WASHINGTON – Daily treatment with valacyclovir for at least 6 weeks safely cut the cytomegalovirus (CMV) vertical transmission rate from mothers to fetuses in women with a primary CMV infection during the three weeks before conception through their first trimester. That finding emerged from a randomized, controlled, single-center Israeli study with 92 women.

The rate of congenital fetal infection with CMV was 11% among neonates born to 45 women treated with 8 g/day of valacyclovir, compared with a 30% rate among the infants born to 47 women who received placebo, a statistically significant difference, Keren Shahar-Nissan, MD, said at an annual scientific meeting on infectious diseases. The results also showed that the valacyclovir regimen was well tolerated, with no increase compared with placebo in adverse events and with no need for dosage adjustment regardless of a 16 pill/day regimen to deliver the 8 g/day of valacyclovir or placebo that participants received.

Dr. Shahar-Nissan said that she and her associates felt comfortable administering this amount of valacyclovir to pregnant woman given previous reports of the safety of this dosage for both women and their fetuses. These reports included 20 pregnant women safely treated for 7 weeks with 8 g/day during the late second or early third trimester (BJOG. 2007 Sept;114[9]:1113-21); more than 600 women in a Danish nationwide study treated with any dosage of valacyclovir during preconception, the first trimester, or the second or third trimesters with a prevalence of births defects not significantly different from unexposed pregnancies (JAMA. 2010 Aug 25;304[8]:859-66); and a prospective, open-label study of 8 g/day valacyclovir to treat 43 women carrying CMV-infected fetuses starting at a median 26 weeks gestation and continuing through delivery (Am J Obstet Gynecol. 2016 Oct;215[4]:462.e1-462.e10).

The study she ran enrolled women seen at Helen Schneider Hospital for Women in Petah Tikva, Israel, during November 2015-October 2018 who had a serologically-proven primary CMV infection that began at any time from 3 weeks before conception through the first trimester, excluding patients with renal dysfunction, liver disease, bone-marrow suppression, or acyclovir sensitivity. Screening for active CMV infection is common among newly-pregnant Israeli women, usually at the time of their first obstetrical consultation for a suspected pregnancy, noted Dr. Shahar-Nissan, a pediatrician at Schneider Children’s Medical Center of Israel in Petah Tikva. About a quarter of the enrolled women became infected during the 3 weeks prior to conception, and nearly two-thirds became infected during the first 8 weeks of pregnancy.

The valacyclovir intervention appeared to be effective specifically for preventing vertical transmission of infection acquired early during pregnancy. In this subgroup the transmission rate was 11% with valacyclovir treatment and 48% on placebo. Valacyclovir seemed to have no effect on vertical transmission of infections that began before conception, likely because treatment began too late to prevent transmission.

“I think this study is enough” to convince the U.S. Food and Drug Administration to add this treatment indication to the labeling of valacyclovir, a drug that has been available in generic formulations for many years, Dr. Shahar-Nissan said in an interview. Before approaching the FDA, her first goal is publishing the findings, she added.

[email protected]

On Twitter @mitchelzoler

WASHINGTON – Daily treatment with valacyclovir for at least 6 weeks safely cut the cytomegalovirus (CMV) vertical transmission rate from mothers to fetuses in women with a primary CMV infection during the three weeks before conception through their first trimester. That finding emerged from a randomized, controlled, single-center Israeli study with 92 women.

The rate of congenital fetal infection with CMV was 11% among neonates born to 45 women treated with 8 g/day of valacyclovir, compared with a 30% rate among the infants born to 47 women who received placebo, a statistically significant difference, Keren Shahar-Nissan, MD, said at an annual scientific meeting on infectious diseases. The results also showed that the valacyclovir regimen was well tolerated, with no increase compared with placebo in adverse events and with no need for dosage adjustment regardless of a 16 pill/day regimen to deliver the 8 g/day of valacyclovir or placebo that participants received.

Dr. Shahar-Nissan said that she and her associates felt comfortable administering this amount of valacyclovir to pregnant woman given previous reports of the safety of this dosage for both women and their fetuses. These reports included 20 pregnant women safely treated for 7 weeks with 8 g/day during the late second or early third trimester (BJOG. 2007 Sept;114[9]:1113-21); more than 600 women in a Danish nationwide study treated with any dosage of valacyclovir during preconception, the first trimester, or the second or third trimesters with a prevalence of births defects not significantly different from unexposed pregnancies (JAMA. 2010 Aug 25;304[8]:859-66); and a prospective, open-label study of 8 g/day valacyclovir to treat 43 women carrying CMV-infected fetuses starting at a median 26 weeks gestation and continuing through delivery (Am J Obstet Gynecol. 2016 Oct;215[4]:462.e1-462.e10).

The study she ran enrolled women seen at Helen Schneider Hospital for Women in Petah Tikva, Israel, during November 2015-October 2018 who had a serologically-proven primary CMV infection that began at any time from 3 weeks before conception through the first trimester, excluding patients with renal dysfunction, liver disease, bone-marrow suppression, or acyclovir sensitivity. Screening for active CMV infection is common among newly-pregnant Israeli women, usually at the time of their first obstetrical consultation for a suspected pregnancy, noted Dr. Shahar-Nissan, a pediatrician at Schneider Children’s Medical Center of Israel in Petah Tikva. About a quarter of the enrolled women became infected during the 3 weeks prior to conception, and nearly two-thirds became infected during the first 8 weeks of pregnancy.

The valacyclovir intervention appeared to be effective specifically for preventing vertical transmission of infection acquired early during pregnancy. In this subgroup the transmission rate was 11% with valacyclovir treatment and 48% on placebo. Valacyclovir seemed to have no effect on vertical transmission of infections that began before conception, likely because treatment began too late to prevent transmission.

“I think this study is enough” to convince the U.S. Food and Drug Administration to add this treatment indication to the labeling of valacyclovir, a drug that has been available in generic formulations for many years, Dr. Shahar-Nissan said in an interview. Before approaching the FDA, her first goal is publishing the findings, she added.

[email protected]

On Twitter @mitchelzoler

WASHINGTON – Daily treatment with valacyclovir for at least 6 weeks safely cut the cytomegalovirus (CMV) vertical transmission rate from mothers to fetuses in women with a primary CMV infection during the three weeks before conception through their first trimester. That finding emerged from a randomized, controlled, single-center Israeli study with 92 women.

The rate of congenital fetal infection with CMV was 11% among neonates born to 45 women treated with 8 g/day of valacyclovir, compared with a 30% rate among the infants born to 47 women who received placebo, a statistically significant difference, Keren Shahar-Nissan, MD, said at an annual scientific meeting on infectious diseases. The results also showed that the valacyclovir regimen was well tolerated, with no increase compared with placebo in adverse events and with no need for dosage adjustment regardless of a 16 pill/day regimen to deliver the 8 g/day of valacyclovir or placebo that participants received.

Dr. Shahar-Nissan said that she and her associates felt comfortable administering this amount of valacyclovir to pregnant woman given previous reports of the safety of this dosage for both women and their fetuses. These reports included 20 pregnant women safely treated for 7 weeks with 8 g/day during the late second or early third trimester (BJOG. 2007 Sept;114[9]:1113-21); more than 600 women in a Danish nationwide study treated with any dosage of valacyclovir during preconception, the first trimester, or the second or third trimesters with a prevalence of births defects not significantly different from unexposed pregnancies (JAMA. 2010 Aug 25;304[8]:859-66); and a prospective, open-label study of 8 g/day valacyclovir to treat 43 women carrying CMV-infected fetuses starting at a median 26 weeks gestation and continuing through delivery (Am J Obstet Gynecol. 2016 Oct;215[4]:462.e1-462.e10).

The study she ran enrolled women seen at Helen Schneider Hospital for Women in Petah Tikva, Israel, during November 2015-October 2018 who had a serologically-proven primary CMV infection that began at any time from 3 weeks before conception through the first trimester, excluding patients with renal dysfunction, liver disease, bone-marrow suppression, or acyclovir sensitivity. Screening for active CMV infection is common among newly-pregnant Israeli women, usually at the time of their first obstetrical consultation for a suspected pregnancy, noted Dr. Shahar-Nissan, a pediatrician at Schneider Children’s Medical Center of Israel in Petah Tikva. About a quarter of the enrolled women became infected during the 3 weeks prior to conception, and nearly two-thirds became infected during the first 8 weeks of pregnancy.

The valacyclovir intervention appeared to be effective specifically for preventing vertical transmission of infection acquired early during pregnancy. In this subgroup the transmission rate was 11% with valacyclovir treatment and 48% on placebo. Valacyclovir seemed to have no effect on vertical transmission of infections that began before conception, likely because treatment began too late to prevent transmission.

“I think this study is enough” to convince the U.S. Food and Drug Administration to add this treatment indication to the labeling of valacyclovir, a drug that has been available in generic formulations for many years, Dr. Shahar-Nissan said in an interview. Before approaching the FDA, her first goal is publishing the findings, she added.

[email protected]

On Twitter @mitchelzoler

LAS VEGAS – Cannabinoids and stem cells may intrigue patients as potential treatments for osteoarthritis (OA), but evidence does not support their use. Planned clinical trials may clarify whether they benefit patients, said Joel A. Block, MD, professor of rheumatology at Rush University in Chicago.

Jake Remaly/MDedge News

Cannabinoid therapy “is on everybody’s mind, including our patients,” Dr. Block said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “Cannabinoid receptors are widely present in all joint tissues, and endocannabinoids are clearly present in OA joint tissue. There is good evidence that the receptors regulate pain responses and central sensitization in a variety of OA animal models.” Where cannabis is legal, many people use it for chronic noncancer pain. Side effects may include altered perception, dizziness, drowsiness, and gastrointestinal adverse events.

Cannabis in the literature

“Nonetheless, if you do a systematic review of all of the randomized clinical trials of cannabinoids in human rheumatic diseases, what you will find is there is a grand total of four,” he said. The trials included patients with rheumatoid arthritis, OA, and fibromyalgia. An analysis of aggregated data found that cannabinoids improved pain and sleep, but all of the trials had a high risk of bias, poor allocation concealment, and poor blinding, said Dr. Block (Arthritis Care Res [Hoboken]. 2016 May;68[5]:681-8.). “In OA, there is one randomized trial, and it was entirely null,” he said. “There was no positive effect on pain or on function in human OA” (Pain. 2012 Sep;153[9]:1837-46.).

ClinicalTrials.gov lists two planned randomized controlled trials of cannabinoids – one using vaporized cannabis in patients with knee OA, and one using cannabidiol for hand OA and psoriatic arthritis. “Clinical trials are still scarce as of right now, so it will take a while before we have evidence for or against,” said Dr. Block.

Stem cell injections

Intra-articular stem cell injections are widely offered in the United States and abroad, he said. “In every newspaper, wherever I go, I open it up and there are full-page ads on stem cell injections that will cure everything that you want,” he said.

A systematic review of the effect of stem cell injections on structural outcomes and pain-related behaviors in animals found that “for all outcomes, the evidence quality was either low or very low,” Dr. Block said (Osteoarthritis Cartilage. 2018 Apr;26[4]:445-61.). “Even in the animal models, it has been very hard to demonstrate any effect at all from just injecting stem cells into the joint.”

Systematic reviews of the evidence in humans have found that the data do not support the use of stem cell injections. The authors of one review concluded, “In the absence of high-level evidence, we do not recommend stem cell therapy” for knee OA (Br J Sports Med. 2017 Aug;51[15]:1125-33.).

For another recent review, researchers screened hundreds of articles and identified 5 trials that met their inclusion criteria. They concluded, “Current evidence does not support the use of intra-articular [mesenchymal stem cells] for improving cartilage repair in knee osteoarthritis” (Arch Orthop Trauma Surg. 2019 Jul;139[7]:971-80.).

Many clinical trials are planned, however. “Over the next several years, I would expect that we are going to get some real data on whether these are helpful or not,” Dr. Block said.

Meanwhile, some patients spend thousands of dollars to receive stem cell injections, and clinics report average patient satisfaction rates of 82%. “How can they be getting so much relief when there is no evidence that it is helpful? In fact, whatever evidence we have says that it is no better than placebo,” said Dr. Block. “Placebo itself is very potent....People always do what they feel helps them regardless of objective data, because placebo itself is very palliative.”

Dr. Block is a consultant for GlaxoSmithKline, Medivir, and Zynerba Pharmaceuticals. He has received royalties from Agios, Daiichi Sankyo, and Omeros. In addition, he has received grant or research support from AbbVie, Janssen, Novartis, Pfizer, and Kolon TissueGene.

Global Academy for Medical Education and this news organization are owned by the same parent company.
 

[email protected]

LAS VEGAS – Cannabinoids and stem cells may intrigue patients as potential treatments for osteoarthritis (OA), but evidence does not support their use. Planned clinical trials may clarify whether they benefit patients, said Joel A. Block, MD, professor of rheumatology at Rush University in Chicago.

Jake Remaly/MDedge News

Cannabinoid therapy “is on everybody’s mind, including our patients,” Dr. Block said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “Cannabinoid receptors are widely present in all joint tissues, and endocannabinoids are clearly present in OA joint tissue. There is good evidence that the receptors regulate pain responses and central sensitization in a variety of OA animal models.” Where cannabis is legal, many people use it for chronic noncancer pain. Side effects may include altered perception, dizziness, drowsiness, and gastrointestinal adverse events.

Cannabis in the literature

“Nonetheless, if you do a systematic review of all of the randomized clinical trials of cannabinoids in human rheumatic diseases, what you will find is there is a grand total of four,” he said. The trials included patients with rheumatoid arthritis, OA, and fibromyalgia. An analysis of aggregated data found that cannabinoids improved pain and sleep, but all of the trials had a high risk of bias, poor allocation concealment, and poor blinding, said Dr. Block (Arthritis Care Res [Hoboken]. 2016 May;68[5]:681-8.). “In OA, there is one randomized trial, and it was entirely null,” he said. “There was no positive effect on pain or on function in human OA” (Pain. 2012 Sep;153[9]:1837-46.).

ClinicalTrials.gov lists two planned randomized controlled trials of cannabinoids – one using vaporized cannabis in patients with knee OA, and one using cannabidiol for hand OA and psoriatic arthritis. “Clinical trials are still scarce as of right now, so it will take a while before we have evidence for or against,” said Dr. Block.

Stem cell injections

Intra-articular stem cell injections are widely offered in the United States and abroad, he said. “In every newspaper, wherever I go, I open it up and there are full-page ads on stem cell injections that will cure everything that you want,” he said.

A systematic review of the effect of stem cell injections on structural outcomes and pain-related behaviors in animals found that “for all outcomes, the evidence quality was either low or very low,” Dr. Block said (Osteoarthritis Cartilage. 2018 Apr;26[4]:445-61.). “Even in the animal models, it has been very hard to demonstrate any effect at all from just injecting stem cells into the joint.”

Systematic reviews of the evidence in humans have found that the data do not support the use of stem cell injections. The authors of one review concluded, “In the absence of high-level evidence, we do not recommend stem cell therapy” for knee OA (Br J Sports Med. 2017 Aug;51[15]:1125-33.).

For another recent review, researchers screened hundreds of articles and identified 5 trials that met their inclusion criteria. They concluded, “Current evidence does not support the use of intra-articular [mesenchymal stem cells] for improving cartilage repair in knee osteoarthritis” (Arch Orthop Trauma Surg. 2019 Jul;139[7]:971-80.).

Many clinical trials are planned, however. “Over the next several years, I would expect that we are going to get some real data on whether these are helpful or not,” Dr. Block said.

Meanwhile, some patients spend thousands of dollars to receive stem cell injections, and clinics report average patient satisfaction rates of 82%. “How can they be getting so much relief when there is no evidence that it is helpful? In fact, whatever evidence we have says that it is no better than placebo,” said Dr. Block. “Placebo itself is very potent....People always do what they feel helps them regardless of objective data, because placebo itself is very palliative.”

Dr. Block is a consultant for GlaxoSmithKline, Medivir, and Zynerba Pharmaceuticals. He has received royalties from Agios, Daiichi Sankyo, and Omeros. In addition, he has received grant or research support from AbbVie, Janssen, Novartis, Pfizer, and Kolon TissueGene.

Global Academy for Medical Education and this news organization are owned by the same parent company.
 

[email protected]

LAS VEGAS – Cannabinoids and stem cells may intrigue patients as potential treatments for osteoarthritis (OA), but evidence does not support their use. Planned clinical trials may clarify whether they benefit patients, said Joel A. Block, MD, professor of rheumatology at Rush University in Chicago.

Jake Remaly/MDedge News

Cannabinoid therapy “is on everybody’s mind, including our patients,” Dr. Block said at the annual Perspectives in Rheumatic Diseases held by Global Academy for Medical Education. “Cannabinoid receptors are widely present in all joint tissues, and endocannabinoids are clearly present in OA joint tissue. There is good evidence that the receptors regulate pain responses and central sensitization in a variety of OA animal models.” Where cannabis is legal, many people use it for chronic noncancer pain. Side effects may include altered perception, dizziness, drowsiness, and gastrointestinal adverse events.

Cannabis in the literature

“Nonetheless, if you do a systematic review of all of the randomized clinical trials of cannabinoids in human rheumatic diseases, what you will find is there is a grand total of four,” he said. The trials included patients with rheumatoid arthritis, OA, and fibromyalgia. An analysis of aggregated data found that cannabinoids improved pain and sleep, but all of the trials had a high risk of bias, poor allocation concealment, and poor blinding, said Dr. Block (Arthritis Care Res [Hoboken]. 2016 May;68[5]:681-8.). “In OA, there is one randomized trial, and it was entirely null,” he said. “There was no positive effect on pain or on function in human OA” (Pain. 2012 Sep;153[9]:1837-46.).

ClinicalTrials.gov lists two planned randomized controlled trials of cannabinoids – one using vaporized cannabis in patients with knee OA, and one using cannabidiol for hand OA and psoriatic arthritis. “Clinical trials are still scarce as of right now, so it will take a while before we have evidence for or against,” said Dr. Block.

Stem cell injections

Intra-articular stem cell injections are widely offered in the United States and abroad, he said. “In every newspaper, wherever I go, I open it up and there are full-page ads on stem cell injections that will cure everything that you want,” he said.

A systematic review of the effect of stem cell injections on structural outcomes and pain-related behaviors in animals found that “for all outcomes, the evidence quality was either low or very low,” Dr. Block said (Osteoarthritis Cartilage. 2018 Apr;26[4]:445-61.). “Even in the animal models, it has been very hard to demonstrate any effect at all from just injecting stem cells into the joint.”

Systematic reviews of the evidence in humans have found that the data do not support the use of stem cell injections. The authors of one review concluded, “In the absence of high-level evidence, we do not recommend stem cell therapy” for knee OA (Br J Sports Med. 2017 Aug;51[15]:1125-33.).

For another recent review, researchers screened hundreds of articles and identified 5 trials that met their inclusion criteria. They concluded, “Current evidence does not support the use of intra-articular [mesenchymal stem cells] for improving cartilage repair in knee osteoarthritis” (Arch Orthop Trauma Surg. 2019 Jul;139[7]:971-80.).

Many clinical trials are planned, however. “Over the next several years, I would expect that we are going to get some real data on whether these are helpful or not,” Dr. Block said.

Meanwhile, some patients spend thousands of dollars to receive stem cell injections, and clinics report average patient satisfaction rates of 82%. “How can they be getting so much relief when there is no evidence that it is helpful? In fact, whatever evidence we have says that it is no better than placebo,” said Dr. Block. “Placebo itself is very potent....People always do what they feel helps them regardless of objective data, because placebo itself is very palliative.”

Dr. Block is a consultant for GlaxoSmithKline, Medivir, and Zynerba Pharmaceuticals. He has received royalties from Agios, Daiichi Sankyo, and Omeros. In addition, he has received grant or research support from AbbVie, Janssen, Novartis, Pfizer, and Kolon TissueGene.

Global Academy for Medical Education and this news organization are owned by the same parent company.
 

[email protected]

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

A diet low in fermentable carbohydrates can reduce gut symptoms related to inflammatory bowel disease (IBD), according to a study by U.K. researchers.

Fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) occur in a number of common foods, including certain fruits, vegetables, and dairy products. They can draw increased water to the gut, and through microbial fermentation increase hydrogen in the colon.

While previous research has shown that a low-FODMAP diet can relieve gut symptoms such as swelling and flatulence in people with irritable bowel syndrome, the diet has been little studied in IBD patients, for whom gut symptoms often persist even in the absence of gastrointestinal inflammation. In a study published in Gastroenterology, Selina Cox, MD, of King’s College, London, and colleagues randomized 52 people with ulcerative colitis or Crohn’s disease with persistent gut symptoms but without active inflammation to 4 weeks on a low-FODMAP diet (n = 27) or a control diet comprising sham dietary advice (n = 25). Investigators were not blinded to treatment allocation.

At 4 weeks, Dr. Cox and her colleagues reported more patients on the low-FODMAP diet reported “adequate” relief of gut symptoms (52% vs. 16%, P = .007), and saw slight improvements in health-related quality of life scores, compared with the control group. Patient-reported flatulence and bloating were significantly lower in the treatment group, while few other symptom-specific differences were seen between groups.

Stool samples collected at baseline and at the study’s endpoint showed significantly reduced abundance of three types of gut bacteria thought to have a role in immune response – Bifidobacterium adolescentis, B longum, and Faecalibacterium prausnitzii – compared with control subjects. But there were no significant between-group differences in bacterial diversity or in biomarkers of inflammation.

“A major strength of this trial is that low-FODMAP dietary advice was compared to sham dietary advice, providing the first placebo-controlled evidence of effectiveness in IBD,” the researchers wrote in their analysis. Weaknesses of the study include its single-blinded design and inability to control for nutritional alterations related to the low-FODMAP diet.

Ms. Cox and her colleagues recommended a 4-week low-FODMAP diet along with “expert advice and intensive follow-up” for the management of gut symptoms in IBD, but cautioned that longer-term use may not be appropriate.

The study was funded by the U.S.-based Kenneth Rainin Foundation. Two of Dr. Cox’s coauthors declared financial conflicts of interest from a patent on a mobile application to support the low-FODMAP diet; the study’s corresponding author, Kevin Whelan, PhD, additionally reported receiving fees or research support from food and nutrition firms.

SOURCE: Cox S et al. Gastroenterology 2019. doi: 10.1053/j.gastro.2019.09.024.

AGA’s patient education can help your patients better understand the low-FODMAP diet. Learn more at https://www.gastro.org/practice-guidance/gi-patient-center/topic/low-fodmap-diet.

The introduction of the Medicare Inpatient Prospective Payment System (IPPS) through amendment of the Social Security Act in 1983 transformed hospital reimbursement in the United States. Under the IPPS, a new form of Medicare prospective payment that paid hospitals a fixed amount per discharge for inpatient services was created: the diagnosis-related group (DRG). This eliminated the preceding retrospective cost reimbursement system in an attempt to stop health care price inflation.

Each DRG represents a grouping of similar conditions and procedures for services provided during an inpatient hospitalization reimbursed under Medicare Part A. The Centers for Medicare & Medicaid Services uses the Medicare Severity DRG (MS-DRG) system to account for severity of illness and resource consumption. There are three levels of severity based upon secondary diagnosis: major complication/comorbidity (MCC), complication/comorbidity (CC), and noncomplication/comorbidity (non-CC).

Payment rates are defined by base rates for operating costs and capital-related costs which are adjusted for relative weight (the average cost within a DRG, compared with the average Medicare case cost) and market condition adjustments. As the largest single health care payer in the United States, CMS’ annual changes to the IPPS have a major impact on hospital reimbursement.

In May 2019, CMS released its annual proposed rule for the Hospital IPPS suggesting extensive changes to MS-DRG reimbursements. Notably, CMS proposed changing the severity level of nearly 1,500 diagnosis codes by adjusting their categorization between MCC, CC, or non-CC. The majority of these changes included downgrading MCCs to CCs or non-CCs. In fact, 87% of the changes involved a downgrade from one of the higher severity levels to a non-CC level, while only 13% involved an upgrade from a lower severity level to MCC level.

The CMS derived these changes from an algorithmic review and input from their clinical advisors to determine each diagnoses impact on resource utilization. Multiple major groups of codes were included in the downgraded groups, including secondary cancer diagnoses, organ transplant status, and hip fracture.

Evaluating codes based on coded resource use alone could have had a major negative impact on the clinical practice of hospitalists as it undervalues cognitive and clinical work associated with these secondary diagnoses. As an example, malignant neoplasm of head of pancreas (ICD-10, C25.0) was proposed to move to a non-CC. Under CMS’ proposed rule, if a patient was admitted with complications of pancreatic cancer such as cholangitis caused by biliary obstruction, the pancreatic cancer diagnosis would not serve as a CC since the primary condition for which the patient was hospitalized would be cholangitis. The anticipated increase in such a patient’s length of stay, severity of illness, and expected resource utilization would be grossly misrepresented in this case by CMS’ proposed rule changes. CMS also proposed to move major organ-transplant status (including heart, lung, kidney, and pancreas) from CC to non-CC status. Again, the cognitive work and resource utilization required to manage these patients would be underrepresented with this change, given the increased complexity of managing immunosuppressant medications or conducting an infectious diagnostic work-up in immunosuppressed patients.

The Society of Hospital Medicine Public Policy Committee provides comments annually to CMS on the IPPS, advocating for hospitalists and patients. After advocacy efforts from SHM and other groups, expressing concern about making such significant changes to the DRG system without further study, the IPPS final rule was released on August 2, 2019. SHM’s efforts paid off. The final rule excluded the proposed broad changes to the MS-DRG system that were in the proposed rule.

In deciding not to finalize the proposed severity level changes, CMS wrote that the adoption of these broad changes will be postponed in order “to fully consider the technical feedback provided” regarding the proposal. The final rule also describes making a “test GROUPER [software program] publicly available to allow for impact testing,” and allows for the possibility of phasing in changes and eliciting feedback. SHM is fully supportive of the decision to postpone major changes to the MS-DRG system in the IPPS until further review is obtained, and will continue to monitor this issue and provide appropriate input to CMS for our hospitalist members.

As hospitalists, it is important to understand the foundational role that public policy and CMS rule creation have on our work. Influencing change to the MS-DRG system is yet another example of how SHM’s work has impacted the policy domain, limiting negative effects on our members and advancing the practice of hospital medicine.

Dr. Biebelhausen is head of the section of hospital medicine at Virginia Mason Medical Center, Seattle. Dr. Cowart is a hospitalist at the Mayo Clinic in Jacksonville, Fla. Dr. Hamilton is a hospitalist and associate chief quality officer at the Cleveland Clinic.

The introduction of the Medicare Inpatient Prospective Payment System (IPPS) through amendment of the Social Security Act in 1983 transformed hospital reimbursement in the United States. Under the IPPS, a new form of Medicare prospective payment that paid hospitals a fixed amount per discharge for inpatient services was created: the diagnosis-related group (DRG). This eliminated the preceding retrospective cost reimbursement system in an attempt to stop health care price inflation.

Each DRG represents a grouping of similar conditions and procedures for services provided during an inpatient hospitalization reimbursed under Medicare Part A. The Centers for Medicare & Medicaid Services uses the Medicare Severity DRG (MS-DRG) system to account for severity of illness and resource consumption. There are three levels of severity based upon secondary diagnosis: major complication/comorbidity (MCC), complication/comorbidity (CC), and noncomplication/comorbidity (non-CC).

Payment rates are defined by base rates for operating costs and capital-related costs which are adjusted for relative weight (the average cost within a DRG, compared with the average Medicare case cost) and market condition adjustments. As the largest single health care payer in the United States, CMS’ annual changes to the IPPS have a major impact on hospital reimbursement.

In May 2019, CMS released its annual proposed rule for the Hospital IPPS suggesting extensive changes to MS-DRG reimbursements. Notably, CMS proposed changing the severity level of nearly 1,500 diagnosis codes by adjusting their categorization between MCC, CC, or non-CC. The majority of these changes included downgrading MCCs to CCs or non-CCs. In fact, 87% of the changes involved a downgrade from one of the higher severity levels to a non-CC level, while only 13% involved an upgrade from a lower severity level to MCC level.

The CMS derived these changes from an algorithmic review and input from their clinical advisors to determine each diagnoses impact on resource utilization. Multiple major groups of codes were included in the downgraded groups, including secondary cancer diagnoses, organ transplant status, and hip fracture.

Evaluating codes based on coded resource use alone could have had a major negative impact on the clinical practice of hospitalists as it undervalues cognitive and clinical work associated with these secondary diagnoses. As an example, malignant neoplasm of head of pancreas (ICD-10, C25.0) was proposed to move to a non-CC. Under CMS’ proposed rule, if a patient was admitted with complications of pancreatic cancer such as cholangitis caused by biliary obstruction, the pancreatic cancer diagnosis would not serve as a CC since the primary condition for which the patient was hospitalized would be cholangitis. The anticipated increase in such a patient’s length of stay, severity of illness, and expected resource utilization would be grossly misrepresented in this case by CMS’ proposed rule changes. CMS also proposed to move major organ-transplant status (including heart, lung, kidney, and pancreas) from CC to non-CC status. Again, the cognitive work and resource utilization required to manage these patients would be underrepresented with this change, given the increased complexity of managing immunosuppressant medications or conducting an infectious diagnostic work-up in immunosuppressed patients.

The Society of Hospital Medicine Public Policy Committee provides comments annually to CMS on the IPPS, advocating for hospitalists and patients. After advocacy efforts from SHM and other groups, expressing concern about making such significant changes to the DRG system without further study, the IPPS final rule was released on August 2, 2019. SHM’s efforts paid off. The final rule excluded the proposed broad changes to the MS-DRG system that were in the proposed rule.

In deciding not to finalize the proposed severity level changes, CMS wrote that the adoption of these broad changes will be postponed in order “to fully consider the technical feedback provided” regarding the proposal. The final rule also describes making a “test GROUPER [software program] publicly available to allow for impact testing,” and allows for the possibility of phasing in changes and eliciting feedback. SHM is fully supportive of the decision to postpone major changes to the MS-DRG system in the IPPS until further review is obtained, and will continue to monitor this issue and provide appropriate input to CMS for our hospitalist members.

As hospitalists, it is important to understand the foundational role that public policy and CMS rule creation have on our work. Influencing change to the MS-DRG system is yet another example of how SHM’s work has impacted the policy domain, limiting negative effects on our members and advancing the practice of hospital medicine.

Dr. Biebelhausen is head of the section of hospital medicine at Virginia Mason Medical Center, Seattle. Dr. Cowart is a hospitalist at the Mayo Clinic in Jacksonville, Fla. Dr. Hamilton is a hospitalist and associate chief quality officer at the Cleveland Clinic.

The introduction of the Medicare Inpatient Prospective Payment System (IPPS) through amendment of the Social Security Act in 1983 transformed hospital reimbursement in the United States. Under the IPPS, a new form of Medicare prospective payment that paid hospitals a fixed amount per discharge for inpatient services was created: the diagnosis-related group (DRG). This eliminated the preceding retrospective cost reimbursement system in an attempt to stop health care price inflation.

Each DRG represents a grouping of similar conditions and procedures for services provided during an inpatient hospitalization reimbursed under Medicare Part A. The Centers for Medicare & Medicaid Services uses the Medicare Severity DRG (MS-DRG) system to account for severity of illness and resource consumption. There are three levels of severity based upon secondary diagnosis: major complication/comorbidity (MCC), complication/comorbidity (CC), and noncomplication/comorbidity (non-CC).

Payment rates are defined by base rates for operating costs and capital-related costs which are adjusted for relative weight (the average cost within a DRG, compared with the average Medicare case cost) and market condition adjustments. As the largest single health care payer in the United States, CMS’ annual changes to the IPPS have a major impact on hospital reimbursement.

In May 2019, CMS released its annual proposed rule for the Hospital IPPS suggesting extensive changes to MS-DRG reimbursements. Notably, CMS proposed changing the severity level of nearly 1,500 diagnosis codes by adjusting their categorization between MCC, CC, or non-CC. The majority of these changes included downgrading MCCs to CCs or non-CCs. In fact, 87% of the changes involved a downgrade from one of the higher severity levels to a non-CC level, while only 13% involved an upgrade from a lower severity level to MCC level.

The CMS derived these changes from an algorithmic review and input from their clinical advisors to determine each diagnoses impact on resource utilization. Multiple major groups of codes were included in the downgraded groups, including secondary cancer diagnoses, organ transplant status, and hip fracture.

Evaluating codes based on coded resource use alone could have had a major negative impact on the clinical practice of hospitalists as it undervalues cognitive and clinical work associated with these secondary diagnoses. As an example, malignant neoplasm of head of pancreas (ICD-10, C25.0) was proposed to move to a non-CC. Under CMS’ proposed rule, if a patient was admitted with complications of pancreatic cancer such as cholangitis caused by biliary obstruction, the pancreatic cancer diagnosis would not serve as a CC since the primary condition for which the patient was hospitalized would be cholangitis. The anticipated increase in such a patient’s length of stay, severity of illness, and expected resource utilization would be grossly misrepresented in this case by CMS’ proposed rule changes. CMS also proposed to move major organ-transplant status (including heart, lung, kidney, and pancreas) from CC to non-CC status. Again, the cognitive work and resource utilization required to manage these patients would be underrepresented with this change, given the increased complexity of managing immunosuppressant medications or conducting an infectious diagnostic work-up in immunosuppressed patients.

The Society of Hospital Medicine Public Policy Committee provides comments annually to CMS on the IPPS, advocating for hospitalists and patients. After advocacy efforts from SHM and other groups, expressing concern about making such significant changes to the DRG system without further study, the IPPS final rule was released on August 2, 2019. SHM’s efforts paid off. The final rule excluded the proposed broad changes to the MS-DRG system that were in the proposed rule.

In deciding not to finalize the proposed severity level changes, CMS wrote that the adoption of these broad changes will be postponed in order “to fully consider the technical feedback provided” regarding the proposal. The final rule also describes making a “test GROUPER [software program] publicly available to allow for impact testing,” and allows for the possibility of phasing in changes and eliciting feedback. SHM is fully supportive of the decision to postpone major changes to the MS-DRG system in the IPPS until further review is obtained, and will continue to monitor this issue and provide appropriate input to CMS for our hospitalist members.

As hospitalists, it is important to understand the foundational role that public policy and CMS rule creation have on our work. Influencing change to the MS-DRG system is yet another example of how SHM’s work has impacted the policy domain, limiting negative effects on our members and advancing the practice of hospital medicine.

Dr. Biebelhausen is head of the section of hospital medicine at Virginia Mason Medical Center, Seattle. Dr. Cowart is a hospitalist at the Mayo Clinic in Jacksonville, Fla. Dr. Hamilton is a hospitalist and associate chief quality officer at the Cleveland Clinic.

Why do we forget some dreams and remember others? Researchers in a study funded by the National Institute of Neurological Disorders and Stroke say our dream memory may be controlled by a group of neurons commonly associated with appetite. Their findings could shed light on a wide range of memory-related conditions, including posttraumatic stress disorder (PTSD) and Alzheimer disease.

Studies have already shown that sleep helps the brain store new memories and eliminate excess information. Recent mouse studies have found that during sleep the brain prunes synaptic connections made between neurons involved in some types of learning.

But this study shows how that might happen.

The researchers have previously demonstrated that narcolepsy might be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus. In this study, they looked at neighboring cells that produce melanin-concentrating hormone (MCH), which is involved in the control of both sleep and appetite. A majority (53%) of hypothalamic MCH cells fired in mice during REM sleep; 35% fired when they were awake, and 12% fired at both times.

Those cells also may play a role in learning and memory, the researchers suggest. To test their theory that MCH cells might help the brain store memories, they used “genetic tools” to turn MCH neurons on and off during memory tests.

Surprisingly, the researchers say, pharmacogenetic activation—turning on the MCH cells—worsened memory; genetic ablation—turning them off—improved memory. Further experiments suggested MCH neurons exclusively played this role during REM sleep.

The results suggest that MCH neurons help the brain actively forget new, possibly unimportant information. “Since dreams are thought to primarily occur during REM sleep,” says Thomas Kilduff, PhD, senior author of the study, “the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus—consequently, the dream is quickly forgotten.”

Why do we forget some dreams and remember others? Researchers in a study funded by the National Institute of Neurological Disorders and Stroke say our dream memory may be controlled by a group of neurons commonly associated with appetite. Their findings could shed light on a wide range of memory-related conditions, including posttraumatic stress disorder (PTSD) and Alzheimer disease.

Studies have already shown that sleep helps the brain store new memories and eliminate excess information. Recent mouse studies have found that during sleep the brain prunes synaptic connections made between neurons involved in some types of learning.

But this study shows how that might happen.

The researchers have previously demonstrated that narcolepsy might be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus. In this study, they looked at neighboring cells that produce melanin-concentrating hormone (MCH), which is involved in the control of both sleep and appetite. A majority (53%) of hypothalamic MCH cells fired in mice during REM sleep; 35% fired when they were awake, and 12% fired at both times.

Those cells also may play a role in learning and memory, the researchers suggest. To test their theory that MCH cells might help the brain store memories, they used “genetic tools” to turn MCH neurons on and off during memory tests.

Surprisingly, the researchers say, pharmacogenetic activation—turning on the MCH cells—worsened memory; genetic ablation—turning them off—improved memory. Further experiments suggested MCH neurons exclusively played this role during REM sleep.

The results suggest that MCH neurons help the brain actively forget new, possibly unimportant information. “Since dreams are thought to primarily occur during REM sleep,” says Thomas Kilduff, PhD, senior author of the study, “the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus—consequently, the dream is quickly forgotten.”

Why do we forget some dreams and remember others? Researchers in a study funded by the National Institute of Neurological Disorders and Stroke say our dream memory may be controlled by a group of neurons commonly associated with appetite. Their findings could shed light on a wide range of memory-related conditions, including posttraumatic stress disorder (PTSD) and Alzheimer disease.

Studies have already shown that sleep helps the brain store new memories and eliminate excess information. Recent mouse studies have found that during sleep the brain prunes synaptic connections made between neurons involved in some types of learning.

But this study shows how that might happen.

The researchers have previously demonstrated that narcolepsy might be linked to the loss of hypocretin/orexin-making neurons in the hypothalamus. In this study, they looked at neighboring cells that produce melanin-concentrating hormone (MCH), which is involved in the control of both sleep and appetite. A majority (53%) of hypothalamic MCH cells fired in mice during REM sleep; 35% fired when they were awake, and 12% fired at both times.

Those cells also may play a role in learning and memory, the researchers suggest. To test their theory that MCH cells might help the brain store memories, they used “genetic tools” to turn MCH neurons on and off during memory tests.

Surprisingly, the researchers say, pharmacogenetic activation—turning on the MCH cells—worsened memory; genetic ablation—turning them off—improved memory. Further experiments suggested MCH neurons exclusively played this role during REM sleep.

The results suggest that MCH neurons help the brain actively forget new, possibly unimportant information. “Since dreams are thought to primarily occur during REM sleep,” says Thomas Kilduff, PhD, senior author of the study, “the sleep stage when the MCH cells turn on, activation of these cells may prevent the content of a dream from being stored in the hippocampus—consequently, the dream is quickly forgotten.”

Pregnancy-related mental health conditions are the most common complication of pregnancy, yet half of all women suffering will not be treated.

I wanted to address the stigma associated with these conditions as well as the rampant misinformation online. So, I reached out to Jen Schwartz, patient advocate and founder of Motherhood Understand, an online community for moms impacted by maternal mental health conditions. Together, we conceived the idea for the #MomsNeedToKnow maternal mental health awareness campaign, which will run from Oct. 14 to 25. This is an evidence-based campaign, complete with references and citations, that speaks to patients where they are at, i.e., social media.

With my clinical expertise and Jen’s reach, we felt like it was a natural partnership, as well as an innovative approach to empowering women to take control of their mental health during the perinatal period. We teamed up with Jamina Bone, an illustrator, and developed 2 weeks of Instagram posts, focused on the themes of lesser-known diagnoses, maternal mental health myths, and treatment options. This campaign is designed to help women understand risk factors for perinatal mood and anxiety disorders, as well as the signs of these conditions. It will cover lesser-known diagnoses like postpartum obsessive-compulsive disorder and posttraumatic stress disorder, and will address topics such as the impact of infertility on mental health and clarify the roles of different clinicians who can help.

Moreover, the campaign aims to address stigma and myths around psychiatric treatment during pregnancy – and also provides resources.

Dr. Lakshmin, a perinatal psychiatrist, is clinical assistant professor of psychiatry at George Washington University in Washington.

This article was updated 10/12/19.

Pregnancy-related mental health conditions are the most common complication of pregnancy, yet half of all women suffering will not be treated.

I wanted to address the stigma associated with these conditions as well as the rampant misinformation online. So, I reached out to Jen Schwartz, patient advocate and founder of Motherhood Understand, an online community for moms impacted by maternal mental health conditions. Together, we conceived the idea for the #MomsNeedToKnow maternal mental health awareness campaign, which will run from Oct. 14 to 25. This is an evidence-based campaign, complete with references and citations, that speaks to patients where they are at, i.e., social media.

With my clinical expertise and Jen’s reach, we felt like it was a natural partnership, as well as an innovative approach to empowering women to take control of their mental health during the perinatal period. We teamed up with Jamina Bone, an illustrator, and developed 2 weeks of Instagram posts, focused on the themes of lesser-known diagnoses, maternal mental health myths, and treatment options. This campaign is designed to help women understand risk factors for perinatal mood and anxiety disorders, as well as the signs of these conditions. It will cover lesser-known diagnoses like postpartum obsessive-compulsive disorder and posttraumatic stress disorder, and will address topics such as the impact of infertility on mental health and clarify the roles of different clinicians who can help.

Moreover, the campaign aims to address stigma and myths around psychiatric treatment during pregnancy – and also provides resources.

Dr. Lakshmin, a perinatal psychiatrist, is clinical assistant professor of psychiatry at George Washington University in Washington.

This article was updated 10/12/19.

Pregnancy-related mental health conditions are the most common complication of pregnancy, yet half of all women suffering will not be treated.

I wanted to address the stigma associated with these conditions as well as the rampant misinformation online. So, I reached out to Jen Schwartz, patient advocate and founder of Motherhood Understand, an online community for moms impacted by maternal mental health conditions. Together, we conceived the idea for the #MomsNeedToKnow maternal mental health awareness campaign, which will run from Oct. 14 to 25. This is an evidence-based campaign, complete with references and citations, that speaks to patients where they are at, i.e., social media.

With my clinical expertise and Jen’s reach, we felt like it was a natural partnership, as well as an innovative approach to empowering women to take control of their mental health during the perinatal period. We teamed up with Jamina Bone, an illustrator, and developed 2 weeks of Instagram posts, focused on the themes of lesser-known diagnoses, maternal mental health myths, and treatment options. This campaign is designed to help women understand risk factors for perinatal mood and anxiety disorders, as well as the signs of these conditions. It will cover lesser-known diagnoses like postpartum obsessive-compulsive disorder and posttraumatic stress disorder, and will address topics such as the impact of infertility on mental health and clarify the roles of different clinicians who can help.

Moreover, the campaign aims to address stigma and myths around psychiatric treatment during pregnancy – and also provides resources.

Dr. Lakshmin, a perinatal psychiatrist, is clinical assistant professor of psychiatry at George Washington University in Washington.

This article was updated 10/12/19.

Genentech has identified translucent particles in its hemophilia A product Hemlibra (emicizumab-kxwh) that are outside the prespecified particle specification. But toxicology and safety assessments conducted by the company found that the benefit-risk profile of the product remains unchanged.

Severin Schweiger/ThinkStock

Hemlibra is a bispecific factor IXa– and factor X–directed antibody that has been approved in the United States and other countries for routine prophylaxis in adult and pediatric patients with hemophilia A, with or without factor VIII inhibitors. It is administered as a subcutaneous injection.

The particles were first identified in March 2019 during a routine examination of drug product batches by Genentech. At the time, the company informed the U.S. Food and Drug Administration; the European Medicines Agency; Swissmedic; Health Canada; and the Ministry for Health, Labour, and Welfare in Japan. An initial company assessment found that the particles consisted of protein (Hemlibra drug substance) and silicone oil (polydimethylsiloxane), an organic polymer included in all parenteral medicines, according to Genentech.

Since the health authorities all agreed with the company’s initial conclusion that the product’s safety remained unchanged, no further action was taken.

The presence of the particles became more widely known in early October 2019, when Genentech notified the National Hemophilia Foundation, the NHF’s Medical and Scientific Advisory Council (MASAC), and the Hemophilia Federation of America. Genentech officials reached out to these groups after finishing a root cause investigation and issuing a final report to health authorities concluding that there was no change in the benefit-risk profile, according to a company spokesman.

MASAC issued its own statement recommending no change in prescribing or interruption in the use of Hemlibra. This is an “interim recommendation pending our assessment of the full review by Roche/Genentech of their manufacturing and quality control,” MASAC said. The council noted that it had been informed by representatives from Roche/Genentech that there have been no reports of adverse events linked to the particulate matter. Additionally, the problem had been present since the initial clinical trials of the product, but was only recently identified.

But at least one patient advocate is raising concerns about the timing of this notification. Jesse Clark, president and CEO of HemoAware, wants to know why patients were not informed of the particle issue for more than 6 months.

“The bleeding disorder community was never notified by either Genentech or any other agency,” Mr. Clark said in an interview. “The lack of transparency and communication is extremely concerning.”

A spokesman for Genentech said the company had not alerted patients earlier because there was no indication of an impact on the safety of the product. “We take inquiries from the community very seriously and are providing context and additional details in response to requests from patient organizations,” he said in an interview.

The company does not expect this issue to impact any patients in the United States and the availability of Hemlibra will not be affected, he added.

[email protected]

Genentech has identified translucent particles in its hemophilia A product Hemlibra (emicizumab-kxwh) that are outside the prespecified particle specification. But toxicology and safety assessments conducted by the company found that the benefit-risk profile of the product remains unchanged.

Severin Schweiger/ThinkStock

Hemlibra is a bispecific factor IXa– and factor X–directed antibody that has been approved in the United States and other countries for routine prophylaxis in adult and pediatric patients with hemophilia A, with or without factor VIII inhibitors. It is administered as a subcutaneous injection.

The particles were first identified in March 2019 during a routine examination of drug product batches by Genentech. At the time, the company informed the U.S. Food and Drug Administration; the European Medicines Agency; Swissmedic; Health Canada; and the Ministry for Health, Labour, and Welfare in Japan. An initial company assessment found that the particles consisted of protein (Hemlibra drug substance) and silicone oil (polydimethylsiloxane), an organic polymer included in all parenteral medicines, according to Genentech.

Since the health authorities all agreed with the company’s initial conclusion that the product’s safety remained unchanged, no further action was taken.

The presence of the particles became more widely known in early October 2019, when Genentech notified the National Hemophilia Foundation, the NHF’s Medical and Scientific Advisory Council (MASAC), and the Hemophilia Federation of America. Genentech officials reached out to these groups after finishing a root cause investigation and issuing a final report to health authorities concluding that there was no change in the benefit-risk profile, according to a company spokesman.

MASAC issued its own statement recommending no change in prescribing or interruption in the use of Hemlibra. This is an “interim recommendation pending our assessment of the full review by Roche/Genentech of their manufacturing and quality control,” MASAC said. The council noted that it had been informed by representatives from Roche/Genentech that there have been no reports of adverse events linked to the particulate matter. Additionally, the problem had been present since the initial clinical trials of the product, but was only recently identified.

But at least one patient advocate is raising concerns about the timing of this notification. Jesse Clark, president and CEO of HemoAware, wants to know why patients were not informed of the particle issue for more than 6 months.

“The bleeding disorder community was never notified by either Genentech or any other agency,” Mr. Clark said in an interview. “The lack of transparency and communication is extremely concerning.”

A spokesman for Genentech said the company had not alerted patients earlier because there was no indication of an impact on the safety of the product. “We take inquiries from the community very seriously and are providing context and additional details in response to requests from patient organizations,” he said in an interview.

The company does not expect this issue to impact any patients in the United States and the availability of Hemlibra will not be affected, he added.

[email protected]

Genentech has identified translucent particles in its hemophilia A product Hemlibra (emicizumab-kxwh) that are outside the prespecified particle specification. But toxicology and safety assessments conducted by the company found that the benefit-risk profile of the product remains unchanged.

Severin Schweiger/ThinkStock

Hemlibra is a bispecific factor IXa– and factor X–directed antibody that has been approved in the United States and other countries for routine prophylaxis in adult and pediatric patients with hemophilia A, with or without factor VIII inhibitors. It is administered as a subcutaneous injection.

The particles were first identified in March 2019 during a routine examination of drug product batches by Genentech. At the time, the company informed the U.S. Food and Drug Administration; the European Medicines Agency; Swissmedic; Health Canada; and the Ministry for Health, Labour, and Welfare in Japan. An initial company assessment found that the particles consisted of protein (Hemlibra drug substance) and silicone oil (polydimethylsiloxane), an organic polymer included in all parenteral medicines, according to Genentech.

Since the health authorities all agreed with the company’s initial conclusion that the product’s safety remained unchanged, no further action was taken.

The presence of the particles became more widely known in early October 2019, when Genentech notified the National Hemophilia Foundation, the NHF’s Medical and Scientific Advisory Council (MASAC), and the Hemophilia Federation of America. Genentech officials reached out to these groups after finishing a root cause investigation and issuing a final report to health authorities concluding that there was no change in the benefit-risk profile, according to a company spokesman.

MASAC issued its own statement recommending no change in prescribing or interruption in the use of Hemlibra. This is an “interim recommendation pending our assessment of the full review by Roche/Genentech of their manufacturing and quality control,” MASAC said. The council noted that it had been informed by representatives from Roche/Genentech that there have been no reports of adverse events linked to the particulate matter. Additionally, the problem had been present since the initial clinical trials of the product, but was only recently identified.

But at least one patient advocate is raising concerns about the timing of this notification. Jesse Clark, president and CEO of HemoAware, wants to know why patients were not informed of the particle issue for more than 6 months.

“The bleeding disorder community was never notified by either Genentech or any other agency,” Mr. Clark said in an interview. “The lack of transparency and communication is extremely concerning.”

A spokesman for Genentech said the company had not alerted patients earlier because there was no indication of an impact on the safety of the product. “We take inquiries from the community very seriously and are providing context and additional details in response to requests from patient organizations,” he said in an interview.

The company does not expect this issue to impact any patients in the United States and the availability of Hemlibra will not be affected, he added.

[email protected]

Wasteful spending in health care could reach almost $1 trillion, according to new research published in JAMA.

utah778/Thinkstock

Review “of the current literature of the cost of waste in the U.S. health care system and evidence about projected savings from interventions that reduce waste suggest that the estimated total costs of waste and potential savings from interventions that address waste are as high as $760 billion to $935 billion and $191 billion to $282 billion, respectively,” William Shrank, MD, chief medical and corporate affairs officer at Humana, and colleagues wrote in an article published Oct. 7, 2019, in JAMA.

“These estimates represent approximately 25% of total health care expenditures in the Unites States, which have been projected to be $3.82 trillion for 2019,” the authors noted, adding that it is a little lower than other estimates that have waste as high as 34% of spending.

Authors looked at waste across six domains, including failure of care delivery, failure of care coordination, overtreatment or low-value care, pricing failure, fraud and abuse, and administrative complexity.

Dr. Shrank and colleagues noted that administrative complexity was associated with the greatest contribution to waste, accounting for $265.6 billion in waste, adding that there are no studies that identified savings from interventions to alleviate administrative complexity.

“Some of that complexity results from fragmentation in the health care system,” they stated. “Recent proposals by CMS [the Centers for Medicare & Medicaid Services] and the Office of the National Coordinator of [sic] Health Information Technology to foster data interoperability and government initiatives such as Blue Button 2.0 will hopefully alleviate some burden as information flows more freely and billing and authorization processes become more automated.”

They also point to greater use of value-based payments as a possible avenue toward greater cost savings in this category.

The second largest contributor is pricing failure, which is estimated to be in the range from $230.7 billion to $240.5 billion, with interventions generating savings ranging from $81.4 billion to $91.2 billion.

And as the health care system evolves to a value-based paradigm, it is expected to have the least impact in this category “since pharmaceutical pricing represents a major component of this waste domain and would not be affected by new approaches to care delivery and reimbursement,” Dr. Shrank and colleagues wrote.

That being said, the authors stated that policy interventions “are needed to drive meaningful reductions in waste in this domain. Additionally, in the dynamic health care marketplace, where profit-motivated firms will respond to any new policy with strategies to protect their margins, no single policy is likely to suffice; a coordinated policy effort is likely needed to create long-standing change that will meaningfully reduce waste resulting from pricing failure.”

The three domains of failure of care delivery, failure of care coordination, and overtreatment or low-value care combined to account for $200 billion in waste, and the authors stated that there is “compelling empirical evidence in all three categories that interventions can produce meaningful savings and may reduce waste by as much as half.”

[email protected]

SOURCE: Shrank W et al. JAMA. 2019 Oct 7. doi: 10.1001/jama.2019.13978.

Wasteful spending in health care could reach almost $1 trillion, according to new research published in JAMA.

utah778/Thinkstock

Review “of the current literature of the cost of waste in the U.S. health care system and evidence about projected savings from interventions that reduce waste suggest that the estimated total costs of waste and potential savings from interventions that address waste are as high as $760 billion to $935 billion and $191 billion to $282 billion, respectively,” William Shrank, MD, chief medical and corporate affairs officer at Humana, and colleagues wrote in an article published Oct. 7, 2019, in JAMA.

“These estimates represent approximately 25% of total health care expenditures in the Unites States, which have been projected to be $3.82 trillion for 2019,” the authors noted, adding that it is a little lower than other estimates that have waste as high as 34% of spending.

Authors looked at waste across six domains, including failure of care delivery, failure of care coordination, overtreatment or low-value care, pricing failure, fraud and abuse, and administrative complexity.

Dr. Shrank and colleagues noted that administrative complexity was associated with the greatest contribution to waste, accounting for $265.6 billion in waste, adding that there are no studies that identified savings from interventions to alleviate administrative complexity.

“Some of that complexity results from fragmentation in the health care system,” they stated. “Recent proposals by CMS [the Centers for Medicare & Medicaid Services] and the Office of the National Coordinator of [sic] Health Information Technology to foster data interoperability and government initiatives such as Blue Button 2.0 will hopefully alleviate some burden as information flows more freely and billing and authorization processes become more automated.”

They also point to greater use of value-based payments as a possible avenue toward greater cost savings in this category.

The second largest contributor is pricing failure, which is estimated to be in the range from $230.7 billion to $240.5 billion, with interventions generating savings ranging from $81.4 billion to $91.2 billion.

And as the health care system evolves to a value-based paradigm, it is expected to have the least impact in this category “since pharmaceutical pricing represents a major component of this waste domain and would not be affected by new approaches to care delivery and reimbursement,” Dr. Shrank and colleagues wrote.

That being said, the authors stated that policy interventions “are needed to drive meaningful reductions in waste in this domain. Additionally, in the dynamic health care marketplace, where profit-motivated firms will respond to any new policy with strategies to protect their margins, no single policy is likely to suffice; a coordinated policy effort is likely needed to create long-standing change that will meaningfully reduce waste resulting from pricing failure.”

The three domains of failure of care delivery, failure of care coordination, and overtreatment or low-value care combined to account for $200 billion in waste, and the authors stated that there is “compelling empirical evidence in all three categories that interventions can produce meaningful savings and may reduce waste by as much as half.”

[email protected]

SOURCE: Shrank W et al. JAMA. 2019 Oct 7. doi: 10.1001/jama.2019.13978.

Wasteful spending in health care could reach almost $1 trillion, according to new research published in JAMA.

utah778/Thinkstock

Review “of the current literature of the cost of waste in the U.S. health care system and evidence about projected savings from interventions that reduce waste suggest that the estimated total costs of waste and potential savings from interventions that address waste are as high as $760 billion to $935 billion and $191 billion to $282 billion, respectively,” William Shrank, MD, chief medical and corporate affairs officer at Humana, and colleagues wrote in an article published Oct. 7, 2019, in JAMA.

“These estimates represent approximately 25% of total health care expenditures in the Unites States, which have been projected to be $3.82 trillion for 2019,” the authors noted, adding that it is a little lower than other estimates that have waste as high as 34% of spending.

Authors looked at waste across six domains, including failure of care delivery, failure of care coordination, overtreatment or low-value care, pricing failure, fraud and abuse, and administrative complexity.

Dr. Shrank and colleagues noted that administrative complexity was associated with the greatest contribution to waste, accounting for $265.6 billion in waste, adding that there are no studies that identified savings from interventions to alleviate administrative complexity.

“Some of that complexity results from fragmentation in the health care system,” they stated. “Recent proposals by CMS [the Centers for Medicare & Medicaid Services] and the Office of the National Coordinator of [sic] Health Information Technology to foster data interoperability and government initiatives such as Blue Button 2.0 will hopefully alleviate some burden as information flows more freely and billing and authorization processes become more automated.”

They also point to greater use of value-based payments as a possible avenue toward greater cost savings in this category.

The second largest contributor is pricing failure, which is estimated to be in the range from $230.7 billion to $240.5 billion, with interventions generating savings ranging from $81.4 billion to $91.2 billion.

And as the health care system evolves to a value-based paradigm, it is expected to have the least impact in this category “since pharmaceutical pricing represents a major component of this waste domain and would not be affected by new approaches to care delivery and reimbursement,” Dr. Shrank and colleagues wrote.

That being said, the authors stated that policy interventions “are needed to drive meaningful reductions in waste in this domain. Additionally, in the dynamic health care marketplace, where profit-motivated firms will respond to any new policy with strategies to protect their margins, no single policy is likely to suffice; a coordinated policy effort is likely needed to create long-standing change that will meaningfully reduce waste resulting from pricing failure.”

The three domains of failure of care delivery, failure of care coordination, and overtreatment or low-value care combined to account for $200 billion in waste, and the authors stated that there is “compelling empirical evidence in all three categories that interventions can produce meaningful savings and may reduce waste by as much as half.”

[email protected]

SOURCE: Shrank W et al. JAMA. 2019 Oct 7. doi: 10.1001/jama.2019.13978.

The Centers for Disease Control and Prevention has released an updated interim clinical guidance for health providers for evaluating and treating patients with lung injury associated with e-cigarette use or vaping.

In a telebriefing, Anne Schuchat, MD, CDC principal deputy director, and her colleagues answered questions about the current investigation into the source of this lung injury outbreak and the updated clinical guidance. Dr. Schuchat said, “I can’t stress enough the seriousness of these injuries.” She added, “We are not seeing a drop in cases” but a continuation of the trend of hospitalization and deaths that started in August 2019.

Investigation update

The investigation to date has yielded some information about current cases of lung injury related to vaping:

• The acronym EVALI has been developed to refer to e-cigarette, or vaping products use associated lung injury;

• 1,299 EVALI cases have been reported as of Oct. 8;

• No single compound or ingredient has emerged as the cause of these injuries, and more than one substance may be involved;

• Among the 573 patients for whom data are available on vaping products used in the previous 90 days, 76% reported using THC-containing products; 58% reported using nicotine-containing products; 32% reported exclusive use of THC-containing products, and 13% reported exclusive use of nicotine-containing products;

• Of the 700+ samples sent to the CDC for analysis, most had little or no liquid remaining in the device, limiting content analysis. In 28 THC-containing samples, THC concentrations were found to be 13% - 77% (mean 41%).

• A “handful” of cases of readmission have been reported and the CDC is currently investigating whether these cases included patients who took up vaping again or had some other possible contributing factor.

• The CDC is currently developing an ICD-10 code relevant to EVALI.

Clinical guidance update

The CDC provided detailed guidance on evaluating and caring for patients with EVALI. The recommendations focus on patient history, lab testing, criteria for hospitalization, and follow-up of these patients.

Detailed history of patients presenting with suspected EVALI is especially important for this patient population, given the many unknowns surrounding this condition. The updated guidance states, “All health care providers evaluating patients for EVALI should ask about the use of e-cigarette, or vaping, products and ideally should ask about types of substances used (e.g.,THC, cannabis [oil, dabs], nicotine, modified products or the addition of substances not intended by the manufacturer); product source, specific product brand and name; duration and frequency of use, time of last use; product delivery system, and method of use (aerosolization, dabbing, or dripping).” The approach recommended for soliciting accurate information is “empathetic, nonjudgmental” and, the guidelines say, patients should be questioned in private regarding sensitive information to assure confidentiality.

A respiratory virus panel is recommended for all suspected EVALI patients, although at this time, these tests cannot be used to distinguish EVALI from infectious etiologies. All patients should be considered for urine toxicology testing, including testing for THC.

Imaging guidance for suspected EVALI patients includes chest x-ray, with additional CT scan when the x-ray result does not correlate with clinical findings or to evaluate severe or worsening disease.

Recommended criteria for hospitalization of patients with suspected EVALI are those patients with decreased O₂ saturation (less than 95%) on room air, are in respiratory distress, or have comorbidities that compromise pulmonary reserve. As of Oct. 8, 96% of patients with suspected EVALI reported to CDC have been hospitalized.

As for medical treatment of these patients, corticosteroids have been found helpful. The statement noted, “Among 140 cases reported nationally to CDC that received corticosteroids, 82% of patients improved

The natural progression of this injury is not known, however, and it is possible that patients might recover without corticosteroids. Given the unknown etiology of the disease and “because the diagnosis remains one of exclusion, aggressive empiric therapy with corticosteroids, antimicrobial, and antiviral therapy might be warranted for patients with severe illness. A range of corticosteroid doses, durations, and taper plans might be considered on a case-by-case basis.”

The report concludes with a strong recommendation that patients hospitalized with EVALI are followed closely with a visit 1-2 weeks after discharge and again with additional testing 1-2 months later. Health care providers are also advised to consult medical specialists, in particular pulmonologists, who can offer further evaluation, recommend empiric treatment, and review indications for bronchoscopy.

Mitch Zeller, JD, director, Center for Tobacco Products with the Food and Drug Administration emphasized the extraordinary complexity of the EVALI problem but noted that the FDA and CDC “will leave no stone unturned until we get to the bottom of it.”

[email protected]

The Centers for Disease Control and Prevention has released an updated interim clinical guidance for health providers for evaluating and treating patients with lung injury associated with e-cigarette use or vaping.

In a telebriefing, Anne Schuchat, MD, CDC principal deputy director, and her colleagues answered questions about the current investigation into the source of this lung injury outbreak and the updated clinical guidance. Dr. Schuchat said, “I can’t stress enough the seriousness of these injuries.” She added, “We are not seeing a drop in cases” but a continuation of the trend of hospitalization and deaths that started in August 2019.

Investigation update

The investigation to date has yielded some information about current cases of lung injury related to vaping:

• The acronym EVALI has been developed to refer to e-cigarette, or vaping products use associated lung injury;

• 1,299 EVALI cases have been reported as of Oct. 8;

• No single compound or ingredient has emerged as the cause of these injuries, and more than one substance may be involved;

• Among the 573 patients for whom data are available on vaping products used in the previous 90 days, 76% reported using THC-containing products; 58% reported using nicotine-containing products; 32% reported exclusive use of THC-containing products, and 13% reported exclusive use of nicotine-containing products;

• Of the 700+ samples sent to the CDC for analysis, most had little or no liquid remaining in the device, limiting content analysis. In 28 THC-containing samples, THC concentrations were found to be 13% - 77% (mean 41%).

• A “handful” of cases of readmission have been reported and the CDC is currently investigating whether these cases included patients who took up vaping again or had some other possible contributing factor.

• The CDC is currently developing an ICD-10 code relevant to EVALI.

Clinical guidance update

The CDC provided detailed guidance on evaluating and caring for patients with EVALI. The recommendations focus on patient history, lab testing, criteria for hospitalization, and follow-up of these patients.

Detailed history of patients presenting with suspected EVALI is especially important for this patient population, given the many unknowns surrounding this condition. The updated guidance states, “All health care providers evaluating patients for EVALI should ask about the use of e-cigarette, or vaping, products and ideally should ask about types of substances used (e.g.,THC, cannabis [oil, dabs], nicotine, modified products or the addition of substances not intended by the manufacturer); product source, specific product brand and name; duration and frequency of use, time of last use; product delivery system, and method of use (aerosolization, dabbing, or dripping).” The approach recommended for soliciting accurate information is “empathetic, nonjudgmental” and, the guidelines say, patients should be questioned in private regarding sensitive information to assure confidentiality.

A respiratory virus panel is recommended for all suspected EVALI patients, although at this time, these tests cannot be used to distinguish EVALI from infectious etiologies. All patients should be considered for urine toxicology testing, including testing for THC.

Imaging guidance for suspected EVALI patients includes chest x-ray, with additional CT scan when the x-ray result does not correlate with clinical findings or to evaluate severe or worsening disease.

Recommended criteria for hospitalization of patients with suspected EVALI are those patients with decreased O₂ saturation (less than 95%) on room air, are in respiratory distress, or have comorbidities that compromise pulmonary reserve. As of Oct. 8, 96% of patients with suspected EVALI reported to CDC have been hospitalized.

As for medical treatment of these patients, corticosteroids have been found helpful. The statement noted, “Among 140 cases reported nationally to CDC that received corticosteroids, 82% of patients improved

The natural progression of this injury is not known, however, and it is possible that patients might recover without corticosteroids. Given the unknown etiology of the disease and “because the diagnosis remains one of exclusion, aggressive empiric therapy with corticosteroids, antimicrobial, and antiviral therapy might be warranted for patients with severe illness. A range of corticosteroid doses, durations, and taper plans might be considered on a case-by-case basis.”

The report concludes with a strong recommendation that patients hospitalized with EVALI are followed closely with a visit 1-2 weeks after discharge and again with additional testing 1-2 months later. Health care providers are also advised to consult medical specialists, in particular pulmonologists, who can offer further evaluation, recommend empiric treatment, and review indications for bronchoscopy.

Mitch Zeller, JD, director, Center for Tobacco Products with the Food and Drug Administration emphasized the extraordinary complexity of the EVALI problem but noted that the FDA and CDC “will leave no stone unturned until we get to the bottom of it.”

[email protected]

The Centers for Disease Control and Prevention has released an updated interim clinical guidance for health providers for evaluating and treating patients with lung injury associated with e-cigarette use or vaping.

In a telebriefing, Anne Schuchat, MD, CDC principal deputy director, and her colleagues answered questions about the current investigation into the source of this lung injury outbreak and the updated clinical guidance. Dr. Schuchat said, “I can’t stress enough the seriousness of these injuries.” She added, “We are not seeing a drop in cases” but a continuation of the trend of hospitalization and deaths that started in August 2019.

Investigation update

The investigation to date has yielded some information about current cases of lung injury related to vaping:

• The acronym EVALI has been developed to refer to e-cigarette, or vaping products use associated lung injury;

• 1,299 EVALI cases have been reported as of Oct. 8;

• No single compound or ingredient has emerged as the cause of these injuries, and more than one substance may be involved;

• Among the 573 patients for whom data are available on vaping products used in the previous 90 days, 76% reported using THC-containing products; 58% reported using nicotine-containing products; 32% reported exclusive use of THC-containing products, and 13% reported exclusive use of nicotine-containing products;

• Of the 700+ samples sent to the CDC for analysis, most had little or no liquid remaining in the device, limiting content analysis. In 28 THC-containing samples, THC concentrations were found to be 13% - 77% (mean 41%).

• A “handful” of cases of readmission have been reported and the CDC is currently investigating whether these cases included patients who took up vaping again or had some other possible contributing factor.

• The CDC is currently developing an ICD-10 code relevant to EVALI.

Clinical guidance update

The CDC provided detailed guidance on evaluating and caring for patients with EVALI. The recommendations focus on patient history, lab testing, criteria for hospitalization, and follow-up of these patients.

Detailed history of patients presenting with suspected EVALI is especially important for this patient population, given the many unknowns surrounding this condition. The updated guidance states, “All health care providers evaluating patients for EVALI should ask about the use of e-cigarette, or vaping, products and ideally should ask about types of substances used (e.g.,THC, cannabis [oil, dabs], nicotine, modified products or the addition of substances not intended by the manufacturer); product source, specific product brand and name; duration and frequency of use, time of last use; product delivery system, and method of use (aerosolization, dabbing, or dripping).” The approach recommended for soliciting accurate information is “empathetic, nonjudgmental” and, the guidelines say, patients should be questioned in private regarding sensitive information to assure confidentiality.

A respiratory virus panel is recommended for all suspected EVALI patients, although at this time, these tests cannot be used to distinguish EVALI from infectious etiologies. All patients should be considered for urine toxicology testing, including testing for THC.

Imaging guidance for suspected EVALI patients includes chest x-ray, with additional CT scan when the x-ray result does not correlate with clinical findings or to evaluate severe or worsening disease.

Recommended criteria for hospitalization of patients with suspected EVALI are those patients with decreased O₂ saturation (less than 95%) on room air, are in respiratory distress, or have comorbidities that compromise pulmonary reserve. As of Oct. 8, 96% of patients with suspected EVALI reported to CDC have been hospitalized.

As for medical treatment of these patients, corticosteroids have been found helpful. The statement noted, “Among 140 cases reported nationally to CDC that received corticosteroids, 82% of patients improved

The natural progression of this injury is not known, however, and it is possible that patients might recover without corticosteroids. Given the unknown etiology of the disease and “because the diagnosis remains one of exclusion, aggressive empiric therapy with corticosteroids, antimicrobial, and antiviral therapy might be warranted for patients with severe illness. A range of corticosteroid doses, durations, and taper plans might be considered on a case-by-case basis.”

The report concludes with a strong recommendation that patients hospitalized with EVALI are followed closely with a visit 1-2 weeks after discharge and again with additional testing 1-2 months later. Health care providers are also advised to consult medical specialists, in particular pulmonologists, who can offer further evaluation, recommend empiric treatment, and review indications for bronchoscopy.

Mitch Zeller, JD, director, Center for Tobacco Products with the Food and Drug Administration emphasized the extraordinary complexity of the EVALI problem but noted that the FDA and CDC “will leave no stone unturned until we get to the bottom of it.”

[email protected]

Statin use for a minimum of 3 months was significantly associated with an increased risk of skin and soft tissue infections (SSTIs), according to a sequence symmetry analysis of prescription claims over a 10-year period reported in the British Journal of Clinical Pharmacology.

In the study, statin use for as little as 91 days was linked with elevated risks of SSTIs and diabetes. However, the increased risk of infection was seen in individuals who did and did not develop diabetes, wrote Humphrey Ko, of the school of pharmacy and biomedical sciences, Curtin University, Perth, Australia, and colleagues.

The current literature on the impact of statins on SSTIs is conflicted, they noted. Previous research shows that statins “may reduce the risk of community-acquired [Staphylococcus aureus] bacteremia and exert antibacterial effects against S. aureus,” and therefore may have potential for reducing SSTI risk “or evolve into promising novel treatments for SSTIs,” the researchers said; they noted, however, that other data show that statins may induce new-onset diabetes.

They examined prescription claims (for statins, antidiabetic medications, and antistaphylococcal antibiotics) from 2001 to 2011 from the Australian Department of Veterans’ Affairs that included more than 228,000 veterans, war widows, and widowers. Prescriptions for antistaphylococcal antibiotics were used as a marker of SSTIs.

Overall, statins were significantly associated with an increased risk of SSTIs at 91 days (adjusted sequence ratio, 1.40). The risk of SSTIs from statin use was similar at 182 (ASR, 1.41) and 365 days (ASR, 1.40). In this case, the ASRs represent the incidence rate ratios of prescribing antibiotics in statin-exposed versus statin-nonexposed person-time.

Statins were associated with a significantly increased risk of new onset diabetes, but the SSTI risk was not significantly different between statin users with and without diabetes. Statin users who did not have diabetes had significant SSTI risks at 91, 182, and 365 days (ASR, 1.39, 1.41, and 1.37, respectively) and statin users with diabetes had similarly significant risks of SSTIs (ASR,1.43, 1.42, and 1.49, respectively).

In addition, socioeconomic status appeared to have no significant effect on the relationship between statin use, SSTIs, and diabetes, the researchers noted.

The findings were limited by several factors including the inability to account for patient compliance in taking the medications, a lack of dosage data to determine the impact of dosage on outcomes, and potential confounding by the presence of diabetes, they said. However, the results suggest that “it would seem prudent for clinicians to monitor blood glucose levels of statin users who are predisposed to diabetes, and be mindful of possible increased SSTI risks in such patients,” they concluded. Statins, they added, “may increase SSTI risk via direct or indirect mechanisms.”

More clinical trials are needed to confirm the mechanisms, and “to ascertain the effect of statins on gut dysbiosis, impaired bile acid metabolism, vitamin D levels, and cholesterol inhibition on skin function,” they wrote.

The study was supported in part by the Australian Government Research Training Program Scholarship, the Curtin Health Innovation Research Institute Biosciences Research Precinct Core Facility, and the School of Pharmacy and Biomedical Sciences (Curtin University). The researchers had no financial conflicts to disclose.

SOURCE: Ko H et al. Br J Clin Pharmacol. 2019 Oct 9. doi: 10.1111/bcp.14077.

Statin use for a minimum of 3 months was significantly associated with an increased risk of skin and soft tissue infections (SSTIs), according to a sequence symmetry analysis of prescription claims over a 10-year period reported in the British Journal of Clinical Pharmacology.

In the study, statin use for as little as 91 days was linked with elevated risks of SSTIs and diabetes. However, the increased risk of infection was seen in individuals who did and did not develop diabetes, wrote Humphrey Ko, of the school of pharmacy and biomedical sciences, Curtin University, Perth, Australia, and colleagues.

The current literature on the impact of statins on SSTIs is conflicted, they noted. Previous research shows that statins “may reduce the risk of community-acquired [Staphylococcus aureus] bacteremia and exert antibacterial effects against S. aureus,” and therefore may have potential for reducing SSTI risk “or evolve into promising novel treatments for SSTIs,” the researchers said; they noted, however, that other data show that statins may induce new-onset diabetes.

They examined prescription claims (for statins, antidiabetic medications, and antistaphylococcal antibiotics) from 2001 to 2011 from the Australian Department of Veterans’ Affairs that included more than 228,000 veterans, war widows, and widowers. Prescriptions for antistaphylococcal antibiotics were used as a marker of SSTIs.

Overall, statins were significantly associated with an increased risk of SSTIs at 91 days (adjusted sequence ratio, 1.40). The risk of SSTIs from statin use was similar at 182 (ASR, 1.41) and 365 days (ASR, 1.40). In this case, the ASRs represent the incidence rate ratios of prescribing antibiotics in statin-exposed versus statin-nonexposed person-time.

Statins were associated with a significantly increased risk of new onset diabetes, but the SSTI risk was not significantly different between statin users with and without diabetes. Statin users who did not have diabetes had significant SSTI risks at 91, 182, and 365 days (ASR, 1.39, 1.41, and 1.37, respectively) and statin users with diabetes had similarly significant risks of SSTIs (ASR,1.43, 1.42, and 1.49, respectively).

In addition, socioeconomic status appeared to have no significant effect on the relationship between statin use, SSTIs, and diabetes, the researchers noted.

The findings were limited by several factors including the inability to account for patient compliance in taking the medications, a lack of dosage data to determine the impact of dosage on outcomes, and potential confounding by the presence of diabetes, they said. However, the results suggest that “it would seem prudent for clinicians to monitor blood glucose levels of statin users who are predisposed to diabetes, and be mindful of possible increased SSTI risks in such patients,” they concluded. Statins, they added, “may increase SSTI risk via direct or indirect mechanisms.”

More clinical trials are needed to confirm the mechanisms, and “to ascertain the effect of statins on gut dysbiosis, impaired bile acid metabolism, vitamin D levels, and cholesterol inhibition on skin function,” they wrote.

The study was supported in part by the Australian Government Research Training Program Scholarship, the Curtin Health Innovation Research Institute Biosciences Research Precinct Core Facility, and the School of Pharmacy and Biomedical Sciences (Curtin University). The researchers had no financial conflicts to disclose.

SOURCE: Ko H et al. Br J Clin Pharmacol. 2019 Oct 9. doi: 10.1111/bcp.14077.

Statin use for a minimum of 3 months was significantly associated with an increased risk of skin and soft tissue infections (SSTIs), according to a sequence symmetry analysis of prescription claims over a 10-year period reported in the British Journal of Clinical Pharmacology.

In the study, statin use for as little as 91 days was linked with elevated risks of SSTIs and diabetes. However, the increased risk of infection was seen in individuals who did and did not develop diabetes, wrote Humphrey Ko, of the school of pharmacy and biomedical sciences, Curtin University, Perth, Australia, and colleagues.

The current literature on the impact of statins on SSTIs is conflicted, they noted. Previous research shows that statins “may reduce the risk of community-acquired [Staphylococcus aureus] bacteremia and exert antibacterial effects against S. aureus,” and therefore may have potential for reducing SSTI risk “or evolve into promising novel treatments for SSTIs,” the researchers said; they noted, however, that other data show that statins may induce new-onset diabetes.

They examined prescription claims (for statins, antidiabetic medications, and antistaphylococcal antibiotics) from 2001 to 2011 from the Australian Department of Veterans’ Affairs that included more than 228,000 veterans, war widows, and widowers. Prescriptions for antistaphylococcal antibiotics were used as a marker of SSTIs.

Overall, statins were significantly associated with an increased risk of SSTIs at 91 days (adjusted sequence ratio, 1.40). The risk of SSTIs from statin use was similar at 182 (ASR, 1.41) and 365 days (ASR, 1.40). In this case, the ASRs represent the incidence rate ratios of prescribing antibiotics in statin-exposed versus statin-nonexposed person-time.

Statins were associated with a significantly increased risk of new onset diabetes, but the SSTI risk was not significantly different between statin users with and without diabetes. Statin users who did not have diabetes had significant SSTI risks at 91, 182, and 365 days (ASR, 1.39, 1.41, and 1.37, respectively) and statin users with diabetes had similarly significant risks of SSTIs (ASR,1.43, 1.42, and 1.49, respectively).

In addition, socioeconomic status appeared to have no significant effect on the relationship between statin use, SSTIs, and diabetes, the researchers noted.

The findings were limited by several factors including the inability to account for patient compliance in taking the medications, a lack of dosage data to determine the impact of dosage on outcomes, and potential confounding by the presence of diabetes, they said. However, the results suggest that “it would seem prudent for clinicians to monitor blood glucose levels of statin users who are predisposed to diabetes, and be mindful of possible increased SSTI risks in such patients,” they concluded. Statins, they added, “may increase SSTI risk via direct or indirect mechanisms.”

More clinical trials are needed to confirm the mechanisms, and “to ascertain the effect of statins on gut dysbiosis, impaired bile acid metabolism, vitamin D levels, and cholesterol inhibition on skin function,” they wrote.

The study was supported in part by the Australian Government Research Training Program Scholarship, the Curtin Health Innovation Research Institute Biosciences Research Precinct Core Facility, and the School of Pharmacy and Biomedical Sciences (Curtin University). The researchers had no financial conflicts to disclose.

SOURCE: Ko H et al. Br J Clin Pharmacol. 2019 Oct 9. doi: 10.1111/bcp.14077.