SAN ANTONIO – The ADVENT-HF trial, designed to test whether adaptive servo ventilation (ASV) improves cardiovascular outcomes in heart failure patients with sleep apnea, so far has better compliance than previous trials, with no safety concerns to date, according to investigator T. Douglas Bradley, MD.

On average, patients with obstructive sleep apnea were using the device 4.6 hours per night at 1 month and 4.1 hours at 12 months, while patients with central sleep apnea were using the device 5.2 hours per night both at 1 month and 12 months, Dr. Bradley said.

“This represents much better compliance than the other trials that have looked into this area, so we are quite happy about that,” Dr. Bradley said at the annual meeting of the American College of Chest Physicians.

The study has been reviewed five times by the data safety monitoring board since the announcement of SERVE-HF trial results, with no safety concerns in either obstructive sleep apnea or central sleep apnea patients, Dr. Bradley noted in a podium presentation.

The compliance results have been submitted for publication, though efficacy results of the study will have to wait. The estimated study completion date is June 2020, according to the latest study information on ClinicalTrials.gov.

More than 600 patients have been enrolled in ADVENT-HF to date, and the investigators hope to enroll more than 800: “We should be there by the end of next year,” Dr. Bradley said.

He provided disclosures related to Philips Respironics (funding and devices) and the Canadian Institutes of Health Research.

SAN ANTONIO – The ADVENT-HF trial, designed to test whether adaptive servo ventilation (ASV) improves cardiovascular outcomes in heart failure patients with sleep apnea, so far has better compliance than previous trials, with no safety concerns to date, according to investigator T. Douglas Bradley, MD.

On average, patients with obstructive sleep apnea were using the device 4.6 hours per night at 1 month and 4.1 hours at 12 months, while patients with central sleep apnea were using the device 5.2 hours per night both at 1 month and 12 months, Dr. Bradley said.

“This represents much better compliance than the other trials that have looked into this area, so we are quite happy about that,” Dr. Bradley said at the annual meeting of the American College of Chest Physicians.

The study has been reviewed five times by the data safety monitoring board since the announcement of SERVE-HF trial results, with no safety concerns in either obstructive sleep apnea or central sleep apnea patients, Dr. Bradley noted in a podium presentation.

The compliance results have been submitted for publication, though efficacy results of the study will have to wait. The estimated study completion date is June 2020, according to the latest study information on ClinicalTrials.gov.

More than 600 patients have been enrolled in ADVENT-HF to date, and the investigators hope to enroll more than 800: “We should be there by the end of next year,” Dr. Bradley said.

He provided disclosures related to Philips Respironics (funding and devices) and the Canadian Institutes of Health Research.

SAN ANTONIO – The ADVENT-HF trial, designed to test whether adaptive servo ventilation (ASV) improves cardiovascular outcomes in heart failure patients with sleep apnea, so far has better compliance than previous trials, with no safety concerns to date, according to investigator T. Douglas Bradley, MD.

On average, patients with obstructive sleep apnea were using the device 4.6 hours per night at 1 month and 4.1 hours at 12 months, while patients with central sleep apnea were using the device 5.2 hours per night both at 1 month and 12 months, Dr. Bradley said.

“This represents much better compliance than the other trials that have looked into this area, so we are quite happy about that,” Dr. Bradley said at the annual meeting of the American College of Chest Physicians.

The study has been reviewed five times by the data safety monitoring board since the announcement of SERVE-HF trial results, with no safety concerns in either obstructive sleep apnea or central sleep apnea patients, Dr. Bradley noted in a podium presentation.

The compliance results have been submitted for publication, though efficacy results of the study will have to wait. The estimated study completion date is June 2020, according to the latest study information on ClinicalTrials.gov.

More than 600 patients have been enrolled in ADVENT-HF to date, and the investigators hope to enroll more than 800: “We should be there by the end of next year,” Dr. Bradley said.

He provided disclosures related to Philips Respironics (funding and devices) and the Canadian Institutes of Health Research.

Women who take a 3- to 5-year break from bisphosphonates after 3-5 years on treatment could significantly reduce their risk of atypical femur fractures, according to a study of more than 150,000 Southern California health plan members presented at the annual meeting of the American Society for Bone and Mineral Research in Montreal.

A second study in the same group of women found that higher bone mineral density levels before bisphosphonate treatment may put women at greater risk for these fractures.

“Our findings suggest really strongly that among women who have achieved some level of bisphosphonate exposure a drug holiday is certainly a reasonable approach to trying to balance the risk of these atypical fractures versus the benefit of preventing more typical, or classic, hip fractures,” said presenter Annette L. Adams, PhD, MPH, a research scientist with Kaiser Permanente Southern California, who was an author on both studies.

Atypical femur fractures (AFFs) occur below the trochanters in the femoral shaft area, around mid-thigh, Dr. Adams said. They appear different from other fractures, usually breaking in just two pieces transversely through the center of the bone, and occur with minimal to no trauma, she said.

“We’ve heard stories of women that are just sitting in a chair, and they stand up and their femur fractures,” Dr. Adams said. “Or they’re out in the garden on their knees, and they try to stand up and it fractures. These are not necessarily fall-related like many traditional hip fractures.”

The researchers observed a 44% reduction in women’s risk of AFFs in the first year of a so-called drug holiday, or discontinuation of bisphosphonates, after 3-5 years on treatment when compared with those who stayed on the medications (hazard ratio = 0.56; 95% confidence interval, 0.38-0.82). During the first to fourth years after discontinuation, AFF risk was decreased by 80% (HR = 0.20; 95% CI, 0.10-0.37), and after 4 years, AFF risk was reduced by 78% (HR = 0.22; 95% CI, 0.08-0.59) in comparison to bisphosphonate users.

Dr. Adams and her colleagues reviewed records from 152,934 women aged 50 or older who were members of Kaiser Permanente Southern California between Jan. 1, 2007, and Sept. 30, 2015. There were 185 AFFs overall (incidence rate 1.70 per 10,000 person-years).

The cohort included women who used a bisphosphonate and had at least one available pretreatment bone mineral density (BMD) total hip scan. AFFs were identified and verified by physician review of x-ray images for fractures occurring during the study period with ICD-9 codes for subtrochanteric or femoral shaft fractures. Women were considered to have discontinued bisphosphonates if there was a gap of over 3 months between the last bisphosphonate use and cohort entry anniversaries. Researchers included information on potential confounders of the association between discontinuation time and AFF such as age, race/ethnicity, smoking status, fracture history, duration of bisphosphonate use, discontinuation of glucocorticoid use, and pretreatment total hip T-score.

A second study in the same cohort consistently showed that women with higher pretreatment BMD had a larger risk of AFFs.

Researchers assessed the relationship of bisphosphonate duration to AFF risk before and after treatment, including pretreatment BMD in multivariate Cox models. In a multivariate model without pretreatment BMD, those with longer bisphosphonate duration had higher AFF risk. Compared to those taking the drug for less than 1 year, the relative hazard (RH) for 1-4 years of bisphosphonate use was 3 (95% CI, 1.4-7.3), for 4-8 years of bisphosphonate use was 15 (95% CI, 7-33), and for over 8 years was 37 (95% CI, 16-83).

Pretreatment BMD, when added to the model, did not attenuate the relationship of bisphosphonate duration and AFF risk. However, it showed those with higher BMD had a 40% increase in AFF risk per standard deviation of BMD increase (HR = 1.4; 95% CI, 1.2-1.7).

In those with normal pretreatment BMD (T-score greater than –1), the RH for 4-8 years of bisphosphonate use (versus less than 1 year) was 35, compared with 15 in those with osteopenic BMD (T-score –1 to –2.5) and 6 in those with osteoporotic BMD (T-score less than –2.5).

If confirmed in other studies, the results suggest that pretreatment BMD could impact clinical decisions around patient selection for bisphosphonate initiation and drug holidays, Dr. Adams said.

She reported receiving grant and research support from Merck.

SOURCES: Adams A et al. ASBMR 2018 Abstract 1005, and Black D et al. ASBMR 2018 Abstract 1007

Women who take a 3- to 5-year break from bisphosphonates after 3-5 years on treatment could significantly reduce their risk of atypical femur fractures, according to a study of more than 150,000 Southern California health plan members presented at the annual meeting of the American Society for Bone and Mineral Research in Montreal.

A second study in the same group of women found that higher bone mineral density levels before bisphosphonate treatment may put women at greater risk for these fractures.

“Our findings suggest really strongly that among women who have achieved some level of bisphosphonate exposure a drug holiday is certainly a reasonable approach to trying to balance the risk of these atypical fractures versus the benefit of preventing more typical, or classic, hip fractures,” said presenter Annette L. Adams, PhD, MPH, a research scientist with Kaiser Permanente Southern California, who was an author on both studies.

Atypical femur fractures (AFFs) occur below the trochanters in the femoral shaft area, around mid-thigh, Dr. Adams said. They appear different from other fractures, usually breaking in just two pieces transversely through the center of the bone, and occur with minimal to no trauma, she said.

“We’ve heard stories of women that are just sitting in a chair, and they stand up and their femur fractures,” Dr. Adams said. “Or they’re out in the garden on their knees, and they try to stand up and it fractures. These are not necessarily fall-related like many traditional hip fractures.”

The researchers observed a 44% reduction in women’s risk of AFFs in the first year of a so-called drug holiday, or discontinuation of bisphosphonates, after 3-5 years on treatment when compared with those who stayed on the medications (hazard ratio = 0.56; 95% confidence interval, 0.38-0.82). During the first to fourth years after discontinuation, AFF risk was decreased by 80% (HR = 0.20; 95% CI, 0.10-0.37), and after 4 years, AFF risk was reduced by 78% (HR = 0.22; 95% CI, 0.08-0.59) in comparison to bisphosphonate users.

Dr. Adams and her colleagues reviewed records from 152,934 women aged 50 or older who were members of Kaiser Permanente Southern California between Jan. 1, 2007, and Sept. 30, 2015. There were 185 AFFs overall (incidence rate 1.70 per 10,000 person-years).

The cohort included women who used a bisphosphonate and had at least one available pretreatment bone mineral density (BMD) total hip scan. AFFs were identified and verified by physician review of x-ray images for fractures occurring during the study period with ICD-9 codes for subtrochanteric or femoral shaft fractures. Women were considered to have discontinued bisphosphonates if there was a gap of over 3 months between the last bisphosphonate use and cohort entry anniversaries. Researchers included information on potential confounders of the association between discontinuation time and AFF such as age, race/ethnicity, smoking status, fracture history, duration of bisphosphonate use, discontinuation of glucocorticoid use, and pretreatment total hip T-score.

A second study in the same cohort consistently showed that women with higher pretreatment BMD had a larger risk of AFFs.

Researchers assessed the relationship of bisphosphonate duration to AFF risk before and after treatment, including pretreatment BMD in multivariate Cox models. In a multivariate model without pretreatment BMD, those with longer bisphosphonate duration had higher AFF risk. Compared to those taking the drug for less than 1 year, the relative hazard (RH) for 1-4 years of bisphosphonate use was 3 (95% CI, 1.4-7.3), for 4-8 years of bisphosphonate use was 15 (95% CI, 7-33), and for over 8 years was 37 (95% CI, 16-83).

Pretreatment BMD, when added to the model, did not attenuate the relationship of bisphosphonate duration and AFF risk. However, it showed those with higher BMD had a 40% increase in AFF risk per standard deviation of BMD increase (HR = 1.4; 95% CI, 1.2-1.7).

In those with normal pretreatment BMD (T-score greater than –1), the RH for 4-8 years of bisphosphonate use (versus less than 1 year) was 35, compared with 15 in those with osteopenic BMD (T-score –1 to –2.5) and 6 in those with osteoporotic BMD (T-score less than –2.5).

If confirmed in other studies, the results suggest that pretreatment BMD could impact clinical decisions around patient selection for bisphosphonate initiation and drug holidays, Dr. Adams said.

She reported receiving grant and research support from Merck.

SOURCES: Adams A et al. ASBMR 2018 Abstract 1005, and Black D et al. ASBMR 2018 Abstract 1007

Women who take a 3- to 5-year break from bisphosphonates after 3-5 years on treatment could significantly reduce their risk of atypical femur fractures, according to a study of more than 150,000 Southern California health plan members presented at the annual meeting of the American Society for Bone and Mineral Research in Montreal.

A second study in the same group of women found that higher bone mineral density levels before bisphosphonate treatment may put women at greater risk for these fractures.

“Our findings suggest really strongly that among women who have achieved some level of bisphosphonate exposure a drug holiday is certainly a reasonable approach to trying to balance the risk of these atypical fractures versus the benefit of preventing more typical, or classic, hip fractures,” said presenter Annette L. Adams, PhD, MPH, a research scientist with Kaiser Permanente Southern California, who was an author on both studies.

Atypical femur fractures (AFFs) occur below the trochanters in the femoral shaft area, around mid-thigh, Dr. Adams said. They appear different from other fractures, usually breaking in just two pieces transversely through the center of the bone, and occur with minimal to no trauma, she said.

“We’ve heard stories of women that are just sitting in a chair, and they stand up and their femur fractures,” Dr. Adams said. “Or they’re out in the garden on their knees, and they try to stand up and it fractures. These are not necessarily fall-related like many traditional hip fractures.”

The researchers observed a 44% reduction in women’s risk of AFFs in the first year of a so-called drug holiday, or discontinuation of bisphosphonates, after 3-5 years on treatment when compared with those who stayed on the medications (hazard ratio = 0.56; 95% confidence interval, 0.38-0.82). During the first to fourth years after discontinuation, AFF risk was decreased by 80% (HR = 0.20; 95% CI, 0.10-0.37), and after 4 years, AFF risk was reduced by 78% (HR = 0.22; 95% CI, 0.08-0.59) in comparison to bisphosphonate users.

Dr. Adams and her colleagues reviewed records from 152,934 women aged 50 or older who were members of Kaiser Permanente Southern California between Jan. 1, 2007, and Sept. 30, 2015. There were 185 AFFs overall (incidence rate 1.70 per 10,000 person-years).

The cohort included women who used a bisphosphonate and had at least one available pretreatment bone mineral density (BMD) total hip scan. AFFs were identified and verified by physician review of x-ray images for fractures occurring during the study period with ICD-9 codes for subtrochanteric or femoral shaft fractures. Women were considered to have discontinued bisphosphonates if there was a gap of over 3 months between the last bisphosphonate use and cohort entry anniversaries. Researchers included information on potential confounders of the association between discontinuation time and AFF such as age, race/ethnicity, smoking status, fracture history, duration of bisphosphonate use, discontinuation of glucocorticoid use, and pretreatment total hip T-score.

A second study in the same cohort consistently showed that women with higher pretreatment BMD had a larger risk of AFFs.

Researchers assessed the relationship of bisphosphonate duration to AFF risk before and after treatment, including pretreatment BMD in multivariate Cox models. In a multivariate model without pretreatment BMD, those with longer bisphosphonate duration had higher AFF risk. Compared to those taking the drug for less than 1 year, the relative hazard (RH) for 1-4 years of bisphosphonate use was 3 (95% CI, 1.4-7.3), for 4-8 years of bisphosphonate use was 15 (95% CI, 7-33), and for over 8 years was 37 (95% CI, 16-83).

Pretreatment BMD, when added to the model, did not attenuate the relationship of bisphosphonate duration and AFF risk. However, it showed those with higher BMD had a 40% increase in AFF risk per standard deviation of BMD increase (HR = 1.4; 95% CI, 1.2-1.7).

In those with normal pretreatment BMD (T-score greater than –1), the RH for 4-8 years of bisphosphonate use (versus less than 1 year) was 35, compared with 15 in those with osteopenic BMD (T-score –1 to –2.5) and 6 in those with osteoporotic BMD (T-score less than –2.5).

If confirmed in other studies, the results suggest that pretreatment BMD could impact clinical decisions around patient selection for bisphosphonate initiation and drug holidays, Dr. Adams said.

She reported receiving grant and research support from Merck.

SOURCES: Adams A et al. ASBMR 2018 Abstract 1005, and Black D et al. ASBMR 2018 Abstract 1007

New data on neonatal screening, protocols for adults and pregnant women, and approaches to genital reconstruction surgery are key elements of the guidelines on the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency recently updated by the Endocrine Society.

The guidelines are an update to the 2010 Endocrine Society Clinical Practice Guideline on congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency. They were published in The Journal of Clinical Endocrinology and Metabolism.

Richard J. Auchus, MD, PhD, of the University of Michigan, Ann Arbor, and coauthor of the 2018 guidelines, said many of the guidelines remain the same, such as use of neonatal screening. However, neonatal diagnosis methods should use gestational age and birth weight or liquid chromatography–tandem mass spectrometry for secondary screening. The authors also noted that the addition of commercially available serum 21-deoxycortisol measurements, while untested, could potentially help identify CAH carriers.

Changes in genital reconstructive surgery were also addressed in the new guidelines, and a recent systematic review and meta-analysis found a “favorable benefit to risk ratio” for both early and late genital reconstructive surgery. Dr. Auchus said the timing of the surgery remains controversial and that there were “downsides of both approaches.”

“I wish there was a straightforward and perfect solution, but I don’t think there is,” he said in an interview.

Dexamethasone for the prenatal treatment of CAH, and prenatal therapy in general is still regarded as experimental and is not recommended, Dr. Auchus said. The authors encouraged pregnant women who are considering prenatal treatment of CAH to go through Institutional Review Board–approved centers that can obtain outcomes. Pregnant women should not receive a glucocorticoid that traverses the placenta, such as dexamethasone.

Classical CAH should be treated with hydrocortisone maintenance therapy, while nonclassic CAH patients should receive glucocorticoid treatment, such as in cases of early onset and rapid progression of pubarche or bone age in children and overt virilization in adolescents.

Dr. Auchus said the new guidelines have been reorganized so information is easier to find, with recommendations beginning at birth before transitioning into recommendations for childhood and adulthood.

“I think the pediatric endocrinologists are familiar with the management of this disease, but I think a lot of the internal medicine endocrinologists don’t get much training in fellowships, and I think it will be easy for them now to find the information,” Dr. Auchus said. “[I]n the previous set of guidelines, it would’ve been difficult for them to find the information that’s scattered throughout.”

However, Dr. Auchus noted, the guidelines were careful to avoid recommendations of specific levels for analyzing biomarkers for monitoring treatment and specific doses. “[W]e gave some general ideas about ranges: that they should be low, they should be normal, they should be not very high, but it’s okay if it’s a little bit high,” he added.

Also, the evidence for the recommendations is limited to best practice guidelines because of a lack of randomized controlled trials, he noted.

“We certainly do need additional long-term data on these patients,” Dr. Auchus said. “[I]t’s our hope that with some of the networks that have been developed for studying adrenal diseases that we can collect that information in a minimally intrusive way for the benefit of all the current and future patients.”

The guidelines were funded by the Intramural Research Program of the National Institutes of Health. The authors report various personal and organizational financial interests in the form of paid consultancies, researcher support positions, advisory board memberships and investigator roles. See the full study for a complete list of disclosures.

SOURCE: Speiser PW et al. J Clin Endocrinol Metab. 2018 Sep 27. doi: 10.1210/jc.2018-01865.

New data on neonatal screening, protocols for adults and pregnant women, and approaches to genital reconstruction surgery are key elements of the guidelines on the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency recently updated by the Endocrine Society.

The guidelines are an update to the 2010 Endocrine Society Clinical Practice Guideline on congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency. They were published in The Journal of Clinical Endocrinology and Metabolism.

Richard J. Auchus, MD, PhD, of the University of Michigan, Ann Arbor, and coauthor of the 2018 guidelines, said many of the guidelines remain the same, such as use of neonatal screening. However, neonatal diagnosis methods should use gestational age and birth weight or liquid chromatography–tandem mass spectrometry for secondary screening. The authors also noted that the addition of commercially available serum 21-deoxycortisol measurements, while untested, could potentially help identify CAH carriers.

Changes in genital reconstructive surgery were also addressed in the new guidelines, and a recent systematic review and meta-analysis found a “favorable benefit to risk ratio” for both early and late genital reconstructive surgery. Dr. Auchus said the timing of the surgery remains controversial and that there were “downsides of both approaches.”

“I wish there was a straightforward and perfect solution, but I don’t think there is,” he said in an interview.

Dexamethasone for the prenatal treatment of CAH, and prenatal therapy in general is still regarded as experimental and is not recommended, Dr. Auchus said. The authors encouraged pregnant women who are considering prenatal treatment of CAH to go through Institutional Review Board–approved centers that can obtain outcomes. Pregnant women should not receive a glucocorticoid that traverses the placenta, such as dexamethasone.

Classical CAH should be treated with hydrocortisone maintenance therapy, while nonclassic CAH patients should receive glucocorticoid treatment, such as in cases of early onset and rapid progression of pubarche or bone age in children and overt virilization in adolescents.

Dr. Auchus said the new guidelines have been reorganized so information is easier to find, with recommendations beginning at birth before transitioning into recommendations for childhood and adulthood.

“I think the pediatric endocrinologists are familiar with the management of this disease, but I think a lot of the internal medicine endocrinologists don’t get much training in fellowships, and I think it will be easy for them now to find the information,” Dr. Auchus said. “[I]n the previous set of guidelines, it would’ve been difficult for them to find the information that’s scattered throughout.”

However, Dr. Auchus noted, the guidelines were careful to avoid recommendations of specific levels for analyzing biomarkers for monitoring treatment and specific doses. “[W]e gave some general ideas about ranges: that they should be low, they should be normal, they should be not very high, but it’s okay if it’s a little bit high,” he added.

Also, the evidence for the recommendations is limited to best practice guidelines because of a lack of randomized controlled trials, he noted.

“We certainly do need additional long-term data on these patients,” Dr. Auchus said. “[I]t’s our hope that with some of the networks that have been developed for studying adrenal diseases that we can collect that information in a minimally intrusive way for the benefit of all the current and future patients.”

The guidelines were funded by the Intramural Research Program of the National Institutes of Health. The authors report various personal and organizational financial interests in the form of paid consultancies, researcher support positions, advisory board memberships and investigator roles. See the full study for a complete list of disclosures.

SOURCE: Speiser PW et al. J Clin Endocrinol Metab. 2018 Sep 27. doi: 10.1210/jc.2018-01865.

New data on neonatal screening, protocols for adults and pregnant women, and approaches to genital reconstruction surgery are key elements of the guidelines on the congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency recently updated by the Endocrine Society.

The guidelines are an update to the 2010 Endocrine Society Clinical Practice Guideline on congenital adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency. They were published in The Journal of Clinical Endocrinology and Metabolism.

Richard J. Auchus, MD, PhD, of the University of Michigan, Ann Arbor, and coauthor of the 2018 guidelines, said many of the guidelines remain the same, such as use of neonatal screening. However, neonatal diagnosis methods should use gestational age and birth weight or liquid chromatography–tandem mass spectrometry for secondary screening. The authors also noted that the addition of commercially available serum 21-deoxycortisol measurements, while untested, could potentially help identify CAH carriers.

Changes in genital reconstructive surgery were also addressed in the new guidelines, and a recent systematic review and meta-analysis found a “favorable benefit to risk ratio” for both early and late genital reconstructive surgery. Dr. Auchus said the timing of the surgery remains controversial and that there were “downsides of both approaches.”

“I wish there was a straightforward and perfect solution, but I don’t think there is,” he said in an interview.

Dexamethasone for the prenatal treatment of CAH, and prenatal therapy in general is still regarded as experimental and is not recommended, Dr. Auchus said. The authors encouraged pregnant women who are considering prenatal treatment of CAH to go through Institutional Review Board–approved centers that can obtain outcomes. Pregnant women should not receive a glucocorticoid that traverses the placenta, such as dexamethasone.

Classical CAH should be treated with hydrocortisone maintenance therapy, while nonclassic CAH patients should receive glucocorticoid treatment, such as in cases of early onset and rapid progression of pubarche or bone age in children and overt virilization in adolescents.

Dr. Auchus said the new guidelines have been reorganized so information is easier to find, with recommendations beginning at birth before transitioning into recommendations for childhood and adulthood.

“I think the pediatric endocrinologists are familiar with the management of this disease, but I think a lot of the internal medicine endocrinologists don’t get much training in fellowships, and I think it will be easy for them now to find the information,” Dr. Auchus said. “[I]n the previous set of guidelines, it would’ve been difficult for them to find the information that’s scattered throughout.”

However, Dr. Auchus noted, the guidelines were careful to avoid recommendations of specific levels for analyzing biomarkers for monitoring treatment and specific doses. “[W]e gave some general ideas about ranges: that they should be low, they should be normal, they should be not very high, but it’s okay if it’s a little bit high,” he added.

Also, the evidence for the recommendations is limited to best practice guidelines because of a lack of randomized controlled trials, he noted.

“We certainly do need additional long-term data on these patients,” Dr. Auchus said. “[I]t’s our hope that with some of the networks that have been developed for studying adrenal diseases that we can collect that information in a minimally intrusive way for the benefit of all the current and future patients.”

The guidelines were funded by the Intramural Research Program of the National Institutes of Health. The authors report various personal and organizational financial interests in the form of paid consultancies, researcher support positions, advisory board memberships and investigator roles. See the full study for a complete list of disclosures.

SOURCE: Speiser PW et al. J Clin Endocrinol Metab. 2018 Sep 27. doi: 10.1210/jc.2018-01865.

Half of outpatient antibiotics are prescribed with no infectious disease code: Jeffery Linder, MD, MPH. Also today, how to vaccinate patients who are on biologics, opiate use is tied to hepatitis C risk in youth, and for patients with rosacea, a single treatment may not be enough.
Apple Podcasts
Spotify

Half of outpatient antibiotics are prescribed with no infectious disease code: Jeffery Linder, MD, MPH. Also today, how to vaccinate patients who are on biologics, opiate use is tied to hepatitis C risk in youth, and for patients with rosacea, a single treatment may not be enough.
Apple Podcasts
Spotify

Half of outpatient antibiotics are prescribed with no infectious disease code: Jeffery Linder, MD, MPH. Also today, how to vaccinate patients who are on biologics, opiate use is tied to hepatitis C risk in youth, and for patients with rosacea, a single treatment may not be enough.
Apple Podcasts
Spotify

Marko Lucijanić, MD, PhD

DUBROVNIK, CROATIA—The Glasgow Prognostic Score (GPS) may predict survival in patients with myelofibrosis (MF), according to research presented at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

In a retrospective study, MF patients who were considered intermediate-risk according to the GPS had roughly twice the risk of death as good-risk patients.

High-risk patients had a nearly 24-fold greater risk of death than good-risk patients.

Marko Lucijanić, MD, PhD, of the University Hospital Dubrava in Zagreb, Croatia, presented these findings at the meeting. Results were also published in a recent issue of Blood Cells, Molecules, and Diseases.¹

Dr. Lucijanić and his colleagues analyzed 88 patients—67 with primary MF and 21 with secondary MF—who were treated at the University Hospital Dubrava from 2004 to 2018.

Patients were divided into GPS risk categories:

• Good-risk patients had C reactive protein (CRP) ≤10 mg/L and albumin ≥35 g/L
• Intermediate-risk patients had either CRP >10 mg/L or albumin <35 g/L
• Poor-risk patients had both CRP >10 mg/L and albumin <35 g/L.

Results

The researchers found that CRP and albumin were independent predictors of overall survival (OS) in MF.

“What we saw is that both CRP and albumin were univariately associated with inferior overall survival when the patients were divided at the proposed cutoff levels,” Dr. Lucijanić said.

“And both CRP and albumin remained statistically significant when analyzed together in a Cox regression model additionally adjusted for DIPPS [Dynamic International Prognostic Scoring System].”

In the univariate analysis, the hazard ratio (HR) for death was 3.42 (P<0.001) for patients with CRP >10 mg/L and 4.68 (P<0.001) for patients with albumin <35 g/L.

In a multivariate analysis, the HR for death was 2.49 (P=0.013) for patients with CRP >10 mg/L and 2.74 (P=0.031) for patients with albumin <35 g/L.

“So no surprise that, when [CRP and albumin were] combined into the Glasgow Prognostic Score, the GPS could identify three subgroups of patients with distinct prognosis,” Dr. Lucijanić said.

When the researchers assessed OS according to GPS, they found the HR for death was:

• 2.77 for intermediate-risk patients compared to good-risk patients (P<0.001).
• 15.78 for poor-risk patients compared to good-risk patients (P<0.001).
• 5.82 for poor-risk patients compared to intermediate-risk patients (P<0.001).

In a Cox-regression model for OS that was adjusted for DIPPS, age, and gender, the HR was:

• 2.08 for intermediate-risk patients compared to good-risk patients (P=0.040)
• 23.52 for poor-risk patients compared to good-risk patients (P<0.001).

Dr. Lucijanić noted that patients who were intermediate- or poor-risk according to the GPS were more likely to have symptoms of aggressive disease that are associated with non-response to JAK inhibitors.

The intermediate- or poor-risk patients were more likely to have constitutional symptoms, massive splenomegaly, blast phase disease, circulatory blasts, higher absolute monocyte counts, lower hemoglobin, lower platelets, higher lactate dehydrogenase, higher red cell distribution width, transfusion dependency, and higher ferritin. The patients also had higher DIPSS scores.

“So, to summarize, higher GPS recognizes patients with more aggressive disease features at a higher risk of death,” Dr. Lucijanić said. “And not only does it discriminate survival of myelofibrosis patients, it seems to do so in a DIPPS-independent manner. However, you should be aware that this is a small, retrospective study from a single center with a very long follow-up period during which patients were exposed to different types of therapies.”

Dr. Lucijanić did not declare any conflicts of interest.

1. Lucijanić M et al. Blood Cells Mol Dis. 2018 Sep;72:14-16. doi: 10.1016/j.bcmd.2018.06.001.

Marko Lucijanić, MD, PhD

DUBROVNIK, CROATIA—The Glasgow Prognostic Score (GPS) may predict survival in patients with myelofibrosis (MF), according to research presented at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

In a retrospective study, MF patients who were considered intermediate-risk according to the GPS had roughly twice the risk of death as good-risk patients.

High-risk patients had a nearly 24-fold greater risk of death than good-risk patients.

Marko Lucijanić, MD, PhD, of the University Hospital Dubrava in Zagreb, Croatia, presented these findings at the meeting. Results were also published in a recent issue of Blood Cells, Molecules, and Diseases.¹

Dr. Lucijanić and his colleagues analyzed 88 patients—67 with primary MF and 21 with secondary MF—who were treated at the University Hospital Dubrava from 2004 to 2018.

Patients were divided into GPS risk categories:

• Good-risk patients had C reactive protein (CRP) ≤10 mg/L and albumin ≥35 g/L
• Intermediate-risk patients had either CRP >10 mg/L or albumin <35 g/L
• Poor-risk patients had both CRP >10 mg/L and albumin <35 g/L.

Results

The researchers found that CRP and albumin were independent predictors of overall survival (OS) in MF.

“What we saw is that both CRP and albumin were univariately associated with inferior overall survival when the patients were divided at the proposed cutoff levels,” Dr. Lucijanić said.

“And both CRP and albumin remained statistically significant when analyzed together in a Cox regression model additionally adjusted for DIPPS [Dynamic International Prognostic Scoring System].”

In the univariate analysis, the hazard ratio (HR) for death was 3.42 (P<0.001) for patients with CRP >10 mg/L and 4.68 (P<0.001) for patients with albumin <35 g/L.

In a multivariate analysis, the HR for death was 2.49 (P=0.013) for patients with CRP >10 mg/L and 2.74 (P=0.031) for patients with albumin <35 g/L.

“So no surprise that, when [CRP and albumin were] combined into the Glasgow Prognostic Score, the GPS could identify three subgroups of patients with distinct prognosis,” Dr. Lucijanić said.

When the researchers assessed OS according to GPS, they found the HR for death was:

• 2.77 for intermediate-risk patients compared to good-risk patients (P<0.001).
• 15.78 for poor-risk patients compared to good-risk patients (P<0.001).
• 5.82 for poor-risk patients compared to intermediate-risk patients (P<0.001).

In a Cox-regression model for OS that was adjusted for DIPPS, age, and gender, the HR was:

• 2.08 for intermediate-risk patients compared to good-risk patients (P=0.040)
• 23.52 for poor-risk patients compared to good-risk patients (P<0.001).

Dr. Lucijanić noted that patients who were intermediate- or poor-risk according to the GPS were more likely to have symptoms of aggressive disease that are associated with non-response to JAK inhibitors.

The intermediate- or poor-risk patients were more likely to have constitutional symptoms, massive splenomegaly, blast phase disease, circulatory blasts, higher absolute monocyte counts, lower hemoglobin, lower platelets, higher lactate dehydrogenase, higher red cell distribution width, transfusion dependency, and higher ferritin. The patients also had higher DIPSS scores.

“So, to summarize, higher GPS recognizes patients with more aggressive disease features at a higher risk of death,” Dr. Lucijanić said. “And not only does it discriminate survival of myelofibrosis patients, it seems to do so in a DIPPS-independent manner. However, you should be aware that this is a small, retrospective study from a single center with a very long follow-up period during which patients were exposed to different types of therapies.”

Dr. Lucijanić did not declare any conflicts of interest.

1. Lucijanić M et al. Blood Cells Mol Dis. 2018 Sep;72:14-16. doi: 10.1016/j.bcmd.2018.06.001.

Marko Lucijanić, MD, PhD

DUBROVNIK, CROATIA—The Glasgow Prognostic Score (GPS) may predict survival in patients with myelofibrosis (MF), according to research presented at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

In a retrospective study, MF patients who were considered intermediate-risk according to the GPS had roughly twice the risk of death as good-risk patients.

High-risk patients had a nearly 24-fold greater risk of death than good-risk patients.

Marko Lucijanić, MD, PhD, of the University Hospital Dubrava in Zagreb, Croatia, presented these findings at the meeting. Results were also published in a recent issue of Blood Cells, Molecules, and Diseases.¹

Dr. Lucijanić and his colleagues analyzed 88 patients—67 with primary MF and 21 with secondary MF—who were treated at the University Hospital Dubrava from 2004 to 2018.

Patients were divided into GPS risk categories:

• Good-risk patients had C reactive protein (CRP) ≤10 mg/L and albumin ≥35 g/L
• Intermediate-risk patients had either CRP >10 mg/L or albumin <35 g/L
• Poor-risk patients had both CRP >10 mg/L and albumin <35 g/L.

Results

The researchers found that CRP and albumin were independent predictors of overall survival (OS) in MF.

“What we saw is that both CRP and albumin were univariately associated with inferior overall survival when the patients were divided at the proposed cutoff levels,” Dr. Lucijanić said.

“And both CRP and albumin remained statistically significant when analyzed together in a Cox regression model additionally adjusted for DIPPS [Dynamic International Prognostic Scoring System].”

In the univariate analysis, the hazard ratio (HR) for death was 3.42 (P<0.001) for patients with CRP >10 mg/L and 4.68 (P<0.001) for patients with albumin <35 g/L.

In a multivariate analysis, the HR for death was 2.49 (P=0.013) for patients with CRP >10 mg/L and 2.74 (P=0.031) for patients with albumin <35 g/L.

“So no surprise that, when [CRP and albumin were] combined into the Glasgow Prognostic Score, the GPS could identify three subgroups of patients with distinct prognosis,” Dr. Lucijanić said.

When the researchers assessed OS according to GPS, they found the HR for death was:

• 2.77 for intermediate-risk patients compared to good-risk patients (P<0.001).
• 15.78 for poor-risk patients compared to good-risk patients (P<0.001).
• 5.82 for poor-risk patients compared to intermediate-risk patients (P<0.001).

In a Cox-regression model for OS that was adjusted for DIPPS, age, and gender, the HR was:

• 2.08 for intermediate-risk patients compared to good-risk patients (P=0.040)
• 23.52 for poor-risk patients compared to good-risk patients (P<0.001).

Dr. Lucijanić noted that patients who were intermediate- or poor-risk according to the GPS were more likely to have symptoms of aggressive disease that are associated with non-response to JAK inhibitors.

The intermediate- or poor-risk patients were more likely to have constitutional symptoms, massive splenomegaly, blast phase disease, circulatory blasts, higher absolute monocyte counts, lower hemoglobin, lower platelets, higher lactate dehydrogenase, higher red cell distribution width, transfusion dependency, and higher ferritin. The patients also had higher DIPSS scores.

“So, to summarize, higher GPS recognizes patients with more aggressive disease features at a higher risk of death,” Dr. Lucijanić said. “And not only does it discriminate survival of myelofibrosis patients, it seems to do so in a DIPPS-independent manner. However, you should be aware that this is a small, retrospective study from a single center with a very long follow-up period during which patients were exposed to different types of therapies.”

Dr. Lucijanić did not declare any conflicts of interest.

1. Lucijanić M et al. Blood Cells Mol Dis. 2018 Sep;72:14-16. doi: 10.1016/j.bcmd.2018.06.001.

Micrograph showing MM

The U.S. Food and Drug Administration (FDA) has accepted for priority review the new drug application (NDA) for selinexor.

With this NDA, Karyopharm Therapeutics Inc., is seeking accelerated approval for selinexor, an oral selective inhibitor of nuclear export compound, as a treatment for penta-refractory multiple myeloma (MM).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

The FDA plans to make a decision on the NDA for selinexor by April 6, 2019.

Selinexor also has orphan drug and fast track designations from the FDA for the treatment of penta-refractory MM.

Selinexor has demonstrated a clinical benefit in penta-refractory MM patients in the phase 2 STORM trial, according to researchers.

Results from this trial were recently presented at the Society of Hematologic Oncology (SOHO) 2018 Annual Meeting.

STORM included 122 patients with penta-refractory MM. They received selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression.

Two patients (1.6%) achieved stringent complete responses (with minimal residual disease negativity), six patients (4.9%) had very good partial responses, 24 (19.7%) had partial responses, and 16 (13.1%) had minimal responses.

Forty-eight patients (39.3%) had stable disease, 16 (13.1%) had progressive disease, and 10 (8.2%) were not evaluable for response.

The median progression-free survival was 3.7 months, and the median overall survival was 8.6 months.

Common treatment-related adverse events included fatigue/asthenia (69.9%), nausea (69.1%), thrombocytopenia (67.5%), anorexia (52.0%), anemia (48.0%), weight loss (47.2%), neutropenia (35.8%), vomiting (35.0%), diarrhea (33.3%), hyponatremia (30.9%), leukopenia (29.3%), and lymphopenia (13.8%).

Trials of selinexor were placed on partial clinical hold in March 2017 due to a lack of information about serious adverse events. However, the hold was lifted for trials of patients with hematologic malignancies at the end of that same month.

Micrograph showing MM

The U.S. Food and Drug Administration (FDA) has accepted for priority review the new drug application (NDA) for selinexor.

With this NDA, Karyopharm Therapeutics Inc., is seeking accelerated approval for selinexor, an oral selective inhibitor of nuclear export compound, as a treatment for penta-refractory multiple myeloma (MM).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

The FDA plans to make a decision on the NDA for selinexor by April 6, 2019.

Selinexor also has orphan drug and fast track designations from the FDA for the treatment of penta-refractory MM.

Selinexor has demonstrated a clinical benefit in penta-refractory MM patients in the phase 2 STORM trial, according to researchers.

Results from this trial were recently presented at the Society of Hematologic Oncology (SOHO) 2018 Annual Meeting.

STORM included 122 patients with penta-refractory MM. They received selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression.

Two patients (1.6%) achieved stringent complete responses (with minimal residual disease negativity), six patients (4.9%) had very good partial responses, 24 (19.7%) had partial responses, and 16 (13.1%) had minimal responses.

Forty-eight patients (39.3%) had stable disease, 16 (13.1%) had progressive disease, and 10 (8.2%) were not evaluable for response.

The median progression-free survival was 3.7 months, and the median overall survival was 8.6 months.

Common treatment-related adverse events included fatigue/asthenia (69.9%), nausea (69.1%), thrombocytopenia (67.5%), anorexia (52.0%), anemia (48.0%), weight loss (47.2%), neutropenia (35.8%), vomiting (35.0%), diarrhea (33.3%), hyponatremia (30.9%), leukopenia (29.3%), and lymphopenia (13.8%).

Trials of selinexor were placed on partial clinical hold in March 2017 due to a lack of information about serious adverse events. However, the hold was lifted for trials of patients with hematologic malignancies at the end of that same month.

Micrograph showing MM

The U.S. Food and Drug Administration (FDA) has accepted for priority review the new drug application (NDA) for selinexor.

With this NDA, Karyopharm Therapeutics Inc., is seeking accelerated approval for selinexor, an oral selective inhibitor of nuclear export compound, as a treatment for penta-refractory multiple myeloma (MM).

The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.

The agency intends to take action on a priority review application within 6 months of receiving it rather than the standard 10 months.

The FDA plans to make a decision on the NDA for selinexor by April 6, 2019.

Selinexor also has orphan drug and fast track designations from the FDA for the treatment of penta-refractory MM.

Selinexor has demonstrated a clinical benefit in penta-refractory MM patients in the phase 2 STORM trial, according to researchers.

Results from this trial were recently presented at the Society of Hematologic Oncology (SOHO) 2018 Annual Meeting.

STORM included 122 patients with penta-refractory MM. They received selinexor at 80 mg twice weekly plus dexamethasone at 20 mg twice weekly until disease progression.

Two patients (1.6%) achieved stringent complete responses (with minimal residual disease negativity), six patients (4.9%) had very good partial responses, 24 (19.7%) had partial responses, and 16 (13.1%) had minimal responses.

Forty-eight patients (39.3%) had stable disease, 16 (13.1%) had progressive disease, and 10 (8.2%) were not evaluable for response.

The median progression-free survival was 3.7 months, and the median overall survival was 8.6 months.

Common treatment-related adverse events included fatigue/asthenia (69.9%), nausea (69.1%), thrombocytopenia (67.5%), anorexia (52.0%), anemia (48.0%), weight loss (47.2%), neutropenia (35.8%), vomiting (35.0%), diarrhea (33.3%), hyponatremia (30.9%), leukopenia (29.3%), and lymphopenia (13.8%).

Trials of selinexor were placed on partial clinical hold in March 2017 due to a lack of information about serious adverse events. However, the hold was lifted for trials of patients with hematologic malignancies at the end of that same month.

ANSWER

The radiograph demonstrates an abnormal-appearing patella; there is a longitudinal lucency along the lateral portion. There is some mild soft-tissue swelling but no evidence of a definite joint effusion. The lucency could represent a fracture, especially in the setting of trauma. The other possibility is that the patient has a bipartite patella. This is a rare congenital condition in which the patella does not completely fuse; it remains two separate bones. CT of the knee for further evaluation, as well as orthopedic consultation, were ordered.

ANSWER

The radiograph demonstrates an abnormal-appearing patella; there is a longitudinal lucency along the lateral portion. There is some mild soft-tissue swelling but no evidence of a definite joint effusion. The lucency could represent a fracture, especially in the setting of trauma. The other possibility is that the patient has a bipartite patella. This is a rare congenital condition in which the patella does not completely fuse; it remains two separate bones. CT of the knee for further evaluation, as well as orthopedic consultation, were ordered.

ANSWER

The radiograph demonstrates an abnormal-appearing patella; there is a longitudinal lucency along the lateral portion. There is some mild soft-tissue swelling but no evidence of a definite joint effusion. The lucency could represent a fracture, especially in the setting of trauma. The other possibility is that the patient has a bipartite patella. This is a rare congenital condition in which the patella does not completely fuse; it remains two separate bones. CT of the knee for further evaluation, as well as orthopedic consultation, were ordered.

Image by Spencer Phillips

DUBROVNIK, CROATIA—New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.

Past studies have shown an association between the PTPN22 R620W variant and both CLL¹ and autoimmune diseases² in patients from Northwest Europe.

However, a study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.

Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.

Therefore, she and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.

The researchers evaluated 320 patients—168 with CLL, 66 with AIHA, and 86 with ITP—and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.

The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients.

Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.

She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.

Dr. Panovska-Stavridis did not declare any conflicts of interest.

1. Hebbring S et al. Blood. 2013 121:237-238; doi: https://doi.org/10.1182/blood-2012-08-450221

2. Burb GL et al. FEBS Lett. 2011 Dec 1;585(23):3689-98. doi: 10.1016/j.febslet.2011.04.032

Image by Spencer Phillips

DUBROVNIK, CROATIA—New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.

Past studies have shown an association between the PTPN22 R620W variant and both CLL¹ and autoimmune diseases² in patients from Northwest Europe.

However, a study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.

Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.

Therefore, she and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.

The researchers evaluated 320 patients—168 with CLL, 66 with AIHA, and 86 with ITP—and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.

The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients.

Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.

She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.

Dr. Panovska-Stavridis did not declare any conflicts of interest.

1. Hebbring S et al. Blood. 2013 121:237-238; doi: https://doi.org/10.1182/blood-2012-08-450221

2. Burb GL et al. FEBS Lett. 2011 Dec 1;585(23):3689-98. doi: 10.1016/j.febslet.2011.04.032

Image by Spencer Phillips

DUBROVNIK, CROATIA—New research suggests there is no association between the PTPN22 R620W polymorphism and chronic lymphocytic leukemia (CLL) or autoimmune hematologic disorders in patients from the Republic of Macedonia.

Past studies have shown an association between the PTPN22 R620W variant and both CLL¹ and autoimmune diseases² in patients from Northwest Europe.

However, a study of Macedonian patients suggests there is no association between the variant and CLL, autoimmune hemolytic anemia (AIHA), or idiopathic thrombocytopenic purpura (ITP) for patients from Southeast Europe.

Irina Panovska-Stavridis, PhD, of Ss. Cyril and Methodius University in Skopje, Republic of Macedonia, and her colleagues presented this finding at Leukemia and Lymphoma: Europe and the USA, Linking Knowledge and Practice.

“A lot of data from the literature suggests [the PTPN22 R620W variant ] has a role in developing multiple immune diseases, but it is validated just in patients from Northwest Europe,” Dr. Panovska-Stavridis noted.

Therefore, she and her colleagues decided to assess the frequency of the PTPN22 R620W variant (C1858T, rs2476601) in individuals from Southeast Europe, particularly the Republic of Macedonia.

The researchers evaluated 320 patients—168 with CLL, 66 with AIHA, and 86 with ITP—and 182 age- and sex-matched control subjects with no history of malignant or autoimmune disease.

The team found a similar frequency of the minor T allele and genotype distribution in control subjects and patients.

Dr. Panovska-Stavridis said these results suggest the PTPN22 R620W variant is not a risk factor for the development of CLL, AIHA, or ITP in patients from Southeast Europe.

She also said the results suggest the influence of the variant on lymphocytic homeostasis is affected by certain genetic and environmental factors, and the development of CLL and autoimmune diseases is influenced by race/ethnicity-based variations in the germline composition of the IGHV locus in correlation with environmental factors.

Dr. Panovska-Stavridis did not declare any conflicts of interest.

1. Hebbring S et al. Blood. 2013 121:237-238; doi: https://doi.org/10.1182/blood-2012-08-450221

2. Burb GL et al. FEBS Lett. 2011 Dec 1;585(23):3689-98. doi: 10.1016/j.febslet.2011.04.032

SAN ANTONIO – Therapy Animals of San Antonio, a non-profit organization that trains and places therapy pets, delighted the attendees of CHEST 2018 with a number of therapy dogs. Christopher L. Carroll, MD, FCCP, and Kathy Jewett, CHEST Director, Membership and Brand Development, spoke about the many benefits pets can bring to patients, including stress reduction and emotional comfort. The therapy dogs also will be visiting the CHEST 2018 meeting on Tuesday and Wednesday, 11:30 a.m. to 1:30 p.m., in the Exhibit Hall.

[email protected]

SAN ANTONIO – Therapy Animals of San Antonio, a non-profit organization that trains and places therapy pets, delighted the attendees of CHEST 2018 with a number of therapy dogs. Christopher L. Carroll, MD, FCCP, and Kathy Jewett, CHEST Director, Membership and Brand Development, spoke about the many benefits pets can bring to patients, including stress reduction and emotional comfort. The therapy dogs also will be visiting the CHEST 2018 meeting on Tuesday and Wednesday, 11:30 a.m. to 1:30 p.m., in the Exhibit Hall.

[email protected]

SAN ANTONIO – Therapy Animals of San Antonio, a non-profit organization that trains and places therapy pets, delighted the attendees of CHEST 2018 with a number of therapy dogs. Christopher L. Carroll, MD, FCCP, and Kathy Jewett, CHEST Director, Membership and Brand Development, spoke about the many benefits pets can bring to patients, including stress reduction and emotional comfort. The therapy dogs also will be visiting the CHEST 2018 meeting on Tuesday and Wednesday, 11:30 a.m. to 1:30 p.m., in the Exhibit Hall.

[email protected]

CHICAGO – A common reason why a women stops breastfeeding is the use of medication her doctor has claimed is unsafe during lactation. But most drugs have little or no effect on an infant’s well-being or milk supply, explained Jenny Eileen Murase, MD, of Palo Alto (Calif.) Foundation Medical Group.

“The bottom line I want you to take away from this [session] is that the vast majority of the medicines you are prescribing as a dermatologist are safe during lactation,” Dr. Murase told attendees at the American Academy of Dermatology summer meeting. “I really want everyone in this room to understand that most of the time, you should not be recommending that a woman is pumping and dumping her milk or stopping breastfeeding because she’s on an agent.”

Dr. Murase, also affiliated with the University of California, San Francisco, provided an overview of drug safety during lactation for major categories of medications that dermatologists prescribe. She recommended that physicians get a copy of Medications and Mother’s Milk by Thomas Hale, PhD, which she considers the best reference for looking up specific drugs. It categorizes drugs as L1 (safest) to L5 (contraindicated), and L2 as “safer,” L3 as “moderately safe,” and L4 as “possibly hazardous.”

Steroids

Contrary to what many believe, prednisone is not contraindicated in breastfeeding, Dr. Murase said. Instead of advising patients to “pump and dump their milk,” she said, “the only recommendation you need to make is that they wait 4 hours after taking the medicine to breastfeed.” For example, a mother can take prednisone before bed and then wake 4 hours later to nurse. Higher doses, such as more than 40 mg daily over long periods, may have the potential to affect growth and development, but more typical doses don’t pose the same risk.

Topical steroids (except for those that are class 1) also are safe to apply directly to the nipple in breastfeeding women, she noted.

Biologics and immunosuppressants

One of the few medications that are contraindicated are topical pimecrolimus and tacrolimus if applied directly to the nipple, since “oral consumption in the infant could be significant,” Dr. Murase said.

Biologics, on the other hand, are not a concern during lactation. “They have low oral bioavailability because of their large molecular size,” and are broken down in the stomach “in a proteolytic environment,” Dr. Murase explained. The CRADLE study, for example, examined the concentration of certolizumab (Cimzia) in mothers’ mature breast milk and found the highest concentration to be just 0.077 mcg/mL, resulting in an average daily infant dose of less than 0.01 mg/kg per day.

Antihistamines and cosmetic topicals

The major antihistamines – brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, cetirizine, fexofenadine and loratadine – are likewise safe as L1-L3 drugs. It is preferable to prescribe nonsedating antihistamines, opting for loratadine as the first-line choice. But dermatologists should be reassured that no data support concerns about milk supply reduction from antihistamines, Dr. Murase said.

It’s best to avoid cosmetic topical products, but hydroquinone (L3), topical minoxidil (L2), and botulinum toxin A (L3) do not pose significant risk to the infant. Neither do the anesthetics lidocaine (L2) and epinephrine (L1) for breastfeeding women who need surgery.

Antibiotics

The vast majority of antibiotics are safe for women to use while breastfeeding, but a few notable exceptions exist, including erythromycin.

“People associate erythromycin as safe in lactation because it’s safe in pregnancy, but that’s not the case,” Dr. Murase pointed out. Erythromycin has been linked to pyloric stenosis in newborns and therefore should be avoided in the early months of breastfeeding. In older infants, however, erythromycin becomes an L1 medication.”

Tetracyclines fall into a borderline category. “Tetracyclines would be fine for a complicated infection,” but should not be used for more than 3 weeks, at which point they are regarded as L4, Dr. Murase said. “So long-term use of the tetracyclines should be avoided.”

Aside from these, topical antibiotics are considered safe. Women taking other oral antibiotics should be monitored for gastrointestinal symptoms or allergic responses.

Antifungals

As for antifungals, topicals are safe, and nystatin and clotrimazole are the best first-line options (both L1). Oral antifungals are similarly fine, with griseofulvin, fluconazole, ketoconazole, itraconazole, and terbinafine all classified as L2 and amphotericin B as L3.

If antifungals or antibiotics are being prescribed for a breast fungal infection or for mastitis, Dr. Murase underscored the importance of not stopping breastfeeding.

“The most important thing is that they continue to actually breastfeed on the affected breast that has the staph infection,” she said. She then reiterated that physicians should “reassure new mothers that the majority of oral and topical medications are safe.”

Dr. Murase disclosed serving on the advisory boards of Dermira, UCB, and Genzyme/Sanofi, and she has consulted for Ferndale and UpToDate.

CHICAGO – A common reason why a women stops breastfeeding is the use of medication her doctor has claimed is unsafe during lactation. But most drugs have little or no effect on an infant’s well-being or milk supply, explained Jenny Eileen Murase, MD, of Palo Alto (Calif.) Foundation Medical Group.

“The bottom line I want you to take away from this [session] is that the vast majority of the medicines you are prescribing as a dermatologist are safe during lactation,” Dr. Murase told attendees at the American Academy of Dermatology summer meeting. “I really want everyone in this room to understand that most of the time, you should not be recommending that a woman is pumping and dumping her milk or stopping breastfeeding because she’s on an agent.”

Dr. Murase, also affiliated with the University of California, San Francisco, provided an overview of drug safety during lactation for major categories of medications that dermatologists prescribe. She recommended that physicians get a copy of Medications and Mother’s Milk by Thomas Hale, PhD, which she considers the best reference for looking up specific drugs. It categorizes drugs as L1 (safest) to L5 (contraindicated), and L2 as “safer,” L3 as “moderately safe,” and L4 as “possibly hazardous.”

Steroids

Contrary to what many believe, prednisone is not contraindicated in breastfeeding, Dr. Murase said. Instead of advising patients to “pump and dump their milk,” she said, “the only recommendation you need to make is that they wait 4 hours after taking the medicine to breastfeed.” For example, a mother can take prednisone before bed and then wake 4 hours later to nurse. Higher doses, such as more than 40 mg daily over long periods, may have the potential to affect growth and development, but more typical doses don’t pose the same risk.

Topical steroids (except for those that are class 1) also are safe to apply directly to the nipple in breastfeeding women, she noted.

Biologics and immunosuppressants

One of the few medications that are contraindicated are topical pimecrolimus and tacrolimus if applied directly to the nipple, since “oral consumption in the infant could be significant,” Dr. Murase said.

Biologics, on the other hand, are not a concern during lactation. “They have low oral bioavailability because of their large molecular size,” and are broken down in the stomach “in a proteolytic environment,” Dr. Murase explained. The CRADLE study, for example, examined the concentration of certolizumab (Cimzia) in mothers’ mature breast milk and found the highest concentration to be just 0.077 mcg/mL, resulting in an average daily infant dose of less than 0.01 mg/kg per day.

Antihistamines and cosmetic topicals

The major antihistamines – brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, cetirizine, fexofenadine and loratadine – are likewise safe as L1-L3 drugs. It is preferable to prescribe nonsedating antihistamines, opting for loratadine as the first-line choice. But dermatologists should be reassured that no data support concerns about milk supply reduction from antihistamines, Dr. Murase said.

It’s best to avoid cosmetic topical products, but hydroquinone (L3), topical minoxidil (L2), and botulinum toxin A (L3) do not pose significant risk to the infant. Neither do the anesthetics lidocaine (L2) and epinephrine (L1) for breastfeeding women who need surgery.

Antibiotics

The vast majority of antibiotics are safe for women to use while breastfeeding, but a few notable exceptions exist, including erythromycin.

“People associate erythromycin as safe in lactation because it’s safe in pregnancy, but that’s not the case,” Dr. Murase pointed out. Erythromycin has been linked to pyloric stenosis in newborns and therefore should be avoided in the early months of breastfeeding. In older infants, however, erythromycin becomes an L1 medication.”

Tetracyclines fall into a borderline category. “Tetracyclines would be fine for a complicated infection,” but should not be used for more than 3 weeks, at which point they are regarded as L4, Dr. Murase said. “So long-term use of the tetracyclines should be avoided.”

Aside from these, topical antibiotics are considered safe. Women taking other oral antibiotics should be monitored for gastrointestinal symptoms or allergic responses.

Antifungals

As for antifungals, topicals are safe, and nystatin and clotrimazole are the best first-line options (both L1). Oral antifungals are similarly fine, with griseofulvin, fluconazole, ketoconazole, itraconazole, and terbinafine all classified as L2 and amphotericin B as L3.

If antifungals or antibiotics are being prescribed for a breast fungal infection or for mastitis, Dr. Murase underscored the importance of not stopping breastfeeding.

“The most important thing is that they continue to actually breastfeed on the affected breast that has the staph infection,” she said. She then reiterated that physicians should “reassure new mothers that the majority of oral and topical medications are safe.”

Dr. Murase disclosed serving on the advisory boards of Dermira, UCB, and Genzyme/Sanofi, and she has consulted for Ferndale and UpToDate.

CHICAGO – A common reason why a women stops breastfeeding is the use of medication her doctor has claimed is unsafe during lactation. But most drugs have little or no effect on an infant’s well-being or milk supply, explained Jenny Eileen Murase, MD, of Palo Alto (Calif.) Foundation Medical Group.

“The bottom line I want you to take away from this [session] is that the vast majority of the medicines you are prescribing as a dermatologist are safe during lactation,” Dr. Murase told attendees at the American Academy of Dermatology summer meeting. “I really want everyone in this room to understand that most of the time, you should not be recommending that a woman is pumping and dumping her milk or stopping breastfeeding because she’s on an agent.”

Dr. Murase, also affiliated with the University of California, San Francisco, provided an overview of drug safety during lactation for major categories of medications that dermatologists prescribe. She recommended that physicians get a copy of Medications and Mother’s Milk by Thomas Hale, PhD, which she considers the best reference for looking up specific drugs. It categorizes drugs as L1 (safest) to L5 (contraindicated), and L2 as “safer,” L3 as “moderately safe,” and L4 as “possibly hazardous.”

Steroids

Contrary to what many believe, prednisone is not contraindicated in breastfeeding, Dr. Murase said. Instead of advising patients to “pump and dump their milk,” she said, “the only recommendation you need to make is that they wait 4 hours after taking the medicine to breastfeed.” For example, a mother can take prednisone before bed and then wake 4 hours later to nurse. Higher doses, such as more than 40 mg daily over long periods, may have the potential to affect growth and development, but more typical doses don’t pose the same risk.

Topical steroids (except for those that are class 1) also are safe to apply directly to the nipple in breastfeeding women, she noted.

Biologics and immunosuppressants

One of the few medications that are contraindicated are topical pimecrolimus and tacrolimus if applied directly to the nipple, since “oral consumption in the infant could be significant,” Dr. Murase said.

Biologics, on the other hand, are not a concern during lactation. “They have low oral bioavailability because of their large molecular size,” and are broken down in the stomach “in a proteolytic environment,” Dr. Murase explained. The CRADLE study, for example, examined the concentration of certolizumab (Cimzia) in mothers’ mature breast milk and found the highest concentration to be just 0.077 mcg/mL, resulting in an average daily infant dose of less than 0.01 mg/kg per day.

Antihistamines and cosmetic topicals

The major antihistamines – brompheniramine, chlorpheniramine, diphenhydramine, hydroxyzine, cetirizine, fexofenadine and loratadine – are likewise safe as L1-L3 drugs. It is preferable to prescribe nonsedating antihistamines, opting for loratadine as the first-line choice. But dermatologists should be reassured that no data support concerns about milk supply reduction from antihistamines, Dr. Murase said.

It’s best to avoid cosmetic topical products, but hydroquinone (L3), topical minoxidil (L2), and botulinum toxin A (L3) do not pose significant risk to the infant. Neither do the anesthetics lidocaine (L2) and epinephrine (L1) for breastfeeding women who need surgery.

Antibiotics

The vast majority of antibiotics are safe for women to use while breastfeeding, but a few notable exceptions exist, including erythromycin.

“People associate erythromycin as safe in lactation because it’s safe in pregnancy, but that’s not the case,” Dr. Murase pointed out. Erythromycin has been linked to pyloric stenosis in newborns and therefore should be avoided in the early months of breastfeeding. In older infants, however, erythromycin becomes an L1 medication.”

Tetracyclines fall into a borderline category. “Tetracyclines would be fine for a complicated infection,” but should not be used for more than 3 weeks, at which point they are regarded as L4, Dr. Murase said. “So long-term use of the tetracyclines should be avoided.”

Aside from these, topical antibiotics are considered safe. Women taking other oral antibiotics should be monitored for gastrointestinal symptoms or allergic responses.

Antifungals

As for antifungals, topicals are safe, and nystatin and clotrimazole are the best first-line options (both L1). Oral antifungals are similarly fine, with griseofulvin, fluconazole, ketoconazole, itraconazole, and terbinafine all classified as L2 and amphotericin B as L3.

If antifungals or antibiotics are being prescribed for a breast fungal infection or for mastitis, Dr. Murase underscored the importance of not stopping breastfeeding.

“The most important thing is that they continue to actually breastfeed on the affected breast that has the staph infection,” she said. She then reiterated that physicians should “reassure new mothers that the majority of oral and topical medications are safe.”

Dr. Murase disclosed serving on the advisory boards of Dermira, UCB, and Genzyme/Sanofi, and she has consulted for Ferndale and UpToDate.