SAN ANTONIO – Chronic liver disease increased mortality risk by up to about 80% in patients with pneumonia, according to an investigator who presented results of a large retrospective analysis.

Andrew Bowser/MDedge News

Liver disease increased the risk of intubation by 39% and increased length of stay by 1 day in the study, presented at the annual meeting of the American College of Chest Physicians.

These findings have implications for clinicians and the scoring systems they use to evaluate patients with pneumonia, according to investigator Zin Mar Htun, MD, internal medicine resident at Louis A. Weiss Memorial Hospital and Presence Saint Joseph Hospital, Chicago.

“We should recognize the importance of chronic liver disease as an independent risk factor for worse outcomes in pneumonia, regardless of the clinical findings or other coexisting comorbidities,” Dr. Htun said in a podium presentation.

Traditional scoring systems for evaluating pneumonia severity do not incorporate hepatic function status, she said.

“We need to come up with a better scoring system that recognizes comorbidities better than the Patient Safety Indicator scoring,” she told attendees at the meeting.

In their study, Dr. Htun and coinvestigator Muhammad Gul, MD, used the 2014 Nationwide Inpatient Sample database to look at pneumonia patients with or without a liver disease diagnosis.

Intubation was done in 14.2% of pneumonia patients with chronic liver disease present, compared with 10.6% of patients with no chronic liver disease (odds ratio [OR], 1.39; 95% confidence interval, 1.30-1.48) in one of their analyses, which included 17,528 pneumonia patients with a liver disease diagnosis and 17,528 pneumonia patients with no such diagnosis, propensity score-matched for age, gender, and Charlson comorbidities.

Length of stay was 8.76 and 7.83 days, respectively, for pneumonia patients with and without chronic liver disease (P less than .001), the propensity score-matched analysis further showed. In-hospital mortality was 10.5% and 6.9% for the liver disease and no liver disease groups in this analysis (OR, 1.57; 95% CI, 1.46-1.70).

In a regression analysis looking at 1.5 million pneumonia patients, of whom about 51,000 had chronic liver disease, the odds ratio for mortality was 1.82 (95% CI, 1.76-1.88; P less than .001), Dr. Htun further reported.

The pathogens causing pneumonia in patients with chronic liver disease were about the same as those in other hospitalized patients, she said in her presentation.

These are “compelling” results that suggest liver disease should considered as a factor in the development of future pneumonia scoring systems, according to Zachary Q. Morris, MD, of Henry Ford Hospital.

Creators of scoring systems may err on the side of making them “simplistic” so they are accessible and easy to analyze, Dr. Morris said in an interview.

“There comes a point in time that maybe you do need to have another layer of complexity to it,” added Dr. Morris, who moderated the original research session where Dr. Htun presented her results.

Both Dr. Htun and Dr. Gul reported that they had no relationships relevant to their study.

SOURCE: Htun ZM, et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.862.

SAN ANTONIO – Chronic liver disease increased mortality risk by up to about 80% in patients with pneumonia, according to an investigator who presented results of a large retrospective analysis.

Andrew Bowser/MDedge News

Liver disease increased the risk of intubation by 39% and increased length of stay by 1 day in the study, presented at the annual meeting of the American College of Chest Physicians.

These findings have implications for clinicians and the scoring systems they use to evaluate patients with pneumonia, according to investigator Zin Mar Htun, MD, internal medicine resident at Louis A. Weiss Memorial Hospital and Presence Saint Joseph Hospital, Chicago.

“We should recognize the importance of chronic liver disease as an independent risk factor for worse outcomes in pneumonia, regardless of the clinical findings or other coexisting comorbidities,” Dr. Htun said in a podium presentation.

Traditional scoring systems for evaluating pneumonia severity do not incorporate hepatic function status, she said.

“We need to come up with a better scoring system that recognizes comorbidities better than the Patient Safety Indicator scoring,” she told attendees at the meeting.

In their study, Dr. Htun and coinvestigator Muhammad Gul, MD, used the 2014 Nationwide Inpatient Sample database to look at pneumonia patients with or without a liver disease diagnosis.

Intubation was done in 14.2% of pneumonia patients with chronic liver disease present, compared with 10.6% of patients with no chronic liver disease (odds ratio [OR], 1.39; 95% confidence interval, 1.30-1.48) in one of their analyses, which included 17,528 pneumonia patients with a liver disease diagnosis and 17,528 pneumonia patients with no such diagnosis, propensity score-matched for age, gender, and Charlson comorbidities.

Length of stay was 8.76 and 7.83 days, respectively, for pneumonia patients with and without chronic liver disease (P less than .001), the propensity score-matched analysis further showed. In-hospital mortality was 10.5% and 6.9% for the liver disease and no liver disease groups in this analysis (OR, 1.57; 95% CI, 1.46-1.70).

In a regression analysis looking at 1.5 million pneumonia patients, of whom about 51,000 had chronic liver disease, the odds ratio for mortality was 1.82 (95% CI, 1.76-1.88; P less than .001), Dr. Htun further reported.

The pathogens causing pneumonia in patients with chronic liver disease were about the same as those in other hospitalized patients, she said in her presentation.

These are “compelling” results that suggest liver disease should considered as a factor in the development of future pneumonia scoring systems, according to Zachary Q. Morris, MD, of Henry Ford Hospital.

Creators of scoring systems may err on the side of making them “simplistic” so they are accessible and easy to analyze, Dr. Morris said in an interview.

“There comes a point in time that maybe you do need to have another layer of complexity to it,” added Dr. Morris, who moderated the original research session where Dr. Htun presented her results.

Both Dr. Htun and Dr. Gul reported that they had no relationships relevant to their study.

SOURCE: Htun ZM, et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.862.

SAN ANTONIO – Chronic liver disease increased mortality risk by up to about 80% in patients with pneumonia, according to an investigator who presented results of a large retrospective analysis.

Andrew Bowser/MDedge News

Liver disease increased the risk of intubation by 39% and increased length of stay by 1 day in the study, presented at the annual meeting of the American College of Chest Physicians.

These findings have implications for clinicians and the scoring systems they use to evaluate patients with pneumonia, according to investigator Zin Mar Htun, MD, internal medicine resident at Louis A. Weiss Memorial Hospital and Presence Saint Joseph Hospital, Chicago.

“We should recognize the importance of chronic liver disease as an independent risk factor for worse outcomes in pneumonia, regardless of the clinical findings or other coexisting comorbidities,” Dr. Htun said in a podium presentation.

Traditional scoring systems for evaluating pneumonia severity do not incorporate hepatic function status, she said.

“We need to come up with a better scoring system that recognizes comorbidities better than the Patient Safety Indicator scoring,” she told attendees at the meeting.

In their study, Dr. Htun and coinvestigator Muhammad Gul, MD, used the 2014 Nationwide Inpatient Sample database to look at pneumonia patients with or without a liver disease diagnosis.

Intubation was done in 14.2% of pneumonia patients with chronic liver disease present, compared with 10.6% of patients with no chronic liver disease (odds ratio [OR], 1.39; 95% confidence interval, 1.30-1.48) in one of their analyses, which included 17,528 pneumonia patients with a liver disease diagnosis and 17,528 pneumonia patients with no such diagnosis, propensity score-matched for age, gender, and Charlson comorbidities.

Length of stay was 8.76 and 7.83 days, respectively, for pneumonia patients with and without chronic liver disease (P less than .001), the propensity score-matched analysis further showed. In-hospital mortality was 10.5% and 6.9% for the liver disease and no liver disease groups in this analysis (OR, 1.57; 95% CI, 1.46-1.70).

In a regression analysis looking at 1.5 million pneumonia patients, of whom about 51,000 had chronic liver disease, the odds ratio for mortality was 1.82 (95% CI, 1.76-1.88; P less than .001), Dr. Htun further reported.

The pathogens causing pneumonia in patients with chronic liver disease were about the same as those in other hospitalized patients, she said in her presentation.

These are “compelling” results that suggest liver disease should considered as a factor in the development of future pneumonia scoring systems, according to Zachary Q. Morris, MD, of Henry Ford Hospital.

Creators of scoring systems may err on the side of making them “simplistic” so they are accessible and easy to analyze, Dr. Morris said in an interview.

“There comes a point in time that maybe you do need to have another layer of complexity to it,” added Dr. Morris, who moderated the original research session where Dr. Htun presented her results.

Both Dr. Htun and Dr. Gul reported that they had no relationships relevant to their study.

SOURCE: Htun ZM, et al. CHEST 2018. doi: 10.1016/j.chest.2018.08.862.

SAN ANTONIO – Interventions that address variations in inflammation type and metabolism unique to obese patients with asthma or COPD might prove useful for improving their management, Cherry Wongtrakool, MD, of Emory University, Atlanta, said in a presentation at the annual meeting of the American College of Chest Physicians.

Obese patients with asthma or COPD typically have metabolic and inflammatory profiles that differ from those of nonobese patients with the disorders. Obesity is associated with the development of asthma as well as its severity and the risk for exacerbations. Obese patients with asthma are less likely to have controlled disease or to respond to medication.

The variations in asthma related to obesity even can be traced to infancy for some. Children with rapid weight gain after birth, for example, have an increased risk for developing asthma. In the recently published Boston Birth Cohort study, more than 500 babies from urban, low income families were followed from birth until age 16. Babies with rapid weight gain at 4 months and at 24 months had an increased risk for developing asthma by age 16. Even after adjusting for multiple risk factors, the increased risk for developing asthma persisted in these obese infants.

Higher BMIs during infancy may affect lung development, which continues up to age 5-8 years, Dr. Wongtrakool said. Obesity may affect immune system development. Asthma may develop when persistent inflammation during infancy gets a second hit from genetic factors or from risk factors such as atopy or maternal smoking.

Dr. Wongtrakool noted that obese patients with asthma, unlike nonobese asthma patients, tend to have non-TH2 inflammation. Their TH1/TH2 ratio in stimulated T cells is higher and is directly associated with insulin resistance. Similar to obese patients without asthma, they have higher levels of circulating TNF-alpha, interferon-gamma inducible protein 10, and monocyte chemoattractant protein-1 (MCP-1). They are more likely to have insulin resistance, low high-density lipid levels, differences in gut microbiota, increased leptin, decreased adiponectin, increased asymmetric dimethylarginine, and decreased exhaled nitrous oxide (NO).

In broncheoalveolar lavage samples, obese asthma patients have more cells that secrete interleukin-17, Dr. Wontrakool said. TH17-associated inflammation also has an influence in asthma with obesity. A recent study of 30 obese and lean asthma patients found a difference in metabolites measured in breath samples of obese people with asthma, compared with lean people with asthma and obese people without asthma.

In terms of metabolites in their breath, obese asthma patients clustered together and differed from lean patients with asthma and obese patients without asthma.

Obese people with asthma also differ in their gut microbiota, having more firmicutes species and decreased bacteroides species. Studies in mice indicate that these species have a role in body weight and that altering gut microbiota via fecal transplant was associated with weight loss when obese mice received fecal transplants from lean mice, and vice versa.

In the Supplemental Nutrition in Asthma Control (SNAC) study, preadolescents with asthma were given a nutrition bar designed by researchers at the Children’s Hospital Oakland (Calif.) Research Institute. The children also received asthma education and exercise classes, but the intervention was not designed to reduce weight. FVC and FEV₁ improved in all study participants, but those participants in the low inflammation subgroup had the most pronounced improvements in FVC and FEV₁ after 2 months.

Dr. Wongtrakool called the study “intriguing,” as it indicates asthma patients with lower level inflammation appear more likely to benefit from nutritional supplementation.

In another study of 55 obese adult asthma patients, a hypocaloric diet, access to a nutritionist and psychologist, and exercise classes were associated with improved asthma control and an improved inflammatory and metabolic profile.

In a British registry of the outcomes of bariatric surgery for obesity, patients who also had asthma had a decrease in asthma prevalence in the year after surgery that persisted over 5 years.

The association of COPD with obesity has been less studied than asthma and COPD, but metabolic syndrome appears to be on the rise in these patients. In a study performed over a decade ago, 47% of COPD patients met the definition of metabolic syndrome; a more recent study found 77% of COPD patients met the standard.

Admission glucose levels also have been found to influence the severity of COPD exacerbation. With higher blood glucose levels, there was a higher risk of mortality—from 12% in those with glucose levels of less than 6.0 mmol/l to 31% among those with glucose levels exceeding 9.0 mmol/l, one study showed.

Bariatric surgery may reduce the risk of acute exacerbations of COPD in obese patients, another recent study found. In a study of 480 obese patients with COPD who underwent bariatric surgery, their 28% presurgical risk of acute exacerbations of COPD was cut in half by 12 months after surgery, and the reduction persisted at 24 months.

SAN ANTONIO – Interventions that address variations in inflammation type and metabolism unique to obese patients with asthma or COPD might prove useful for improving their management, Cherry Wongtrakool, MD, of Emory University, Atlanta, said in a presentation at the annual meeting of the American College of Chest Physicians.

Obese patients with asthma or COPD typically have metabolic and inflammatory profiles that differ from those of nonobese patients with the disorders. Obesity is associated with the development of asthma as well as its severity and the risk for exacerbations. Obese patients with asthma are less likely to have controlled disease or to respond to medication.

The variations in asthma related to obesity even can be traced to infancy for some. Children with rapid weight gain after birth, for example, have an increased risk for developing asthma. In the recently published Boston Birth Cohort study, more than 500 babies from urban, low income families were followed from birth until age 16. Babies with rapid weight gain at 4 months and at 24 months had an increased risk for developing asthma by age 16. Even after adjusting for multiple risk factors, the increased risk for developing asthma persisted in these obese infants.

Higher BMIs during infancy may affect lung development, which continues up to age 5-8 years, Dr. Wongtrakool said. Obesity may affect immune system development. Asthma may develop when persistent inflammation during infancy gets a second hit from genetic factors or from risk factors such as atopy or maternal smoking.

Dr. Wongtrakool noted that obese patients with asthma, unlike nonobese asthma patients, tend to have non-TH2 inflammation. Their TH1/TH2 ratio in stimulated T cells is higher and is directly associated with insulin resistance. Similar to obese patients without asthma, they have higher levels of circulating TNF-alpha, interferon-gamma inducible protein 10, and monocyte chemoattractant protein-1 (MCP-1). They are more likely to have insulin resistance, low high-density lipid levels, differences in gut microbiota, increased leptin, decreased adiponectin, increased asymmetric dimethylarginine, and decreased exhaled nitrous oxide (NO).

In broncheoalveolar lavage samples, obese asthma patients have more cells that secrete interleukin-17, Dr. Wontrakool said. TH17-associated inflammation also has an influence in asthma with obesity. A recent study of 30 obese and lean asthma patients found a difference in metabolites measured in breath samples of obese people with asthma, compared with lean people with asthma and obese people without asthma.

In terms of metabolites in their breath, obese asthma patients clustered together and differed from lean patients with asthma and obese patients without asthma.

Obese people with asthma also differ in their gut microbiota, having more firmicutes species and decreased bacteroides species. Studies in mice indicate that these species have a role in body weight and that altering gut microbiota via fecal transplant was associated with weight loss when obese mice received fecal transplants from lean mice, and vice versa.

In the Supplemental Nutrition in Asthma Control (SNAC) study, preadolescents with asthma were given a nutrition bar designed by researchers at the Children’s Hospital Oakland (Calif.) Research Institute. The children also received asthma education and exercise classes, but the intervention was not designed to reduce weight. FVC and FEV₁ improved in all study participants, but those participants in the low inflammation subgroup had the most pronounced improvements in FVC and FEV₁ after 2 months.

Dr. Wongtrakool called the study “intriguing,” as it indicates asthma patients with lower level inflammation appear more likely to benefit from nutritional supplementation.

In another study of 55 obese adult asthma patients, a hypocaloric diet, access to a nutritionist and psychologist, and exercise classes were associated with improved asthma control and an improved inflammatory and metabolic profile.

In a British registry of the outcomes of bariatric surgery for obesity, patients who also had asthma had a decrease in asthma prevalence in the year after surgery that persisted over 5 years.

The association of COPD with obesity has been less studied than asthma and COPD, but metabolic syndrome appears to be on the rise in these patients. In a study performed over a decade ago, 47% of COPD patients met the definition of metabolic syndrome; a more recent study found 77% of COPD patients met the standard.

Admission glucose levels also have been found to influence the severity of COPD exacerbation. With higher blood glucose levels, there was a higher risk of mortality—from 12% in those with glucose levels of less than 6.0 mmol/l to 31% among those with glucose levels exceeding 9.0 mmol/l, one study showed.

Bariatric surgery may reduce the risk of acute exacerbations of COPD in obese patients, another recent study found. In a study of 480 obese patients with COPD who underwent bariatric surgery, their 28% presurgical risk of acute exacerbations of COPD was cut in half by 12 months after surgery, and the reduction persisted at 24 months.

SAN ANTONIO – Interventions that address variations in inflammation type and metabolism unique to obese patients with asthma or COPD might prove useful for improving their management, Cherry Wongtrakool, MD, of Emory University, Atlanta, said in a presentation at the annual meeting of the American College of Chest Physicians.

Obese patients with asthma or COPD typically have metabolic and inflammatory profiles that differ from those of nonobese patients with the disorders. Obesity is associated with the development of asthma as well as its severity and the risk for exacerbations. Obese patients with asthma are less likely to have controlled disease or to respond to medication.

The variations in asthma related to obesity even can be traced to infancy for some. Children with rapid weight gain after birth, for example, have an increased risk for developing asthma. In the recently published Boston Birth Cohort study, more than 500 babies from urban, low income families were followed from birth until age 16. Babies with rapid weight gain at 4 months and at 24 months had an increased risk for developing asthma by age 16. Even after adjusting for multiple risk factors, the increased risk for developing asthma persisted in these obese infants.

Higher BMIs during infancy may affect lung development, which continues up to age 5-8 years, Dr. Wongtrakool said. Obesity may affect immune system development. Asthma may develop when persistent inflammation during infancy gets a second hit from genetic factors or from risk factors such as atopy or maternal smoking.

Dr. Wongtrakool noted that obese patients with asthma, unlike nonobese asthma patients, tend to have non-TH2 inflammation. Their TH1/TH2 ratio in stimulated T cells is higher and is directly associated with insulin resistance. Similar to obese patients without asthma, they have higher levels of circulating TNF-alpha, interferon-gamma inducible protein 10, and monocyte chemoattractant protein-1 (MCP-1). They are more likely to have insulin resistance, low high-density lipid levels, differences in gut microbiota, increased leptin, decreased adiponectin, increased asymmetric dimethylarginine, and decreased exhaled nitrous oxide (NO).

In broncheoalveolar lavage samples, obese asthma patients have more cells that secrete interleukin-17, Dr. Wontrakool said. TH17-associated inflammation also has an influence in asthma with obesity. A recent study of 30 obese and lean asthma patients found a difference in metabolites measured in breath samples of obese people with asthma, compared with lean people with asthma and obese people without asthma.

In terms of metabolites in their breath, obese asthma patients clustered together and differed from lean patients with asthma and obese patients without asthma.

Obese people with asthma also differ in their gut microbiota, having more firmicutes species and decreased bacteroides species. Studies in mice indicate that these species have a role in body weight and that altering gut microbiota via fecal transplant was associated with weight loss when obese mice received fecal transplants from lean mice, and vice versa.

In the Supplemental Nutrition in Asthma Control (SNAC) study, preadolescents with asthma were given a nutrition bar designed by researchers at the Children’s Hospital Oakland (Calif.) Research Institute. The children also received asthma education and exercise classes, but the intervention was not designed to reduce weight. FVC and FEV₁ improved in all study participants, but those participants in the low inflammation subgroup had the most pronounced improvements in FVC and FEV₁ after 2 months.

Dr. Wongtrakool called the study “intriguing,” as it indicates asthma patients with lower level inflammation appear more likely to benefit from nutritional supplementation.

In another study of 55 obese adult asthma patients, a hypocaloric diet, access to a nutritionist and psychologist, and exercise classes were associated with improved asthma control and an improved inflammatory and metabolic profile.

In a British registry of the outcomes of bariatric surgery for obesity, patients who also had asthma had a decrease in asthma prevalence in the year after surgery that persisted over 5 years.

The association of COPD with obesity has been less studied than asthma and COPD, but metabolic syndrome appears to be on the rise in these patients. In a study performed over a decade ago, 47% of COPD patients met the definition of metabolic syndrome; a more recent study found 77% of COPD patients met the standard.

Admission glucose levels also have been found to influence the severity of COPD exacerbation. With higher blood glucose levels, there was a higher risk of mortality—from 12% in those with glucose levels of less than 6.0 mmol/l to 31% among those with glucose levels exceeding 9.0 mmol/l, one study showed.

Bariatric surgery may reduce the risk of acute exacerbations of COPD in obese patients, another recent study found. In a study of 480 obese patients with COPD who underwent bariatric surgery, their 28% presurgical risk of acute exacerbations of COPD was cut in half by 12 months after surgery, and the reduction persisted at 24 months.

The American Venous Forum Foundation will accept applications until Oct. 21 for the $100,000 BSN-JOBST Research Grant. The grant is for original, basic or clinical research in venous or lymphatic disease and provides $50,000 for each of two years. It is named after patient Conrad Jobst, who suffered from vascular disease and developed gradient compression garments to help relieve symptoms of venous disease.

The American Venous Forum Foundation will accept applications until Oct. 21 for the $100,000 BSN-JOBST Research Grant. The grant is for original, basic or clinical research in venous or lymphatic disease and provides $50,000 for each of two years. It is named after patient Conrad Jobst, who suffered from vascular disease and developed gradient compression garments to help relieve symptoms of venous disease.

The American Venous Forum Foundation will accept applications until Oct. 21 for the $100,000 BSN-JOBST Research Grant. The grant is for original, basic or clinical research in venous or lymphatic disease and provides $50,000 for each of two years. It is named after patient Conrad Jobst, who suffered from vascular disease and developed gradient compression garments to help relieve symptoms of venous disease.

The National Heart, Lung and Blood institute has extended the combined number of years of K training support from six to eight years for the K08 and K23 grants. Clinician scientists who have received either award can stay on a K12 or KL2 program for up to three years and then request a five-year individual K award. This will help support the transition from training to independent investigators for those clinicians.

The National Heart, Lung and Blood institute has extended the combined number of years of K training support from six to eight years for the K08 and K23 grants. Clinician scientists who have received either award can stay on a K12 or KL2 program for up to three years and then request a five-year individual K award. This will help support the transition from training to independent investigators for those clinicians.

The National Heart, Lung and Blood institute has extended the combined number of years of K training support from six to eight years for the K08 and K23 grants. Clinician scientists who have received either award can stay on a K12 or KL2 program for up to three years and then request a five-year individual K award. This will help support the transition from training to independent investigators for those clinicians.

BARCELONA – An investigational antidepressant known for now simply as MIN-117 shows the potential – at least, in phase 2 development – of offering significant advantages over currently available antidepressants in patients with major depressive disorder, Michael Davidson, MD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“This is a compound with a very, very rich pharmacology – so rich that we don’t know exactly which of the pharmacologic effects are really making the difference. This rich pharmacology is related to pathways that may confer to MIN-117 a unique positioning in the field of antidepressants and address unmet medical needs not well covered by existing therapies. For example, faster onset of action, complete restoration of euthymia, and beneficial effects on cognition and sexual functioning,” according to Michael Davidson, MD, chief medical officer at Minerva Neurosciences, which is developing the drug..

In the completed phase 2 study, the drug also displayed a strong anxiolytic effect and no prolongation of REM sleep latency in polysomnographic testing.

“So it may be that this is the first antidepressant which does not affect sleep architecture,” observed Dr. Davidson, professor of psychiatry at the Sackler School of Medicine in Tel Aviv.

Preclinical studies established that MIN-117 has high affinity for the 5HT serotonin transporter, serotonin 1A and 2A receptors, the dopamine transporter, and the alpha-1A and -1B adrenergic receptors. In animal models of depression, the drug results in sustained release of dopamine and serotonin. In human studies, the drug has a long half-life of roughly 60 hours.

“One possibility is that MIN-117 will be administered not once a day, but once or twice a week. It may be that here we have an antidepressant that doesn’t have to be administered every day,” the psychiatrist said.

In the completed phase 2 study, however, the drug was given once daily in what he described as a “classic design” for an antidepressant clinical trial: a 4-week washout period, then 6 weeks of double-blind treatment with MIN-117 at 2.5 or 0.5 mg/day, paroxetine at 20 mg/day, or placebo, then a 2-week posttreatment follow-up phase.

In describing the results of the study of 84 patients with major depressive disorder, Dr. Davidson painted a picture of MIN-117’s safety and efficacy with broad strokes because the trial wasn’t powered to demonstrate statistically significant differences. But the treatment effect sizes for the novel drug were impressive. A much more complete picture of the safety and efficacy of MIN-117 will be provided by an ongoing 324-patient phase 2b multicenter U.S. and European trial of the drug given at 2.5 or 5 mg/day or placebo.

The primary endpoint in the completed trial was change from baseline to 6 weeks in mean Montgomery-Åsberg Rating Depression Scale (MADRS) score. From a baseline score of about 33, MADRS scores improved by 9 points with placebo, 11 with MIN-117 at 0.5 mg, and by 12 points with 2.5 mg of the drug. MIN-117 was superior to placebo in this regard from the time of the earliest assessment, at 2 weeks.

One-quarter of patients on MIN-117 at 2.5 mg/day achieved remission, prospectively defined as a MADRS score below 12. Remission was 2.1-fold more likely in this group than with placebo at week 4 and 3.1-fold more likely at 6 weeks. The remission rate with MIN-117 also was better than with paroxetine.

“So the hope is that the drug will not be the usual antidepressant, where you see some improvement but you carry over dysthymia, and that we’ll be able to produce full remission of the depressive symptoms,” Dr. Davidson said.

MIN-117 also showed a solid anxiolytic effect, with mean scores on the Hamilton Anxiety Rating Scale – a secondary endpoint – improving by 10 points in both the 0.5- and 2.5-mg groups from a baseline of 26 points. As a result of this impressive showing, the large ongoing phase 2b study is recruiting patients with an ongoing episode of major depressive disorder and prominent secondary anxiety.

Both doses of MIN-117 were well tolerated. Scores on the Arizona Sexual Experiences Scale showed that the drug did not result in any impairment of sexual function. Nor was MIN-117 associated with evidence of cognitive impairment; in fact, scores on the Digit-Symbol Substitution Test and Digit Span Backwards tool were better than in the placebo arm.

The study was sponsored by Minerva Neurosciences and presented by the company’s chief medical officer.

[email protected]

BARCELONA – An investigational antidepressant known for now simply as MIN-117 shows the potential – at least, in phase 2 development – of offering significant advantages over currently available antidepressants in patients with major depressive disorder, Michael Davidson, MD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“This is a compound with a very, very rich pharmacology – so rich that we don’t know exactly which of the pharmacologic effects are really making the difference. This rich pharmacology is related to pathways that may confer to MIN-117 a unique positioning in the field of antidepressants and address unmet medical needs not well covered by existing therapies. For example, faster onset of action, complete restoration of euthymia, and beneficial effects on cognition and sexual functioning,” according to Michael Davidson, MD, chief medical officer at Minerva Neurosciences, which is developing the drug..

In the completed phase 2 study, the drug also displayed a strong anxiolytic effect and no prolongation of REM sleep latency in polysomnographic testing.

“So it may be that this is the first antidepressant which does not affect sleep architecture,” observed Dr. Davidson, professor of psychiatry at the Sackler School of Medicine in Tel Aviv.

Preclinical studies established that MIN-117 has high affinity for the 5HT serotonin transporter, serotonin 1A and 2A receptors, the dopamine transporter, and the alpha-1A and -1B adrenergic receptors. In animal models of depression, the drug results in sustained release of dopamine and serotonin. In human studies, the drug has a long half-life of roughly 60 hours.

“One possibility is that MIN-117 will be administered not once a day, but once or twice a week. It may be that here we have an antidepressant that doesn’t have to be administered every day,” the psychiatrist said.

In the completed phase 2 study, however, the drug was given once daily in what he described as a “classic design” for an antidepressant clinical trial: a 4-week washout period, then 6 weeks of double-blind treatment with MIN-117 at 2.5 or 0.5 mg/day, paroxetine at 20 mg/day, or placebo, then a 2-week posttreatment follow-up phase.

In describing the results of the study of 84 patients with major depressive disorder, Dr. Davidson painted a picture of MIN-117’s safety and efficacy with broad strokes because the trial wasn’t powered to demonstrate statistically significant differences. But the treatment effect sizes for the novel drug were impressive. A much more complete picture of the safety and efficacy of MIN-117 will be provided by an ongoing 324-patient phase 2b multicenter U.S. and European trial of the drug given at 2.5 or 5 mg/day or placebo.

The primary endpoint in the completed trial was change from baseline to 6 weeks in mean Montgomery-Åsberg Rating Depression Scale (MADRS) score. From a baseline score of about 33, MADRS scores improved by 9 points with placebo, 11 with MIN-117 at 0.5 mg, and by 12 points with 2.5 mg of the drug. MIN-117 was superior to placebo in this regard from the time of the earliest assessment, at 2 weeks.

One-quarter of patients on MIN-117 at 2.5 mg/day achieved remission, prospectively defined as a MADRS score below 12. Remission was 2.1-fold more likely in this group than with placebo at week 4 and 3.1-fold more likely at 6 weeks. The remission rate with MIN-117 also was better than with paroxetine.

“So the hope is that the drug will not be the usual antidepressant, where you see some improvement but you carry over dysthymia, and that we’ll be able to produce full remission of the depressive symptoms,” Dr. Davidson said.

MIN-117 also showed a solid anxiolytic effect, with mean scores on the Hamilton Anxiety Rating Scale – a secondary endpoint – improving by 10 points in both the 0.5- and 2.5-mg groups from a baseline of 26 points. As a result of this impressive showing, the large ongoing phase 2b study is recruiting patients with an ongoing episode of major depressive disorder and prominent secondary anxiety.

Both doses of MIN-117 were well tolerated. Scores on the Arizona Sexual Experiences Scale showed that the drug did not result in any impairment of sexual function. Nor was MIN-117 associated with evidence of cognitive impairment; in fact, scores on the Digit-Symbol Substitution Test and Digit Span Backwards tool were better than in the placebo arm.

The study was sponsored by Minerva Neurosciences and presented by the company’s chief medical officer.

[email protected]

BARCELONA – An investigational antidepressant known for now simply as MIN-117 shows the potential – at least, in phase 2 development – of offering significant advantages over currently available antidepressants in patients with major depressive disorder, Michael Davidson, MD, said at the annual congress of the European College of Neuropsychopharmacology.

Bruce Jancin/MDedge News

“This is a compound with a very, very rich pharmacology – so rich that we don’t know exactly which of the pharmacologic effects are really making the difference. This rich pharmacology is related to pathways that may confer to MIN-117 a unique positioning in the field of antidepressants and address unmet medical needs not well covered by existing therapies. For example, faster onset of action, complete restoration of euthymia, and beneficial effects on cognition and sexual functioning,” according to Michael Davidson, MD, chief medical officer at Minerva Neurosciences, which is developing the drug..

In the completed phase 2 study, the drug also displayed a strong anxiolytic effect and no prolongation of REM sleep latency in polysomnographic testing.

“So it may be that this is the first antidepressant which does not affect sleep architecture,” observed Dr. Davidson, professor of psychiatry at the Sackler School of Medicine in Tel Aviv.

Preclinical studies established that MIN-117 has high affinity for the 5HT serotonin transporter, serotonin 1A and 2A receptors, the dopamine transporter, and the alpha-1A and -1B adrenergic receptors. In animal models of depression, the drug results in sustained release of dopamine and serotonin. In human studies, the drug has a long half-life of roughly 60 hours.

“One possibility is that MIN-117 will be administered not once a day, but once or twice a week. It may be that here we have an antidepressant that doesn’t have to be administered every day,” the psychiatrist said.

In the completed phase 2 study, however, the drug was given once daily in what he described as a “classic design” for an antidepressant clinical trial: a 4-week washout period, then 6 weeks of double-blind treatment with MIN-117 at 2.5 or 0.5 mg/day, paroxetine at 20 mg/day, or placebo, then a 2-week posttreatment follow-up phase.

In describing the results of the study of 84 patients with major depressive disorder, Dr. Davidson painted a picture of MIN-117’s safety and efficacy with broad strokes because the trial wasn’t powered to demonstrate statistically significant differences. But the treatment effect sizes for the novel drug were impressive. A much more complete picture of the safety and efficacy of MIN-117 will be provided by an ongoing 324-patient phase 2b multicenter U.S. and European trial of the drug given at 2.5 or 5 mg/day or placebo.

The primary endpoint in the completed trial was change from baseline to 6 weeks in mean Montgomery-Åsberg Rating Depression Scale (MADRS) score. From a baseline score of about 33, MADRS scores improved by 9 points with placebo, 11 with MIN-117 at 0.5 mg, and by 12 points with 2.5 mg of the drug. MIN-117 was superior to placebo in this regard from the time of the earliest assessment, at 2 weeks.

One-quarter of patients on MIN-117 at 2.5 mg/day achieved remission, prospectively defined as a MADRS score below 12. Remission was 2.1-fold more likely in this group than with placebo at week 4 and 3.1-fold more likely at 6 weeks. The remission rate with MIN-117 also was better than with paroxetine.

“So the hope is that the drug will not be the usual antidepressant, where you see some improvement but you carry over dysthymia, and that we’ll be able to produce full remission of the depressive symptoms,” Dr. Davidson said.

MIN-117 also showed a solid anxiolytic effect, with mean scores on the Hamilton Anxiety Rating Scale – a secondary endpoint – improving by 10 points in both the 0.5- and 2.5-mg groups from a baseline of 26 points. As a result of this impressive showing, the large ongoing phase 2b study is recruiting patients with an ongoing episode of major depressive disorder and prominent secondary anxiety.

Both doses of MIN-117 were well tolerated. Scores on the Arizona Sexual Experiences Scale showed that the drug did not result in any impairment of sexual function. Nor was MIN-117 associated with evidence of cognitive impairment; in fact, scores on the Digit-Symbol Substitution Test and Digit Span Backwards tool were better than in the placebo arm.

The study was sponsored by Minerva Neurosciences and presented by the company’s chief medical officer.

[email protected]

Despite being largely preventable, heart attacks, strokes, heart failure, and related conditions caused 2.2 million hospitalizations and 415,000 deaths in 2016, according to a Vital Signs report. Many of the events were in adults aged 35 to 64 years—middle-aged adults who would not normally be considered at risk.

But “many opportunities to find and treat risk factors are missed every day,” the CDC says. “Many of these [cardiovascular] events can be prevented through daily actions to help lower risk and better manage medical conditions,” said Dr. Anne Schuchat, principal deputy director of CDC. For instance, the report reveals that:

• 9 million American adults are not yet taking aspirin as recommended
• 40 million adults with high blood pressure are not yet under safe control
• 39 million adults can benefit from managing their cholesterol
• 54 million adults are smokers
• 71 million adults are not physically active

The CDC recommends that health care professionals can help by focusing on the ABCS (aspirin, blood pressure, cholesterol, smoking cessation), and using technology, customized processes, and the “skills of everyone in the health care system” to find and fill gaps in care.

Despite being largely preventable, heart attacks, strokes, heart failure, and related conditions caused 2.2 million hospitalizations and 415,000 deaths in 2016, according to a Vital Signs report. Many of the events were in adults aged 35 to 64 years—middle-aged adults who would not normally be considered at risk.

But “many opportunities to find and treat risk factors are missed every day,” the CDC says. “Many of these [cardiovascular] events can be prevented through daily actions to help lower risk and better manage medical conditions,” said Dr. Anne Schuchat, principal deputy director of CDC. For instance, the report reveals that:

• 9 million American adults are not yet taking aspirin as recommended
• 40 million adults with high blood pressure are not yet under safe control
• 39 million adults can benefit from managing their cholesterol
• 54 million adults are smokers
• 71 million adults are not physically active

The CDC recommends that health care professionals can help by focusing on the ABCS (aspirin, blood pressure, cholesterol, smoking cessation), and using technology, customized processes, and the “skills of everyone in the health care system” to find and fill gaps in care.

Despite being largely preventable, heart attacks, strokes, heart failure, and related conditions caused 2.2 million hospitalizations and 415,000 deaths in 2016, according to a Vital Signs report. Many of the events were in adults aged 35 to 64 years—middle-aged adults who would not normally be considered at risk.

But “many opportunities to find and treat risk factors are missed every day,” the CDC says. “Many of these [cardiovascular] events can be prevented through daily actions to help lower risk and better manage medical conditions,” said Dr. Anne Schuchat, principal deputy director of CDC. For instance, the report reveals that:

• 9 million American adults are not yet taking aspirin as recommended
• 40 million adults with high blood pressure are not yet under safe control
• 39 million adults can benefit from managing their cholesterol
• 54 million adults are smokers
• 71 million adults are not physically active

The CDC recommends that health care professionals can help by focusing on the ABCS (aspirin, blood pressure, cholesterol, smoking cessation), and using technology, customized processes, and the “skills of everyone in the health care system” to find and fill gaps in care.

Image by Kevin MacKenzie

Danish researchers conducted a large, 16-year study of patients with venous thromboembolism (VTE) and found a high recurrence risk in all types of VTE.

At 6 months of follow-up, patients with unprovoked and provoked VTE had similar risk of recurrence, lower than that for patients with cancer-related VTE.

But at a 10-year follow-up, patients with unprovoked VTE had a recurrence risk similar to cancer-related VTE.

Based on these findings, the investigators concluded that risk stratification for these patients needs to be optimized.

“Our findings indicate that we may need to rethink arbitrary categorization, considering the heterogeneity of patients with venous thromboembolism,” they wrote.

They published their findings in The American Journal of Medicine.

The investigators used data from 3 nationwide Danish registries to analyze the risk of recurrent VTE in 73,993 patients with incident VTE. They stratified the patients according to whether the VTE was unprovoked, provoked, or cancer-related.

Provoked VTE occurs in patients without cancer but with other contributing factors such as surgery or trauma, and unprovoked VTE occurs without well-known provoking risk factors. Investigators did not include non-melanoma skin cancer in the cancer-related VTE classification.

Median age of the study population was 62.3 years and 54.1% were women.

During a median follow-up of 3.7 years, 9,205 patients experienced a recurrent event.

At the 6-month follow-up, the recurrence rates per 100 person-years were 6.92 for provoked, 6.80 for unprovoked, and 9.06 for cancer-related VTE.

And at the 10-year follow-up, recurrence rates were 2.22 (provoked), 2.84 (unprovoked), and 3.70 (cancer-related). This corresponded to an 18% higher adjusted relative risk of recurrence for patients with unprovoked VTE than patients with provoked VTE.

The investigators observed that at 10 years, the recurrence risk following an unprovoked VTE resembled the risk of patients with cancer-related VTE.

They suggested the mechanism for this could be a “rebound thrombosis” caused by a discontinuation of oral anticoagulants after an unprovoked VTE.

The investigators noted that the findings persisted through various sensitivity analyses “conducted to challenge the robustness of our finding.”

Two areas of concern, they wrote, arise from these findings: how long to anticoagulate patients and which patients to treat.

"Optimal duration of anticoagulation is a pivotal and an ongoing scientific and clinical concern," explained lead investigator Ida Ehlers Albertsen, MD, of Aalborg University in Denmark.

"The emergence of the non-vitamin K antagonist oral anticoagulants has changed the landscape for prevention of thrombosis, and contemporary risk stratification approaches may need to be adjusted according to these effective and safer agents." 

Image by Kevin MacKenzie

Danish researchers conducted a large, 16-year study of patients with venous thromboembolism (VTE) and found a high recurrence risk in all types of VTE.

At 6 months of follow-up, patients with unprovoked and provoked VTE had similar risk of recurrence, lower than that for patients with cancer-related VTE.

But at a 10-year follow-up, patients with unprovoked VTE had a recurrence risk similar to cancer-related VTE.

Based on these findings, the investigators concluded that risk stratification for these patients needs to be optimized.

“Our findings indicate that we may need to rethink arbitrary categorization, considering the heterogeneity of patients with venous thromboembolism,” they wrote.

They published their findings in The American Journal of Medicine.

The investigators used data from 3 nationwide Danish registries to analyze the risk of recurrent VTE in 73,993 patients with incident VTE. They stratified the patients according to whether the VTE was unprovoked, provoked, or cancer-related.

Provoked VTE occurs in patients without cancer but with other contributing factors such as surgery or trauma, and unprovoked VTE occurs without well-known provoking risk factors. Investigators did not include non-melanoma skin cancer in the cancer-related VTE classification.

Median age of the study population was 62.3 years and 54.1% were women.

During a median follow-up of 3.7 years, 9,205 patients experienced a recurrent event.

At the 6-month follow-up, the recurrence rates per 100 person-years were 6.92 for provoked, 6.80 for unprovoked, and 9.06 for cancer-related VTE.

And at the 10-year follow-up, recurrence rates were 2.22 (provoked), 2.84 (unprovoked), and 3.70 (cancer-related). This corresponded to an 18% higher adjusted relative risk of recurrence for patients with unprovoked VTE than patients with provoked VTE.

The investigators observed that at 10 years, the recurrence risk following an unprovoked VTE resembled the risk of patients with cancer-related VTE.

They suggested the mechanism for this could be a “rebound thrombosis” caused by a discontinuation of oral anticoagulants after an unprovoked VTE.

The investigators noted that the findings persisted through various sensitivity analyses “conducted to challenge the robustness of our finding.”

Two areas of concern, they wrote, arise from these findings: how long to anticoagulate patients and which patients to treat.

"Optimal duration of anticoagulation is a pivotal and an ongoing scientific and clinical concern," explained lead investigator Ida Ehlers Albertsen, MD, of Aalborg University in Denmark.

"The emergence of the non-vitamin K antagonist oral anticoagulants has changed the landscape for prevention of thrombosis, and contemporary risk stratification approaches may need to be adjusted according to these effective and safer agents." 

Image by Kevin MacKenzie

Danish researchers conducted a large, 16-year study of patients with venous thromboembolism (VTE) and found a high recurrence risk in all types of VTE.

At 6 months of follow-up, patients with unprovoked and provoked VTE had similar risk of recurrence, lower than that for patients with cancer-related VTE.

But at a 10-year follow-up, patients with unprovoked VTE had a recurrence risk similar to cancer-related VTE.

Based on these findings, the investigators concluded that risk stratification for these patients needs to be optimized.

“Our findings indicate that we may need to rethink arbitrary categorization, considering the heterogeneity of patients with venous thromboembolism,” they wrote.

They published their findings in The American Journal of Medicine.

The investigators used data from 3 nationwide Danish registries to analyze the risk of recurrent VTE in 73,993 patients with incident VTE. They stratified the patients according to whether the VTE was unprovoked, provoked, or cancer-related.

Provoked VTE occurs in patients without cancer but with other contributing factors such as surgery or trauma, and unprovoked VTE occurs without well-known provoking risk factors. Investigators did not include non-melanoma skin cancer in the cancer-related VTE classification.

Median age of the study population was 62.3 years and 54.1% were women.

During a median follow-up of 3.7 years, 9,205 patients experienced a recurrent event.

At the 6-month follow-up, the recurrence rates per 100 person-years were 6.92 for provoked, 6.80 for unprovoked, and 9.06 for cancer-related VTE.

And at the 10-year follow-up, recurrence rates were 2.22 (provoked), 2.84 (unprovoked), and 3.70 (cancer-related). This corresponded to an 18% higher adjusted relative risk of recurrence for patients with unprovoked VTE than patients with provoked VTE.

The investigators observed that at 10 years, the recurrence risk following an unprovoked VTE resembled the risk of patients with cancer-related VTE.

They suggested the mechanism for this could be a “rebound thrombosis” caused by a discontinuation of oral anticoagulants after an unprovoked VTE.

The investigators noted that the findings persisted through various sensitivity analyses “conducted to challenge the robustness of our finding.”

Two areas of concern, they wrote, arise from these findings: how long to anticoagulate patients and which patients to treat.

"Optimal duration of anticoagulation is a pivotal and an ongoing scientific and clinical concern," explained lead investigator Ida Ehlers Albertsen, MD, of Aalborg University in Denmark.

"The emergence of the non-vitamin K antagonist oral anticoagulants has changed the landscape for prevention of thrombosis, and contemporary risk stratification approaches may need to be adjusted according to these effective and safer agents." 

Q) Many total joint replacements and other orthopedic procedures are performed at the surgical center where I work. To decrease the use of narcotics, the anesthesiology department often uses IV push ketorolac postop. Our nephrology colleagues in the community are unhappy about this—but we think they’re overreacting, since these patients are often generally healthy. Is there any data on the use of ketorolac and orthopedic surgery?

All medications have associated risks. For example, while therapeutic dosages for a limited time are considered safe and effective, prolonged use of any NSAID can increase the risk for acute kidney injury (AKI) or chronic kidney disease (CKD) progression. We tend to associate these issues only with patients who are at higher risk for CKD: those who are older or who have diabetes or hypertension.

Thus, it was shocking to read a clinical report on four previously healthy young adults who were admitted for AKI three to four days after postoperative administration of ketorolac. None of these patients had risk factors that would predispose them to kidney disease. All had complained of gastrointestinal symptoms along with mild dehydration and flank pain; one young man even required a kidney biopsy and dialysis. All four did eventually recover kidney function. ¹

Continue to: Ketorolac—like most NSAIDs...

Ketorolac—like most NSAIDs—can affect kidney function, decreasing renal plasma flow and causing a dysfunction in salt and water balance. Postoperative patients may have activity limitations (eg, the young healthy patient on crutches). Factor in kidney damage from presurgical/outpatient NSAID use (which is usually reversible) and dehydration due to decreased fluid intake and nausea, and AKI is a real danger.

With the opioid crisis at the forefront of national health news, nonnarcotic alternatives for pain control are much in demand. This puts a whole new population at risk for AKI. Educate patients and their families about preventive measures, such as controlling nausea, maintaining hydration, and monitoring urine output. Fever, flank pain, or any untoward symptoms should be reported. Remember, AKI may be more common in the older patient with diabetes—but it can occur in anyone.   —EA

Ellen Apple
Dickson Schools Family Clinic, Tennessee

Q) Many total joint replacements and other orthopedic procedures are performed at the surgical center where I work. To decrease the use of narcotics, the anesthesiology department often uses IV push ketorolac postop. Our nephrology colleagues in the community are unhappy about this—but we think they’re overreacting, since these patients are often generally healthy. Is there any data on the use of ketorolac and orthopedic surgery?

All medications have associated risks. For example, while therapeutic dosages for a limited time are considered safe and effective, prolonged use of any NSAID can increase the risk for acute kidney injury (AKI) or chronic kidney disease (CKD) progression. We tend to associate these issues only with patients who are at higher risk for CKD: those who are older or who have diabetes or hypertension.

Thus, it was shocking to read a clinical report on four previously healthy young adults who were admitted for AKI three to four days after postoperative administration of ketorolac. None of these patients had risk factors that would predispose them to kidney disease. All had complained of gastrointestinal symptoms along with mild dehydration and flank pain; one young man even required a kidney biopsy and dialysis. All four did eventually recover kidney function. ¹

Continue to: Ketorolac—like most NSAIDs...

Ketorolac—like most NSAIDs—can affect kidney function, decreasing renal plasma flow and causing a dysfunction in salt and water balance. Postoperative patients may have activity limitations (eg, the young healthy patient on crutches). Factor in kidney damage from presurgical/outpatient NSAID use (which is usually reversible) and dehydration due to decreased fluid intake and nausea, and AKI is a real danger.

With the opioid crisis at the forefront of national health news, nonnarcotic alternatives for pain control are much in demand. This puts a whole new population at risk for AKI. Educate patients and their families about preventive measures, such as controlling nausea, maintaining hydration, and monitoring urine output. Fever, flank pain, or any untoward symptoms should be reported. Remember, AKI may be more common in the older patient with diabetes—but it can occur in anyone.   —EA

Ellen Apple
Dickson Schools Family Clinic, Tennessee

Q) Many total joint replacements and other orthopedic procedures are performed at the surgical center where I work. To decrease the use of narcotics, the anesthesiology department often uses IV push ketorolac postop. Our nephrology colleagues in the community are unhappy about this—but we think they’re overreacting, since these patients are often generally healthy. Is there any data on the use of ketorolac and orthopedic surgery?

All medications have associated risks. For example, while therapeutic dosages for a limited time are considered safe and effective, prolonged use of any NSAID can increase the risk for acute kidney injury (AKI) or chronic kidney disease (CKD) progression. We tend to associate these issues only with patients who are at higher risk for CKD: those who are older or who have diabetes or hypertension.

Thus, it was shocking to read a clinical report on four previously healthy young adults who were admitted for AKI three to four days after postoperative administration of ketorolac. None of these patients had risk factors that would predispose them to kidney disease. All had complained of gastrointestinal symptoms along with mild dehydration and flank pain; one young man even required a kidney biopsy and dialysis. All four did eventually recover kidney function. ¹

Continue to: Ketorolac—like most NSAIDs...

Ketorolac—like most NSAIDs—can affect kidney function, decreasing renal plasma flow and causing a dysfunction in salt and water balance. Postoperative patients may have activity limitations (eg, the young healthy patient on crutches). Factor in kidney damage from presurgical/outpatient NSAID use (which is usually reversible) and dehydration due to decreased fluid intake and nausea, and AKI is a real danger.

With the opioid crisis at the forefront of national health news, nonnarcotic alternatives for pain control are much in demand. This puts a whole new population at risk for AKI. Educate patients and their families about preventive measures, such as controlling nausea, maintaining hydration, and monitoring urine output. Fever, flank pain, or any untoward symptoms should be reported. Remember, AKI may be more common in the older patient with diabetes—but it can occur in anyone.   —EA

Ellen Apple
Dickson Schools Family Clinic, Tennessee

The Food and Drug Administration has approved inotersen for treating polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults, the second treatment approved in 2 months for the rare genetic disorder.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Inotersen is a transthyretin-directed antisense oligonucleotide that inhibits production of the transthyretin (TTR) protein (amyloid), according to the FDA statement announcing the approval on Oct. 5. It is administered in a subcutaneous injection once a week and will be marketed as Tegsedi. In August, the FDA approved the first treatment for hATTR, patisiran (Onpattro).

The FDA statement described hATTR as a “rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs,” with signs and symptoms that include effects on “sensation (pain and temperature), autonomic function (blood pressure changes and bowel and digestive problems), and muscle strength (weakness and immobility in the arms, legs, hands, and feet),” caused by amyloid deposition in the peripheral nervous system.

The mechanism-of-action section of the prescribing information states that inotersen “causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.”

A statement issued by the manufacturer, Ionis Pharmaceuticals, said that approval was based on a phase 3 study of patients with hATTR amyloidosis and polyneuropathy symptoms, which found significantly greater benefits among those treated with inotersen, compared with placebo, using primary endpoints that measured quality of life related to neuropathy and a measure of neuropathic disease progression.

Contraindications to inotersen include a history of acute glomerulonephritis caused by inotersen, history of a hypersensitivity reaction to the agent, and a platelet count below 100 × 10⁹/L; the label includes a boxed warning about thrombocytopenia and glomerulonephritis associated with treatment. The drug also is being marketed with a risk evaluation and mitigation strategy (REMS).

Patisiran, the treatment approved in August, results in “degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues,” according to its prescribing information.

[email protected]

The Food and Drug Administration has approved inotersen for treating polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults, the second treatment approved in 2 months for the rare genetic disorder.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Inotersen is a transthyretin-directed antisense oligonucleotide that inhibits production of the transthyretin (TTR) protein (amyloid), according to the FDA statement announcing the approval on Oct. 5. It is administered in a subcutaneous injection once a week and will be marketed as Tegsedi. In August, the FDA approved the first treatment for hATTR, patisiran (Onpattro).

The FDA statement described hATTR as a “rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs,” with signs and symptoms that include effects on “sensation (pain and temperature), autonomic function (blood pressure changes and bowel and digestive problems), and muscle strength (weakness and immobility in the arms, legs, hands, and feet),” caused by amyloid deposition in the peripheral nervous system.

The mechanism-of-action section of the prescribing information states that inotersen “causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.”

A statement issued by the manufacturer, Ionis Pharmaceuticals, said that approval was based on a phase 3 study of patients with hATTR amyloidosis and polyneuropathy symptoms, which found significantly greater benefits among those treated with inotersen, compared with placebo, using primary endpoints that measured quality of life related to neuropathy and a measure of neuropathic disease progression.

Contraindications to inotersen include a history of acute glomerulonephritis caused by inotersen, history of a hypersensitivity reaction to the agent, and a platelet count below 100 × 10⁹/L; the label includes a boxed warning about thrombocytopenia and glomerulonephritis associated with treatment. The drug also is being marketed with a risk evaluation and mitigation strategy (REMS).

Patisiran, the treatment approved in August, results in “degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues,” according to its prescribing information.

[email protected]

The Food and Drug Administration has approved inotersen for treating polyneuropathy of hereditary transthyretin-mediated amyloidosis (hATTR) in adults, the second treatment approved in 2 months for the rare genetic disorder.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Inotersen is a transthyretin-directed antisense oligonucleotide that inhibits production of the transthyretin (TTR) protein (amyloid), according to the FDA statement announcing the approval on Oct. 5. It is administered in a subcutaneous injection once a week and will be marketed as Tegsedi. In August, the FDA approved the first treatment for hATTR, patisiran (Onpattro).

The FDA statement described hATTR as a “rare, debilitating, and often fatal genetic disease characterized by the buildup of abnormal amyloid protein in peripheral nerves, the heart, and other organs,” with signs and symptoms that include effects on “sensation (pain and temperature), autonomic function (blood pressure changes and bowel and digestive problems), and muscle strength (weakness and immobility in the arms, legs, hands, and feet),” caused by amyloid deposition in the peripheral nervous system.

The mechanism-of-action section of the prescribing information states that inotersen “causes degradation of mutant and wild-type TTR mRNA through binding to the TTR mRNA, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.”

A statement issued by the manufacturer, Ionis Pharmaceuticals, said that approval was based on a phase 3 study of patients with hATTR amyloidosis and polyneuropathy symptoms, which found significantly greater benefits among those treated with inotersen, compared with placebo, using primary endpoints that measured quality of life related to neuropathy and a measure of neuropathic disease progression.

Contraindications to inotersen include a history of acute glomerulonephritis caused by inotersen, history of a hypersensitivity reaction to the agent, and a platelet count below 100 × 10⁹/L; the label includes a boxed warning about thrombocytopenia and glomerulonephritis associated with treatment. The drug also is being marketed with a risk evaluation and mitigation strategy (REMS).

Patisiran, the treatment approved in August, results in “degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues,” according to its prescribing information.

[email protected]

SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*

Vidyard Video

The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.

In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.

It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.

*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.

SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.

SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*

Vidyard Video

The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.

In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.

It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.

*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.

SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.

SAN FRANCISCO – In a phase II study, Vaxart’s oral flu vaccine was compared with a commercial injectable quadrivalent flu vaccine or placebo. The study found rates of illness were comparable between the oral vaccine and quadrivalent vaccinated groups.*

Vidyard Video

The recombinant adenovirus-based vaccine expresses hemagglutinin. It elicited a mucosal immune response, hinting that the mechanism of protection in flu vaccines may be dependent on the route of administration. It is also believed that a strong mucosal response is key to preventing future infections.

In an interview at IDWeek 2018, an annual scientific meeting on infectious diseases, Nikita Kolhatkar, PhD, a salaried employee of Vaxart, which makes the drug, describes the results of the study and explains the potential advantages of an oral flu vaccine versus a traditional injectable one. The oral formulation is cell-based and so is not vulnerable to the mutation and genetic drift that can occur in egg-based vaccines.

It is also more stable and, of course, less invasive than injectable vaccines, according to Dr. Kolhatkar.

*Correction, 10/9/2018: An earlier vs. of this article did not stress the comparability.

SOURCE: Kolhatkar N. IDWeek 2018. Poster abstract 1947.