The U.S. Preventive Services Task Force neither supports nor rejects screening asymptomatic adults for obstructive sleep apnea in the primary-care setting, because the current evidence is inadequate to assess the benefits and harms of doing so, according to a Recommendation Statement published online Jan. 23 in JAMA.

The USPSTF makes recommendations about the effectiveness of specific health care services for patients who don’t have related signs or symptoms. In this case, the Recommendation Statement addresses adults who don’t snore excessively; gasp or choke while sleeping; or report the daytime sleepiness, impaired cognition, or mood changes typically associated with obstructive sleep apnea, said Kirsten Bobbins-Domingo, PhD, MD, chair of the organization and lead author of the Recommendation Statement, and her associates (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.20325).

The USPSTF commissioned a comprehensive review of the literature to examine whether screening such patients by primary caregivers would effectively identify those who have obstructive sleep apnea and lead to treatment that would prevent the elevated rates of death, cognitive impairment, motor vehicle crashes, cardiovascular events, and cerebrovascular events related to the disorder. Daniel E. Jonas, MD, of the University of North Carolina at Chapel Hill and his associates reviewed 110 relevant studies involving 46,188 participants.

They found that the accuracy and clinical utility of numerous OSA screening tools was uncertain. In particular, the Epworth Sleepiness Scale, the STOP (Snoring, Tiredness, Observed Apnea, and High Blood Pressure) questionnaire, the STOP-BANG (STOP plus BMI, Age, Neck Circumference, and Gender) questionnaire, the Berlin Questionnaire, the Wisconsin Sleep Questionnaire, and the Multivariable Apnea Prediction (MVAP) tool have not been adequately validated in primary care settings.

Moreover, no studies directly assessed whether screening had an impact on actual health outcomes. Several treatments, notably CPAP and mandibular advancement devices, did improve intermediate outcomes such as scores on the apnea-hypopnea index, scores on the Epworth Sleepiness Scale, and blood pressure levels, but the evidence did not show that this in turn improved mortality, cardiovascular events, or the other “hard” outcomes of interest, Dr. Jonas and his associates said in their Evidence Report (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.19635).

Dr. Bobbins-Domingo and her associates on the task force noted that this Recommendation Statement is consistent with that of the American Academy of Family Physicians, which also concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening asymptomatic adults for obstructive sleep apnea.

The American College of Physicians offers a “weak” recommendation based on low-quality evidence that patients with unexplained daytime sleepiness and patients suspected of having apnea undergo a sleep study, said Dr. Bobbins-Domingo, professor of medicine at the University of California, San Francisco, and her associates.

In contrast, the American Academy of Sleep Medicine recommends that routine health visits should include questions about OSA and evaluation of risk factors such as obesity, retrognathia, and treatment-refractory hypertension. If there are positive findings, a comprehensive sleep evaluation should follow, according to the AASM.

The USPSTF is an independent voluntary group supported by the Agency for Healthcare Research and Quality as mandated by the U.S. Congress. The authors’ conflict of interest disclosures are available at www.uspreventiveservicestaskforce.org.

The U.S. Preventive Services Task Force neither supports nor rejects screening asymptomatic adults for obstructive sleep apnea in the primary-care setting, because the current evidence is inadequate to assess the benefits and harms of doing so, according to a Recommendation Statement published online Jan. 23 in JAMA.

The USPSTF makes recommendations about the effectiveness of specific health care services for patients who don’t have related signs or symptoms. In this case, the Recommendation Statement addresses adults who don’t snore excessively; gasp or choke while sleeping; or report the daytime sleepiness, impaired cognition, or mood changes typically associated with obstructive sleep apnea, said Kirsten Bobbins-Domingo, PhD, MD, chair of the organization and lead author of the Recommendation Statement, and her associates (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.20325).

The USPSTF commissioned a comprehensive review of the literature to examine whether screening such patients by primary caregivers would effectively identify those who have obstructive sleep apnea and lead to treatment that would prevent the elevated rates of death, cognitive impairment, motor vehicle crashes, cardiovascular events, and cerebrovascular events related to the disorder. Daniel E. Jonas, MD, of the University of North Carolina at Chapel Hill and his associates reviewed 110 relevant studies involving 46,188 participants.

They found that the accuracy and clinical utility of numerous OSA screening tools was uncertain. In particular, the Epworth Sleepiness Scale, the STOP (Snoring, Tiredness, Observed Apnea, and High Blood Pressure) questionnaire, the STOP-BANG (STOP plus BMI, Age, Neck Circumference, and Gender) questionnaire, the Berlin Questionnaire, the Wisconsin Sleep Questionnaire, and the Multivariable Apnea Prediction (MVAP) tool have not been adequately validated in primary care settings.

Moreover, no studies directly assessed whether screening had an impact on actual health outcomes. Several treatments, notably CPAP and mandibular advancement devices, did improve intermediate outcomes such as scores on the apnea-hypopnea index, scores on the Epworth Sleepiness Scale, and blood pressure levels, but the evidence did not show that this in turn improved mortality, cardiovascular events, or the other “hard” outcomes of interest, Dr. Jonas and his associates said in their Evidence Report (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.19635).

Dr. Bobbins-Domingo and her associates on the task force noted that this Recommendation Statement is consistent with that of the American Academy of Family Physicians, which also concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening asymptomatic adults for obstructive sleep apnea.

The American College of Physicians offers a “weak” recommendation based on low-quality evidence that patients with unexplained daytime sleepiness and patients suspected of having apnea undergo a sleep study, said Dr. Bobbins-Domingo, professor of medicine at the University of California, San Francisco, and her associates.

In contrast, the American Academy of Sleep Medicine recommends that routine health visits should include questions about OSA and evaluation of risk factors such as obesity, retrognathia, and treatment-refractory hypertension. If there are positive findings, a comprehensive sleep evaluation should follow, according to the AASM.

The USPSTF is an independent voluntary group supported by the Agency for Healthcare Research and Quality as mandated by the U.S. Congress. The authors’ conflict of interest disclosures are available at www.uspreventiveservicestaskforce.org.

The U.S. Preventive Services Task Force neither supports nor rejects screening asymptomatic adults for obstructive sleep apnea in the primary-care setting, because the current evidence is inadequate to assess the benefits and harms of doing so, according to a Recommendation Statement published online Jan. 23 in JAMA.

The USPSTF makes recommendations about the effectiveness of specific health care services for patients who don’t have related signs or symptoms. In this case, the Recommendation Statement addresses adults who don’t snore excessively; gasp or choke while sleeping; or report the daytime sleepiness, impaired cognition, or mood changes typically associated with obstructive sleep apnea, said Kirsten Bobbins-Domingo, PhD, MD, chair of the organization and lead author of the Recommendation Statement, and her associates (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.20325).

The USPSTF commissioned a comprehensive review of the literature to examine whether screening such patients by primary caregivers would effectively identify those who have obstructive sleep apnea and lead to treatment that would prevent the elevated rates of death, cognitive impairment, motor vehicle crashes, cardiovascular events, and cerebrovascular events related to the disorder. Daniel E. Jonas, MD, of the University of North Carolina at Chapel Hill and his associates reviewed 110 relevant studies involving 46,188 participants.

They found that the accuracy and clinical utility of numerous OSA screening tools was uncertain. In particular, the Epworth Sleepiness Scale, the STOP (Snoring, Tiredness, Observed Apnea, and High Blood Pressure) questionnaire, the STOP-BANG (STOP plus BMI, Age, Neck Circumference, and Gender) questionnaire, the Berlin Questionnaire, the Wisconsin Sleep Questionnaire, and the Multivariable Apnea Prediction (MVAP) tool have not been adequately validated in primary care settings.

Moreover, no studies directly assessed whether screening had an impact on actual health outcomes. Several treatments, notably CPAP and mandibular advancement devices, did improve intermediate outcomes such as scores on the apnea-hypopnea index, scores on the Epworth Sleepiness Scale, and blood pressure levels, but the evidence did not show that this in turn improved mortality, cardiovascular events, or the other “hard” outcomes of interest, Dr. Jonas and his associates said in their Evidence Report (JAMA 2017 Jan 23. doi: 10.1001/jama.2016.19635).

Dr. Bobbins-Domingo and her associates on the task force noted that this Recommendation Statement is consistent with that of the American Academy of Family Physicians, which also concluded that the current evidence is insufficient to assess the balance of benefits and harms of screening asymptomatic adults for obstructive sleep apnea.

The American College of Physicians offers a “weak” recommendation based on low-quality evidence that patients with unexplained daytime sleepiness and patients suspected of having apnea undergo a sleep study, said Dr. Bobbins-Domingo, professor of medicine at the University of California, San Francisco, and her associates.

In contrast, the American Academy of Sleep Medicine recommends that routine health visits should include questions about OSA and evaluation of risk factors such as obesity, retrognathia, and treatment-refractory hypertension. If there are positive findings, a comprehensive sleep evaluation should follow, according to the AASM.

The USPSTF is an independent voluntary group supported by the Agency for Healthcare Research and Quality as mandated by the U.S. Congress. The authors’ conflict of interest disclosures are available at www.uspreventiveservicestaskforce.org.

A topical cream containing the vasoconstrictor oxymetazoline has been approved by the Food and Drug Administration to treat symptoms of rosacea, its manufacturer announced.

Oxymetazoline hydrochloride cream 1%, which will be marketed as Rhofade by Allergan, is indicated for the treatment of “persistent facial erythema associated with rosacea in adults.” While nasal sprays containing a lower concentration of oxymetazoline HCl, an alpha_1A-adrenoceptor agonist, have been used off label for a decade, this is the first time this ingredient has been harnessed to formulate an approved rosacea treatment.

[email protected]

A topical cream containing the vasoconstrictor oxymetazoline has been approved by the Food and Drug Administration to treat symptoms of rosacea, its manufacturer announced.

Oxymetazoline hydrochloride cream 1%, which will be marketed as Rhofade by Allergan, is indicated for the treatment of “persistent facial erythema associated with rosacea in adults.” While nasal sprays containing a lower concentration of oxymetazoline HCl, an alpha_1A-adrenoceptor agonist, have been used off label for a decade, this is the first time this ingredient has been harnessed to formulate an approved rosacea treatment.

[email protected]

A topical cream containing the vasoconstrictor oxymetazoline has been approved by the Food and Drug Administration to treat symptoms of rosacea, its manufacturer announced.

Oxymetazoline hydrochloride cream 1%, which will be marketed as Rhofade by Allergan, is indicated for the treatment of “persistent facial erythema associated with rosacea in adults.” While nasal sprays containing a lower concentration of oxymetazoline HCl, an alpha_1A-adrenoceptor agonist, have been used off label for a decade, this is the first time this ingredient has been harnessed to formulate an approved rosacea treatment.

[email protected]

Take-Home Points

• History and physical examination are key in identifying possible etiologies of orthopedic infections.
• If identified in the acute setting, periprosthetic infections can successfully be treated with irrigation, débridement, and polyethylene liner exchange.
• Discussion with an interdisciplinary medical team, including infectious disease specialists, can aide in improved diagnosis and treatment of periprosthetic infections.

Periprosthetic infection is a leading cause of morbidity after total joint arthroplasty.¹ Despite advances in modern surgical practices, infection rates continue to range from 1% to 3% among all arthroplasty procedures performed in the United States.^2-5 The most common causes of periprosthetic infection include Staphylococcus aureus, streptococcus, enterococcus, Escherichia coli, and Pseudomonas aeruginosa.⁶ However, many other pathogens that cause periprosthetic infection should be considered in the clinical setting. In this case report, periprosthetic knee infection with P shigelloides occurred after consumption of raw oysters.

P shigelloides is a gram-negative facultative anaerobic organism in the Vibrionaceae family,⁷ which also includes Vibrio vulnificus and Vibrio parahaemolyticus. P shigelloides is most well-known for causing diarrhea and septicemia in people who have consumed raw oysters or shellfish in the United States.^8,9 Although P shigelloides infection is rare, there have been clinically significant outbreaks from contaminated water in Japan,¹⁰ consumption of freshwater fish in the Democratic Republic of the Congo,¹¹ and consumption of raw oysters in the United States.^8,9 Children and immunosuppressed people are most susceptible to the disease, which most commonly manifests as self-limiting watery diarrhea, with septicemia only in advanced cases.¹²There are very few reports of P shigelloides in the orthopedic population. In the medical literature, we found only 1 case of septic arthritis in a native knee; disease progression resulted in the patient’s death.¹³In this article, we report a case of P shigelloides septicemia that caused periprosthetic knee infection in a chemically and biologically immunosuppressed patient. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

Out of concern about a periprosthetic knee infection, a 66-year-old man was transferred from a regional medical center to our tertiary referral center. The patient reported a 3-day history of significant knee pain, swelling, and erythema that started the day after he consumed raw oysters at a seafood bar. He was unable to bear weight on the right knee and remained at home 1 day before presenting to the regional medical center.

The patient had undergone elective right total knee arthroplasty 18 months earlier, without previous issue (Figures A, B), and had a medical history of type 2 diabetes mellitus, psoriatic arthritis, hypertension, hyperlipidemia, hypothyroidism, and benign prostatic hypertrophy.

Discussion

This case is a reminder that periprosthetic knee infection can occur from a variety of pathologic organisms and that obtaining a complete history is an important part of any diagnostic work-up. Although P shigelloides infection is rare, our patient had important historical findings that led to suspicion of Vibrionaceae infection: recent consumption of raw oysters, immunosuppression with etanercept and prednisone for psoriatic arthritis, and diabetes with hemoglobin A_1c of 9.9% and presenting blood sugar of 338 mg/dL. His positive blood cultures represented P shigelloides septicemia, which seeded the knee prosthesis and led to acute periprosthetic infection. To our knowledge, this is the first report of P shigelloides periprosthetic infection in the orthopedic literature. The only other reported case of P shigelloides septicemia leading to septic arthritis in a native knee occurred in a 68-year-old Australian man who had end-stage liver disease and eventually died from complications of the P shigelloides infection.¹³

Although P shigelloides infection is rare, outbreaks have occurred around the world.^7-11,14 Infections are most commonly associated with consumption of raw shellfish or freshwater fish or with water contamination.¹² In the United States, the only described vector for disease has been consumption of raw oysters and shellfish—in particular, those harvested from the warm waters of the Gulf Coast.^8,9P shigelloides usually causes a self-limiting watery diarrhea. However, in children and immunosuppressed patients, P shigelloides can lead to life-threatening septicemia.¹² In the United States, P shigelloides cases often occur in the summer, likely related to the easy growth of the bacteria from shellfish in the Gulf Coast’s warm water and mud.⁸ This predilection for summer infections has been documented around the world.¹⁵Our patient reported eating raw oysters imported to the US Southwest from an unknown location. He likely was susceptible to P shigelloides infection, as he was immunosuppressed with etanercept and prednisone. However, there were no traditional diarrheal symptoms. Case reports have described nondiarrheal symptoms in children and other immunosuppressed people.¹²There is much to learn from this case report. Most important, it highlights the need to obtain a complete history and perform a thorough physical examination. Our patient’s 2 key historical findings, immunosuppressive medication use and raw oyster consumption, point strongly toward Vibrionaceae infection. Although a majority of periprosthetic infections are caused by common organisms, such as Staphylococcus and Streptococcus species, orthopedic clinicians should continue to expand their knowledge of periprosthetic infections, as many other pathogens can cause disease.

Am J Orthop. 2017;46(1):E32-E34. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• History and physical examination are key in identifying possible etiologies of orthopedic infections.
• If identified in the acute setting, periprosthetic infections can successfully be treated with irrigation, débridement, and polyethylene liner exchange.
• Discussion with an interdisciplinary medical team, including infectious disease specialists, can aide in improved diagnosis and treatment of periprosthetic infections.

Periprosthetic infection is a leading cause of morbidity after total joint arthroplasty.¹ Despite advances in modern surgical practices, infection rates continue to range from 1% to 3% among all arthroplasty procedures performed in the United States.^2-5 The most common causes of periprosthetic infection include Staphylococcus aureus, streptococcus, enterococcus, Escherichia coli, and Pseudomonas aeruginosa.⁶ However, many other pathogens that cause periprosthetic infection should be considered in the clinical setting. In this case report, periprosthetic knee infection with P shigelloides occurred after consumption of raw oysters.

P shigelloides is a gram-negative facultative anaerobic organism in the Vibrionaceae family,⁷ which also includes Vibrio vulnificus and Vibrio parahaemolyticus. P shigelloides is most well-known for causing diarrhea and septicemia in people who have consumed raw oysters or shellfish in the United States.^8,9 Although P shigelloides infection is rare, there have been clinically significant outbreaks from contaminated water in Japan,¹⁰ consumption of freshwater fish in the Democratic Republic of the Congo,¹¹ and consumption of raw oysters in the United States.^8,9 Children and immunosuppressed people are most susceptible to the disease, which most commonly manifests as self-limiting watery diarrhea, with septicemia only in advanced cases.¹²There are very few reports of P shigelloides in the orthopedic population. In the medical literature, we found only 1 case of septic arthritis in a native knee; disease progression resulted in the patient’s death.¹³In this article, we report a case of P shigelloides septicemia that caused periprosthetic knee infection in a chemically and biologically immunosuppressed patient. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

Out of concern about a periprosthetic knee infection, a 66-year-old man was transferred from a regional medical center to our tertiary referral center. The patient reported a 3-day history of significant knee pain, swelling, and erythema that started the day after he consumed raw oysters at a seafood bar. He was unable to bear weight on the right knee and remained at home 1 day before presenting to the regional medical center.

The patient had undergone elective right total knee arthroplasty 18 months earlier, without previous issue (Figures A, B), and had a medical history of type 2 diabetes mellitus, psoriatic arthritis, hypertension, hyperlipidemia, hypothyroidism, and benign prostatic hypertrophy.

Discussion

This case is a reminder that periprosthetic knee infection can occur from a variety of pathologic organisms and that obtaining a complete history is an important part of any diagnostic work-up. Although P shigelloides infection is rare, our patient had important historical findings that led to suspicion of Vibrionaceae infection: recent consumption of raw oysters, immunosuppression with etanercept and prednisone for psoriatic arthritis, and diabetes with hemoglobin A_1c of 9.9% and presenting blood sugar of 338 mg/dL. His positive blood cultures represented P shigelloides septicemia, which seeded the knee prosthesis and led to acute periprosthetic infection. To our knowledge, this is the first report of P shigelloides periprosthetic infection in the orthopedic literature. The only other reported case of P shigelloides septicemia leading to septic arthritis in a native knee occurred in a 68-year-old Australian man who had end-stage liver disease and eventually died from complications of the P shigelloides infection.¹³

Although P shigelloides infection is rare, outbreaks have occurred around the world.^7-11,14 Infections are most commonly associated with consumption of raw shellfish or freshwater fish or with water contamination.¹² In the United States, the only described vector for disease has been consumption of raw oysters and shellfish—in particular, those harvested from the warm waters of the Gulf Coast.^8,9P shigelloides usually causes a self-limiting watery diarrhea. However, in children and immunosuppressed patients, P shigelloides can lead to life-threatening septicemia.¹² In the United States, P shigelloides cases often occur in the summer, likely related to the easy growth of the bacteria from shellfish in the Gulf Coast’s warm water and mud.⁸ This predilection for summer infections has been documented around the world.¹⁵Our patient reported eating raw oysters imported to the US Southwest from an unknown location. He likely was susceptible to P shigelloides infection, as he was immunosuppressed with etanercept and prednisone. However, there were no traditional diarrheal symptoms. Case reports have described nondiarrheal symptoms in children and other immunosuppressed people.¹²There is much to learn from this case report. Most important, it highlights the need to obtain a complete history and perform a thorough physical examination. Our patient’s 2 key historical findings, immunosuppressive medication use and raw oyster consumption, point strongly toward Vibrionaceae infection. Although a majority of periprosthetic infections are caused by common organisms, such as Staphylococcus and Streptococcus species, orthopedic clinicians should continue to expand their knowledge of periprosthetic infections, as many other pathogens can cause disease.

Am J Orthop. 2017;46(1):E32-E34. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

Take-Home Points

• History and physical examination are key in identifying possible etiologies of orthopedic infections.
• If identified in the acute setting, periprosthetic infections can successfully be treated with irrigation, débridement, and polyethylene liner exchange.
• Discussion with an interdisciplinary medical team, including infectious disease specialists, can aide in improved diagnosis and treatment of periprosthetic infections.

Periprosthetic infection is a leading cause of morbidity after total joint arthroplasty.¹ Despite advances in modern surgical practices, infection rates continue to range from 1% to 3% among all arthroplasty procedures performed in the United States.^2-5 The most common causes of periprosthetic infection include Staphylococcus aureus, streptococcus, enterococcus, Escherichia coli, and Pseudomonas aeruginosa.⁶ However, many other pathogens that cause periprosthetic infection should be considered in the clinical setting. In this case report, periprosthetic knee infection with P shigelloides occurred after consumption of raw oysters.

P shigelloides is a gram-negative facultative anaerobic organism in the Vibrionaceae family,⁷ which also includes Vibrio vulnificus and Vibrio parahaemolyticus. P shigelloides is most well-known for causing diarrhea and septicemia in people who have consumed raw oysters or shellfish in the United States.^8,9 Although P shigelloides infection is rare, there have been clinically significant outbreaks from contaminated water in Japan,¹⁰ consumption of freshwater fish in the Democratic Republic of the Congo,¹¹ and consumption of raw oysters in the United States.^8,9 Children and immunosuppressed people are most susceptible to the disease, which most commonly manifests as self-limiting watery diarrhea, with septicemia only in advanced cases.¹²There are very few reports of P shigelloides in the orthopedic population. In the medical literature, we found only 1 case of septic arthritis in a native knee; disease progression resulted in the patient’s death.¹³In this article, we report a case of P shigelloides septicemia that caused periprosthetic knee infection in a chemically and biologically immunosuppressed patient. The patient provided written informed consent for print and electronic publication of this case report.

Case Report

Out of concern about a periprosthetic knee infection, a 66-year-old man was transferred from a regional medical center to our tertiary referral center. The patient reported a 3-day history of significant knee pain, swelling, and erythema that started the day after he consumed raw oysters at a seafood bar. He was unable to bear weight on the right knee and remained at home 1 day before presenting to the regional medical center.

The patient had undergone elective right total knee arthroplasty 18 months earlier, without previous issue (Figures A, B), and had a medical history of type 2 diabetes mellitus, psoriatic arthritis, hypertension, hyperlipidemia, hypothyroidism, and benign prostatic hypertrophy.

Discussion

This case is a reminder that periprosthetic knee infection can occur from a variety of pathologic organisms and that obtaining a complete history is an important part of any diagnostic work-up. Although P shigelloides infection is rare, our patient had important historical findings that led to suspicion of Vibrionaceae infection: recent consumption of raw oysters, immunosuppression with etanercept and prednisone for psoriatic arthritis, and diabetes with hemoglobin A_1c of 9.9% and presenting blood sugar of 338 mg/dL. His positive blood cultures represented P shigelloides septicemia, which seeded the knee prosthesis and led to acute periprosthetic infection. To our knowledge, this is the first report of P shigelloides periprosthetic infection in the orthopedic literature. The only other reported case of P shigelloides septicemia leading to septic arthritis in a native knee occurred in a 68-year-old Australian man who had end-stage liver disease and eventually died from complications of the P shigelloides infection.¹³

Although P shigelloides infection is rare, outbreaks have occurred around the world.^7-11,14 Infections are most commonly associated with consumption of raw shellfish or freshwater fish or with water contamination.¹² In the United States, the only described vector for disease has been consumption of raw oysters and shellfish—in particular, those harvested from the warm waters of the Gulf Coast.^8,9P shigelloides usually causes a self-limiting watery diarrhea. However, in children and immunosuppressed patients, P shigelloides can lead to life-threatening septicemia.¹² In the United States, P shigelloides cases often occur in the summer, likely related to the easy growth of the bacteria from shellfish in the Gulf Coast’s warm water and mud.⁸ This predilection for summer infections has been documented around the world.¹⁵Our patient reported eating raw oysters imported to the US Southwest from an unknown location. He likely was susceptible to P shigelloides infection, as he was immunosuppressed with etanercept and prednisone. However, there were no traditional diarrheal symptoms. Case reports have described nondiarrheal symptoms in children and other immunosuppressed people.¹²There is much to learn from this case report. Most important, it highlights the need to obtain a complete history and perform a thorough physical examination. Our patient’s 2 key historical findings, immunosuppressive medication use and raw oyster consumption, point strongly toward Vibrionaceae infection. Although a majority of periprosthetic infections are caused by common organisms, such as Staphylococcus and Streptococcus species, orthopedic clinicians should continue to expand their knowledge of periprosthetic infections, as many other pathogens can cause disease.

Am J Orthop. 2017;46(1):E32-E34. Copyright Frontline Medical Communications Inc. 2017. All rights reserved.

There’s a new addition to the armamentarium for atopic dermatitis: a topical phosphodiesterase 4 (PDE-4) inhibitor.

“It’s a real boon to patients, now that we have crisaborole as a first-line treatment for mild to moderate atopic dermatitis,” Joseph F. Fowler Jr., MD, of the University of Louisville (Ky.), said in an interview. “In the trials leading up to its approval, crisaborole was impressive in that it was well tolerated, and the results held up across all age groups over time.” Dr. Fowler spoke at the meeting provided by Global Academy for Medical Education.

[email protected]

On Twitter @whitneymcknight

There’s a new addition to the armamentarium for atopic dermatitis: a topical phosphodiesterase 4 (PDE-4) inhibitor.

“It’s a real boon to patients, now that we have crisaborole as a first-line treatment for mild to moderate atopic dermatitis,” Joseph F. Fowler Jr., MD, of the University of Louisville (Ky.), said in an interview. “In the trials leading up to its approval, crisaborole was impressive in that it was well tolerated, and the results held up across all age groups over time.” Dr. Fowler spoke at the meeting provided by Global Academy for Medical Education.

[email protected]

On Twitter @whitneymcknight

There’s a new addition to the armamentarium for atopic dermatitis: a topical phosphodiesterase 4 (PDE-4) inhibitor.

“It’s a real boon to patients, now that we have crisaborole as a first-line treatment for mild to moderate atopic dermatitis,” Joseph F. Fowler Jr., MD, of the University of Louisville (Ky.), said in an interview. “In the trials leading up to its approval, crisaborole was impressive in that it was well tolerated, and the results held up across all age groups over time.” Dr. Fowler spoke at the meeting provided by Global Academy for Medical Education.

[email protected]

On Twitter @whitneymcknight

Two recent reports that provide opposing evidence about the potential for inflammatory bowel disease patients to develop articular manifestations after starting vedolizumab raise questions for future studies to answer in regard to a plausible mechanism for the adverse event and its relative importance.

The two reports, one a case series of 5 patients with inflammatory bowel disease (IBD) who developed articular manifestations after beginning vedolizumab (Entyvio) and the other a prospective cohort study of 53 patients with IBD who started vedolizumab without any subsequent cases of induction or flare of arthritis and/or sacroiliitis, came to somewhat different conclusions about the beneficial or paradoxical effects of vedolizumab’s blockade of the alpha4beta7 receptor on articular manifestations of IBD.

The five-patient cases series reported by Gaëlle Varkas, MD, a doctoral student at the University of Ghent, Belgium, and her colleagues consisted of five IBD patients, aged 26-50 years, who developed either new onset or an exacerbation of sacroiliitis or arthritis soon after starting vedolizumab. All but one of the patients was female (Ann Rheum Dis. 2016 Nov 29. doi: 10.1136/annrheumdis-2016-210233). In these patients, the investigators said, vedolizumab did not “seem to show any efficacy in and might even induce arthritis and/or sacroiliitis.”

The first was a 50-year-old woman who had progressive back pain with MRI-confirmed bilateral sacroiliitis about 2 months after beginning vedolizumab. The second patient, a 28-year-old woman with no previous history of spondyloarthropathy, had lower limb pain, a painful left shoulder, and arthritis of one wrist. Ultrasound examination confirmed intercarpal effusions and synovial hyperproliferation.

The third patient was 30 years old and male. He had both ankylosing spondylitis and Crohn’s disease, and experienced arthralgias, elevated C-reactive protein, and MRI-confirmed axial skeletal inflammation 4 weeks after starting vedolizumab.

The fourth patient was a 47-year-old woman with no previous history of spondyloarthropathy who developed MRI-confirmed sacroiliitis after beginning vedolizumab. The fifth patient, a 26-year-old woman, developed polyarticular joint pain after starting vedolizumab. Examination of this patient showed synovitis and enthesitis of multiple joints of the appendicular skeleton.

In discussion, Dr. Varkas and her colleagues noted that “one of the many hypotheses is that integrins and adhesion molecules play a role in the interception of recirculating activated lymphocytes between the gut and the synovial membrane due to the inhibition of the alpha4beta7 integrin homing at the level of the gut.” However, the investigators also acknowledged that other hypotheses may also account for their findings. “Alternatively, in the presence of vedolizumab, cellular recruitment may be mediated by yet to be determined adhesion molecules. This recirculation theory might explain the short mean interval of 64 days between vedolizumab initiation and the expression of symptoms.”

Another group, publishing its prospective cohort study in a letter, had different findings (Ann Rheum Dis. 2017 Jan 17. doi: 10.1136/annrheumdis-2016-211011).

“Although the hypotheses proposed by the authors to explain such events sounds reasonable,” wrote Ambrogio Orlando, MD, and his coauthors, their experience of the effect of vedolizumab on spondyloarthritis differed.

In the report on 53 patients who began treatment with vedolizumab at Villa Sofia-Cervello Hospital, Palermo, Italy, where Dr. Orlando and his associates work, almost all (96%) had been steroid dependent and 81% had been treated with at least one tumor necrosis factor inhibitor. About two-thirds had completed the induction phase of vedolizumab treatment during follow-up, which lasted a mean of 2.6 months. Of the 14 patients (26%) who had active IBD-associated spondyloarthropathy when starting vedolizumab, 6 (46.2%) saw “a sharp clinical benefit after the initiation of vedolizumab,” wrote Dr. Orlando and his colleagues. Five of these six patients experienced clinical remission of gut symptoms by 12 weeks of therapy.

Dr. Orlando and his colleagues wrote that “our preliminary prospective data indicate a potential benefit of vedolizumab on IBD-associated spondyloarthropathy.”

Looking for mechanistic reasons for this apparent benefit, Dr. Orlando and his collaborators wrote that “the previous demonstration of alpha4beta7 in the joint and the recent evidence of the upregulation of mucosal vascular address in cell adhesion molecule (MadCAM-1) in the high endothelial venules of bone marrow in patients with active axial SpA seem to strengthen the hypothesis of a beneficial rather than a paradoxical effect of alpha4beta7 blockade on articular manifestations of IBD.”

Two authors of the case series reported relationships with multiple pharmaceutical companies, as did Dr. Orlando and two other authors of the letter describing the prospective study.

[email protected]

On Twitter @karioakes

Two recent reports that provide opposing evidence about the potential for inflammatory bowel disease patients to develop articular manifestations after starting vedolizumab raise questions for future studies to answer in regard to a plausible mechanism for the adverse event and its relative importance.

The two reports, one a case series of 5 patients with inflammatory bowel disease (IBD) who developed articular manifestations after beginning vedolizumab (Entyvio) and the other a prospective cohort study of 53 patients with IBD who started vedolizumab without any subsequent cases of induction or flare of arthritis and/or sacroiliitis, came to somewhat different conclusions about the beneficial or paradoxical effects of vedolizumab’s blockade of the alpha4beta7 receptor on articular manifestations of IBD.

The five-patient cases series reported by Gaëlle Varkas, MD, a doctoral student at the University of Ghent, Belgium, and her colleagues consisted of five IBD patients, aged 26-50 years, who developed either new onset or an exacerbation of sacroiliitis or arthritis soon after starting vedolizumab. All but one of the patients was female (Ann Rheum Dis. 2016 Nov 29. doi: 10.1136/annrheumdis-2016-210233). In these patients, the investigators said, vedolizumab did not “seem to show any efficacy in and might even induce arthritis and/or sacroiliitis.”

The first was a 50-year-old woman who had progressive back pain with MRI-confirmed bilateral sacroiliitis about 2 months after beginning vedolizumab. The second patient, a 28-year-old woman with no previous history of spondyloarthropathy, had lower limb pain, a painful left shoulder, and arthritis of one wrist. Ultrasound examination confirmed intercarpal effusions and synovial hyperproliferation.

The third patient was 30 years old and male. He had both ankylosing spondylitis and Crohn’s disease, and experienced arthralgias, elevated C-reactive protein, and MRI-confirmed axial skeletal inflammation 4 weeks after starting vedolizumab.

The fourth patient was a 47-year-old woman with no previous history of spondyloarthropathy who developed MRI-confirmed sacroiliitis after beginning vedolizumab. The fifth patient, a 26-year-old woman, developed polyarticular joint pain after starting vedolizumab. Examination of this patient showed synovitis and enthesitis of multiple joints of the appendicular skeleton.

In discussion, Dr. Varkas and her colleagues noted that “one of the many hypotheses is that integrins and adhesion molecules play a role in the interception of recirculating activated lymphocytes between the gut and the synovial membrane due to the inhibition of the alpha4beta7 integrin homing at the level of the gut.” However, the investigators also acknowledged that other hypotheses may also account for their findings. “Alternatively, in the presence of vedolizumab, cellular recruitment may be mediated by yet to be determined adhesion molecules. This recirculation theory might explain the short mean interval of 64 days between vedolizumab initiation and the expression of symptoms.”

Another group, publishing its prospective cohort study in a letter, had different findings (Ann Rheum Dis. 2017 Jan 17. doi: 10.1136/annrheumdis-2016-211011).

“Although the hypotheses proposed by the authors to explain such events sounds reasonable,” wrote Ambrogio Orlando, MD, and his coauthors, their experience of the effect of vedolizumab on spondyloarthritis differed.

In the report on 53 patients who began treatment with vedolizumab at Villa Sofia-Cervello Hospital, Palermo, Italy, where Dr. Orlando and his associates work, almost all (96%) had been steroid dependent and 81% had been treated with at least one tumor necrosis factor inhibitor. About two-thirds had completed the induction phase of vedolizumab treatment during follow-up, which lasted a mean of 2.6 months. Of the 14 patients (26%) who had active IBD-associated spondyloarthropathy when starting vedolizumab, 6 (46.2%) saw “a sharp clinical benefit after the initiation of vedolizumab,” wrote Dr. Orlando and his colleagues. Five of these six patients experienced clinical remission of gut symptoms by 12 weeks of therapy.

Dr. Orlando and his colleagues wrote that “our preliminary prospective data indicate a potential benefit of vedolizumab on IBD-associated spondyloarthropathy.”

Looking for mechanistic reasons for this apparent benefit, Dr. Orlando and his collaborators wrote that “the previous demonstration of alpha4beta7 in the joint and the recent evidence of the upregulation of mucosal vascular address in cell adhesion molecule (MadCAM-1) in the high endothelial venules of bone marrow in patients with active axial SpA seem to strengthen the hypothesis of a beneficial rather than a paradoxical effect of alpha4beta7 blockade on articular manifestations of IBD.”

Two authors of the case series reported relationships with multiple pharmaceutical companies, as did Dr. Orlando and two other authors of the letter describing the prospective study.

[email protected]

On Twitter @karioakes

Two recent reports that provide opposing evidence about the potential for inflammatory bowel disease patients to develop articular manifestations after starting vedolizumab raise questions for future studies to answer in regard to a plausible mechanism for the adverse event and its relative importance.

The two reports, one a case series of 5 patients with inflammatory bowel disease (IBD) who developed articular manifestations after beginning vedolizumab (Entyvio) and the other a prospective cohort study of 53 patients with IBD who started vedolizumab without any subsequent cases of induction or flare of arthritis and/or sacroiliitis, came to somewhat different conclusions about the beneficial or paradoxical effects of vedolizumab’s blockade of the alpha4beta7 receptor on articular manifestations of IBD.

The five-patient cases series reported by Gaëlle Varkas, MD, a doctoral student at the University of Ghent, Belgium, and her colleagues consisted of five IBD patients, aged 26-50 years, who developed either new onset or an exacerbation of sacroiliitis or arthritis soon after starting vedolizumab. All but one of the patients was female (Ann Rheum Dis. 2016 Nov 29. doi: 10.1136/annrheumdis-2016-210233). In these patients, the investigators said, vedolizumab did not “seem to show any efficacy in and might even induce arthritis and/or sacroiliitis.”

The first was a 50-year-old woman who had progressive back pain with MRI-confirmed bilateral sacroiliitis about 2 months after beginning vedolizumab. The second patient, a 28-year-old woman with no previous history of spondyloarthropathy, had lower limb pain, a painful left shoulder, and arthritis of one wrist. Ultrasound examination confirmed intercarpal effusions and synovial hyperproliferation.

The third patient was 30 years old and male. He had both ankylosing spondylitis and Crohn’s disease, and experienced arthralgias, elevated C-reactive protein, and MRI-confirmed axial skeletal inflammation 4 weeks after starting vedolizumab.

The fourth patient was a 47-year-old woman with no previous history of spondyloarthropathy who developed MRI-confirmed sacroiliitis after beginning vedolizumab. The fifth patient, a 26-year-old woman, developed polyarticular joint pain after starting vedolizumab. Examination of this patient showed synovitis and enthesitis of multiple joints of the appendicular skeleton.

In discussion, Dr. Varkas and her colleagues noted that “one of the many hypotheses is that integrins and adhesion molecules play a role in the interception of recirculating activated lymphocytes between the gut and the synovial membrane due to the inhibition of the alpha4beta7 integrin homing at the level of the gut.” However, the investigators also acknowledged that other hypotheses may also account for their findings. “Alternatively, in the presence of vedolizumab, cellular recruitment may be mediated by yet to be determined adhesion molecules. This recirculation theory might explain the short mean interval of 64 days between vedolizumab initiation and the expression of symptoms.”

Another group, publishing its prospective cohort study in a letter, had different findings (Ann Rheum Dis. 2017 Jan 17. doi: 10.1136/annrheumdis-2016-211011).

“Although the hypotheses proposed by the authors to explain such events sounds reasonable,” wrote Ambrogio Orlando, MD, and his coauthors, their experience of the effect of vedolizumab on spondyloarthritis differed.

In the report on 53 patients who began treatment with vedolizumab at Villa Sofia-Cervello Hospital, Palermo, Italy, where Dr. Orlando and his associates work, almost all (96%) had been steroid dependent and 81% had been treated with at least one tumor necrosis factor inhibitor. About two-thirds had completed the induction phase of vedolizumab treatment during follow-up, which lasted a mean of 2.6 months. Of the 14 patients (26%) who had active IBD-associated spondyloarthropathy when starting vedolizumab, 6 (46.2%) saw “a sharp clinical benefit after the initiation of vedolizumab,” wrote Dr. Orlando and his colleagues. Five of these six patients experienced clinical remission of gut symptoms by 12 weeks of therapy.

Dr. Orlando and his colleagues wrote that “our preliminary prospective data indicate a potential benefit of vedolizumab on IBD-associated spondyloarthropathy.”

Looking for mechanistic reasons for this apparent benefit, Dr. Orlando and his collaborators wrote that “the previous demonstration of alpha4beta7 in the joint and the recent evidence of the upregulation of mucosal vascular address in cell adhesion molecule (MadCAM-1) in the high endothelial venules of bone marrow in patients with active axial SpA seem to strengthen the hypothesis of a beneficial rather than a paradoxical effect of alpha4beta7 blockade on articular manifestations of IBD.”

Two authors of the case series reported relationships with multiple pharmaceutical companies, as did Dr. Orlando and two other authors of the letter describing the prospective study.

[email protected]

On Twitter @karioakes

For patients with polycythemia vera without splenomegaly who had inadequate responses to hydroxyurea, targeted therapy with the Janus kinase (JAK) inhibitor ruxolitinib (Jakafi) offered better control of hematocrit and better improvement of symptoms than did the best available therapy, according to results of a multinational randomized phase IIIb trial.

Among 74 patients randomly assigned to receive ruxolitinib, 46 (62%) achieved hematocrit control, compared with 14 of 75 patients (19%) assigned to receive one of several different options lumped into the best available therapy category, noted investigators led by Francesco Passamonti, MD, of the University of Insubria in Varese, Italy.

“Ruxolitinib also led to an improved symptom burden and quality of life. Patients treated with ruxolitinib experienced improvements in all polycythemia vera–associated symptoms, including pruritus, whereas patients treated with best available therapy experienced worsening of most symptoms,” they wrote.

Unlike cytoreductive therapies such as hydroxyurea or pegylated interferon, ruxolitinib works by inhibition of JAK1 and JAK2 signaling. A majority of patients with polycythemia vera have an activating JAK2 mutation that leads to overactivation of the JAK-STAT signaling pathway, resulting in erythrocytosis, the hallmark symptom of polycythemia vera, and associated vascular complications.

“In some patients, conventional therapies can lose effectiveness over time. Although hydroxyurea is well tolerated in most patients, about 15%-20% of patients become resistant or intolerant, with hydroxyurea resistance affecting survival and increasing the risk of progression to myelofibrosis. Additionally, patients who are intolerant of hydroxyurea can have adverse side effects, such as drug-induced fever, mouth ulcers, leg ulcers, and skin malignancies, which necessitate discontinuation of first-line therapy,” the investigators noted.
 

RESPONSE trials

Ruxolitinib had previously been shown in the RESPONSE study to be superior to the best available therapy for controlling hematocrit and for improving splenomegaly and other symptoms in patients with polycythemia vera and disease-associated splenomegaly who had an inadequate response or unacceptable toxicities from treatment with hydroxyurea.

In the currently reported study, dubbed RESPONSE-2, patients 18 and older with polycythemia vera with no palpable splenomegaly who were intolerant of hydroxyurea or had disease that was resistant to it were randomized to receive either oral ruxolitinib 10 mg twice daily, or best available therapy at the investigators’ discretion. Best available therapy consisted of either hydroxyurea at the maximum tolerated dose, interferon or pegylated interferon, pipobroman, anagrelide, approved immunomodulators, or no cytoreductive treatment.

As noted, hematocrit control at week 28, the primary endpoint, was significantly higher among patients on ruxolitinib, with an odds ratio (OR) of 7.28 (P less than .0001).

Hematocrit levels among patients on ruxolitinib group decreased from a mean of 42.8% at baseline to 40.2% at week 28. In contrast, hematocrit in the best available therapy group increased from a mean of 42.7% to 44.9% at week 28.

Fewer patients on ruxolitinib required phlebotomy procedures during the 28 weeks of the study compared with patients on best available therapy, and of those patients who did undergo phlebotomy, fewer of those in the ruxolitinib group underwent more than two procedures. There were a total of 98 phlebotomies among best available care patients, vs. 19 among ruxolitinib patients.

Complete hematologic remissions, a secondary endpoint, occurred in 23% of patients on ruxolitinib, compared with 5% of those on best available care (OR 5.58, P = .0019).

The most frequent hematologic adverse events of any grade were anemia, which occurred in 10 patients on ruxolitinib (none grade 3 or greater) vs. two on best available therapy (one grade 3), and thrombocytopenia occurring in two (both grade 1 or 2) and six patients (three grade 1 or 2, two grade 3, and one grade 4) respectively.

Grade 3 or 4 nonhematologic adverse events included hypertension in five patients on ruxolitinib vs. three on best available care, and pruritus in none vs. two, respectively.

Two patients died; both were in the best available therapy group.

“Although the short follow-up of this study precludes any conclusions about vascular complications, an important finding is that patients treated with ruxolitinib in both RESPONSE and RESPONSE-2 had fewer thromboembolic events compared with those given best available therapy; there were two thromboembolic events with ruxolitinib (one in each study) versus nine with best available therapy across both studies (six in RESPONSE and three in RESPONSE-2). This finding could have been attributable to better control of hematocrit or white blood cell count with ruxolitinib, given that baseline risk factors were similar in both treatment groups,” the investigators wrote.

The findings from the two studies support the use of ruxolitinib as a standard of care for second-line therapy of patients with polycythemia vera following treatment with hydroxyurea, they contended.

Several coauthors disclosed ties to Novartis, which supported the study. Two are Novartis employees; one was previously employed by the company.

For patients with polycythemia vera without splenomegaly who had inadequate responses to hydroxyurea, targeted therapy with the Janus kinase (JAK) inhibitor ruxolitinib (Jakafi) offered better control of hematocrit and better improvement of symptoms than did the best available therapy, according to results of a multinational randomized phase IIIb trial.

Among 74 patients randomly assigned to receive ruxolitinib, 46 (62%) achieved hematocrit control, compared with 14 of 75 patients (19%) assigned to receive one of several different options lumped into the best available therapy category, noted investigators led by Francesco Passamonti, MD, of the University of Insubria in Varese, Italy.

“Ruxolitinib also led to an improved symptom burden and quality of life. Patients treated with ruxolitinib experienced improvements in all polycythemia vera–associated symptoms, including pruritus, whereas patients treated with best available therapy experienced worsening of most symptoms,” they wrote.

Unlike cytoreductive therapies such as hydroxyurea or pegylated interferon, ruxolitinib works by inhibition of JAK1 and JAK2 signaling. A majority of patients with polycythemia vera have an activating JAK2 mutation that leads to overactivation of the JAK-STAT signaling pathway, resulting in erythrocytosis, the hallmark symptom of polycythemia vera, and associated vascular complications.

“In some patients, conventional therapies can lose effectiveness over time. Although hydroxyurea is well tolerated in most patients, about 15%-20% of patients become resistant or intolerant, with hydroxyurea resistance affecting survival and increasing the risk of progression to myelofibrosis. Additionally, patients who are intolerant of hydroxyurea can have adverse side effects, such as drug-induced fever, mouth ulcers, leg ulcers, and skin malignancies, which necessitate discontinuation of first-line therapy,” the investigators noted.
 

RESPONSE trials

Ruxolitinib had previously been shown in the RESPONSE study to be superior to the best available therapy for controlling hematocrit and for improving splenomegaly and other symptoms in patients with polycythemia vera and disease-associated splenomegaly who had an inadequate response or unacceptable toxicities from treatment with hydroxyurea.

In the currently reported study, dubbed RESPONSE-2, patients 18 and older with polycythemia vera with no palpable splenomegaly who were intolerant of hydroxyurea or had disease that was resistant to it were randomized to receive either oral ruxolitinib 10 mg twice daily, or best available therapy at the investigators’ discretion. Best available therapy consisted of either hydroxyurea at the maximum tolerated dose, interferon or pegylated interferon, pipobroman, anagrelide, approved immunomodulators, or no cytoreductive treatment.

As noted, hematocrit control at week 28, the primary endpoint, was significantly higher among patients on ruxolitinib, with an odds ratio (OR) of 7.28 (P less than .0001).

Hematocrit levels among patients on ruxolitinib group decreased from a mean of 42.8% at baseline to 40.2% at week 28. In contrast, hematocrit in the best available therapy group increased from a mean of 42.7% to 44.9% at week 28.

Fewer patients on ruxolitinib required phlebotomy procedures during the 28 weeks of the study compared with patients on best available therapy, and of those patients who did undergo phlebotomy, fewer of those in the ruxolitinib group underwent more than two procedures. There were a total of 98 phlebotomies among best available care patients, vs. 19 among ruxolitinib patients.

Complete hematologic remissions, a secondary endpoint, occurred in 23% of patients on ruxolitinib, compared with 5% of those on best available care (OR 5.58, P = .0019).

The most frequent hematologic adverse events of any grade were anemia, which occurred in 10 patients on ruxolitinib (none grade 3 or greater) vs. two on best available therapy (one grade 3), and thrombocytopenia occurring in two (both grade 1 or 2) and six patients (three grade 1 or 2, two grade 3, and one grade 4) respectively.

Grade 3 or 4 nonhematologic adverse events included hypertension in five patients on ruxolitinib vs. three on best available care, and pruritus in none vs. two, respectively.

Two patients died; both were in the best available therapy group.

“Although the short follow-up of this study precludes any conclusions about vascular complications, an important finding is that patients treated with ruxolitinib in both RESPONSE and RESPONSE-2 had fewer thromboembolic events compared with those given best available therapy; there were two thromboembolic events with ruxolitinib (one in each study) versus nine with best available therapy across both studies (six in RESPONSE and three in RESPONSE-2). This finding could have been attributable to better control of hematocrit or white blood cell count with ruxolitinib, given that baseline risk factors were similar in both treatment groups,” the investigators wrote.

The findings from the two studies support the use of ruxolitinib as a standard of care for second-line therapy of patients with polycythemia vera following treatment with hydroxyurea, they contended.

Several coauthors disclosed ties to Novartis, which supported the study. Two are Novartis employees; one was previously employed by the company.

For patients with polycythemia vera without splenomegaly who had inadequate responses to hydroxyurea, targeted therapy with the Janus kinase (JAK) inhibitor ruxolitinib (Jakafi) offered better control of hematocrit and better improvement of symptoms than did the best available therapy, according to results of a multinational randomized phase IIIb trial.

Among 74 patients randomly assigned to receive ruxolitinib, 46 (62%) achieved hematocrit control, compared with 14 of 75 patients (19%) assigned to receive one of several different options lumped into the best available therapy category, noted investigators led by Francesco Passamonti, MD, of the University of Insubria in Varese, Italy.

“Ruxolitinib also led to an improved symptom burden and quality of life. Patients treated with ruxolitinib experienced improvements in all polycythemia vera–associated symptoms, including pruritus, whereas patients treated with best available therapy experienced worsening of most symptoms,” they wrote.

Unlike cytoreductive therapies such as hydroxyurea or pegylated interferon, ruxolitinib works by inhibition of JAK1 and JAK2 signaling. A majority of patients with polycythemia vera have an activating JAK2 mutation that leads to overactivation of the JAK-STAT signaling pathway, resulting in erythrocytosis, the hallmark symptom of polycythemia vera, and associated vascular complications.

“In some patients, conventional therapies can lose effectiveness over time. Although hydroxyurea is well tolerated in most patients, about 15%-20% of patients become resistant or intolerant, with hydroxyurea resistance affecting survival and increasing the risk of progression to myelofibrosis. Additionally, patients who are intolerant of hydroxyurea can have adverse side effects, such as drug-induced fever, mouth ulcers, leg ulcers, and skin malignancies, which necessitate discontinuation of first-line therapy,” the investigators noted.
 

RESPONSE trials

Ruxolitinib had previously been shown in the RESPONSE study to be superior to the best available therapy for controlling hematocrit and for improving splenomegaly and other symptoms in patients with polycythemia vera and disease-associated splenomegaly who had an inadequate response or unacceptable toxicities from treatment with hydroxyurea.

In the currently reported study, dubbed RESPONSE-2, patients 18 and older with polycythemia vera with no palpable splenomegaly who were intolerant of hydroxyurea or had disease that was resistant to it were randomized to receive either oral ruxolitinib 10 mg twice daily, or best available therapy at the investigators’ discretion. Best available therapy consisted of either hydroxyurea at the maximum tolerated dose, interferon or pegylated interferon, pipobroman, anagrelide, approved immunomodulators, or no cytoreductive treatment.

As noted, hematocrit control at week 28, the primary endpoint, was significantly higher among patients on ruxolitinib, with an odds ratio (OR) of 7.28 (P less than .0001).

Hematocrit levels among patients on ruxolitinib group decreased from a mean of 42.8% at baseline to 40.2% at week 28. In contrast, hematocrit in the best available therapy group increased from a mean of 42.7% to 44.9% at week 28.

Fewer patients on ruxolitinib required phlebotomy procedures during the 28 weeks of the study compared with patients on best available therapy, and of those patients who did undergo phlebotomy, fewer of those in the ruxolitinib group underwent more than two procedures. There were a total of 98 phlebotomies among best available care patients, vs. 19 among ruxolitinib patients.

Complete hematologic remissions, a secondary endpoint, occurred in 23% of patients on ruxolitinib, compared with 5% of those on best available care (OR 5.58, P = .0019).

The most frequent hematologic adverse events of any grade were anemia, which occurred in 10 patients on ruxolitinib (none grade 3 or greater) vs. two on best available therapy (one grade 3), and thrombocytopenia occurring in two (both grade 1 or 2) and six patients (three grade 1 or 2, two grade 3, and one grade 4) respectively.

Grade 3 or 4 nonhematologic adverse events included hypertension in five patients on ruxolitinib vs. three on best available care, and pruritus in none vs. two, respectively.

Two patients died; both were in the best available therapy group.

“Although the short follow-up of this study precludes any conclusions about vascular complications, an important finding is that patients treated with ruxolitinib in both RESPONSE and RESPONSE-2 had fewer thromboembolic events compared with those given best available therapy; there were two thromboembolic events with ruxolitinib (one in each study) versus nine with best available therapy across both studies (six in RESPONSE and three in RESPONSE-2). This finding could have been attributable to better control of hematocrit or white blood cell count with ruxolitinib, given that baseline risk factors were similar in both treatment groups,” the investigators wrote.

The findings from the two studies support the use of ruxolitinib as a standard of care for second-line therapy of patients with polycythemia vera following treatment with hydroxyurea, they contended.

Several coauthors disclosed ties to Novartis, which supported the study. Two are Novartis employees; one was previously employed by the company.

This year’s SDEF Hawaii Dermatology Seminar is set to showcase the latest research and expert tips, advice, and perspective on a range of topics.

Linda Stein Gold, MD, director of dermatology research, Henry Ford Health System, Detroit, and a codirector of the meeting, shared a taste of the topics she will be presenting.

In the field of rosacea, “topical ivermectin has proven to be a very effective and safe treatment,” she said in an interview. “On the horizon we will have a new treatment for the erythema of rosacea which seems very well tolerated. Also, topical minocycline foam appears to be very promising in phase II studies.”

This year’s SDEF Hawaii Dermatology Seminar is set to showcase the latest research and expert tips, advice, and perspective on a range of topics.

Linda Stein Gold, MD, director of dermatology research, Henry Ford Health System, Detroit, and a codirector of the meeting, shared a taste of the topics she will be presenting.

In the field of rosacea, “topical ivermectin has proven to be a very effective and safe treatment,” she said in an interview. “On the horizon we will have a new treatment for the erythema of rosacea which seems very well tolerated. Also, topical minocycline foam appears to be very promising in phase II studies.”

This year’s SDEF Hawaii Dermatology Seminar is set to showcase the latest research and expert tips, advice, and perspective on a range of topics.

Linda Stein Gold, MD, director of dermatology research, Henry Ford Health System, Detroit, and a codirector of the meeting, shared a taste of the topics she will be presenting.

In the field of rosacea, “topical ivermectin has proven to be a very effective and safe treatment,” she said in an interview. “On the horizon we will have a new treatment for the erythema of rosacea which seems very well tolerated. Also, topical minocycline foam appears to be very promising in phase II studies.”

Lab mouse

Preclinical research suggests that immune stimulation through Toll-like receptor 7 (TLR7) agonism can enhance the efficacy of obinutuzumab in lymphoma.

Researchers found that combining the anti-CD20 monoclonal antibody obinutuzumab with the TLR7 agonist R848 improved survival in lab mice with lymphoma.

The combination also demonstrated efficacy against chronic lymphocytic leukemia (CLL) cells in vitro.

Tim Illidge, PhD, MBBS, of the University of Manchester in the UK, and his colleagues reported these findings in the journal Leukemia.

The research was funded by the Kay Kendall Leukaemia Fund and Cancer Research UK in collaboration with Roche Pharmaceutical Research and Early Development.

The researchers said they initially found that R848 activates immune cells in vivo and enhances obinutuzumab-mediated antitumor effector mechanisms in vitro.

The team therefore went on to test R848 and obinutuzumab in C57Bl/6 mice bearing human CD20+ lymphoma (EL4). The mice received obinutuzumab modified to express the murine glycoengineered IgG2a Fc region (m2a) starting 1 day after tumor inoculation and systemic R848 once weekly for 4 weeks.

The researchers found that monotherapy with either obinutuzumab or R848 significantly improved survival compared to control (P<0.0001), but only 8% to 15% of mice that received monotherapy were long-term survivors (living more than 90 days).

Mice that received obinutuzumab in combination with R848 had significantly better survival than mice that received either monotherapy (P<0.0001). And about 70% of mice receiving the combination remained tumor-free out to 95 days.

Furthermore, long-term survivors that had received the combination treatment were protected from tumor re-challenge.

The researchers also tested the combination in a second model—human CD20 transgenic mice, which express the human CD20 antigen on normal B cells. The team said this model is more akin to the clinical situation.

The mice received treatment 7 days after the inoculation of EL4hCD20 cells. Mice that received obinutuzumab monotherapy had significantly better survival than control mice (P=0.02), but there were no long-term survivors. For mice that received R848 monotherapy, survival was not significantly different from that of controls.

Mice that received R848 in combination with obinutuzumab had significantly better survival than mice that received obinutuzumab alone (P=0.003).

In fact, 6 of the 12 mice that received the combination were long-term survivors. And 5 of these mice rejected tumor re-challenge.

“We were excited when we discovered that combining obinutuzumab with TLR7 activation significantly enhanced survival of animals with lymphoma by effectively eradicating tumors,” Dr Illidge said. “Clearly, more work needs to be done to assess the impact of this combination on humans, but this study is, nevertheless, very promising.”

The researchers said the primary antitumor activity of the combination is dependent on natural killer cells and CD4 helper T cells but not on CD8 killer T cells.

“While the combination therapy was highly effective, CD8 killer T cells did not play a major role in the therapy,” said Eleanor Cheadle, PhD, also of the University of Manchester.

“Given the important role that killer T cells can play in long-term protection from tumor regrowth, we are looking at ways to enhance activation of these cells after obinutuzumab therapy.”

The researchers also found that, in vitro, R848 significantly enhanced natural killer cell-mediated antibody-dependent cellular cytotoxicity against obinutuzumab-opsonized CLL cells and significantly increased non-specific, antibody-independent killing of CLL cells.

Lab mouse

Preclinical research suggests that immune stimulation through Toll-like receptor 7 (TLR7) agonism can enhance the efficacy of obinutuzumab in lymphoma.

Researchers found that combining the anti-CD20 monoclonal antibody obinutuzumab with the TLR7 agonist R848 improved survival in lab mice with lymphoma.

The combination also demonstrated efficacy against chronic lymphocytic leukemia (CLL) cells in vitro.

Tim Illidge, PhD, MBBS, of the University of Manchester in the UK, and his colleagues reported these findings in the journal Leukemia.

The research was funded by the Kay Kendall Leukaemia Fund and Cancer Research UK in collaboration with Roche Pharmaceutical Research and Early Development.

The researchers said they initially found that R848 activates immune cells in vivo and enhances obinutuzumab-mediated antitumor effector mechanisms in vitro.

The team therefore went on to test R848 and obinutuzumab in C57Bl/6 mice bearing human CD20+ lymphoma (EL4). The mice received obinutuzumab modified to express the murine glycoengineered IgG2a Fc region (m2a) starting 1 day after tumor inoculation and systemic R848 once weekly for 4 weeks.

The researchers found that monotherapy with either obinutuzumab or R848 significantly improved survival compared to control (P<0.0001), but only 8% to 15% of mice that received monotherapy were long-term survivors (living more than 90 days).

Mice that received obinutuzumab in combination with R848 had significantly better survival than mice that received either monotherapy (P<0.0001). And about 70% of mice receiving the combination remained tumor-free out to 95 days.

Furthermore, long-term survivors that had received the combination treatment were protected from tumor re-challenge.

The researchers also tested the combination in a second model—human CD20 transgenic mice, which express the human CD20 antigen on normal B cells. The team said this model is more akin to the clinical situation.

The mice received treatment 7 days after the inoculation of EL4hCD20 cells. Mice that received obinutuzumab monotherapy had significantly better survival than control mice (P=0.02), but there were no long-term survivors. For mice that received R848 monotherapy, survival was not significantly different from that of controls.

Mice that received R848 in combination with obinutuzumab had significantly better survival than mice that received obinutuzumab alone (P=0.003).

In fact, 6 of the 12 mice that received the combination were long-term survivors. And 5 of these mice rejected tumor re-challenge.

“We were excited when we discovered that combining obinutuzumab with TLR7 activation significantly enhanced survival of animals with lymphoma by effectively eradicating tumors,” Dr Illidge said. “Clearly, more work needs to be done to assess the impact of this combination on humans, but this study is, nevertheless, very promising.”

The researchers said the primary antitumor activity of the combination is dependent on natural killer cells and CD4 helper T cells but not on CD8 killer T cells.

“While the combination therapy was highly effective, CD8 killer T cells did not play a major role in the therapy,” said Eleanor Cheadle, PhD, also of the University of Manchester.

“Given the important role that killer T cells can play in long-term protection from tumor regrowth, we are looking at ways to enhance activation of these cells after obinutuzumab therapy.”

The researchers also found that, in vitro, R848 significantly enhanced natural killer cell-mediated antibody-dependent cellular cytotoxicity against obinutuzumab-opsonized CLL cells and significantly increased non-specific, antibody-independent killing of CLL cells.

Lab mouse

Preclinical research suggests that immune stimulation through Toll-like receptor 7 (TLR7) agonism can enhance the efficacy of obinutuzumab in lymphoma.

Researchers found that combining the anti-CD20 monoclonal antibody obinutuzumab with the TLR7 agonist R848 improved survival in lab mice with lymphoma.

The combination also demonstrated efficacy against chronic lymphocytic leukemia (CLL) cells in vitro.

Tim Illidge, PhD, MBBS, of the University of Manchester in the UK, and his colleagues reported these findings in the journal Leukemia.

The research was funded by the Kay Kendall Leukaemia Fund and Cancer Research UK in collaboration with Roche Pharmaceutical Research and Early Development.

The researchers said they initially found that R848 activates immune cells in vivo and enhances obinutuzumab-mediated antitumor effector mechanisms in vitro.

The team therefore went on to test R848 and obinutuzumab in C57Bl/6 mice bearing human CD20+ lymphoma (EL4). The mice received obinutuzumab modified to express the murine glycoengineered IgG2a Fc region (m2a) starting 1 day after tumor inoculation and systemic R848 once weekly for 4 weeks.

The researchers found that monotherapy with either obinutuzumab or R848 significantly improved survival compared to control (P<0.0001), but only 8% to 15% of mice that received monotherapy were long-term survivors (living more than 90 days).

Mice that received obinutuzumab in combination with R848 had significantly better survival than mice that received either monotherapy (P<0.0001). And about 70% of mice receiving the combination remained tumor-free out to 95 days.

Furthermore, long-term survivors that had received the combination treatment were protected from tumor re-challenge.

The researchers also tested the combination in a second model—human CD20 transgenic mice, which express the human CD20 antigen on normal B cells. The team said this model is more akin to the clinical situation.

The mice received treatment 7 days after the inoculation of EL4hCD20 cells. Mice that received obinutuzumab monotherapy had significantly better survival than control mice (P=0.02), but there were no long-term survivors. For mice that received R848 monotherapy, survival was not significantly different from that of controls.

Mice that received R848 in combination with obinutuzumab had significantly better survival than mice that received obinutuzumab alone (P=0.003).

In fact, 6 of the 12 mice that received the combination were long-term survivors. And 5 of these mice rejected tumor re-challenge.

“We were excited when we discovered that combining obinutuzumab with TLR7 activation significantly enhanced survival of animals with lymphoma by effectively eradicating tumors,” Dr Illidge said. “Clearly, more work needs to be done to assess the impact of this combination on humans, but this study is, nevertheless, very promising.”

The researchers said the primary antitumor activity of the combination is dependent on natural killer cells and CD4 helper T cells but not on CD8 killer T cells.

“While the combination therapy was highly effective, CD8 killer T cells did not play a major role in the therapy,” said Eleanor Cheadle, PhD, also of the University of Manchester.

“Given the important role that killer T cells can play in long-term protection from tumor regrowth, we are looking at ways to enhance activation of these cells after obinutuzumab therapy.”

The researchers also found that, in vitro, R848 significantly enhanced natural killer cell-mediated antibody-dependent cellular cytotoxicity against obinutuzumab-opsonized CLL cells and significantly increased non-specific, antibody-independent killing of CLL cells.

Pills

The European Medicines Agency (EMA) has released a report showing both successes and room for improvement regarding conditional marketing authorizations (CMAs).

CMA is one of the tools available to regulators to support the development of and early access to drugs that address unmet medical needs of patients in the European Union.

Drugs are granted CMA if the public health benefit of their immediate availability is thought to outweigh the risk of an authorization on the basis of less comprehensive data than normally required.

A CMA is valid for 1 year. As part of the authorization, the drug’s developer is obliged to carry out further studies to obtain complete data.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) assesses the data generated by these specific post-authorization obligations at least annually to ensure the balance of benefits and risks of the drug continues to remain positive.

At the end of its assessment, the CHMP issues a recommendation regarding the renewal of the CMA or its conversion into a standard marketing authorization.

Overview

The EMA’s report summarizes the experience with CMAs from the first use of this authorization type in 2006 until June 30, 2016.

During this time, a total of 30 drugs have received a CMA, including several

hematology drugs—Adcetris (brentuximab vedotin),

Arzerra (ofatumumab), Blincyto (blinatumomab), Bosulif (bosutinib), Darzalex (daratumumab), and Pixuvri (pixantrone).

Eleven CMAs have been converted into standard marketing authorizations (including Arzerra’s CMA), 2 have been withdrawn for commercial reasons, and 17 are still conditional authorizations.

None of the drugs that still have CMAs have been authorized for more than 5 years. And none of the CMAs issued since 2006 have had to be revoked or suspended.

Successes

According to the EMA’s analysis, marketing authorization holders comply with the specific obligations imposed by the agency.

More than 90% of completed specific obligations did not result in major changes of scope, and about 70% of specific obligations did not require an extension to the originally specified timelines.

The report shows that it took an average of 4 years to generate the additional data needed and to convert a CMA into a full marketing authorization.

This suggests patients with life-threatening or seriously debilitating conditions had access to promising drugs much earlier than they would have under standard authorization.

Areas for improvement

The EMA’s analysis also revealed room for improvement.

The report showed that, relatively frequently, CMA was first

considered only during the assessment of the drug application, which meant granting a CMA took longer than intended.

Therefore, the EMA recommends that drug developers engage in early dialogue with the EMA

and prospectively plan to apply for a CMA.

The agency said this should support

prompt assessment of such applications and could also facilitate prompt

completion of additional studies and timely availability of

comprehensive data.

The EMA said another area for improvement is engaging other stakeholders involved in bringing drugs to patients—in particular, Health Technology Assessment bodies—to facilitate the generation of all data needed for decision-making through one development program.

Pills

The European Medicines Agency (EMA) has released a report showing both successes and room for improvement regarding conditional marketing authorizations (CMAs).

CMA is one of the tools available to regulators to support the development of and early access to drugs that address unmet medical needs of patients in the European Union.

Drugs are granted CMA if the public health benefit of their immediate availability is thought to outweigh the risk of an authorization on the basis of less comprehensive data than normally required.

A CMA is valid for 1 year. As part of the authorization, the drug’s developer is obliged to carry out further studies to obtain complete data.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) assesses the data generated by these specific post-authorization obligations at least annually to ensure the balance of benefits and risks of the drug continues to remain positive.

At the end of its assessment, the CHMP issues a recommendation regarding the renewal of the CMA or its conversion into a standard marketing authorization.

Overview

The EMA’s report summarizes the experience with CMAs from the first use of this authorization type in 2006 until June 30, 2016.

During this time, a total of 30 drugs have received a CMA, including several

hematology drugs—Adcetris (brentuximab vedotin),

Arzerra (ofatumumab), Blincyto (blinatumomab), Bosulif (bosutinib), Darzalex (daratumumab), and Pixuvri (pixantrone).

Eleven CMAs have been converted into standard marketing authorizations (including Arzerra’s CMA), 2 have been withdrawn for commercial reasons, and 17 are still conditional authorizations.

None of the drugs that still have CMAs have been authorized for more than 5 years. And none of the CMAs issued since 2006 have had to be revoked or suspended.

Successes

According to the EMA’s analysis, marketing authorization holders comply with the specific obligations imposed by the agency.

More than 90% of completed specific obligations did not result in major changes of scope, and about 70% of specific obligations did not require an extension to the originally specified timelines.

The report shows that it took an average of 4 years to generate the additional data needed and to convert a CMA into a full marketing authorization.

This suggests patients with life-threatening or seriously debilitating conditions had access to promising drugs much earlier than they would have under standard authorization.

Areas for improvement

The EMA’s analysis also revealed room for improvement.

The report showed that, relatively frequently, CMA was first

considered only during the assessment of the drug application, which meant granting a CMA took longer than intended.

Therefore, the EMA recommends that drug developers engage in early dialogue with the EMA

and prospectively plan to apply for a CMA.

The agency said this should support

prompt assessment of such applications and could also facilitate prompt

completion of additional studies and timely availability of

comprehensive data.

The EMA said another area for improvement is engaging other stakeholders involved in bringing drugs to patients—in particular, Health Technology Assessment bodies—to facilitate the generation of all data needed for decision-making through one development program.

Pills

The European Medicines Agency (EMA) has released a report showing both successes and room for improvement regarding conditional marketing authorizations (CMAs).

CMA is one of the tools available to regulators to support the development of and early access to drugs that address unmet medical needs of patients in the European Union.

Drugs are granted CMA if the public health benefit of their immediate availability is thought to outweigh the risk of an authorization on the basis of less comprehensive data than normally required.

A CMA is valid for 1 year. As part of the authorization, the drug’s developer is obliged to carry out further studies to obtain complete data.

The EMA’s Committee for Medicinal Products for Human Use (CHMP) assesses the data generated by these specific post-authorization obligations at least annually to ensure the balance of benefits and risks of the drug continues to remain positive.

At the end of its assessment, the CHMP issues a recommendation regarding the renewal of the CMA or its conversion into a standard marketing authorization.

Overview

The EMA’s report summarizes the experience with CMAs from the first use of this authorization type in 2006 until June 30, 2016.

During this time, a total of 30 drugs have received a CMA, including several

hematology drugs—Adcetris (brentuximab vedotin),

Arzerra (ofatumumab), Blincyto (blinatumomab), Bosulif (bosutinib), Darzalex (daratumumab), and Pixuvri (pixantrone).

Eleven CMAs have been converted into standard marketing authorizations (including Arzerra’s CMA), 2 have been withdrawn for commercial reasons, and 17 are still conditional authorizations.

None of the drugs that still have CMAs have been authorized for more than 5 years. And none of the CMAs issued since 2006 have had to be revoked or suspended.

Successes

According to the EMA’s analysis, marketing authorization holders comply with the specific obligations imposed by the agency.

More than 90% of completed specific obligations did not result in major changes of scope, and about 70% of specific obligations did not require an extension to the originally specified timelines.

The report shows that it took an average of 4 years to generate the additional data needed and to convert a CMA into a full marketing authorization.

This suggests patients with life-threatening or seriously debilitating conditions had access to promising drugs much earlier than they would have under standard authorization.

Areas for improvement

The EMA’s analysis also revealed room for improvement.

The report showed that, relatively frequently, CMA was first

considered only during the assessment of the drug application, which meant granting a CMA took longer than intended.

Therefore, the EMA recommends that drug developers engage in early dialogue with the EMA

and prospectively plan to apply for a CMA.

The agency said this should support

prompt assessment of such applications and could also facilitate prompt

completion of additional studies and timely availability of

comprehensive data.

The EMA said another area for improvement is engaging other stakeholders involved in bringing drugs to patients—in particular, Health Technology Assessment bodies—to facilitate the generation of all data needed for decision-making through one development program.

Red blood cells

Consuming an iron-fortified nutrition bar daily for a few months can fight anemia without producing side effects, according to research published in the American Journal of Clinical Nutrition.

Anemic

women in India who consumed an iron-fortified nutrition bar each day for 90 days

were much more likely to experience increases in hemoglobin and

hematocrit and to be cured of their anemia than women who did not consume

such bars.

Rajvi Mehta, a medical student at Duke University in Durham, North Carolina, developed the nutrition bars used in this study, known as GudNesS bars.

The bars are made with iron-rich, natural, local (to India), and culturally accepted ingredients. They contain the World Health Organization’s daily recommended dose of iron.

In 2011, Mehta worked with nutritionists and physicians in India to establish a social venture there called Let’s Be Well Red (LBWR) to begin large-scale production of the bars.

The study, conducted from March to August 2014 in Mumbai and Navi Mumbai, India, involved 179 anemic, non-pregnant participants of reproductive age (18-35) at 10 demographically diverse sites.

The sites were randomly placed in either a control group or an intervention group.

Women in the intervention group received 1 iron-fortified nutrition bar (containing 14 mg Fe) daily for 90 days, and women in the control group received nothing. Baseline characteristics were comparable between the groups.

Each group underwent 3 blood tests during the 90-day follow-up period—at 15 days, 45 days, and 90 days—to measure their hemoglobin and hematocrit.

Seventy-six percent of subjects (n=136) completed all follow-up assessments (65 intervention and 71 control subjects).

The primary outcomes were 90-day changes from baseline in hemoglobin concentrations and hematocrit percentages.

The researchers said the mean hemoglobin and hematocrit increases after 90 days were greater for the intervention group than the control group, at 1.4 g/dL and 2.7%, respectively.

And subjects in the intervention group had a much greater decrease in anemia than those in the control group. At 90 days, 29.2% of subjects in the intervention group still had anemia, compared to 98.6% of those in the control group. The odds ratio was 0.007.

The researchers said no side effects were reported.

“We are encouraged by the results of this study, which show a positive connection between consuming an iron-fortified nutrition bar and a reduction in anemia prevalence,” said study author Elizabeth Turner, PhD, of Duke University.

“It appears to be a practical and well-tolerated solution to a significant health challenge in India.”

Let’s Be Well Red is currently operating in 3 locations in India and produces 100,000 bars each year that it distributes throughout the country.

“Anemia is a debilitating condition that can have severe health consequences,” Mehta said. “I am thrilled that my colleagues and I were able to develop a solution that has proven to be effective among a high-risk population. Making an impact in global health has long been a goal of mine.”

Red blood cells

Consuming an iron-fortified nutrition bar daily for a few months can fight anemia without producing side effects, according to research published in the American Journal of Clinical Nutrition.

Anemic

women in India who consumed an iron-fortified nutrition bar each day for 90 days

were much more likely to experience increases in hemoglobin and

hematocrit and to be cured of their anemia than women who did not consume

such bars.

Rajvi Mehta, a medical student at Duke University in Durham, North Carolina, developed the nutrition bars used in this study, known as GudNesS bars.

The bars are made with iron-rich, natural, local (to India), and culturally accepted ingredients. They contain the World Health Organization’s daily recommended dose of iron.

In 2011, Mehta worked with nutritionists and physicians in India to establish a social venture there called Let’s Be Well Red (LBWR) to begin large-scale production of the bars.

The study, conducted from March to August 2014 in Mumbai and Navi Mumbai, India, involved 179 anemic, non-pregnant participants of reproductive age (18-35) at 10 demographically diverse sites.

The sites were randomly placed in either a control group or an intervention group.

Women in the intervention group received 1 iron-fortified nutrition bar (containing 14 mg Fe) daily for 90 days, and women in the control group received nothing. Baseline characteristics were comparable between the groups.

Each group underwent 3 blood tests during the 90-day follow-up period—at 15 days, 45 days, and 90 days—to measure their hemoglobin and hematocrit.

Seventy-six percent of subjects (n=136) completed all follow-up assessments (65 intervention and 71 control subjects).

The primary outcomes were 90-day changes from baseline in hemoglobin concentrations and hematocrit percentages.

The researchers said the mean hemoglobin and hematocrit increases after 90 days were greater for the intervention group than the control group, at 1.4 g/dL and 2.7%, respectively.

And subjects in the intervention group had a much greater decrease in anemia than those in the control group. At 90 days, 29.2% of subjects in the intervention group still had anemia, compared to 98.6% of those in the control group. The odds ratio was 0.007.

The researchers said no side effects were reported.

“We are encouraged by the results of this study, which show a positive connection between consuming an iron-fortified nutrition bar and a reduction in anemia prevalence,” said study author Elizabeth Turner, PhD, of Duke University.

“It appears to be a practical and well-tolerated solution to a significant health challenge in India.”

Let’s Be Well Red is currently operating in 3 locations in India and produces 100,000 bars each year that it distributes throughout the country.

“Anemia is a debilitating condition that can have severe health consequences,” Mehta said. “I am thrilled that my colleagues and I were able to develop a solution that has proven to be effective among a high-risk population. Making an impact in global health has long been a goal of mine.”

Red blood cells

Consuming an iron-fortified nutrition bar daily for a few months can fight anemia without producing side effects, according to research published in the American Journal of Clinical Nutrition.

Anemic

women in India who consumed an iron-fortified nutrition bar each day for 90 days

were much more likely to experience increases in hemoglobin and

hematocrit and to be cured of their anemia than women who did not consume

such bars.

Rajvi Mehta, a medical student at Duke University in Durham, North Carolina, developed the nutrition bars used in this study, known as GudNesS bars.

The bars are made with iron-rich, natural, local (to India), and culturally accepted ingredients. They contain the World Health Organization’s daily recommended dose of iron.

In 2011, Mehta worked with nutritionists and physicians in India to establish a social venture there called Let’s Be Well Red (LBWR) to begin large-scale production of the bars.

The study, conducted from March to August 2014 in Mumbai and Navi Mumbai, India, involved 179 anemic, non-pregnant participants of reproductive age (18-35) at 10 demographically diverse sites.

The sites were randomly placed in either a control group or an intervention group.

Women in the intervention group received 1 iron-fortified nutrition bar (containing 14 mg Fe) daily for 90 days, and women in the control group received nothing. Baseline characteristics were comparable between the groups.

Each group underwent 3 blood tests during the 90-day follow-up period—at 15 days, 45 days, and 90 days—to measure their hemoglobin and hematocrit.

Seventy-six percent of subjects (n=136) completed all follow-up assessments (65 intervention and 71 control subjects).

The primary outcomes were 90-day changes from baseline in hemoglobin concentrations and hematocrit percentages.

The researchers said the mean hemoglobin and hematocrit increases after 90 days were greater for the intervention group than the control group, at 1.4 g/dL and 2.7%, respectively.

And subjects in the intervention group had a much greater decrease in anemia than those in the control group. At 90 days, 29.2% of subjects in the intervention group still had anemia, compared to 98.6% of those in the control group. The odds ratio was 0.007.

The researchers said no side effects were reported.

“We are encouraged by the results of this study, which show a positive connection between consuming an iron-fortified nutrition bar and a reduction in anemia prevalence,” said study author Elizabeth Turner, PhD, of Duke University.

“It appears to be a practical and well-tolerated solution to a significant health challenge in India.”

Let’s Be Well Red is currently operating in 3 locations in India and produces 100,000 bars each year that it distributes throughout the country.

“Anemia is a debilitating condition that can have severe health consequences,” Mehta said. “I am thrilled that my colleagues and I were able to develop a solution that has proven to be effective among a high-risk population. Making an impact in global health has long been a goal of mine.”