for sedation and four-point restraints. He received Versed and Ativan IVP before allowing a blood collection, which revealed dehydration and a WBC count of 17,100. After 4 L of normal saline, his labs normalized with a WBC of 10,100, and he was admitted for a 7-day committal.

Discussion

Neutrophilia can result from granulocytes moving from pericapillary tissue margins into the circulating pool.² It may occur in association with vigorous exercise, seizures, paroxysmal tachycardia, and adrenergic stress.³ The duration is fewer than 30 minutes and usually results in WBC counts of 15,000-20,000.⁴ Beta receptors on endothelial cells may mediate neutrophil adherence and release from marginal sites. A left shift is absent, because there is no change of the inflow of cells from the marrow.

In these two cases, a transient neutrophilia and tachycardia were observed. Neither case was febrile, and the platelet count remained normal. Both patients voluntarily stopped taking their lithium about 2 weeks before decompensating from bipolar I disorders. Stress was evident in both cases, one from walking on a cold December night after a disagreement, while the other patient in case two was highly agitated and aggressive requiring four-point restraints and intravenous sedation in the ED before admission to NMBHI. Past histories of psychiatric admissions were noted in both cases, and neither subject smoked tobacco – which can increase WBC by 25%-50% with the use of one-two packs per day, respectively.⁵

These two cases show that clinicians should consider stress in its many permutations to the long list of causes to explain elevated WBC, particularly in the ED. They also illustrate the power of antianxiety medications for some patients with acute mania who present to the ED.

References

1. J Emerg Med. 2012;43(5):866-70.

2. “Wintrobe’s Clinical Hematology,” Philadelphia: Lea & Febiger, 1981, p.1292.

3. “Diagnostic Hematology,” London: Springer, 2009, p. 324.

4. Gen Hosp Psychiatry. 2005;27(6):454-56.

5. Euro Heart J. 2003 Jul;24(14)1365-72.

Dr. Taylor is a staff physician affiliated with the New Mexico Behavioral Health Institute, New Mexico Department of Health, Santa Fe. He reports no financial disclosures or conflicts of interest. The author wishes to thank Dr. Dan Collins from the NMBHI for recommending that he research and write about this topic. In addition, document access was greatly aided by Lisa Apodaca and Mary Bunker, CNP, from the NMBHI, and Karen Ebler and Dr. Irwin Hoffman from Christus St. Vincent Hospital in Santa Fe. Finally, the following colleagues helped by proofreading the manuscript: Dr. Wendy Dimmette, Dr. Richard Nail, and Dr. Matt Streicherz. Eva Romero and Dr. Troy Jones provided useful historical documentation.

A description of two bipolar I disorder cases presents examples of the phenomenon of transient neutrophilia that occurred during admission into a state psychiatric hospital. A brief review of the mechanisms that may explain this hematologic response is included.

Background

In 1889, the U.S. territory of New Mexico established the New Mexico Insane Asylum, and it was known as such until 1955, when it became the State Hospital. In 1970, it became the Las Vegas Medical Center but changed its name in 2005 to the New Mexico Behavioral Health Institute (NMBHI), which services the entire state for inpatient and long-term care patients. On average, it accepts two admissions per day, of which two patients per month present with neutrophilia (white blood cell [WBC] count greater than 11,000), which resolves after 1-4 days in the hospital.

Case presentations

Case one. A 21-year-old Native American man presented with multiple psychiatric admissions for bipolar I disorder and major depression with suicidal ideation. He was brought into the local emergency department by police, who found him walking down the interstate highway trying to hitch a ride back to his native pueblo after a disagreement with a fellow resident at a local boarding home. He had discontinued his Seroquel and lithium 2 weeks earlier because he felt he no longer needed them and required medical clearance for admission.¹ His presenting hemogram in the ED was normal except for an elevated WBC count of 20,000. His vital signs were normal except for tachycardia of 110 beats per minute. On exam the patient demonstrated a flat affect and anxiety but other than mild ingrown toenails and tachycardia, there were no abnormal findings.

He received a chest x-ray and abdominal computed tomography scan that were both normal, and the patient was cleared for admission. He was cooperative with staff and restarted his lithium. A repeat WBC at day 5 was 9,700.

Case two. A 24-year-old white man with a history of bipolar I disorder and dependency on benzodiazepines and Ritalin was transferred from a distant county jail after 10 days of incarceration. He started screaming in his cell, praying, and perseverating that he “needed to kill himself,” which triggered his transfer to the NMBHI. His aggressive behavior upon arrival necessitated a transfer to the local ED for sedation and four-point restraints. He received Versed and Ativan IVP before allowing a blood collection, which revealed dehydration and a WBC count of 17,100. After 4 L of normal saline, his labs normalized with a WBC of 10,100, and he was admitted for a 7-day committal.

Discussion

Neutrophilia can result from granulocytes moving from pericapillary tissue margins into the circulating pool.² It may occur in association with vigorous exercise, seizures, paroxysmal tachycardia, and adrenergic stress.³ The duration is fewer than 30 minutes and usually results in WBC counts of 15,000-20,000.⁴ Beta receptors on endothelial cells may mediate neutrophil adherence and release from marginal sites. A left shift is absent, because there is no change of the inflow of cells from the marrow.

In these two cases, a transient neutrophilia and tachycardia were observed. Neither case was febrile, and the platelet count remained normal. Both patients voluntarily stopped taking their lithium about 2 weeks before decompensating from bipolar I disorders. Stress was evident in both cases, one from walking on a cold December night after a disagreement, while the other patient in case two was highly agitated and aggressive requiring four-point restraints and intravenous sedation in the ED before admission to NMBHI. Past histories of psychiatric admissions were noted in both cases, and neither subject smoked tobacco – which can increase WBC by 25%-50% with the use of one-two packs per day, respectively.⁵

These two cases show that clinicians should consider stress in its many permutations to the long list of causes to explain elevated WBC, particularly in the ED. They also illustrate the power of antianxiety medications for some patients with acute mania who present to the ED.

References

1. J Emerg Med. 2012;43(5):866-70.

2. “Wintrobe’s Clinical Hematology,” Philadelphia: Lea & Febiger, 1981, p.1292.

3. “Diagnostic Hematology,” London: Springer, 2009, p. 324.

4. Gen Hosp Psychiatry. 2005;27(6):454-56.

5. Euro Heart J. 2003 Jul;24(14)1365-72.

Dr. Taylor is a staff physician affiliated with the New Mexico Behavioral Health Institute, New Mexico Department of Health, Santa Fe. He reports no financial disclosures or conflicts of interest. The author wishes to thank Dr. Dan Collins from the NMBHI for recommending that he research and write about this topic. In addition, document access was greatly aided by Lisa Apodaca and Mary Bunker, CNP, from the NMBHI, and Karen Ebler and Dr. Irwin Hoffman from Christus St. Vincent Hospital in Santa Fe. Finally, the following colleagues helped by proofreading the manuscript: Dr. Wendy Dimmette, Dr. Richard Nail, and Dr. Matt Streicherz. Eva Romero and Dr. Troy Jones provided useful historical documentation.

Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) could result in a “paradigm shift” in prophylaxis regimens for patients with hemophilia B, according to researchers reporting results from a phase III trial.

At dosing intervals of up to 14 days, rIX-FP was a safe and effective factor IX (FIX) replacement product for preventing and treating bleeding episodes in an open-label study of 63 previously treated adolescents and adults with severe hemophilia B.

Compared to standard FIX products, rIX-FP is more active, has a longer half-life, and has better clearance. A study is now underway to see whether a 21-day prophylaxis regimen provides even better results than the 14-day regimen, reported Dr. Elena Santagostino of Istituto di Ricovero e Cura a Carattere Scientifico Ca’ Granda Foundation, Maggiore Hospital Policlinico, Milan, and her associates in the PROLONG-9FP Investigators Study Group.

For prophylaxis, standard FIX products are administered two times per week. Patients are at increased risk of bleeding when their FIX activity is low, particularly just before their next scheduled dose. With the prolonged FIX activity of rIX-FP, the dosing is less frequent and that could potentially improve adherence, the researchers wrote (Blood. 2016;127[14]:1761-9).

In addition, rIX-FP was associated with a reduced risk of spontaneous and trauma-related bleeding episodes.

The findings came from a study of patients who had FIX activity levels of 2% or less and were assigned to one of two groups. The first group received routine prophylaxis once every 7 days for 26 weeks; they were then placed on either a 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively. The second group received on-demand treatment of bleeding episodes for 26 weeks and were then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. Only patients who were previously receiving on-demand treatment were eligible for group 2 assignment.

Patients self-administered rIX-FP for routine prophylaxis and on-demand treatment of bleeding episodes; all home administrations were recorded in an electronic diary. A second dose of rIX-FP was administered at least 24 hours after the first injection, if needed, to achieve hemostasis. Efficacy and safety assessments were performed at study sites on a monthly basis.

The study design controlled for the variability of bleeding frequency within the hemophilia B patient population, as group 2 patients started rIX-FP treatment on-demand and continued on 7-day prophylaxis. During the on-demand phase, rIX-FP controlled 98.6% of bleeding episodes, and 93.6% of bleeds were controlled with one infusion.

Once the group was switched to 7-day prophylaxis, the median annualized spontaneous bleeding rate dropped to 0.0 and all target joints resolved.(P less than .0001). No patient developed an inhibitor, and no safety concerns were identified.

The annualized bleeding rate decreased slightly in group 2 patients during on-demand treatment with rIX-FP, compared with the rate in the 12-month period before they entered the study. The researchers speculated that on-demand treatment with rIX-FP “might provide, to a certain extent, some protection against a subsequent bleeding episode. Therefore, patients with a severe bleeding phenotype treated on-demand might experience fewer bleeding episodes if switched to rIX-FP. Furthermore, such on-demand patients who require more than one infusion per month may have the benefit of a reduction of ABR by administering a similar number of infusions according to a 14-day prophylaxis regimen with rIX-FP.”

The sample size was small, however, and differences of care in the clinical study could have affected the results.

Compared to other FIX products, rIX-FP had an extended terminal half-life of 102 hours, 4.3-fold longer than seen with the patients’ previous FIX treatment. Other pharmacokinetic measures such as area under the curve (7176 h × IU/dL), clearance (0.77 mL/h per kg), and incremental recovery (1.27 IU/dL per IU/kg) also were improved. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg every 7 days and 75 IU/kg every 14 days, respectively. Rather than half-life alone, a slower clearance may be a factor in the success of prophylaxis regimens, the researchers said.

The principal investigators received research support from CSL Behring, which sponsored the study and was responsible for trial operations and data analysis.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) could result in a “paradigm shift” in prophylaxis regimens for patients with hemophilia B, according to researchers reporting results from a phase III trial.

At dosing intervals of up to 14 days, rIX-FP was a safe and effective factor IX (FIX) replacement product for preventing and treating bleeding episodes in an open-label study of 63 previously treated adolescents and adults with severe hemophilia B.

Compared to standard FIX products, rIX-FP is more active, has a longer half-life, and has better clearance. A study is now underway to see whether a 21-day prophylaxis regimen provides even better results than the 14-day regimen, reported Dr. Elena Santagostino of Istituto di Ricovero e Cura a Carattere Scientifico Ca’ Granda Foundation, Maggiore Hospital Policlinico, Milan, and her associates in the PROLONG-9FP Investigators Study Group.

For prophylaxis, standard FIX products are administered two times per week. Patients are at increased risk of bleeding when their FIX activity is low, particularly just before their next scheduled dose. With the prolonged FIX activity of rIX-FP, the dosing is less frequent and that could potentially improve adherence, the researchers wrote (Blood. 2016;127[14]:1761-9).

In addition, rIX-FP was associated with a reduced risk of spontaneous and trauma-related bleeding episodes.

The findings came from a study of patients who had FIX activity levels of 2% or less and were assigned to one of two groups. The first group received routine prophylaxis once every 7 days for 26 weeks; they were then placed on either a 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively. The second group received on-demand treatment of bleeding episodes for 26 weeks and were then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. Only patients who were previously receiving on-demand treatment were eligible for group 2 assignment.

Patients self-administered rIX-FP for routine prophylaxis and on-demand treatment of bleeding episodes; all home administrations were recorded in an electronic diary. A second dose of rIX-FP was administered at least 24 hours after the first injection, if needed, to achieve hemostasis. Efficacy and safety assessments were performed at study sites on a monthly basis.

The study design controlled for the variability of bleeding frequency within the hemophilia B patient population, as group 2 patients started rIX-FP treatment on-demand and continued on 7-day prophylaxis. During the on-demand phase, rIX-FP controlled 98.6% of bleeding episodes, and 93.6% of bleeds were controlled with one infusion.

Once the group was switched to 7-day prophylaxis, the median annualized spontaneous bleeding rate dropped to 0.0 and all target joints resolved.(P less than .0001). No patient developed an inhibitor, and no safety concerns were identified.

The annualized bleeding rate decreased slightly in group 2 patients during on-demand treatment with rIX-FP, compared with the rate in the 12-month period before they entered the study. The researchers speculated that on-demand treatment with rIX-FP “might provide, to a certain extent, some protection against a subsequent bleeding episode. Therefore, patients with a severe bleeding phenotype treated on-demand might experience fewer bleeding episodes if switched to rIX-FP. Furthermore, such on-demand patients who require more than one infusion per month may have the benefit of a reduction of ABR by administering a similar number of infusions according to a 14-day prophylaxis regimen with rIX-FP.”

The sample size was small, however, and differences of care in the clinical study could have affected the results.

Compared to other FIX products, rIX-FP had an extended terminal half-life of 102 hours, 4.3-fold longer than seen with the patients’ previous FIX treatment. Other pharmacokinetic measures such as area under the curve (7176 h × IU/dL), clearance (0.77 mL/h per kg), and incremental recovery (1.27 IU/dL per IU/kg) also were improved. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg every 7 days and 75 IU/kg every 14 days, respectively. Rather than half-life alone, a slower clearance may be a factor in the success of prophylaxis regimens, the researchers said.

The principal investigators received research support from CSL Behring, which sponsored the study and was responsible for trial operations and data analysis.

mdales@frontlinemedcom.com

On Twitter @maryjodales

Recombinant fusion protein linking coagulation factor IX with albumin (rIX-FP) could result in a “paradigm shift” in prophylaxis regimens for patients with hemophilia B, according to researchers reporting results from a phase III trial.

At dosing intervals of up to 14 days, rIX-FP was a safe and effective factor IX (FIX) replacement product for preventing and treating bleeding episodes in an open-label study of 63 previously treated adolescents and adults with severe hemophilia B.

Compared to standard FIX products, rIX-FP is more active, has a longer half-life, and has better clearance. A study is now underway to see whether a 21-day prophylaxis regimen provides even better results than the 14-day regimen, reported Dr. Elena Santagostino of Istituto di Ricovero e Cura a Carattere Scientifico Ca’ Granda Foundation, Maggiore Hospital Policlinico, Milan, and her associates in the PROLONG-9FP Investigators Study Group.

For prophylaxis, standard FIX products are administered two times per week. Patients are at increased risk of bleeding when their FIX activity is low, particularly just before their next scheduled dose. With the prolonged FIX activity of rIX-FP, the dosing is less frequent and that could potentially improve adherence, the researchers wrote (Blood. 2016;127[14]:1761-9).

In addition, rIX-FP was associated with a reduced risk of spontaneous and trauma-related bleeding episodes.

The findings came from a study of patients who had FIX activity levels of 2% or less and were assigned to one of two groups. The first group received routine prophylaxis once every 7 days for 26 weeks; they were then placed on either a 7-, 10-, or 14-day prophylaxis regimen for a mean of 50, 38, or 51 weeks, respectively. The second group received on-demand treatment of bleeding episodes for 26 weeks and were then switched to a 7-day prophylaxis regimen for a mean of 45 weeks. Only patients who were previously receiving on-demand treatment were eligible for group 2 assignment.

Patients self-administered rIX-FP for routine prophylaxis and on-demand treatment of bleeding episodes; all home administrations were recorded in an electronic diary. A second dose of rIX-FP was administered at least 24 hours after the first injection, if needed, to achieve hemostasis. Efficacy and safety assessments were performed at study sites on a monthly basis.

The study design controlled for the variability of bleeding frequency within the hemophilia B patient population, as group 2 patients started rIX-FP treatment on-demand and continued on 7-day prophylaxis. During the on-demand phase, rIX-FP controlled 98.6% of bleeding episodes, and 93.6% of bleeds were controlled with one infusion.

Once the group was switched to 7-day prophylaxis, the median annualized spontaneous bleeding rate dropped to 0.0 and all target joints resolved.(P less than .0001). No patient developed an inhibitor, and no safety concerns were identified.

The annualized bleeding rate decreased slightly in group 2 patients during on-demand treatment with rIX-FP, compared with the rate in the 12-month period before they entered the study. The researchers speculated that on-demand treatment with rIX-FP “might provide, to a certain extent, some protection against a subsequent bleeding episode. Therefore, patients with a severe bleeding phenotype treated on-demand might experience fewer bleeding episodes if switched to rIX-FP. Furthermore, such on-demand patients who require more than one infusion per month may have the benefit of a reduction of ABR by administering a similar number of infusions according to a 14-day prophylaxis regimen with rIX-FP.”

The sample size was small, however, and differences of care in the clinical study could have affected the results.

Compared to other FIX products, rIX-FP had an extended terminal half-life of 102 hours, 4.3-fold longer than seen with the patients’ previous FIX treatment. Other pharmacokinetic measures such as area under the curve (7176 h × IU/dL), clearance (0.77 mL/h per kg), and incremental recovery (1.27 IU/dL per IU/kg) also were improved. Patients maintained a mean trough of 20 and 12 IU/dL FIX activity on prophylaxis with rIX-FP 40 IU/kg every 7 days and 75 IU/kg every 14 days, respectively. Rather than half-life alone, a slower clearance may be a factor in the success of prophylaxis regimens, the researchers said.

The principal investigators received research support from CSL Behring, which sponsored the study and was responsible for trial operations and data analysis.

mdales@frontlinemedcom.com

On Twitter @maryjodales