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FDA aims to squash youth vaping, smoking
The Food and Drug Administration once again has upped the ante in its war on youth smoking and vaping.
“Today, I’m pursuing actions aimed at addressing the disturbing trend of youth nicotine use and continuing to advance the historic declines we’ve achieved in recent years in the rates of combustible cigarette use among kids,” FDA Commissioner Scott Gottlieb, MD, said in a statement.
First and foremost, the FDA wants to reduce the lure of e-cigarettes by limiting the variety of flavored products for sale in retail outlets. Under the proposal unveiled Nov. 15, only electronic nicotine delivery systems (ENDS) that are unflavored or have tobacco, mint, or menthol flavors would be widely available. Flavored products – think cherry, cotton candy, and mango – would be sold in age-restricted environments, such as stand-alone tobacco retailers like vape shops. The FDA also seeks more stringent enforcement of age verification on ENDS products sold online.
The proposal also would reexamine regulations governing flavored cigars, with the possible aim of banning them.
“These efforts to address flavors and protect youth would dramatically impact the ability of American kids to access tobacco products that we know are both appealing and addicting,” Dr. Gottlieb said in a statement. “This policy framework reflects a redoubling of the FDA’s efforts to protect kids from all nicotine-containing products.”
In a move that seems to be aimed at youth-oriented products like Juul, the FDA will be seeking to remove from the market any ENDS product that is marketed specifically to young people.
Finally, the FDA intends to pursue regulation that would ban menthol from combustible tobacco products.
“I believe these menthol-flavored products represent one of the most common and pernicious routes by which kids initiate on combustible cigarettes,” Dr. Gottlieb said. “The menthol serves to mask some of the unattractive features of smoking that might otherwise discourage a child from smoking. Moreover, I believe that menthol products disproportionately and adversely affect underserved communities. And as a matter of public health, they exacerbate troubling disparities in health related to race and socioeconomic status.”
The policy shift comes as the Centers for Disease Control and Prevention released data from the 2018 National Youth Tobacco Survey showing that use of e-cigarettes among high schoolers is on the rise, growing from 1.5% in 2011 to 20.8% in 2018. Middle schoolers saw use over the same time period increase from 0.6% to 4.9%.
The rise of current use of e-cigarettes was enough to reverse a declining trend in overall tobacco use in recent years between 2015 and 2017.
“FDA’s enforcement efforts and policy framework would restrict access to most flavored e-cigarettes and limit the chances of youth beginning to use these products, while ensuring the products are available to adult smokers as an alternative to combustible cigarettes,” Alex M. Azar II, secretary of the Department of Health & Human Services, said in a statement supporting the FDA’s efforts. “Our obligation at HHS is always to the public health, and we believe FDA’s goals strike the right public health balance in addressing the multifaceted challenge we have before us today.”
Under Dr. Gottlieb, the FDA has been aggressively pursuing ways to reduce tobacco consumption, targeting both ENDS and combustible tobacco regulations in an effort to limit nicotine exposure and reduce the number of people addicted to nicotine and the health issues that come with it.
The American College of Cardiology voiced its support of the FDA’s actions.
“The FDA’s announcement restricting the sale of flavored e-cigarettes and other tobacco products shows they are ready to do their part in making tobacco products less available to our children,” ACC President C. Michael Valentine, MD, said in a statement, adding that the medical community needs to continue to do its part to make sure tobacco use continues to decline, especially in the nonadult population.
The FDA proposals were published as part of an advance notice of proposed rulemaking in the Federal Register. Comments can be made at www.regulations.gov through June 19.
The Food and Drug Administration once again has upped the ante in its war on youth smoking and vaping.
“Today, I’m pursuing actions aimed at addressing the disturbing trend of youth nicotine use and continuing to advance the historic declines we’ve achieved in recent years in the rates of combustible cigarette use among kids,” FDA Commissioner Scott Gottlieb, MD, said in a statement.
First and foremost, the FDA wants to reduce the lure of e-cigarettes by limiting the variety of flavored products for sale in retail outlets. Under the proposal unveiled Nov. 15, only electronic nicotine delivery systems (ENDS) that are unflavored or have tobacco, mint, or menthol flavors would be widely available. Flavored products – think cherry, cotton candy, and mango – would be sold in age-restricted environments, such as stand-alone tobacco retailers like vape shops. The FDA also seeks more stringent enforcement of age verification on ENDS products sold online.
The proposal also would reexamine regulations governing flavored cigars, with the possible aim of banning them.
“These efforts to address flavors and protect youth would dramatically impact the ability of American kids to access tobacco products that we know are both appealing and addicting,” Dr. Gottlieb said in a statement. “This policy framework reflects a redoubling of the FDA’s efforts to protect kids from all nicotine-containing products.”
In a move that seems to be aimed at youth-oriented products like Juul, the FDA will be seeking to remove from the market any ENDS product that is marketed specifically to young people.
Finally, the FDA intends to pursue regulation that would ban menthol from combustible tobacco products.
“I believe these menthol-flavored products represent one of the most common and pernicious routes by which kids initiate on combustible cigarettes,” Dr. Gottlieb said. “The menthol serves to mask some of the unattractive features of smoking that might otherwise discourage a child from smoking. Moreover, I believe that menthol products disproportionately and adversely affect underserved communities. And as a matter of public health, they exacerbate troubling disparities in health related to race and socioeconomic status.”
The policy shift comes as the Centers for Disease Control and Prevention released data from the 2018 National Youth Tobacco Survey showing that use of e-cigarettes among high schoolers is on the rise, growing from 1.5% in 2011 to 20.8% in 2018. Middle schoolers saw use over the same time period increase from 0.6% to 4.9%.
The rise of current use of e-cigarettes was enough to reverse a declining trend in overall tobacco use in recent years between 2015 and 2017.
“FDA’s enforcement efforts and policy framework would restrict access to most flavored e-cigarettes and limit the chances of youth beginning to use these products, while ensuring the products are available to adult smokers as an alternative to combustible cigarettes,” Alex M. Azar II, secretary of the Department of Health & Human Services, said in a statement supporting the FDA’s efforts. “Our obligation at HHS is always to the public health, and we believe FDA’s goals strike the right public health balance in addressing the multifaceted challenge we have before us today.”
Under Dr. Gottlieb, the FDA has been aggressively pursuing ways to reduce tobacco consumption, targeting both ENDS and combustible tobacco regulations in an effort to limit nicotine exposure and reduce the number of people addicted to nicotine and the health issues that come with it.
The American College of Cardiology voiced its support of the FDA’s actions.
“The FDA’s announcement restricting the sale of flavored e-cigarettes and other tobacco products shows they are ready to do their part in making tobacco products less available to our children,” ACC President C. Michael Valentine, MD, said in a statement, adding that the medical community needs to continue to do its part to make sure tobacco use continues to decline, especially in the nonadult population.
The FDA proposals were published as part of an advance notice of proposed rulemaking in the Federal Register. Comments can be made at www.regulations.gov through June 19.
The Food and Drug Administration once again has upped the ante in its war on youth smoking and vaping.
“Today, I’m pursuing actions aimed at addressing the disturbing trend of youth nicotine use and continuing to advance the historic declines we’ve achieved in recent years in the rates of combustible cigarette use among kids,” FDA Commissioner Scott Gottlieb, MD, said in a statement.
First and foremost, the FDA wants to reduce the lure of e-cigarettes by limiting the variety of flavored products for sale in retail outlets. Under the proposal unveiled Nov. 15, only electronic nicotine delivery systems (ENDS) that are unflavored or have tobacco, mint, or menthol flavors would be widely available. Flavored products – think cherry, cotton candy, and mango – would be sold in age-restricted environments, such as stand-alone tobacco retailers like vape shops. The FDA also seeks more stringent enforcement of age verification on ENDS products sold online.
The proposal also would reexamine regulations governing flavored cigars, with the possible aim of banning them.
“These efforts to address flavors and protect youth would dramatically impact the ability of American kids to access tobacco products that we know are both appealing and addicting,” Dr. Gottlieb said in a statement. “This policy framework reflects a redoubling of the FDA’s efforts to protect kids from all nicotine-containing products.”
In a move that seems to be aimed at youth-oriented products like Juul, the FDA will be seeking to remove from the market any ENDS product that is marketed specifically to young people.
Finally, the FDA intends to pursue regulation that would ban menthol from combustible tobacco products.
“I believe these menthol-flavored products represent one of the most common and pernicious routes by which kids initiate on combustible cigarettes,” Dr. Gottlieb said. “The menthol serves to mask some of the unattractive features of smoking that might otherwise discourage a child from smoking. Moreover, I believe that menthol products disproportionately and adversely affect underserved communities. And as a matter of public health, they exacerbate troubling disparities in health related to race and socioeconomic status.”
The policy shift comes as the Centers for Disease Control and Prevention released data from the 2018 National Youth Tobacco Survey showing that use of e-cigarettes among high schoolers is on the rise, growing from 1.5% in 2011 to 20.8% in 2018. Middle schoolers saw use over the same time period increase from 0.6% to 4.9%.
The rise of current use of e-cigarettes was enough to reverse a declining trend in overall tobacco use in recent years between 2015 and 2017.
“FDA’s enforcement efforts and policy framework would restrict access to most flavored e-cigarettes and limit the chances of youth beginning to use these products, while ensuring the products are available to adult smokers as an alternative to combustible cigarettes,” Alex M. Azar II, secretary of the Department of Health & Human Services, said in a statement supporting the FDA’s efforts. “Our obligation at HHS is always to the public health, and we believe FDA’s goals strike the right public health balance in addressing the multifaceted challenge we have before us today.”
Under Dr. Gottlieb, the FDA has been aggressively pursuing ways to reduce tobacco consumption, targeting both ENDS and combustible tobacco regulations in an effort to limit nicotine exposure and reduce the number of people addicted to nicotine and the health issues that come with it.
The American College of Cardiology voiced its support of the FDA’s actions.
“The FDA’s announcement restricting the sale of flavored e-cigarettes and other tobacco products shows they are ready to do their part in making tobacco products less available to our children,” ACC President C. Michael Valentine, MD, said in a statement, adding that the medical community needs to continue to do its part to make sure tobacco use continues to decline, especially in the nonadult population.
The FDA proposals were published as part of an advance notice of proposed rulemaking in the Federal Register. Comments can be made at www.regulations.gov through June 19.
MS disease activity returns in one-third after fingolimod withdrawal
BERLIN – At least one-third of patients being treated with fingolimod (Gilenya) for multiple sclerosis (MS) will relapse after stopping the drug, according to data from two “real-world” studies reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis, one of which was undertaken in pregnant women.
In a retrospective analysis of 110 MS patients who discontinued fingolimod from a 433-patient cohort, around 35% experienced a recurrence of disease activity after fingolimod withdrawal. Study investigator Nuria Cerda, MD, of the Neurologic Clinic and Polyclinic at University Hospital Basel (Switzerland), reported that risk factors for increased disease activity were younger rather than older age at MS diagnosis (P = .01) and at discontinuation (P less than .0001), having had a shorter rather than longer disease duration (P = .01), and evidence of MRI-confirmed disease activity occurring while on treatment with fingolimod (P = .02).
“We aimed to describe the frequency of recurrence of disease activity after fingolimod discontinuation in a real-world cohort of MS patients,” Dr. Cerda said. She noted that there were conflicting data on reappearing disease activity after stopping the drug. Case reports and observational data suggest a frequency of 10%-53%, but post hoc analyses of phase 3 trials with fingolimod have not found any higher risk for recurrence versus placebo.
The study also compared “demographic and clinical characteristics in patients with and without recurrence of disease activity, in order to identify possible risk factors for reactivation of the disease.”
The patients included in the study had been treated with fingolimod for a median of 24 months (interquartile range, 10-43 months) and experienced 118 discontinuation events between them. The majority (n = 81) had relapsing-remitting MS, and the remainder (n = 19) were in transition from RRMS to secondary progressive MS.
The mean age at discontinuation was 40 years and, while 60% of patients switched to another disease-modifying therapy (DMT), 40% did not receive further DMT. The reasons for discontinuation were classified as being from disease activity in 44%, side effects in 21%, pregnancy or childbearing preferences in 16%, noncompliance in 2%, and other reasons in 17%.
Recurrence of disease activity was defined as clinical symptoms, gadolinium-enhancing (Gd+) lesions on MRI, or both, within 6 months of stopping fingolimod. This was seen in 38 patients with 41 events, giving a rate of recurrence of 35%. Of these: “almost 60% had clinical and MRI activity, almost 30% had clinical activity only without Gd+ lesions on MRI, and 12% had MRI activity only without ever having a relapse,” Dr. Cerda said. In those who relapsed, the recurrence took a median 8 weeks to happen after fingolimod discontinuation.
A further definition of severe recurrence of disease activity also was used, defined as either a worsening in the Expanded Disability Status Scale (EDSS) score of more than 2 points (signifying a severe relapse) with or without pronounced MRI activity with at least five cerebral Gd+ lesions within 6 months of fingolimod withdrawal. Thirteen severe events were seen in 11 patients, giving a frequency of approximately 11%. Dr. Cerda reported that patients with severe recurrence were significantly younger at MS diagnosis than were those who did not experience recurrence (P = .003). A trend toward a higher annualized relapse rate (ARR) was seen in patients with severely active versus inactive disease (0.84 vs. 0.54), but this was not statistically significant. In addition, “confirmed disability worsening of 1 EDSS point or more was observed in about 3%.”
Relapse rates coming off fingolimod before or during pregnancy
In another study, which used German registry data on 129 pregnancies that occurred around or after the time of fingolimod withdrawal, up to 56% of women who stopped fingolimod before pregnancy experienced a relapse during pregnancy versus 29% of those who stopped fingolimod upon a positive pregnancy test.
In a comparison of women who stopped fingolimod 1 year to 61 days before their last menstrual period against those who stopped less than 60 days prior to or after their last menstrual period, relapse rates were higher during the first (25.8% for early withdrawal vs. 12.5% with late withdrawal) and second trimesters (32.3% vs. 11.5%) than in the third (9.7% vs. 10.4%), Spalmai Hemat, MD, of the department of neurology at St. Josef Hospital, Ruhr University of Bochum (Germany) reported at the congress.
Relapse rates at 6 months postpartum proved to be similar at 36.7% for women who stopped fingolimod before their pregnancy and 38% in those who stopped later. Difference in the percentage of women experiencing disability progression during pregnancy did not prove to be statistically significant for stopping fingolimod before pregnancy (22.7%) vs. stopping later (11.1%; P = .283), while the 23.8% rate of disability progression after pregnancy among women who stopped the drug later versus 13.6% seen with stopping before was also not statistically significant (P = .31). Relapse during pregnancy was the only significant predictor for relapses postpartum.
“The large majority of women did not experience permanent disability,” Dr. Hemat said, but noted that as many as 10%-20% could experience substantial EDSS worsening (2 or more points) at 6 months postpartum.
Dr. Hemat concluded that more data were needed to see if reintroduction of fingolimod very soon after birth, such as within the first 2 weeks, could reduce the postpartum relapse risk.
Dr. Hemat and Dr. Cerda had no relevant disclosures.
SOURCES: Cerda N et al. Mult Scler. 2018;24(S2):73-4, Abstract 206; Hemat S et al. Mult Scler. 2018;24(S2):74-5, Abstract 207.
BERLIN – At least one-third of patients being treated with fingolimod (Gilenya) for multiple sclerosis (MS) will relapse after stopping the drug, according to data from two “real-world” studies reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis, one of which was undertaken in pregnant women.
In a retrospective analysis of 110 MS patients who discontinued fingolimod from a 433-patient cohort, around 35% experienced a recurrence of disease activity after fingolimod withdrawal. Study investigator Nuria Cerda, MD, of the Neurologic Clinic and Polyclinic at University Hospital Basel (Switzerland), reported that risk factors for increased disease activity were younger rather than older age at MS diagnosis (P = .01) and at discontinuation (P less than .0001), having had a shorter rather than longer disease duration (P = .01), and evidence of MRI-confirmed disease activity occurring while on treatment with fingolimod (P = .02).
“We aimed to describe the frequency of recurrence of disease activity after fingolimod discontinuation in a real-world cohort of MS patients,” Dr. Cerda said. She noted that there were conflicting data on reappearing disease activity after stopping the drug. Case reports and observational data suggest a frequency of 10%-53%, but post hoc analyses of phase 3 trials with fingolimod have not found any higher risk for recurrence versus placebo.
The study also compared “demographic and clinical characteristics in patients with and without recurrence of disease activity, in order to identify possible risk factors for reactivation of the disease.”
The patients included in the study had been treated with fingolimod for a median of 24 months (interquartile range, 10-43 months) and experienced 118 discontinuation events between them. The majority (n = 81) had relapsing-remitting MS, and the remainder (n = 19) were in transition from RRMS to secondary progressive MS.
The mean age at discontinuation was 40 years and, while 60% of patients switched to another disease-modifying therapy (DMT), 40% did not receive further DMT. The reasons for discontinuation were classified as being from disease activity in 44%, side effects in 21%, pregnancy or childbearing preferences in 16%, noncompliance in 2%, and other reasons in 17%.
Recurrence of disease activity was defined as clinical symptoms, gadolinium-enhancing (Gd+) lesions on MRI, or both, within 6 months of stopping fingolimod. This was seen in 38 patients with 41 events, giving a rate of recurrence of 35%. Of these: “almost 60% had clinical and MRI activity, almost 30% had clinical activity only without Gd+ lesions on MRI, and 12% had MRI activity only without ever having a relapse,” Dr. Cerda said. In those who relapsed, the recurrence took a median 8 weeks to happen after fingolimod discontinuation.
A further definition of severe recurrence of disease activity also was used, defined as either a worsening in the Expanded Disability Status Scale (EDSS) score of more than 2 points (signifying a severe relapse) with or without pronounced MRI activity with at least five cerebral Gd+ lesions within 6 months of fingolimod withdrawal. Thirteen severe events were seen in 11 patients, giving a frequency of approximately 11%. Dr. Cerda reported that patients with severe recurrence were significantly younger at MS diagnosis than were those who did not experience recurrence (P = .003). A trend toward a higher annualized relapse rate (ARR) was seen in patients with severely active versus inactive disease (0.84 vs. 0.54), but this was not statistically significant. In addition, “confirmed disability worsening of 1 EDSS point or more was observed in about 3%.”
Relapse rates coming off fingolimod before or during pregnancy
In another study, which used German registry data on 129 pregnancies that occurred around or after the time of fingolimod withdrawal, up to 56% of women who stopped fingolimod before pregnancy experienced a relapse during pregnancy versus 29% of those who stopped fingolimod upon a positive pregnancy test.
In a comparison of women who stopped fingolimod 1 year to 61 days before their last menstrual period against those who stopped less than 60 days prior to or after their last menstrual period, relapse rates were higher during the first (25.8% for early withdrawal vs. 12.5% with late withdrawal) and second trimesters (32.3% vs. 11.5%) than in the third (9.7% vs. 10.4%), Spalmai Hemat, MD, of the department of neurology at St. Josef Hospital, Ruhr University of Bochum (Germany) reported at the congress.
Relapse rates at 6 months postpartum proved to be similar at 36.7% for women who stopped fingolimod before their pregnancy and 38% in those who stopped later. Difference in the percentage of women experiencing disability progression during pregnancy did not prove to be statistically significant for stopping fingolimod before pregnancy (22.7%) vs. stopping later (11.1%; P = .283), while the 23.8% rate of disability progression after pregnancy among women who stopped the drug later versus 13.6% seen with stopping before was also not statistically significant (P = .31). Relapse during pregnancy was the only significant predictor for relapses postpartum.
“The large majority of women did not experience permanent disability,” Dr. Hemat said, but noted that as many as 10%-20% could experience substantial EDSS worsening (2 or more points) at 6 months postpartum.
Dr. Hemat concluded that more data were needed to see if reintroduction of fingolimod very soon after birth, such as within the first 2 weeks, could reduce the postpartum relapse risk.
Dr. Hemat and Dr. Cerda had no relevant disclosures.
SOURCES: Cerda N et al. Mult Scler. 2018;24(S2):73-4, Abstract 206; Hemat S et al. Mult Scler. 2018;24(S2):74-5, Abstract 207.
BERLIN – At least one-third of patients being treated with fingolimod (Gilenya) for multiple sclerosis (MS) will relapse after stopping the drug, according to data from two “real-world” studies reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis, one of which was undertaken in pregnant women.
In a retrospective analysis of 110 MS patients who discontinued fingolimod from a 433-patient cohort, around 35% experienced a recurrence of disease activity after fingolimod withdrawal. Study investigator Nuria Cerda, MD, of the Neurologic Clinic and Polyclinic at University Hospital Basel (Switzerland), reported that risk factors for increased disease activity were younger rather than older age at MS diagnosis (P = .01) and at discontinuation (P less than .0001), having had a shorter rather than longer disease duration (P = .01), and evidence of MRI-confirmed disease activity occurring while on treatment with fingolimod (P = .02).
“We aimed to describe the frequency of recurrence of disease activity after fingolimod discontinuation in a real-world cohort of MS patients,” Dr. Cerda said. She noted that there were conflicting data on reappearing disease activity after stopping the drug. Case reports and observational data suggest a frequency of 10%-53%, but post hoc analyses of phase 3 trials with fingolimod have not found any higher risk for recurrence versus placebo.
The study also compared “demographic and clinical characteristics in patients with and without recurrence of disease activity, in order to identify possible risk factors for reactivation of the disease.”
The patients included in the study had been treated with fingolimod for a median of 24 months (interquartile range, 10-43 months) and experienced 118 discontinuation events between them. The majority (n = 81) had relapsing-remitting MS, and the remainder (n = 19) were in transition from RRMS to secondary progressive MS.
The mean age at discontinuation was 40 years and, while 60% of patients switched to another disease-modifying therapy (DMT), 40% did not receive further DMT. The reasons for discontinuation were classified as being from disease activity in 44%, side effects in 21%, pregnancy or childbearing preferences in 16%, noncompliance in 2%, and other reasons in 17%.
Recurrence of disease activity was defined as clinical symptoms, gadolinium-enhancing (Gd+) lesions on MRI, or both, within 6 months of stopping fingolimod. This was seen in 38 patients with 41 events, giving a rate of recurrence of 35%. Of these: “almost 60% had clinical and MRI activity, almost 30% had clinical activity only without Gd+ lesions on MRI, and 12% had MRI activity only without ever having a relapse,” Dr. Cerda said. In those who relapsed, the recurrence took a median 8 weeks to happen after fingolimod discontinuation.
A further definition of severe recurrence of disease activity also was used, defined as either a worsening in the Expanded Disability Status Scale (EDSS) score of more than 2 points (signifying a severe relapse) with or without pronounced MRI activity with at least five cerebral Gd+ lesions within 6 months of fingolimod withdrawal. Thirteen severe events were seen in 11 patients, giving a frequency of approximately 11%. Dr. Cerda reported that patients with severe recurrence were significantly younger at MS diagnosis than were those who did not experience recurrence (P = .003). A trend toward a higher annualized relapse rate (ARR) was seen in patients with severely active versus inactive disease (0.84 vs. 0.54), but this was not statistically significant. In addition, “confirmed disability worsening of 1 EDSS point or more was observed in about 3%.”
Relapse rates coming off fingolimod before or during pregnancy
In another study, which used German registry data on 129 pregnancies that occurred around or after the time of fingolimod withdrawal, up to 56% of women who stopped fingolimod before pregnancy experienced a relapse during pregnancy versus 29% of those who stopped fingolimod upon a positive pregnancy test.
In a comparison of women who stopped fingolimod 1 year to 61 days before their last menstrual period against those who stopped less than 60 days prior to or after their last menstrual period, relapse rates were higher during the first (25.8% for early withdrawal vs. 12.5% with late withdrawal) and second trimesters (32.3% vs. 11.5%) than in the third (9.7% vs. 10.4%), Spalmai Hemat, MD, of the department of neurology at St. Josef Hospital, Ruhr University of Bochum (Germany) reported at the congress.
Relapse rates at 6 months postpartum proved to be similar at 36.7% for women who stopped fingolimod before their pregnancy and 38% in those who stopped later. Difference in the percentage of women experiencing disability progression during pregnancy did not prove to be statistically significant for stopping fingolimod before pregnancy (22.7%) vs. stopping later (11.1%; P = .283), while the 23.8% rate of disability progression after pregnancy among women who stopped the drug later versus 13.6% seen with stopping before was also not statistically significant (P = .31). Relapse during pregnancy was the only significant predictor for relapses postpartum.
“The large majority of women did not experience permanent disability,” Dr. Hemat said, but noted that as many as 10%-20% could experience substantial EDSS worsening (2 or more points) at 6 months postpartum.
Dr. Hemat concluded that more data were needed to see if reintroduction of fingolimod very soon after birth, such as within the first 2 weeks, could reduce the postpartum relapse risk.
Dr. Hemat and Dr. Cerda had no relevant disclosures.
SOURCES: Cerda N et al. Mult Scler. 2018;24(S2):73-4, Abstract 206; Hemat S et al. Mult Scler. 2018;24(S2):74-5, Abstract 207.
REPORTING FROM ECTRIMS 2018
Key clinical point:
Major finding: A higher risk of recurrent disease activity was seen in younger MS patients with shorter disease duration and evidence of disease activity while on fingolimod treatment. Pregnant women who stopped more than 2 months before a planned pregnancy also had a higher risk versus those who stopped after a positive pregnancy test.
Study details: A retrospective analysis of 110 MS patients who discontinued fingolimod from a 433-patient cohort, and German registry data on 129 pregnancies that occurred around or after the time of fingolimod withdrawal.
Disclosures: Dr. Spalmai Hemat and Dr. Nuria Cerda had no relevant disclosures.
Sources: Cerda N et al. Mult Scler. 2018;24(S2):73-4, Abstract 206; Hemat S et al. Mult Scler. 2018;24(S2):74-5, Abstract 207.
Bortezomib may unlock resistance in WM with mutations
The use of bortezomib may help overcome treatment resistance in patients with Waldenström macroglobulinemia (WM) with CXCR4 mutations, according to new research.
Romanos Sklavenitis-Pistofidis, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues compared the effects of treatment with bortezomib/rituximab in patients with WM based on their CXCR4 mutation status. They found no significant difference in progression-free survival (Log-rank, P = .994) or overall survival (Log-rank, P = .407) when comparing patients who have CXCR4 mutations with those who have CXCR4 wild type.
“We report for the first time that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote in Blood. “Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”
The researchers noted, however, that the mechanism at work may be different than that seen with bortezomib in other cancers.
“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma. However, despite the complicated association in those cancer types, in WM there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data,” they wrote.
The researchers recommended that the theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations. Another question to be investigated, they pointed out, is the role of rituximab in the survival results seen in the current analysis.
The study included 63 patients with WM who were treated with bortezomib/rituximab either as upfront treatment or in the relapsed/refractory setting as part of a phase 2 trial.
Bortezomib was given by IV weekly at 1.6 mg/m2 for six cycles and rituximab was given at 375 mg/m2 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.
The researchers excluded 20 patients from the study because of a lack of material for genotyping. However, they noted that their clinical characteristics were not different from those patients who were included.
Out of 43 patients who were genotyped for CXCR4, 17 patients had a mutation. All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations. The median follow-up of the analysis was 90.7 months.
The researchers repeated the analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.
The study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.
SOURCE: Sklavenitis-Pistofidis R et al. Blood. 2018 Oct 26. doi: 10.1182/blood-2018-07-863241.
The use of bortezomib may help overcome treatment resistance in patients with Waldenström macroglobulinemia (WM) with CXCR4 mutations, according to new research.
Romanos Sklavenitis-Pistofidis, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues compared the effects of treatment with bortezomib/rituximab in patients with WM based on their CXCR4 mutation status. They found no significant difference in progression-free survival (Log-rank, P = .994) or overall survival (Log-rank, P = .407) when comparing patients who have CXCR4 mutations with those who have CXCR4 wild type.
“We report for the first time that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote in Blood. “Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”
The researchers noted, however, that the mechanism at work may be different than that seen with bortezomib in other cancers.
“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma. However, despite the complicated association in those cancer types, in WM there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data,” they wrote.
The researchers recommended that the theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations. Another question to be investigated, they pointed out, is the role of rituximab in the survival results seen in the current analysis.
The study included 63 patients with WM who were treated with bortezomib/rituximab either as upfront treatment or in the relapsed/refractory setting as part of a phase 2 trial.
Bortezomib was given by IV weekly at 1.6 mg/m2 for six cycles and rituximab was given at 375 mg/m2 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.
The researchers excluded 20 patients from the study because of a lack of material for genotyping. However, they noted that their clinical characteristics were not different from those patients who were included.
Out of 43 patients who were genotyped for CXCR4, 17 patients had a mutation. All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations. The median follow-up of the analysis was 90.7 months.
The researchers repeated the analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.
The study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.
SOURCE: Sklavenitis-Pistofidis R et al. Blood. 2018 Oct 26. doi: 10.1182/blood-2018-07-863241.
The use of bortezomib may help overcome treatment resistance in patients with Waldenström macroglobulinemia (WM) with CXCR4 mutations, according to new research.
Romanos Sklavenitis-Pistofidis, MD, of the Dana-Farber Cancer Institute in Boston, and his colleagues compared the effects of treatment with bortezomib/rituximab in patients with WM based on their CXCR4 mutation status. They found no significant difference in progression-free survival (Log-rank, P = .994) or overall survival (Log-rank, P = .407) when comparing patients who have CXCR4 mutations with those who have CXCR4 wild type.
“We report for the first time that a bortezomib-based combination is impervious to the impact of CXCR4 mutations in a cohort of patients with WM,” the researchers wrote in Blood. “Previously, we had shown this to be true in WM cell lines, whereby genetically engineering BCWM.1 and MWCL-1 to overexpress CXCR4 had no impact on bortezomib resistance.”
The researchers noted, however, that the mechanism at work may be different than that seen with bortezomib in other cancers.
“Different experiments have linked CXCR4 expression and bortezomib in a variety of ways in other hematological malignancies, including multiple myeloma. However, despite the complicated association in those cancer types, in WM there seems to be a consistently neutral effect of CXCR4 mutations on bortezomib resistance in both cell line and patient data,” they wrote.
The researchers recommended that the theory be tested in a prospective trial of bortezomib-based therapy in WM patients with CXCR4 mutations. Another question to be investigated, they pointed out, is the role of rituximab in the survival results seen in the current analysis.
The study included 63 patients with WM who were treated with bortezomib/rituximab either as upfront treatment or in the relapsed/refractory setting as part of a phase 2 trial.
Bortezomib was given by IV weekly at 1.6 mg/m2 for six cycles and rituximab was given at 375 mg/m2 during cycles one and four. Patients were taken off therapy after two cycles if they had progressive disease.
The researchers excluded 20 patients from the study because of a lack of material for genotyping. However, they noted that their clinical characteristics were not different from those patients who were included.
Out of 43 patients who were genotyped for CXCR4, 17 patients had a mutation. All patients who carried a CXCR4 mutation also had MYD88 L265P. Ten patients had frameshift mutations, one patient had a nonsense mutation, and six patients had missense mutations. The median follow-up of the analysis was 90.7 months.
The researchers repeated the analysis after excluding six patients with missense mutations and accounting for different treatment settings and found that survival remained unchanged.
The study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.
SOURCE: Sklavenitis-Pistofidis R et al. Blood. 2018 Oct 26. doi: 10.1182/blood-2018-07-863241.
FROM BLOOD
Key clinical point:
Major finding: Progression-free and overall survival were not significantly different between WM patients with CXCR4 mutations and those with CXCR4 wild type (log-rank, P = .994 and P = .407, respectively).
Study details: An analysis of 43 WM patients treated with bortezomib/rituximab and genotyped to determine CXCR4 mutation status.
Disclosures: The study was supported by the National Institutes of Health, the Leukemia and Lymphoma Society, and the International Waldenström Macroglobulinemia Foundation. One of the authors reported consulting and research funding from Takeda, which markets bortezomib, and other companies.
Source: Sklavenitis-Pistofidis R et al. Blood. 2018 Oct 26. doi: 10.1182/blood-2018-07-863241.
CKD, and even dialysis, may not be barriers to pregnancy
SAN DIEGO – Nephrologists are often uncomfortable with the idea of advising women with chronic kidney disease (CKD) about pregnancy, a physician told colleagues. They must do better, she said, with sensitivity and insight into once-extreme possibilities like pregnancy during dialysis.
“For many women, having a child is a life goal, and our women with chronic kidney disease are not different,” said Michelle Hladunewich, MD, of Toronto’s Sunnybrook Health Sciences Center. “When we don’t know what we should do, we tend to over-aggressively counsel our women, and that can traumatize them. It’s our role as nephrologists to help them find the safest window to have their pregnancy,” she said at the meeting sponsored by the American Society of Nephrology.
According to Dr. Hladunewich, there are tens of thousands of women of child-bearing age in the United States who have CKD, end-stage renal disease (ESRD), and kidney transplants. However, she said, research presented at Kidney Week 2018 suggested that many nephrologists do not feel confident about counseling patients regarding issues such as pregnancy outcomes in CKD. “We are not that comfortable with it, but we have to become more comfortable,” she said. “We need to be prepared to talk about contraception if they don’t want to have a child or the plan about how to have a child if they do.”
It’s especially important to understand that while women can fear birth defects and the exacerbation of their disease, they may also feel “they’re not fulfilling a societal norm to have a child like everyone else,” she said.
The risks of pregnancy in CKD can affect the mother (via worse kidney function) and/or the fetus (preeclampsia, poor fetal growth, preterm delivery).
In a 2015 study, Italian researchers compared 504 pregnancies in women with CKD to 836 low-risk pregnancies in women without CKD. They found that the risks of adverse outcomes increased in women at higher stages of CKD, compared with those at lower stages: “Renal function matters, and a stepwise increase in the risk of adverse maternal-fetal outcomes is observed from stage 1 to stages 4-5.”
In addition, the researchers noted that their research suggests “the presence of a baseline risk linked to CKD per se” (J Am Soc Nephrol. 2015 Aug; 26[8]:2011-22).
Dr. Hladunewich recommended focusing on “the safest window of opportunity.” Some patients will progress to end-stage renal disease, and an earlier pregnancy during CKD is a better option, she said. As a result, encouraging an earlier pregnancy can be a wise idea.
In some cases, though, a patient may be far into the stages of CKD. Dr. Hladunewich spoke about the case of a 31-year-old patient with a 29-year history of type 1 diabetes mellitus. She’d had one miscarriage, one preterm birth, and one twin pregnancy that was terminated because of safety concerns including rapid loss of kidney function.
The patient saw Dr. Hladunewich when she had a glomerular filtration rate of 25 mL/min, 3.5 g per 24 hour of proteinuria, and hypertension. The patient had a question: “Dr. Michelle, when can I try again?”
Dr. Hladunewich joked that “I had a small stroke.” But then, she said, “I got to the business of pregnancy counseling.”
She told the woman that her progression to end-stage renal disease was likely inevitable, and “adverse pregnancy outcomes were almost guaranteed.”
The woman responded: “Not now? When?” That, Dr. Hladunewich said, “was when I had my second stroke.”
But there is a possible solution: Pregnancy during dialysis. “Historically, we’ve said absolutely no pregnancy on dialysis,” she said, “but times are changing. We believe aggressive dialysis improves fetal maternal and fetal outcomes.”
Indeed, Dr. Hladunewich led a 2014 study that linked extensive dialysis during pregnancy (compared with less dialysis) to a better likelihood of outcomes such as live birth rate and normal birth weight (JASN May 2014;25[5]:1103-9).
As she noted, “we do offer it as a reproductive option” to patients like the one she mentioned – those who are in ESRD, approaching it, or are nearing the end of their child-bearing years with no transplant in sight. In transplant cases, she said, adequate graft function is linked to good pregnancy outcomes.
Dr. Hladunewich added that it’s important to monitor and adjust treatment of patients during the postpartum period. She said it’s especially important to understand the risks of drugs during breastfeeding. Both dialysis and transplant patients can breastfeed, she said.
Dr. Hladunewich reports no disclosures.
SOURCE: Kidney Week 2018, Abstract FR-OR078.
SAN DIEGO – Nephrologists are often uncomfortable with the idea of advising women with chronic kidney disease (CKD) about pregnancy, a physician told colleagues. They must do better, she said, with sensitivity and insight into once-extreme possibilities like pregnancy during dialysis.
“For many women, having a child is a life goal, and our women with chronic kidney disease are not different,” said Michelle Hladunewich, MD, of Toronto’s Sunnybrook Health Sciences Center. “When we don’t know what we should do, we tend to over-aggressively counsel our women, and that can traumatize them. It’s our role as nephrologists to help them find the safest window to have their pregnancy,” she said at the meeting sponsored by the American Society of Nephrology.
According to Dr. Hladunewich, there are tens of thousands of women of child-bearing age in the United States who have CKD, end-stage renal disease (ESRD), and kidney transplants. However, she said, research presented at Kidney Week 2018 suggested that many nephrologists do not feel confident about counseling patients regarding issues such as pregnancy outcomes in CKD. “We are not that comfortable with it, but we have to become more comfortable,” she said. “We need to be prepared to talk about contraception if they don’t want to have a child or the plan about how to have a child if they do.”
It’s especially important to understand that while women can fear birth defects and the exacerbation of their disease, they may also feel “they’re not fulfilling a societal norm to have a child like everyone else,” she said.
The risks of pregnancy in CKD can affect the mother (via worse kidney function) and/or the fetus (preeclampsia, poor fetal growth, preterm delivery).
In a 2015 study, Italian researchers compared 504 pregnancies in women with CKD to 836 low-risk pregnancies in women without CKD. They found that the risks of adverse outcomes increased in women at higher stages of CKD, compared with those at lower stages: “Renal function matters, and a stepwise increase in the risk of adverse maternal-fetal outcomes is observed from stage 1 to stages 4-5.”
In addition, the researchers noted that their research suggests “the presence of a baseline risk linked to CKD per se” (J Am Soc Nephrol. 2015 Aug; 26[8]:2011-22).
Dr. Hladunewich recommended focusing on “the safest window of opportunity.” Some patients will progress to end-stage renal disease, and an earlier pregnancy during CKD is a better option, she said. As a result, encouraging an earlier pregnancy can be a wise idea.
In some cases, though, a patient may be far into the stages of CKD. Dr. Hladunewich spoke about the case of a 31-year-old patient with a 29-year history of type 1 diabetes mellitus. She’d had one miscarriage, one preterm birth, and one twin pregnancy that was terminated because of safety concerns including rapid loss of kidney function.
The patient saw Dr. Hladunewich when she had a glomerular filtration rate of 25 mL/min, 3.5 g per 24 hour of proteinuria, and hypertension. The patient had a question: “Dr. Michelle, when can I try again?”
Dr. Hladunewich joked that “I had a small stroke.” But then, she said, “I got to the business of pregnancy counseling.”
She told the woman that her progression to end-stage renal disease was likely inevitable, and “adverse pregnancy outcomes were almost guaranteed.”
The woman responded: “Not now? When?” That, Dr. Hladunewich said, “was when I had my second stroke.”
But there is a possible solution: Pregnancy during dialysis. “Historically, we’ve said absolutely no pregnancy on dialysis,” she said, “but times are changing. We believe aggressive dialysis improves fetal maternal and fetal outcomes.”
Indeed, Dr. Hladunewich led a 2014 study that linked extensive dialysis during pregnancy (compared with less dialysis) to a better likelihood of outcomes such as live birth rate and normal birth weight (JASN May 2014;25[5]:1103-9).
As she noted, “we do offer it as a reproductive option” to patients like the one she mentioned – those who are in ESRD, approaching it, or are nearing the end of their child-bearing years with no transplant in sight. In transplant cases, she said, adequate graft function is linked to good pregnancy outcomes.
Dr. Hladunewich added that it’s important to monitor and adjust treatment of patients during the postpartum period. She said it’s especially important to understand the risks of drugs during breastfeeding. Both dialysis and transplant patients can breastfeed, she said.
Dr. Hladunewich reports no disclosures.
SOURCE: Kidney Week 2018, Abstract FR-OR078.
SAN DIEGO – Nephrologists are often uncomfortable with the idea of advising women with chronic kidney disease (CKD) about pregnancy, a physician told colleagues. They must do better, she said, with sensitivity and insight into once-extreme possibilities like pregnancy during dialysis.
“For many women, having a child is a life goal, and our women with chronic kidney disease are not different,” said Michelle Hladunewich, MD, of Toronto’s Sunnybrook Health Sciences Center. “When we don’t know what we should do, we tend to over-aggressively counsel our women, and that can traumatize them. It’s our role as nephrologists to help them find the safest window to have their pregnancy,” she said at the meeting sponsored by the American Society of Nephrology.
According to Dr. Hladunewich, there are tens of thousands of women of child-bearing age in the United States who have CKD, end-stage renal disease (ESRD), and kidney transplants. However, she said, research presented at Kidney Week 2018 suggested that many nephrologists do not feel confident about counseling patients regarding issues such as pregnancy outcomes in CKD. “We are not that comfortable with it, but we have to become more comfortable,” she said. “We need to be prepared to talk about contraception if they don’t want to have a child or the plan about how to have a child if they do.”
It’s especially important to understand that while women can fear birth defects and the exacerbation of their disease, they may also feel “they’re not fulfilling a societal norm to have a child like everyone else,” she said.
The risks of pregnancy in CKD can affect the mother (via worse kidney function) and/or the fetus (preeclampsia, poor fetal growth, preterm delivery).
In a 2015 study, Italian researchers compared 504 pregnancies in women with CKD to 836 low-risk pregnancies in women without CKD. They found that the risks of adverse outcomes increased in women at higher stages of CKD, compared with those at lower stages: “Renal function matters, and a stepwise increase in the risk of adverse maternal-fetal outcomes is observed from stage 1 to stages 4-5.”
In addition, the researchers noted that their research suggests “the presence of a baseline risk linked to CKD per se” (J Am Soc Nephrol. 2015 Aug; 26[8]:2011-22).
Dr. Hladunewich recommended focusing on “the safest window of opportunity.” Some patients will progress to end-stage renal disease, and an earlier pregnancy during CKD is a better option, she said. As a result, encouraging an earlier pregnancy can be a wise idea.
In some cases, though, a patient may be far into the stages of CKD. Dr. Hladunewich spoke about the case of a 31-year-old patient with a 29-year history of type 1 diabetes mellitus. She’d had one miscarriage, one preterm birth, and one twin pregnancy that was terminated because of safety concerns including rapid loss of kidney function.
The patient saw Dr. Hladunewich when she had a glomerular filtration rate of 25 mL/min, 3.5 g per 24 hour of proteinuria, and hypertension. The patient had a question: “Dr. Michelle, when can I try again?”
Dr. Hladunewich joked that “I had a small stroke.” But then, she said, “I got to the business of pregnancy counseling.”
She told the woman that her progression to end-stage renal disease was likely inevitable, and “adverse pregnancy outcomes were almost guaranteed.”
The woman responded: “Not now? When?” That, Dr. Hladunewich said, “was when I had my second stroke.”
But there is a possible solution: Pregnancy during dialysis. “Historically, we’ve said absolutely no pregnancy on dialysis,” she said, “but times are changing. We believe aggressive dialysis improves fetal maternal and fetal outcomes.”
Indeed, Dr. Hladunewich led a 2014 study that linked extensive dialysis during pregnancy (compared with less dialysis) to a better likelihood of outcomes such as live birth rate and normal birth weight (JASN May 2014;25[5]:1103-9).
As she noted, “we do offer it as a reproductive option” to patients like the one she mentioned – those who are in ESRD, approaching it, or are nearing the end of their child-bearing years with no transplant in sight. In transplant cases, she said, adequate graft function is linked to good pregnancy outcomes.
Dr. Hladunewich added that it’s important to monitor and adjust treatment of patients during the postpartum period. She said it’s especially important to understand the risks of drugs during breastfeeding. Both dialysis and transplant patients can breastfeed, she said.
Dr. Hladunewich reports no disclosures.
SOURCE: Kidney Week 2018, Abstract FR-OR078.
REPORTING FROM KIDNEY WEEK 2018
CMS modifies the inpatient admission order requirement, or did it?
Ensure inpatient admission orders are completed and signed
When the Centers for Medicare & Medicaid Services make a significant change to the inpatient hospital rules, hospitalists are among the first to feel the effects.
You probably remember that, starting in October 2013, when a resident, nurse practitioner (NP), or physician assistant (PA) entered an inpatient admission order on your behalf, you were told to cosign that order before discharge or the hospital would forfeit payment for the entire stay. This policy was put in place by an annual piece of governmental policy known as the Inpatient Prospective Payment System (IPPS) Final Rule – the same one, in fact, that established the Two Midnight Rule.
The CMS felt that the decision to admit a Medicare beneficiary to inpatient care is such a significant event that it was appropriate to require the attending physician to complete a series of certification requirements to justify every inpatient stay. If not completed and finalized prior to discharge, the CMS would not pay for the stay. After 15 months of enforcing that policy, the CMS backed off on most of the certification requirements for most stays. However, the requirement for an authenticated inpatient order prior to discharge was kept in place for all stays. (“Authenticated” is CMS-speak for signed, or, in the case of inpatient orders initially placed by a resident/NP/PA without admitting privileges, cosigned, by a practitioner with admitting privileges.)
In the spring of 2018, the CMS proposed a change to “revise the admission order documentation requirements by removing the requirement that written inpatient admission orders are a specific requirement for Medicare Part A [inpatient hospital] payment.” The CMS also stated that it did not intend for Medicare auditors to deny hospital inpatient claims based solely on a deficiency in the inpatient order, such as a missing order or one signed after discharge, which the CMS found out was happening.
The description sounded great. In comments to the CMS, many providers assumed that they, too, would be provided similar discretion if they discovered the order defect. Are inpatient orders now optional? What rate of inpatient order technical deficiencies is acceptable to still submit inpatient claims for payment? Can 2-day observation stays where medical necessity for hospital care was present, but no inpatient order given, be billed as an inpatient now?
But these providers had not read the fine print. Consider that the annual IPPS Final Rule has a length of about 2,000 pages. Of those, only about 30 pages represent changes to a group of policies known as the Code of Federal Regulations (CFR). The CFR carries the weight of law (as long as it does not contradict law). When you appeal a Medicare denial to a judge, she will ask what portion of the CFR supports your viewpoint. The other 1,970 pages can be thought of as supporting analysis and reasoning to justify the 30 pages of changes. What changes were actually made to the CFR?
Consider the following two sentences.
- “For purposes of payment under Medicare Part A, an individual is considered an inpatient of a hospital, including a critical access hospital, if formally admitted as an inpatient pursuant to an order for inpatient admission by a physician or other qualified practitioner.”
- “This physician order must be present in the medical record and be supported by the physician admission and progress notes, in order for the hospital to be paid for hospital inpatient services under Medicare Part A.”
These are the first two sentences of 42 CFR 412.3(a), the regulation that defines the inpatient order requirement. On Oct. 1, 2018, the second sentence was removed, but the first sentence still remains. That’s the only change for this section. Does removal of the second sentence absolve providers of the requirement to document inpatient admission orders? Does it absolve providers of the requirement to cosign a resident’s admission order prior to discharge? The Medicare Benefit Policy Manual (MBPM) Chapter 1, Section 10(B) still reads “if the order is not properly documented in the medical record prior to discharge, the hospital should not submit a claim for Part A payment.”
Understanding what changed and what did not change in the CFR is key to understanding why, in this year’s IPPS Final Rule, the CMS repeatedly responded to providers that an inpatient order is still a requirement for a Part A stay and that none of the MBPM guidance regarding the inpatient order, such as the excerpt above, is changing.
At this point, we can only be reasonably certain that if a claim a hospital submits for Part A payment happens to get audited and found to have only one deficiency which is related to the inpatient order, per this guidance it probably won’t get denied. That is very different from saying the attending physician no longer has to provide a signed (or cosigned) inpatient admission order prior to discharge, or at all.
Providers actually did ask the CMS if a hospital could still submit a claim the hospital knows has a missing or incomplete inpatient admission order at the time of discharge. The CMS responded that Medicare contractors have the discretion in extremely rare circumstances to approve cases where an order to admit may be missing or defective, and yet the intent, decision, and recommendation of the ordering practitioner to admit as inpatient can be clearly derived from the medical record. However, note that the discretion belongs to the Medicare contractor, not the provider.
The American College of Physician Advisors (ACPA) asked the CMS the following question about the inpatient order policy change during the 2019 IPPS Final Rule Open Door Forum held on Sept. 11, 2018: “Can providers thus submit a claim, that the provider believes meets all other requirements for Part A payment, in the rare circumstance of an inpatient order deficiency, such as an inpatient order that was cosigned shortly after discharge?”
The CMS declined to answer the question on the call, asking us to submit the question to the Open Door Forum electronic mailbox. If the inpatient order was truly no longer being required for the CMS to pay for inpatient hospital stays, the answer would have been an easy “yes,” but it was not. Subsequently, the CMS responded in writing to the ACPA that “the responsibilities of providers regarding inpatient admission orders is unchanged.” In other words, Medicare auditors have been given discretion to overlook an inpatient order flaw, but providers have not.
At this time, our recommendation is to continue your processes to ensure that the inpatient admission order is completed and signed (or cosigned) prior to discharge by the attending physician for every Medicare patient. This will not only help make sure that the decision to make a hospitalized Medicare beneficiary an inpatient remains with the attending physician, but it will also reduce the risk of nonpayment.
Dr. Hu is executive director of physician advisor services of University of North Carolina Health Care System in Chapel Hill, N.C., and president of the ACPA. Dr. Locke is senior physician advisor at Johns Hopkins Hospital in Baltimore, and president-elect of the ACPA.
Ensure inpatient admission orders are completed and signed
Ensure inpatient admission orders are completed and signed
When the Centers for Medicare & Medicaid Services make a significant change to the inpatient hospital rules, hospitalists are among the first to feel the effects.
You probably remember that, starting in October 2013, when a resident, nurse practitioner (NP), or physician assistant (PA) entered an inpatient admission order on your behalf, you were told to cosign that order before discharge or the hospital would forfeit payment for the entire stay. This policy was put in place by an annual piece of governmental policy known as the Inpatient Prospective Payment System (IPPS) Final Rule – the same one, in fact, that established the Two Midnight Rule.
The CMS felt that the decision to admit a Medicare beneficiary to inpatient care is such a significant event that it was appropriate to require the attending physician to complete a series of certification requirements to justify every inpatient stay. If not completed and finalized prior to discharge, the CMS would not pay for the stay. After 15 months of enforcing that policy, the CMS backed off on most of the certification requirements for most stays. However, the requirement for an authenticated inpatient order prior to discharge was kept in place for all stays. (“Authenticated” is CMS-speak for signed, or, in the case of inpatient orders initially placed by a resident/NP/PA without admitting privileges, cosigned, by a practitioner with admitting privileges.)
In the spring of 2018, the CMS proposed a change to “revise the admission order documentation requirements by removing the requirement that written inpatient admission orders are a specific requirement for Medicare Part A [inpatient hospital] payment.” The CMS also stated that it did not intend for Medicare auditors to deny hospital inpatient claims based solely on a deficiency in the inpatient order, such as a missing order or one signed after discharge, which the CMS found out was happening.
The description sounded great. In comments to the CMS, many providers assumed that they, too, would be provided similar discretion if they discovered the order defect. Are inpatient orders now optional? What rate of inpatient order technical deficiencies is acceptable to still submit inpatient claims for payment? Can 2-day observation stays where medical necessity for hospital care was present, but no inpatient order given, be billed as an inpatient now?
But these providers had not read the fine print. Consider that the annual IPPS Final Rule has a length of about 2,000 pages. Of those, only about 30 pages represent changes to a group of policies known as the Code of Federal Regulations (CFR). The CFR carries the weight of law (as long as it does not contradict law). When you appeal a Medicare denial to a judge, she will ask what portion of the CFR supports your viewpoint. The other 1,970 pages can be thought of as supporting analysis and reasoning to justify the 30 pages of changes. What changes were actually made to the CFR?
Consider the following two sentences.
- “For purposes of payment under Medicare Part A, an individual is considered an inpatient of a hospital, including a critical access hospital, if formally admitted as an inpatient pursuant to an order for inpatient admission by a physician or other qualified practitioner.”
- “This physician order must be present in the medical record and be supported by the physician admission and progress notes, in order for the hospital to be paid for hospital inpatient services under Medicare Part A.”
These are the first two sentences of 42 CFR 412.3(a), the regulation that defines the inpatient order requirement. On Oct. 1, 2018, the second sentence was removed, but the first sentence still remains. That’s the only change for this section. Does removal of the second sentence absolve providers of the requirement to document inpatient admission orders? Does it absolve providers of the requirement to cosign a resident’s admission order prior to discharge? The Medicare Benefit Policy Manual (MBPM) Chapter 1, Section 10(B) still reads “if the order is not properly documented in the medical record prior to discharge, the hospital should not submit a claim for Part A payment.”
Understanding what changed and what did not change in the CFR is key to understanding why, in this year’s IPPS Final Rule, the CMS repeatedly responded to providers that an inpatient order is still a requirement for a Part A stay and that none of the MBPM guidance regarding the inpatient order, such as the excerpt above, is changing.
At this point, we can only be reasonably certain that if a claim a hospital submits for Part A payment happens to get audited and found to have only one deficiency which is related to the inpatient order, per this guidance it probably won’t get denied. That is very different from saying the attending physician no longer has to provide a signed (or cosigned) inpatient admission order prior to discharge, or at all.
Providers actually did ask the CMS if a hospital could still submit a claim the hospital knows has a missing or incomplete inpatient admission order at the time of discharge. The CMS responded that Medicare contractors have the discretion in extremely rare circumstances to approve cases where an order to admit may be missing or defective, and yet the intent, decision, and recommendation of the ordering practitioner to admit as inpatient can be clearly derived from the medical record. However, note that the discretion belongs to the Medicare contractor, not the provider.
The American College of Physician Advisors (ACPA) asked the CMS the following question about the inpatient order policy change during the 2019 IPPS Final Rule Open Door Forum held on Sept. 11, 2018: “Can providers thus submit a claim, that the provider believes meets all other requirements for Part A payment, in the rare circumstance of an inpatient order deficiency, such as an inpatient order that was cosigned shortly after discharge?”
The CMS declined to answer the question on the call, asking us to submit the question to the Open Door Forum electronic mailbox. If the inpatient order was truly no longer being required for the CMS to pay for inpatient hospital stays, the answer would have been an easy “yes,” but it was not. Subsequently, the CMS responded in writing to the ACPA that “the responsibilities of providers regarding inpatient admission orders is unchanged.” In other words, Medicare auditors have been given discretion to overlook an inpatient order flaw, but providers have not.
At this time, our recommendation is to continue your processes to ensure that the inpatient admission order is completed and signed (or cosigned) prior to discharge by the attending physician for every Medicare patient. This will not only help make sure that the decision to make a hospitalized Medicare beneficiary an inpatient remains with the attending physician, but it will also reduce the risk of nonpayment.
Dr. Hu is executive director of physician advisor services of University of North Carolina Health Care System in Chapel Hill, N.C., and president of the ACPA. Dr. Locke is senior physician advisor at Johns Hopkins Hospital in Baltimore, and president-elect of the ACPA.
When the Centers for Medicare & Medicaid Services make a significant change to the inpatient hospital rules, hospitalists are among the first to feel the effects.
You probably remember that, starting in October 2013, when a resident, nurse practitioner (NP), or physician assistant (PA) entered an inpatient admission order on your behalf, you were told to cosign that order before discharge or the hospital would forfeit payment for the entire stay. This policy was put in place by an annual piece of governmental policy known as the Inpatient Prospective Payment System (IPPS) Final Rule – the same one, in fact, that established the Two Midnight Rule.
The CMS felt that the decision to admit a Medicare beneficiary to inpatient care is such a significant event that it was appropriate to require the attending physician to complete a series of certification requirements to justify every inpatient stay. If not completed and finalized prior to discharge, the CMS would not pay for the stay. After 15 months of enforcing that policy, the CMS backed off on most of the certification requirements for most stays. However, the requirement for an authenticated inpatient order prior to discharge was kept in place for all stays. (“Authenticated” is CMS-speak for signed, or, in the case of inpatient orders initially placed by a resident/NP/PA without admitting privileges, cosigned, by a practitioner with admitting privileges.)
In the spring of 2018, the CMS proposed a change to “revise the admission order documentation requirements by removing the requirement that written inpatient admission orders are a specific requirement for Medicare Part A [inpatient hospital] payment.” The CMS also stated that it did not intend for Medicare auditors to deny hospital inpatient claims based solely on a deficiency in the inpatient order, such as a missing order or one signed after discharge, which the CMS found out was happening.
The description sounded great. In comments to the CMS, many providers assumed that they, too, would be provided similar discretion if they discovered the order defect. Are inpatient orders now optional? What rate of inpatient order technical deficiencies is acceptable to still submit inpatient claims for payment? Can 2-day observation stays where medical necessity for hospital care was present, but no inpatient order given, be billed as an inpatient now?
But these providers had not read the fine print. Consider that the annual IPPS Final Rule has a length of about 2,000 pages. Of those, only about 30 pages represent changes to a group of policies known as the Code of Federal Regulations (CFR). The CFR carries the weight of law (as long as it does not contradict law). When you appeal a Medicare denial to a judge, she will ask what portion of the CFR supports your viewpoint. The other 1,970 pages can be thought of as supporting analysis and reasoning to justify the 30 pages of changes. What changes were actually made to the CFR?
Consider the following two sentences.
- “For purposes of payment under Medicare Part A, an individual is considered an inpatient of a hospital, including a critical access hospital, if formally admitted as an inpatient pursuant to an order for inpatient admission by a physician or other qualified practitioner.”
- “This physician order must be present in the medical record and be supported by the physician admission and progress notes, in order for the hospital to be paid for hospital inpatient services under Medicare Part A.”
These are the first two sentences of 42 CFR 412.3(a), the regulation that defines the inpatient order requirement. On Oct. 1, 2018, the second sentence was removed, but the first sentence still remains. That’s the only change for this section. Does removal of the second sentence absolve providers of the requirement to document inpatient admission orders? Does it absolve providers of the requirement to cosign a resident’s admission order prior to discharge? The Medicare Benefit Policy Manual (MBPM) Chapter 1, Section 10(B) still reads “if the order is not properly documented in the medical record prior to discharge, the hospital should not submit a claim for Part A payment.”
Understanding what changed and what did not change in the CFR is key to understanding why, in this year’s IPPS Final Rule, the CMS repeatedly responded to providers that an inpatient order is still a requirement for a Part A stay and that none of the MBPM guidance regarding the inpatient order, such as the excerpt above, is changing.
At this point, we can only be reasonably certain that if a claim a hospital submits for Part A payment happens to get audited and found to have only one deficiency which is related to the inpatient order, per this guidance it probably won’t get denied. That is very different from saying the attending physician no longer has to provide a signed (or cosigned) inpatient admission order prior to discharge, or at all.
Providers actually did ask the CMS if a hospital could still submit a claim the hospital knows has a missing or incomplete inpatient admission order at the time of discharge. The CMS responded that Medicare contractors have the discretion in extremely rare circumstances to approve cases where an order to admit may be missing or defective, and yet the intent, decision, and recommendation of the ordering practitioner to admit as inpatient can be clearly derived from the medical record. However, note that the discretion belongs to the Medicare contractor, not the provider.
The American College of Physician Advisors (ACPA) asked the CMS the following question about the inpatient order policy change during the 2019 IPPS Final Rule Open Door Forum held on Sept. 11, 2018: “Can providers thus submit a claim, that the provider believes meets all other requirements for Part A payment, in the rare circumstance of an inpatient order deficiency, such as an inpatient order that was cosigned shortly after discharge?”
The CMS declined to answer the question on the call, asking us to submit the question to the Open Door Forum electronic mailbox. If the inpatient order was truly no longer being required for the CMS to pay for inpatient hospital stays, the answer would have been an easy “yes,” but it was not. Subsequently, the CMS responded in writing to the ACPA that “the responsibilities of providers regarding inpatient admission orders is unchanged.” In other words, Medicare auditors have been given discretion to overlook an inpatient order flaw, but providers have not.
At this time, our recommendation is to continue your processes to ensure that the inpatient admission order is completed and signed (or cosigned) prior to discharge by the attending physician for every Medicare patient. This will not only help make sure that the decision to make a hospitalized Medicare beneficiary an inpatient remains with the attending physician, but it will also reduce the risk of nonpayment.
Dr. Hu is executive director of physician advisor services of University of North Carolina Health Care System in Chapel Hill, N.C., and president of the ACPA. Dr. Locke is senior physician advisor at Johns Hopkins Hospital in Baltimore, and president-elect of the ACPA.
High rates of HCV treatment completion seen in people who inject drugs
SAN FRANCISCO – , preliminary results from an ongoing study showed.
“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”
In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.
The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).
Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.
Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.
When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”
Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”
Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.
Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.
SAN FRANCISCO – , preliminary results from an ongoing study showed.
“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”
In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.
The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).
Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.
Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.
When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”
Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”
Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.
Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.
SAN FRANCISCO – , preliminary results from an ongoing study showed.
“Both from a public health and a human rights perspective, hepatitis C elimination in people who inject drugs is critical,” study coauthor Elana Rosenthal, MD, said during a press briefing at the annual meeting of the American Association for the Study of Liver Diseases. “People who inject drugs are the main progenitors of ongoing transmission of hepatitis C. However, they are often denied access to hepatitis C treatment due to concerns about their ability to take medication consistently and achieve cure. This is especially true amongst patients with challenging demographic factors, frequent drug use, and those not on treatment for opioid use disorder. However, there are limited data on hepatitis C adherence in people who inject drugs outside of vigorous clinical trial settings.”
In an effort to understand whether a marginalized population with ongoing injection drug use could adhere to HCV treatment, and how this adherence would impact cure, Dr. Rosenthal and her associates enrolled 100 subjects in ANCHOR, a single-center study evaluating HCV treatment in patients who have chronic HCV, opioid use disorder, and ongoing injection drug use. “We did not preferentially enroll patients who we thought we would be most likely to cure, and we did not exclude patients who seemed unlikely to adhere to treatment,” said Dr. Rosenthal, codirector of the DC Partnership for HIV/AIDS Progress hepatitis clinical research program at the University of Maryland, Baltimore. “All patients were treated with sofosbuvir/velpatasvir, with a plan to complete 12 weeks of treatment.” Medication was dispensed monthly in bottles containing 28 pills, and patients were seen for monthly visits, mirroring standard clinical care for HCV. The researchers monitored patients for medication adherence through pill counts and evaluated them for hepatitis C cure 12 weeks after treatment.
The median age of the 100 patients was 57 years, 76% were black, 33% had cirrhosis, 51% were unstably housed, 92% had a history of incarceration, and 92% had no income source or relied exclusively on government benefits. “The patients represent an incredibly marginalized population,” she said. At baseline, 58% reported daily or more frequent injection drug use, 33% reported medication-assisted treatment, 29% shared injection drug use equipment within the past 3 months, and 40% met criteria for hazardous drinking based on the Alcohol Use Disorders Identification Test (AUDIT-C).
Of the 100 patients, 59 received 12 weeks of treatment. Of these 59 patients, 28 finished 1-7 days after the anticipated end date, 9 finished between 8 and 14 days late, and 9 patients finished more than 14 days late.
Of the 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response. This cure rate was associated with having an HCV viral load less than 200 IU/mL at week 4, and with taking 12 weeks of treatment. Nonsustained virologic response was driven by virologic failure, loss to follow-up, and death.
When the researchers compared subjects who achieved sustained virologic response with those who did not, baseline demographics including frequent drug use, unstable housing status, and not being on medication to treat opioid use disorder were not associated with decreased cure rates. “While we found high rates of treatment completion in this population, because of external factors such as incarceration, hospitalization, and having medications stolen, 13 patients had interruptions in treatment,” Dr. Rosenthal said. “Further, while 21 patients had near-perfect medication adherence, 46 patients took longer than 12 weeks to complete the full treatment course due to intermittent missed doses. However, as long as patients completed the prescribed amount, imperfect adherence was not associated with decreased cure rates.”
Based on ANCHOR’s preliminary results, Dr. Rosenthal concluded that concerns about HCV treatment adherence such as baseline housing status, drug use frequency, and being on medication for opioid use disorder “are not likely to influence treatment outcome of HCV and should not be used to justify exclusion from treatment in this population. The ANCHOR investigation adds to the growing body of literature supporting expansion of HCV treatment to all patients, including people who inject drugs. Treatment of people who inject drugs is a critical factor in HCV elimination and, most importantly, reducing morbidity and mortality in this population.”
Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.
Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.
AT THE LIVER MEETING 2018
Key clinical point: People who inject drugs have high rates of HCV treatment adherence, treatment completion, and sustained virologic response.
Major finding: Of 58 patients who attended an office visit at week 24 of their treatment, 52 (90%) achieved a sustained virologic response.
Study details: Preliminary results from an ongoing, single-center study of 100 people with a median age of 57 years.
Disclosures: Dr. Rosenthal disclosed that she has received grant/research support from Gilead Sciences and from Merck.
Source: Rosenthal E et al. Hepatol. 2018;68[S1], Abstract 18.
Despite declines in prenatal use of alcohol and cigarettes, cannabis use is on the rise
Despite general decreases in cigarette and alcohol use among pregnant women during 2002-2016, cannabis use in pregnancy persisted and has actually increased slightly over the past 14 years, reported Arpana Agrawal, PhD, and her associates, of the Washington University, St. Louis.
Dr. Agrawal and her associates analyzed data from the National Survey of Drug Use and Health from 2002-2016 to quantify changes in alcohol, cigarette, and cannabis use among pregnant women aged 18-44 years. Survey-adjusted prevalence estimates of alcohol, cigarette, and cannabis use in 2002 were 10%, 18%, and 3%, respectively, versus corresponding rates in 2016 of 8%, 10%, and 5%, according to their research letter in JAMA Pediatrics.
A sampling of 12,058 women aged 18-25 years (n = 8,170) or 26-44 years (n = 3,888) was taken from a population of more than 436,056 women included in the National Survey database. Fully 3,554 of the women included in the final study group were in their first trimester of pregnancy.
The findings in Dr. Agrawal’s study were similar to another study conducted by Brown et al., although the exact prevalence for cannabis use differed slightly.
In addition to observing a reduction in the use of alcohol and cigarettes, the authors also noted a significant decline in the combined use of alcohol and cigarettes together. For alcohol use specifically, the greatest decrease was seen among women aged 18-25 years. For cigarette smoking in pregnancy, the most significant decreases were seen in white women, those aged 18-25 years, and those who had achieved completion of high school or more advanced studies.
Overall, the effects were modest when sample sizes were stratified by trimester: decreases in cigarette smoking were observed in the first trimester, and more significantly, later in pregnancy. For alcohol, nominal reductions were observed in the second and third trimesters. Cannabis use, on the other hand, increased in the first trimester, but showed no significant increases during the second and third trimesters.
“Greater public awareness regarding the consequences of prenatal cannabis exposure in offspring health is necessary,” Dr. Agrawal and her colleagues wrote.
The authors had no relevant disclosures to report. Funding was provided by grants from the National Institute on Drug Abuse, the National Institute of Child Health and Human Development, and the National Institute on Alcohol Abuse and Alcoholism.
SOURCE: Agrawal A et al. JAMA Pediatr. 2018 Nov 5. doi: 10.1001/jamapediatrics.2018.3096.
Despite general decreases in cigarette and alcohol use among pregnant women during 2002-2016, cannabis use in pregnancy persisted and has actually increased slightly over the past 14 years, reported Arpana Agrawal, PhD, and her associates, of the Washington University, St. Louis.
Dr. Agrawal and her associates analyzed data from the National Survey of Drug Use and Health from 2002-2016 to quantify changes in alcohol, cigarette, and cannabis use among pregnant women aged 18-44 years. Survey-adjusted prevalence estimates of alcohol, cigarette, and cannabis use in 2002 were 10%, 18%, and 3%, respectively, versus corresponding rates in 2016 of 8%, 10%, and 5%, according to their research letter in JAMA Pediatrics.
A sampling of 12,058 women aged 18-25 years (n = 8,170) or 26-44 years (n = 3,888) was taken from a population of more than 436,056 women included in the National Survey database. Fully 3,554 of the women included in the final study group were in their first trimester of pregnancy.
The findings in Dr. Agrawal’s study were similar to another study conducted by Brown et al., although the exact prevalence for cannabis use differed slightly.
In addition to observing a reduction in the use of alcohol and cigarettes, the authors also noted a significant decline in the combined use of alcohol and cigarettes together. For alcohol use specifically, the greatest decrease was seen among women aged 18-25 years. For cigarette smoking in pregnancy, the most significant decreases were seen in white women, those aged 18-25 years, and those who had achieved completion of high school or more advanced studies.
Overall, the effects were modest when sample sizes were stratified by trimester: decreases in cigarette smoking were observed in the first trimester, and more significantly, later in pregnancy. For alcohol, nominal reductions were observed in the second and third trimesters. Cannabis use, on the other hand, increased in the first trimester, but showed no significant increases during the second and third trimesters.
“Greater public awareness regarding the consequences of prenatal cannabis exposure in offspring health is necessary,” Dr. Agrawal and her colleagues wrote.
The authors had no relevant disclosures to report. Funding was provided by grants from the National Institute on Drug Abuse, the National Institute of Child Health and Human Development, and the National Institute on Alcohol Abuse and Alcoholism.
SOURCE: Agrawal A et al. JAMA Pediatr. 2018 Nov 5. doi: 10.1001/jamapediatrics.2018.3096.
Despite general decreases in cigarette and alcohol use among pregnant women during 2002-2016, cannabis use in pregnancy persisted and has actually increased slightly over the past 14 years, reported Arpana Agrawal, PhD, and her associates, of the Washington University, St. Louis.
Dr. Agrawal and her associates analyzed data from the National Survey of Drug Use and Health from 2002-2016 to quantify changes in alcohol, cigarette, and cannabis use among pregnant women aged 18-44 years. Survey-adjusted prevalence estimates of alcohol, cigarette, and cannabis use in 2002 were 10%, 18%, and 3%, respectively, versus corresponding rates in 2016 of 8%, 10%, and 5%, according to their research letter in JAMA Pediatrics.
A sampling of 12,058 women aged 18-25 years (n = 8,170) or 26-44 years (n = 3,888) was taken from a population of more than 436,056 women included in the National Survey database. Fully 3,554 of the women included in the final study group were in their first trimester of pregnancy.
The findings in Dr. Agrawal’s study were similar to another study conducted by Brown et al., although the exact prevalence for cannabis use differed slightly.
In addition to observing a reduction in the use of alcohol and cigarettes, the authors also noted a significant decline in the combined use of alcohol and cigarettes together. For alcohol use specifically, the greatest decrease was seen among women aged 18-25 years. For cigarette smoking in pregnancy, the most significant decreases were seen in white women, those aged 18-25 years, and those who had achieved completion of high school or more advanced studies.
Overall, the effects were modest when sample sizes were stratified by trimester: decreases in cigarette smoking were observed in the first trimester, and more significantly, later in pregnancy. For alcohol, nominal reductions were observed in the second and third trimesters. Cannabis use, on the other hand, increased in the first trimester, but showed no significant increases during the second and third trimesters.
“Greater public awareness regarding the consequences of prenatal cannabis exposure in offspring health is necessary,” Dr. Agrawal and her colleagues wrote.
The authors had no relevant disclosures to report. Funding was provided by grants from the National Institute on Drug Abuse, the National Institute of Child Health and Human Development, and the National Institute on Alcohol Abuse and Alcoholism.
SOURCE: Agrawal A et al. JAMA Pediatr. 2018 Nov 5. doi: 10.1001/jamapediatrics.2018.3096.
FROM JAMA PEDIATRICS
Key clinical point:
Major finding: Greatest increase in use of cannabis over the 14 years of the study was seen during the first trimester; the increase in use of cannabis in the second and third trimesters was not significant.
Study details: A study of 12,058 pregnant women from 2002-2016.
Disclosures: The authors had no relevant financial disclosures. Funding was provided by grants from the National Institute on Drug Abuse, the National Institute of Child Health and Human Development, and the National Institute on Alcohol Abuse and Alcoholism.
Source: Agrawal A et al. JAMA Pediatr. 2018 Nov 5. doi: 10.1001/jamapediatrics.2018.3096.
Single-port robotic sacrocolpopexy has same learning curve as multiport
LAS VEGAS – according to Israeli investigators.
Multiport sacrocolpopexy is common, but the single-port approach hasn’t really caught on yet. That’s likely to change, however, with ongoing development of the da Vinci robotic platform, said lead investigator Emad Matanes, MD, of the Rambam Medical Center, Haifa, Israel.
The medical center recently has been switching over to the single-port approach, and Dr. Matanes and his colleagues wanted to share their experience with surgeons considering doing the same.
They compared their first 52 multiport cases during Dec. 2011-Dec. 2012 to their first 52 single-port cases during Aug. 2015-Aug. 2017.
It took about 15 cases with either approach for operative times to stabilize, dropping from an average of 222 minutes to 161 minutes after the first 15 single-port cases, and from 224 to 198 minutes after the first 15 multiport cases (J Minim Invasive Gynecol. 2018 Nov-Dec;25[7]:S47-S8).
With both, “we reached our steady state after the first 15. Both approaches are feasible, and for both, surgery times improve after 15 cases,” Dr. Matanes said at the American Association of Gynecologic Laparoscopists Global Congress.
Overall, the single-port approach proved about 20 minutes quicker, due to shorter docking and anesthesia times.
There wasn’t a single prolapse recurrence in either group, even after the first few cases. There was slightly less postoperative pain with single-port surgery (visual analogue scale sore 1.5 vs. 2 points), and slightly less estimated blood loss (38 mL vs. 54 mL), but neither difference was statistically significant.
There were no statistically significant differences between women in the two groups. Their average age was 58 years, mean body mass index was 28 kg/m2, and most women had a preoperative Pelvic Organ Prolapse Quantification score of 3.
There was no outside funding, and Dr. Matanes didn’t disclose any relevant financial disclosures.
LAS VEGAS – according to Israeli investigators.
Multiport sacrocolpopexy is common, but the single-port approach hasn’t really caught on yet. That’s likely to change, however, with ongoing development of the da Vinci robotic platform, said lead investigator Emad Matanes, MD, of the Rambam Medical Center, Haifa, Israel.
The medical center recently has been switching over to the single-port approach, and Dr. Matanes and his colleagues wanted to share their experience with surgeons considering doing the same.
They compared their first 52 multiport cases during Dec. 2011-Dec. 2012 to their first 52 single-port cases during Aug. 2015-Aug. 2017.
It took about 15 cases with either approach for operative times to stabilize, dropping from an average of 222 minutes to 161 minutes after the first 15 single-port cases, and from 224 to 198 minutes after the first 15 multiport cases (J Minim Invasive Gynecol. 2018 Nov-Dec;25[7]:S47-S8).
With both, “we reached our steady state after the first 15. Both approaches are feasible, and for both, surgery times improve after 15 cases,” Dr. Matanes said at the American Association of Gynecologic Laparoscopists Global Congress.
Overall, the single-port approach proved about 20 minutes quicker, due to shorter docking and anesthesia times.
There wasn’t a single prolapse recurrence in either group, even after the first few cases. There was slightly less postoperative pain with single-port surgery (visual analogue scale sore 1.5 vs. 2 points), and slightly less estimated blood loss (38 mL vs. 54 mL), but neither difference was statistically significant.
There were no statistically significant differences between women in the two groups. Their average age was 58 years, mean body mass index was 28 kg/m2, and most women had a preoperative Pelvic Organ Prolapse Quantification score of 3.
There was no outside funding, and Dr. Matanes didn’t disclose any relevant financial disclosures.
LAS VEGAS – according to Israeli investigators.
Multiport sacrocolpopexy is common, but the single-port approach hasn’t really caught on yet. That’s likely to change, however, with ongoing development of the da Vinci robotic platform, said lead investigator Emad Matanes, MD, of the Rambam Medical Center, Haifa, Israel.
The medical center recently has been switching over to the single-port approach, and Dr. Matanes and his colleagues wanted to share their experience with surgeons considering doing the same.
They compared their first 52 multiport cases during Dec. 2011-Dec. 2012 to their first 52 single-port cases during Aug. 2015-Aug. 2017.
It took about 15 cases with either approach for operative times to stabilize, dropping from an average of 222 minutes to 161 minutes after the first 15 single-port cases, and from 224 to 198 minutes after the first 15 multiport cases (J Minim Invasive Gynecol. 2018 Nov-Dec;25[7]:S47-S8).
With both, “we reached our steady state after the first 15. Both approaches are feasible, and for both, surgery times improve after 15 cases,” Dr. Matanes said at the American Association of Gynecologic Laparoscopists Global Congress.
Overall, the single-port approach proved about 20 minutes quicker, due to shorter docking and anesthesia times.
There wasn’t a single prolapse recurrence in either group, even after the first few cases. There was slightly less postoperative pain with single-port surgery (visual analogue scale sore 1.5 vs. 2 points), and slightly less estimated blood loss (38 mL vs. 54 mL), but neither difference was statistically significant.
There were no statistically significant differences between women in the two groups. Their average age was 58 years, mean body mass index was 28 kg/m2, and most women had a preoperative Pelvic Organ Prolapse Quantification score of 3.
There was no outside funding, and Dr. Matanes didn’t disclose any relevant financial disclosures.
REPORTING FROM THE AAGL GLOBAL CONGRESS
Anti-MOG antibodies associated with non-MS, monophasic demyelinating disease in young children
BERLIN – In children with an incident acquired demyelinating episode, the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) weighs against an eventual diagnosis of multiple sclerosis, especially if the child is younger than 11 years.
“Anti-MOG antibodies are present in about 30% of children with acquired demyelinating syndromes,” Giulia Fadda, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “About 80% experience a monophasic disease course.”
The antibodies are found in almost all children who have a relapsing non-MS demyelinating disease, said Dr. Fadda, who is a postdoctoral research fellow at the University of Pennsylvania, Philadelphia. But when the antibodies are present in children with an MS diagnosis, they identify a very specific subset with atypical clinical and imaging features.
The large prospective Canadian Pediatric Demyelinating Disease Study provided the sample for the study she presented at ECTRIMS. Children are recruited into the study soon after a first demyelinating event, and they are followed clinically, serologically, and with regular brain MRI.
The cohort in Dr. Fadda’s study comprised 275 children who were a mean of about 11 years old at symptom onset. The mean clinical follow-up was 6.7 years; the mean serologic follow-up, 4 years, and the mean imaging follow-up, 3.5 years. The study examined 1,368 serum samples and 1,459 MRI scans.
Overall, 32% of the children were positive for anti-MOG antibodies. Positivity was not associated with sex, but children with antibodies were significantly younger than those without (7 vs. 12 years). In fact, 77% of anti-MOG–positive children were younger than 11 years; just 15% of older children were positive for the antibodies.
Anti-MOG positivity was also associated with certain clinical phenotypes. Among positive children, 40% presented with optic neuritis, 37% with acute disseminated encephalomyelitis, and 14% with transverse myelitis; the rest had other phenotypes. Optic neuritis was significantly less common among antibody-negative patients (22%), as was encephalomyelitis (17%). Transverse myelitis was significantly more common (31%).
The analysis of MRI scans was stratified according to age younger than 11 years and 11 years and older. “The first thing we noticed among the younger MOG-positive children is that they had a high number of lesions, which were more commonly ill-defined, diffuse, and bilateral,” Dr. Fadda said. “Almost all the brain areas were affected, with a slight preponderance of thalamic and juxtacortical lesions. Among the MOG-negative children, lesions were more often perpendicular to the major axis of the corpus callosum.”
Among the older MOG antibody–positive children, the diffuse pattern was rarer, and the lesions were frequently cerebellar. “But by far, the features that best differentiated positivity from negativity were black holes and enhancing lesions, which we saw in a high proportion of children without the antibodies” at 73% and 49%, respectively.
Over a mean imaging follow-up period of 4 years, lesions were more likely to resolve completely in antibody-positive children than in those without antibodies (50% vs. 21%). Serologically, children who were MOG-antibody negative at baseline were likely to stay that way, with 99% remaining seronegative. Positive children, on the other hand, were significantly more likely to change serologic status, with 56% turning negative and 8% serologically fluctuating over the follow-up period; only 36% remained persistently seropositive. Persistent positive status was significantly associated with younger age (7 vs. 9 years) and an optic neuritis presentation (62% vs. 27%).
Most children (81%) who were antibody positive at baseline experienced no relapses. Among the 16 children who did experience a clinical relapse, the mean time to a second event was about 1 year. Nine of these children stayed persistently positive, while five seroconverted and two had fluctuating status.
Of the 60 antibody-positive children who had a monophasic course, 23 were persistently positive, 34 seroconverted, and 3 had fluctuating serology.
Eventually, 54 children received an MS diagnosis. Of these, 83% were antibody negative at baseline. Ten children received a diagnosis of a relapsing non-MS demyelinating disorder; of these, 91% were antibody positive at baseline.
Dr. Fadda disclosed relationships with Atara Biotherapeutic and Sanofi-Genzyme.
SOURCE: Waters P et al. Mult Scler. 2018;24(S2):29-30, Abstract 65.
BERLIN – In children with an incident acquired demyelinating episode, the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) weighs against an eventual diagnosis of multiple sclerosis, especially if the child is younger than 11 years.
“Anti-MOG antibodies are present in about 30% of children with acquired demyelinating syndromes,” Giulia Fadda, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “About 80% experience a monophasic disease course.”
The antibodies are found in almost all children who have a relapsing non-MS demyelinating disease, said Dr. Fadda, who is a postdoctoral research fellow at the University of Pennsylvania, Philadelphia. But when the antibodies are present in children with an MS diagnosis, they identify a very specific subset with atypical clinical and imaging features.
The large prospective Canadian Pediatric Demyelinating Disease Study provided the sample for the study she presented at ECTRIMS. Children are recruited into the study soon after a first demyelinating event, and they are followed clinically, serologically, and with regular brain MRI.
The cohort in Dr. Fadda’s study comprised 275 children who were a mean of about 11 years old at symptom onset. The mean clinical follow-up was 6.7 years; the mean serologic follow-up, 4 years, and the mean imaging follow-up, 3.5 years. The study examined 1,368 serum samples and 1,459 MRI scans.
Overall, 32% of the children were positive for anti-MOG antibodies. Positivity was not associated with sex, but children with antibodies were significantly younger than those without (7 vs. 12 years). In fact, 77% of anti-MOG–positive children were younger than 11 years; just 15% of older children were positive for the antibodies.
Anti-MOG positivity was also associated with certain clinical phenotypes. Among positive children, 40% presented with optic neuritis, 37% with acute disseminated encephalomyelitis, and 14% with transverse myelitis; the rest had other phenotypes. Optic neuritis was significantly less common among antibody-negative patients (22%), as was encephalomyelitis (17%). Transverse myelitis was significantly more common (31%).
The analysis of MRI scans was stratified according to age younger than 11 years and 11 years and older. “The first thing we noticed among the younger MOG-positive children is that they had a high number of lesions, which were more commonly ill-defined, diffuse, and bilateral,” Dr. Fadda said. “Almost all the brain areas were affected, with a slight preponderance of thalamic and juxtacortical lesions. Among the MOG-negative children, lesions were more often perpendicular to the major axis of the corpus callosum.”
Among the older MOG antibody–positive children, the diffuse pattern was rarer, and the lesions were frequently cerebellar. “But by far, the features that best differentiated positivity from negativity were black holes and enhancing lesions, which we saw in a high proportion of children without the antibodies” at 73% and 49%, respectively.
Over a mean imaging follow-up period of 4 years, lesions were more likely to resolve completely in antibody-positive children than in those without antibodies (50% vs. 21%). Serologically, children who were MOG-antibody negative at baseline were likely to stay that way, with 99% remaining seronegative. Positive children, on the other hand, were significantly more likely to change serologic status, with 56% turning negative and 8% serologically fluctuating over the follow-up period; only 36% remained persistently seropositive. Persistent positive status was significantly associated with younger age (7 vs. 9 years) and an optic neuritis presentation (62% vs. 27%).
Most children (81%) who were antibody positive at baseline experienced no relapses. Among the 16 children who did experience a clinical relapse, the mean time to a second event was about 1 year. Nine of these children stayed persistently positive, while five seroconverted and two had fluctuating status.
Of the 60 antibody-positive children who had a monophasic course, 23 were persistently positive, 34 seroconverted, and 3 had fluctuating serology.
Eventually, 54 children received an MS diagnosis. Of these, 83% were antibody negative at baseline. Ten children received a diagnosis of a relapsing non-MS demyelinating disorder; of these, 91% were antibody positive at baseline.
Dr. Fadda disclosed relationships with Atara Biotherapeutic and Sanofi-Genzyme.
SOURCE: Waters P et al. Mult Scler. 2018;24(S2):29-30, Abstract 65.
BERLIN – In children with an incident acquired demyelinating episode, the presence of antibodies against myelin oligodendrocyte glycoprotein (MOG) weighs against an eventual diagnosis of multiple sclerosis, especially if the child is younger than 11 years.
“Anti-MOG antibodies are present in about 30% of children with acquired demyelinating syndromes,” Giulia Fadda, MD, said at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. “About 80% experience a monophasic disease course.”
The antibodies are found in almost all children who have a relapsing non-MS demyelinating disease, said Dr. Fadda, who is a postdoctoral research fellow at the University of Pennsylvania, Philadelphia. But when the antibodies are present in children with an MS diagnosis, they identify a very specific subset with atypical clinical and imaging features.
The large prospective Canadian Pediatric Demyelinating Disease Study provided the sample for the study she presented at ECTRIMS. Children are recruited into the study soon after a first demyelinating event, and they are followed clinically, serologically, and with regular brain MRI.
The cohort in Dr. Fadda’s study comprised 275 children who were a mean of about 11 years old at symptom onset. The mean clinical follow-up was 6.7 years; the mean serologic follow-up, 4 years, and the mean imaging follow-up, 3.5 years. The study examined 1,368 serum samples and 1,459 MRI scans.
Overall, 32% of the children were positive for anti-MOG antibodies. Positivity was not associated with sex, but children with antibodies were significantly younger than those without (7 vs. 12 years). In fact, 77% of anti-MOG–positive children were younger than 11 years; just 15% of older children were positive for the antibodies.
Anti-MOG positivity was also associated with certain clinical phenotypes. Among positive children, 40% presented with optic neuritis, 37% with acute disseminated encephalomyelitis, and 14% with transverse myelitis; the rest had other phenotypes. Optic neuritis was significantly less common among antibody-negative patients (22%), as was encephalomyelitis (17%). Transverse myelitis was significantly more common (31%).
The analysis of MRI scans was stratified according to age younger than 11 years and 11 years and older. “The first thing we noticed among the younger MOG-positive children is that they had a high number of lesions, which were more commonly ill-defined, diffuse, and bilateral,” Dr. Fadda said. “Almost all the brain areas were affected, with a slight preponderance of thalamic and juxtacortical lesions. Among the MOG-negative children, lesions were more often perpendicular to the major axis of the corpus callosum.”
Among the older MOG antibody–positive children, the diffuse pattern was rarer, and the lesions were frequently cerebellar. “But by far, the features that best differentiated positivity from negativity were black holes and enhancing lesions, which we saw in a high proportion of children without the antibodies” at 73% and 49%, respectively.
Over a mean imaging follow-up period of 4 years, lesions were more likely to resolve completely in antibody-positive children than in those without antibodies (50% vs. 21%). Serologically, children who were MOG-antibody negative at baseline were likely to stay that way, with 99% remaining seronegative. Positive children, on the other hand, were significantly more likely to change serologic status, with 56% turning negative and 8% serologically fluctuating over the follow-up period; only 36% remained persistently seropositive. Persistent positive status was significantly associated with younger age (7 vs. 9 years) and an optic neuritis presentation (62% vs. 27%).
Most children (81%) who were antibody positive at baseline experienced no relapses. Among the 16 children who did experience a clinical relapse, the mean time to a second event was about 1 year. Nine of these children stayed persistently positive, while five seroconverted and two had fluctuating status.
Of the 60 antibody-positive children who had a monophasic course, 23 were persistently positive, 34 seroconverted, and 3 had fluctuating serology.
Eventually, 54 children received an MS diagnosis. Of these, 83% were antibody negative at baseline. Ten children received a diagnosis of a relapsing non-MS demyelinating disorder; of these, 91% were antibody positive at baseline.
Dr. Fadda disclosed relationships with Atara Biotherapeutic and Sanofi-Genzyme.
SOURCE: Waters P et al. Mult Scler. 2018;24(S2):29-30, Abstract 65.
REPORTING FROM ECTRIMS 2018
Key clinical point:
Major finding: Most children (81%) who were antibody positive at baseline experienced no relapses.
Study details: A cohort of 275 children from the prospective Canadian Pediatric Demyelinating Disease Study.
Disclosures: Dr. Fadda disclosed relationships with Atara Biotherapeutics and Sanofi-Genzyme.
Source: Waters P et al. Mult Scler. 2018;24(S2):29-30, Abstract 65.
FDA approves Primatene Mist return
After a long absence, Primatene Mist, an over-the-counter asthma inhaler removed from the market in 2011, is being reintroduced in a metered-dose inhaler with a new, environmentally friendly propellant.
But the inhaler’s comeback may prove as controversial as its removal. Respiratory medicine associations have taken issue with the Food and Drug Administration’s decision, warning patients that asthma is not a “do-it-yourself” disease that can be managed with over-the-counter medications.
The American College of Allergy, Asthma, and Immunology, American College of Chest Physicians, American Lung Association, American Thoracic Society, and the American Association of Asthma Educators have each individually protested the decision, and together sent a joint resolution to FDA decrying it. At the core of their protest are the facts that epinephrine is a symptomatic, not therapeutic, asthma treatment and that racemic epinephrine is not a not a recommended asthma treatment under the National Institutes of Health’s “Guidelines for the Diagnosis and Management of Asthma.”
CHEST has published the following statement: “The American College of Chest Physicians (CHEST) is disappointed with the FDA’s decision to approve over-the counter epinephrine (Primatene® Mist HFA) for the treatment of asthma. CHEST is a nonprofit organization dedicated to advancing best patient outcomes. Our membership of more than 19,000 members from around the world provides patient care in pulmonary, critical care, and sleep medicine.
Asthma is a serious and chronic condition with associated high health-care burden. Care for ALL patients with asthma should be under the guidance of a health-care provider. The majority of asthma patients requires treatment with a controller medication, which is only available by prescription. Frequent rescue inhaler use has been associated with increased morbidity and mortality. Over the counter availability of a reliever medication like Primatene Mist can endanger a patient’s wellbeing by providing temporary relief in symptoms, resulting in delay in seeking medical care.”
The inhaler was pulled from sales as part of an international pact to reduce ozone-depleting substances. The 1989 Montreal Protocol of Substances that Deplete the Ozone Layer and the Clean Air Act of 1990 targeted chlorofluorocarbons among those substances, and epinephrine inhalers that contained CFCs were phased out.
The new Primatene Mist HFA (Amphastar Pharmaceuticals) contains hydrofluoroalkane (HFA) propellants, which are permitted under current international and U.S. law. This puts Primatene in the same category with other inhalers, including albuterol and levalbuterol, which also use HFAs as propellants. Each dose delivers 125 mcg of epinephrine.
The inhaler itself has also been redesigned, according to Theresa Michele, MD, director of the FDA’s Division of Nonprescription Drug Products in the Center for Drug Evaluation and Research. The active ingredient is still epinephrine, albeit a smaller dose than found in the original 200-mcg mist. However, the inhaler needs to be activated before first use and cleaned every day after use to prevent a medication buildup. Like other metered-dose inhalers, it requires a priming spray before the inhalation dose, Dr. Michele noted in her online column.
“The inhaler also needs to be shaken and then sprayed once into the air before each use. It may seem strange to shake and spray the inhaler into the air each time before using it. But these two steps are critical to ensure that the medicine is properly mixed before each dose,” Dr. Michele wrote.
A public statement by FDA Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, asserted that the inhaler fills a clinical gap for patients with mild to moderate intermittent asthma.
“The scientific information we reviewed to approve the new version of OTC Primatene Mist shows there is a narrow population of those diagnosed with asthma that may benefit from having access to this type of OTC asthma inhaler. But the product has certain cautions. Making sure that patients can understand and apply the instructions for use was a critical consideration for the FDA. The new product is only appropriate for those with a diagnosis of mild, intermittent asthma. Patients with more severe asthma should not rely on it. Instead, they should be working with their health care provider to ensure an appropriate treatment plan for their condition.”
Before this approval, Amphastar had unsuccessfully brought the reformulated Primatene before FDA several times. The move to finally reinstate it comes after a long, and sometimes contentious, debate among patients and FDA’s Nonprescription Drugs and Pulmonary-Allergy Drugs advisory committee. A quick Internet or Facebook search brings up dozens of stories from patients who say they effectively managed their mild to moderate asthma for years with Primatene. Typically, the stories describe changing to prescription asthma medications that, for some, run into the hundreds of dollars per month. Supporters often negatively compare decades of using the inexpensive Primatene with no ill effects to their recent experiences using prescription corticosteroid inhalers.
It was 4 years ago when Amphastar first appeared before the advisory committee with the reformulated inhaler and positive safety and efficacy data. Although agreeing with the efficacy data, the advisory committee voted against approval, because some felt that asthma should always be managed by a physician; an OTC bronchodilator encouraged self-medicating and discouraged patients from seeking medical care, they said.
“On the one hand, it has been stated that a quick-relief medication available OTC is needed for use in low-income, elderly, and uninsured individuals who might otherwise not have access to treatment or be able to see a health care practitioner,” FDA documents noted. “In contrast, there is also a concern that because asthma is a potentially life-threatening condition that should be diagnosed and treated by a health care professional, availability of an OTC bronchodilator product may discourage consumers from seeking appropriate care, resulting in worse asthma outcomes.”
Two years later, the company received another blow to Primatene program. FDA’s Complete Response Letter required Amphastar to make additional changes to the packaging and run a consumer product safety study, intended to show that people could learn to use the metered-dose inhaler correctly.
In Amphastar’s 2018 first-quarter report, however, company CEO Jack Zhang, PhD, finally shared some good news. “We are pleased to announce that we have resubmitted our NDA for Primatene Mist after receiving good results from our recent human factors study. While we don’t have a Prescription Free User Drug Act [PDUFA] date yet, we plan to begin producing inventory in preparation for a launch.”
That day arrived on Nov. 8, when the PDUFA was granted. In their public letter, Dr. Gottlieb and Dr. Woodcock acknowledged the long and difficult approval path and offered reassurance that Primatene is safe and effective.
“For the right patient, our analysis of the data, including new information that was developed since this product was previously on the market, shows that there are no serious safety concerns when Primatene Mist is used as directed. The product is appropriate for mild symptoms of intermittent asthma, however, even patients with mild asthma can have severe exacerbations – so it’s still important to consult a health care provider about appropriate care and have their condition reassessed. And, of course, all patients who experience severe exacerbations should go to the emergency room right away.”
Primatene Mist HFA is intended for the temporary relief of mild symptoms of intermittent asthma (wheezing, tightness of chest, shortness of breath) in patients aged 12 years and older. It should not be considered a replacement for prescription asthma medications. It should be available in stores early next year.
After a long absence, Primatene Mist, an over-the-counter asthma inhaler removed from the market in 2011, is being reintroduced in a metered-dose inhaler with a new, environmentally friendly propellant.
But the inhaler’s comeback may prove as controversial as its removal. Respiratory medicine associations have taken issue with the Food and Drug Administration’s decision, warning patients that asthma is not a “do-it-yourself” disease that can be managed with over-the-counter medications.
The American College of Allergy, Asthma, and Immunology, American College of Chest Physicians, American Lung Association, American Thoracic Society, and the American Association of Asthma Educators have each individually protested the decision, and together sent a joint resolution to FDA decrying it. At the core of their protest are the facts that epinephrine is a symptomatic, not therapeutic, asthma treatment and that racemic epinephrine is not a not a recommended asthma treatment under the National Institutes of Health’s “Guidelines for the Diagnosis and Management of Asthma.”
CHEST has published the following statement: “The American College of Chest Physicians (CHEST) is disappointed with the FDA’s decision to approve over-the counter epinephrine (Primatene® Mist HFA) for the treatment of asthma. CHEST is a nonprofit organization dedicated to advancing best patient outcomes. Our membership of more than 19,000 members from around the world provides patient care in pulmonary, critical care, and sleep medicine.
Asthma is a serious and chronic condition with associated high health-care burden. Care for ALL patients with asthma should be under the guidance of a health-care provider. The majority of asthma patients requires treatment with a controller medication, which is only available by prescription. Frequent rescue inhaler use has been associated with increased morbidity and mortality. Over the counter availability of a reliever medication like Primatene Mist can endanger a patient’s wellbeing by providing temporary relief in symptoms, resulting in delay in seeking medical care.”
The inhaler was pulled from sales as part of an international pact to reduce ozone-depleting substances. The 1989 Montreal Protocol of Substances that Deplete the Ozone Layer and the Clean Air Act of 1990 targeted chlorofluorocarbons among those substances, and epinephrine inhalers that contained CFCs were phased out.
The new Primatene Mist HFA (Amphastar Pharmaceuticals) contains hydrofluoroalkane (HFA) propellants, which are permitted under current international and U.S. law. This puts Primatene in the same category with other inhalers, including albuterol and levalbuterol, which also use HFAs as propellants. Each dose delivers 125 mcg of epinephrine.
The inhaler itself has also been redesigned, according to Theresa Michele, MD, director of the FDA’s Division of Nonprescription Drug Products in the Center for Drug Evaluation and Research. The active ingredient is still epinephrine, albeit a smaller dose than found in the original 200-mcg mist. However, the inhaler needs to be activated before first use and cleaned every day after use to prevent a medication buildup. Like other metered-dose inhalers, it requires a priming spray before the inhalation dose, Dr. Michele noted in her online column.
“The inhaler also needs to be shaken and then sprayed once into the air before each use. It may seem strange to shake and spray the inhaler into the air each time before using it. But these two steps are critical to ensure that the medicine is properly mixed before each dose,” Dr. Michele wrote.
A public statement by FDA Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, asserted that the inhaler fills a clinical gap for patients with mild to moderate intermittent asthma.
“The scientific information we reviewed to approve the new version of OTC Primatene Mist shows there is a narrow population of those diagnosed with asthma that may benefit from having access to this type of OTC asthma inhaler. But the product has certain cautions. Making sure that patients can understand and apply the instructions for use was a critical consideration for the FDA. The new product is only appropriate for those with a diagnosis of mild, intermittent asthma. Patients with more severe asthma should not rely on it. Instead, they should be working with their health care provider to ensure an appropriate treatment plan for their condition.”
Before this approval, Amphastar had unsuccessfully brought the reformulated Primatene before FDA several times. The move to finally reinstate it comes after a long, and sometimes contentious, debate among patients and FDA’s Nonprescription Drugs and Pulmonary-Allergy Drugs advisory committee. A quick Internet or Facebook search brings up dozens of stories from patients who say they effectively managed their mild to moderate asthma for years with Primatene. Typically, the stories describe changing to prescription asthma medications that, for some, run into the hundreds of dollars per month. Supporters often negatively compare decades of using the inexpensive Primatene with no ill effects to their recent experiences using prescription corticosteroid inhalers.
It was 4 years ago when Amphastar first appeared before the advisory committee with the reformulated inhaler and positive safety and efficacy data. Although agreeing with the efficacy data, the advisory committee voted against approval, because some felt that asthma should always be managed by a physician; an OTC bronchodilator encouraged self-medicating and discouraged patients from seeking medical care, they said.
“On the one hand, it has been stated that a quick-relief medication available OTC is needed for use in low-income, elderly, and uninsured individuals who might otherwise not have access to treatment or be able to see a health care practitioner,” FDA documents noted. “In contrast, there is also a concern that because asthma is a potentially life-threatening condition that should be diagnosed and treated by a health care professional, availability of an OTC bronchodilator product may discourage consumers from seeking appropriate care, resulting in worse asthma outcomes.”
Two years later, the company received another blow to Primatene program. FDA’s Complete Response Letter required Amphastar to make additional changes to the packaging and run a consumer product safety study, intended to show that people could learn to use the metered-dose inhaler correctly.
In Amphastar’s 2018 first-quarter report, however, company CEO Jack Zhang, PhD, finally shared some good news. “We are pleased to announce that we have resubmitted our NDA for Primatene Mist after receiving good results from our recent human factors study. While we don’t have a Prescription Free User Drug Act [PDUFA] date yet, we plan to begin producing inventory in preparation for a launch.”
That day arrived on Nov. 8, when the PDUFA was granted. In their public letter, Dr. Gottlieb and Dr. Woodcock acknowledged the long and difficult approval path and offered reassurance that Primatene is safe and effective.
“For the right patient, our analysis of the data, including new information that was developed since this product was previously on the market, shows that there are no serious safety concerns when Primatene Mist is used as directed. The product is appropriate for mild symptoms of intermittent asthma, however, even patients with mild asthma can have severe exacerbations – so it’s still important to consult a health care provider about appropriate care and have their condition reassessed. And, of course, all patients who experience severe exacerbations should go to the emergency room right away.”
Primatene Mist HFA is intended for the temporary relief of mild symptoms of intermittent asthma (wheezing, tightness of chest, shortness of breath) in patients aged 12 years and older. It should not be considered a replacement for prescription asthma medications. It should be available in stores early next year.
After a long absence, Primatene Mist, an over-the-counter asthma inhaler removed from the market in 2011, is being reintroduced in a metered-dose inhaler with a new, environmentally friendly propellant.
But the inhaler’s comeback may prove as controversial as its removal. Respiratory medicine associations have taken issue with the Food and Drug Administration’s decision, warning patients that asthma is not a “do-it-yourself” disease that can be managed with over-the-counter medications.
The American College of Allergy, Asthma, and Immunology, American College of Chest Physicians, American Lung Association, American Thoracic Society, and the American Association of Asthma Educators have each individually protested the decision, and together sent a joint resolution to FDA decrying it. At the core of their protest are the facts that epinephrine is a symptomatic, not therapeutic, asthma treatment and that racemic epinephrine is not a not a recommended asthma treatment under the National Institutes of Health’s “Guidelines for the Diagnosis and Management of Asthma.”
CHEST has published the following statement: “The American College of Chest Physicians (CHEST) is disappointed with the FDA’s decision to approve over-the counter epinephrine (Primatene® Mist HFA) for the treatment of asthma. CHEST is a nonprofit organization dedicated to advancing best patient outcomes. Our membership of more than 19,000 members from around the world provides patient care in pulmonary, critical care, and sleep medicine.
Asthma is a serious and chronic condition with associated high health-care burden. Care for ALL patients with asthma should be under the guidance of a health-care provider. The majority of asthma patients requires treatment with a controller medication, which is only available by prescription. Frequent rescue inhaler use has been associated with increased morbidity and mortality. Over the counter availability of a reliever medication like Primatene Mist can endanger a patient’s wellbeing by providing temporary relief in symptoms, resulting in delay in seeking medical care.”
The inhaler was pulled from sales as part of an international pact to reduce ozone-depleting substances. The 1989 Montreal Protocol of Substances that Deplete the Ozone Layer and the Clean Air Act of 1990 targeted chlorofluorocarbons among those substances, and epinephrine inhalers that contained CFCs were phased out.
The new Primatene Mist HFA (Amphastar Pharmaceuticals) contains hydrofluoroalkane (HFA) propellants, which are permitted under current international and U.S. law. This puts Primatene in the same category with other inhalers, including albuterol and levalbuterol, which also use HFAs as propellants. Each dose delivers 125 mcg of epinephrine.
The inhaler itself has also been redesigned, according to Theresa Michele, MD, director of the FDA’s Division of Nonprescription Drug Products in the Center for Drug Evaluation and Research. The active ingredient is still epinephrine, albeit a smaller dose than found in the original 200-mcg mist. However, the inhaler needs to be activated before first use and cleaned every day after use to prevent a medication buildup. Like other metered-dose inhalers, it requires a priming spray before the inhalation dose, Dr. Michele noted in her online column.
“The inhaler also needs to be shaken and then sprayed once into the air before each use. It may seem strange to shake and spray the inhaler into the air each time before using it. But these two steps are critical to ensure that the medicine is properly mixed before each dose,” Dr. Michele wrote.
A public statement by FDA Commissioner Scott Gottlieb, MD, and Janet Woodcock, MD, director of the Center for Drug Evaluation and Research, asserted that the inhaler fills a clinical gap for patients with mild to moderate intermittent asthma.
“The scientific information we reviewed to approve the new version of OTC Primatene Mist shows there is a narrow population of those diagnosed with asthma that may benefit from having access to this type of OTC asthma inhaler. But the product has certain cautions. Making sure that patients can understand and apply the instructions for use was a critical consideration for the FDA. The new product is only appropriate for those with a diagnosis of mild, intermittent asthma. Patients with more severe asthma should not rely on it. Instead, they should be working with their health care provider to ensure an appropriate treatment plan for their condition.”
Before this approval, Amphastar had unsuccessfully brought the reformulated Primatene before FDA several times. The move to finally reinstate it comes after a long, and sometimes contentious, debate among patients and FDA’s Nonprescription Drugs and Pulmonary-Allergy Drugs advisory committee. A quick Internet or Facebook search brings up dozens of stories from patients who say they effectively managed their mild to moderate asthma for years with Primatene. Typically, the stories describe changing to prescription asthma medications that, for some, run into the hundreds of dollars per month. Supporters often negatively compare decades of using the inexpensive Primatene with no ill effects to their recent experiences using prescription corticosteroid inhalers.
It was 4 years ago when Amphastar first appeared before the advisory committee with the reformulated inhaler and positive safety and efficacy data. Although agreeing with the efficacy data, the advisory committee voted against approval, because some felt that asthma should always be managed by a physician; an OTC bronchodilator encouraged self-medicating and discouraged patients from seeking medical care, they said.
“On the one hand, it has been stated that a quick-relief medication available OTC is needed for use in low-income, elderly, and uninsured individuals who might otherwise not have access to treatment or be able to see a health care practitioner,” FDA documents noted. “In contrast, there is also a concern that because asthma is a potentially life-threatening condition that should be diagnosed and treated by a health care professional, availability of an OTC bronchodilator product may discourage consumers from seeking appropriate care, resulting in worse asthma outcomes.”
Two years later, the company received another blow to Primatene program. FDA’s Complete Response Letter required Amphastar to make additional changes to the packaging and run a consumer product safety study, intended to show that people could learn to use the metered-dose inhaler correctly.
In Amphastar’s 2018 first-quarter report, however, company CEO Jack Zhang, PhD, finally shared some good news. “We are pleased to announce that we have resubmitted our NDA for Primatene Mist after receiving good results from our recent human factors study. While we don’t have a Prescription Free User Drug Act [PDUFA] date yet, we plan to begin producing inventory in preparation for a launch.”
That day arrived on Nov. 8, when the PDUFA was granted. In their public letter, Dr. Gottlieb and Dr. Woodcock acknowledged the long and difficult approval path and offered reassurance that Primatene is safe and effective.
“For the right patient, our analysis of the data, including new information that was developed since this product was previously on the market, shows that there are no serious safety concerns when Primatene Mist is used as directed. The product is appropriate for mild symptoms of intermittent asthma, however, even patients with mild asthma can have severe exacerbations – so it’s still important to consult a health care provider about appropriate care and have their condition reassessed. And, of course, all patients who experience severe exacerbations should go to the emergency room right away.”
Primatene Mist HFA is intended for the temporary relief of mild symptoms of intermittent asthma (wheezing, tightness of chest, shortness of breath) in patients aged 12 years and older. It should not be considered a replacement for prescription asthma medications. It should be available in stores early next year.