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FDA advisory committee recommends volanesorsen for rare triglyceride disorder
SILVER SPRING, Md. – A novel drug to treat a rare metabolic disorder was recommended for approval by the Endocrinologic and Metabolic Drugs Advisory Committee in a May 10 meeting.
Advisors voted 12 to 8 to recommend volanesorsen, a novel antisense drug, as an adjunct to diet for the treatment of familial chylomicronemia syndrome (FCS).
“The sponsor provided compelling evidence that the drug lowers triglyceride levels, substantially,” said panelist Jean-Pierre Raufman, MD, of the University of Maryland. I think that there is clearly a group of patients with this disease that can benefit from this agent.”
FCS is an extremely rare genetic disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis caused by a deficiency in lipoprotein lipase. Pancreatitis in the setting of hypertriglyceridemia is particularly severe, often leading to multi-organ failure, pancreatic necrosis, and death.
Volanesorsen targets apolipoprotein C-III (apoC-III), a key regulator of lipoprotein lipase, the essential enzyme involved in chylomicron and triglyceride clearance.
Because of the small number of patients affected, estimated at just 3,000-5,000 patients worldwide, the FDA considers FCS to be an orphan disease.
The application, submitted by Akcea Pharmaceuticals, was based on the results of several phase 3 clinical trials conducted both in FCS patients and, because of the rarity of the disorder, patients with high triglycerides. The APPROACH study looked at patients with FCS. The COMPASS study examined patients with hypertriglyceridemia. Additionally, an ongoing, open-label extension of the APPROACH study examined patients with FCS who had completed APPROACH, COMPASS, and FCS patients who had not participated in a previous volanesorsen trial.
APPROACH APPROACH was a phase 3, double-blind clinical trial to assess the safety and efficacy of volanesorsen in patients with FCS. Because of the extremely small number of patients affected by FCS, non-FCS patients with hypertriglyceridemia were included in the trial.
All patients who had completed a 6 week diet, lifestyle, and medication stabilization period were enrolled in the study. In total, 67 patients were randomized to receive a weekly, subcutaneous 300 mg dose of volanesorsen or a placebo for 52 weeks. Due to the risk of platelet reduction, the study allowed for dosing schedule interruptions or pauses, if needed. To assess efficacy, the study looked at the percent change in fasting triglycerides at month 3 of the study in all randomized patients who received at least one dose of the study drug and who had baseline fasting plasma trigylcerides recorded.
Volanesorsen proved quite effective in reducing fasting triglyceride levels, with a 94% (P < 0.0001) reduction in plasma concentrations at 3 months, compared with placebo.
The effectiveness of volanesorsen extended beyond month 3, with statistically significant reductions in triglyceride concentrations at both month 6 and month 12 compared with placebo. Patients taking volanesorsen had 53% and 40% reductions at month 6 and 12 compared to baseline. Conversely, patients taking placebo experienced increases of 25% and 9%, respectively. The differences between volanesorsen and placebo patients at month 6 (–78%) and month 12 (–49%) were both statistically significant.
Another important finding from this study was that 77% of patients responded to treatment, evidenced by a reduction of triglyceride levels greater than 750 mg/dL, a much better response than the 10% of placebo patients (P =.0001).
Nine patients (27%) discontinued the study due to adverse events (AE). Five of the discontinuations were related to platelet reductions with the other four related to nonplatelet-related adverse events.
COMPASS
The COMPASS study primarily looked at patients without FCS, but severe hypertriglyceridemia, to evaluate the safety and efficacy of volanesorsen in a similarly ill, but less severe, population over a 6 month study period. Patients with FCS had baseline fasting plasma triglyceride levels of 2,644 mg/dL and 2,134 mg/dL in the placebo and volanesorsen groups, respectively. This is nearly double what was seen in non-FCS patients in the study, and is 14-17 higher than the upper limit of normal (ULN).
Researchers enrolled 114 patients and randomized them 2:1 to receive volanesorsen or placebo. This led to 75 patients taking volanesorsen and 34 placebo.
The efficacy results were similar to those in the FCS-focused APPROACH trial, with volanesorsen treatment leading to reductions in triglyceride levels after 3 months, with further reductions over the 6-month study treatment.
Weekly treatment with volanesorsen reduced triglycerides by nearly 71% in the total patient population, compared to placebo, which only achieved a 0.9% decrease in triglycerides. These reductions were conserved at the end of week 26 in patients who had to reduce their dosing to biweekly (62%) and patients who maintained weekly dosing treatments (78%). Overall, a greater than 40% reduction of fasting triglyceride levels after 3 months of treatment was achieved in 87% of volanesorsen-treated patients, compared to 13% of placebo-treated patients (P < 0.0001).
Serious adverse events (SAEs) occurred in nine patients (8%). In the placebo group, two patients (5%) reported acute pancreatitis. Apart from the bouts of pancreatitis, some of the most common AEs were decreased platelet count, thrombocytopenia, and nasopharyngitis.
APPROACH OPEN LABEL
The open label portion of the APPROACH study is ongoing and was designed to assess the safety and efficacy of extended treatment with volanesorsen in patients with FCS who had previously completed APPROACH or COMPASS studies or had never received volanesorsen treatment. Patients received 300 mg of volanesorsen once weekly for 52 weeks. Patients who completed the trial were eligible to continue treatment for an additional 52 weeks or until a product is available. As of August 31, 2017, after the data cutoff, 60 patients were enrolled.
The results of this open label portion of the APPROACH trial were similar to that of the APPROACH trial itself. Patients who transitioned from APPROACH or COMPASS showed decreases in their open label extension (OLE) baseline triglyceride measurements to OLE month 3 of 48.1% and 52.1%, respectively. Treatment-naive patients displayed a nearly 60% decrease in their triglyceride levels 3 months.
Of the 60 patients who started the study, 12 have discontinued the study prematurely. The majority of patients, eight, who discontinued did so because of adverse events and four withdrew voluntarily.
Adverse events were not uncommon, with 56 patients (93%) experiencing an AE during the course of the study. Some of the most common AEs were decreased platelet count, thrombocytopenia, and nasopharyngitis.
Akcea has developed a Risk Evaluation and Mitigation program to mitigate the risk of serious bleeding related to severe thrombocytopenia with volanesorsen use in patients with FCS.
Panelist Susan Z. Yanovksi, MD, of the National Institutes of Health, said she voted no over safety concerns, but felt conflicted.
“There’s no question that volanesorsen is effective in dramatically reducing triglycerides, but I had a lot of concerns whether the data presented by the sponsor actually established favorable risk-benefit ratio.”
The FDA is expected to decide on the application by August 30. The FDA usually follows the recommendations of its advisory panels, which are not binding.
SILVER SPRING, Md. – A novel drug to treat a rare metabolic disorder was recommended for approval by the Endocrinologic and Metabolic Drugs Advisory Committee in a May 10 meeting.
Advisors voted 12 to 8 to recommend volanesorsen, a novel antisense drug, as an adjunct to diet for the treatment of familial chylomicronemia syndrome (FCS).
“The sponsor provided compelling evidence that the drug lowers triglyceride levels, substantially,” said panelist Jean-Pierre Raufman, MD, of the University of Maryland. I think that there is clearly a group of patients with this disease that can benefit from this agent.”
FCS is an extremely rare genetic disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis caused by a deficiency in lipoprotein lipase. Pancreatitis in the setting of hypertriglyceridemia is particularly severe, often leading to multi-organ failure, pancreatic necrosis, and death.
Volanesorsen targets apolipoprotein C-III (apoC-III), a key regulator of lipoprotein lipase, the essential enzyme involved in chylomicron and triglyceride clearance.
Because of the small number of patients affected, estimated at just 3,000-5,000 patients worldwide, the FDA considers FCS to be an orphan disease.
The application, submitted by Akcea Pharmaceuticals, was based on the results of several phase 3 clinical trials conducted both in FCS patients and, because of the rarity of the disorder, patients with high triglycerides. The APPROACH study looked at patients with FCS. The COMPASS study examined patients with hypertriglyceridemia. Additionally, an ongoing, open-label extension of the APPROACH study examined patients with FCS who had completed APPROACH, COMPASS, and FCS patients who had not participated in a previous volanesorsen trial.
APPROACH APPROACH was a phase 3, double-blind clinical trial to assess the safety and efficacy of volanesorsen in patients with FCS. Because of the extremely small number of patients affected by FCS, non-FCS patients with hypertriglyceridemia were included in the trial.
All patients who had completed a 6 week diet, lifestyle, and medication stabilization period were enrolled in the study. In total, 67 patients were randomized to receive a weekly, subcutaneous 300 mg dose of volanesorsen or a placebo for 52 weeks. Due to the risk of platelet reduction, the study allowed for dosing schedule interruptions or pauses, if needed. To assess efficacy, the study looked at the percent change in fasting triglycerides at month 3 of the study in all randomized patients who received at least one dose of the study drug and who had baseline fasting plasma trigylcerides recorded.
Volanesorsen proved quite effective in reducing fasting triglyceride levels, with a 94% (P < 0.0001) reduction in plasma concentrations at 3 months, compared with placebo.
The effectiveness of volanesorsen extended beyond month 3, with statistically significant reductions in triglyceride concentrations at both month 6 and month 12 compared with placebo. Patients taking volanesorsen had 53% and 40% reductions at month 6 and 12 compared to baseline. Conversely, patients taking placebo experienced increases of 25% and 9%, respectively. The differences between volanesorsen and placebo patients at month 6 (–78%) and month 12 (–49%) were both statistically significant.
Another important finding from this study was that 77% of patients responded to treatment, evidenced by a reduction of triglyceride levels greater than 750 mg/dL, a much better response than the 10% of placebo patients (P =.0001).
Nine patients (27%) discontinued the study due to adverse events (AE). Five of the discontinuations were related to platelet reductions with the other four related to nonplatelet-related adverse events.
COMPASS
The COMPASS study primarily looked at patients without FCS, but severe hypertriglyceridemia, to evaluate the safety and efficacy of volanesorsen in a similarly ill, but less severe, population over a 6 month study period. Patients with FCS had baseline fasting plasma triglyceride levels of 2,644 mg/dL and 2,134 mg/dL in the placebo and volanesorsen groups, respectively. This is nearly double what was seen in non-FCS patients in the study, and is 14-17 higher than the upper limit of normal (ULN).
Researchers enrolled 114 patients and randomized them 2:1 to receive volanesorsen or placebo. This led to 75 patients taking volanesorsen and 34 placebo.
The efficacy results were similar to those in the FCS-focused APPROACH trial, with volanesorsen treatment leading to reductions in triglyceride levels after 3 months, with further reductions over the 6-month study treatment.
Weekly treatment with volanesorsen reduced triglycerides by nearly 71% in the total patient population, compared to placebo, which only achieved a 0.9% decrease in triglycerides. These reductions were conserved at the end of week 26 in patients who had to reduce their dosing to biweekly (62%) and patients who maintained weekly dosing treatments (78%). Overall, a greater than 40% reduction of fasting triglyceride levels after 3 months of treatment was achieved in 87% of volanesorsen-treated patients, compared to 13% of placebo-treated patients (P < 0.0001).
Serious adverse events (SAEs) occurred in nine patients (8%). In the placebo group, two patients (5%) reported acute pancreatitis. Apart from the bouts of pancreatitis, some of the most common AEs were decreased platelet count, thrombocytopenia, and nasopharyngitis.
APPROACH OPEN LABEL
The open label portion of the APPROACH study is ongoing and was designed to assess the safety and efficacy of extended treatment with volanesorsen in patients with FCS who had previously completed APPROACH or COMPASS studies or had never received volanesorsen treatment. Patients received 300 mg of volanesorsen once weekly for 52 weeks. Patients who completed the trial were eligible to continue treatment for an additional 52 weeks or until a product is available. As of August 31, 2017, after the data cutoff, 60 patients were enrolled.
The results of this open label portion of the APPROACH trial were similar to that of the APPROACH trial itself. Patients who transitioned from APPROACH or COMPASS showed decreases in their open label extension (OLE) baseline triglyceride measurements to OLE month 3 of 48.1% and 52.1%, respectively. Treatment-naive patients displayed a nearly 60% decrease in their triglyceride levels 3 months.
Of the 60 patients who started the study, 12 have discontinued the study prematurely. The majority of patients, eight, who discontinued did so because of adverse events and four withdrew voluntarily.
Adverse events were not uncommon, with 56 patients (93%) experiencing an AE during the course of the study. Some of the most common AEs were decreased platelet count, thrombocytopenia, and nasopharyngitis.
Akcea has developed a Risk Evaluation and Mitigation program to mitigate the risk of serious bleeding related to severe thrombocytopenia with volanesorsen use in patients with FCS.
Panelist Susan Z. Yanovksi, MD, of the National Institutes of Health, said she voted no over safety concerns, but felt conflicted.
“There’s no question that volanesorsen is effective in dramatically reducing triglycerides, but I had a lot of concerns whether the data presented by the sponsor actually established favorable risk-benefit ratio.”
The FDA is expected to decide on the application by August 30. The FDA usually follows the recommendations of its advisory panels, which are not binding.
SILVER SPRING, Md. – A novel drug to treat a rare metabolic disorder was recommended for approval by the Endocrinologic and Metabolic Drugs Advisory Committee in a May 10 meeting.
Advisors voted 12 to 8 to recommend volanesorsen, a novel antisense drug, as an adjunct to diet for the treatment of familial chylomicronemia syndrome (FCS).
“The sponsor provided compelling evidence that the drug lowers triglyceride levels, substantially,” said panelist Jean-Pierre Raufman, MD, of the University of Maryland. I think that there is clearly a group of patients with this disease that can benefit from this agent.”
FCS is an extremely rare genetic disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis caused by a deficiency in lipoprotein lipase. Pancreatitis in the setting of hypertriglyceridemia is particularly severe, often leading to multi-organ failure, pancreatic necrosis, and death.
Volanesorsen targets apolipoprotein C-III (apoC-III), a key regulator of lipoprotein lipase, the essential enzyme involved in chylomicron and triglyceride clearance.
Because of the small number of patients affected, estimated at just 3,000-5,000 patients worldwide, the FDA considers FCS to be an orphan disease.
The application, submitted by Akcea Pharmaceuticals, was based on the results of several phase 3 clinical trials conducted both in FCS patients and, because of the rarity of the disorder, patients with high triglycerides. The APPROACH study looked at patients with FCS. The COMPASS study examined patients with hypertriglyceridemia. Additionally, an ongoing, open-label extension of the APPROACH study examined patients with FCS who had completed APPROACH, COMPASS, and FCS patients who had not participated in a previous volanesorsen trial.
APPROACH APPROACH was a phase 3, double-blind clinical trial to assess the safety and efficacy of volanesorsen in patients with FCS. Because of the extremely small number of patients affected by FCS, non-FCS patients with hypertriglyceridemia were included in the trial.
All patients who had completed a 6 week diet, lifestyle, and medication stabilization period were enrolled in the study. In total, 67 patients were randomized to receive a weekly, subcutaneous 300 mg dose of volanesorsen or a placebo for 52 weeks. Due to the risk of platelet reduction, the study allowed for dosing schedule interruptions or pauses, if needed. To assess efficacy, the study looked at the percent change in fasting triglycerides at month 3 of the study in all randomized patients who received at least one dose of the study drug and who had baseline fasting plasma trigylcerides recorded.
Volanesorsen proved quite effective in reducing fasting triglyceride levels, with a 94% (P < 0.0001) reduction in plasma concentrations at 3 months, compared with placebo.
The effectiveness of volanesorsen extended beyond month 3, with statistically significant reductions in triglyceride concentrations at both month 6 and month 12 compared with placebo. Patients taking volanesorsen had 53% and 40% reductions at month 6 and 12 compared to baseline. Conversely, patients taking placebo experienced increases of 25% and 9%, respectively. The differences between volanesorsen and placebo patients at month 6 (–78%) and month 12 (–49%) were both statistically significant.
Another important finding from this study was that 77% of patients responded to treatment, evidenced by a reduction of triglyceride levels greater than 750 mg/dL, a much better response than the 10% of placebo patients (P =.0001).
Nine patients (27%) discontinued the study due to adverse events (AE). Five of the discontinuations were related to platelet reductions with the other four related to nonplatelet-related adverse events.
COMPASS
The COMPASS study primarily looked at patients without FCS, but severe hypertriglyceridemia, to evaluate the safety and efficacy of volanesorsen in a similarly ill, but less severe, population over a 6 month study period. Patients with FCS had baseline fasting plasma triglyceride levels of 2,644 mg/dL and 2,134 mg/dL in the placebo and volanesorsen groups, respectively. This is nearly double what was seen in non-FCS patients in the study, and is 14-17 higher than the upper limit of normal (ULN).
Researchers enrolled 114 patients and randomized them 2:1 to receive volanesorsen or placebo. This led to 75 patients taking volanesorsen and 34 placebo.
The efficacy results were similar to those in the FCS-focused APPROACH trial, with volanesorsen treatment leading to reductions in triglyceride levels after 3 months, with further reductions over the 6-month study treatment.
Weekly treatment with volanesorsen reduced triglycerides by nearly 71% in the total patient population, compared to placebo, which only achieved a 0.9% decrease in triglycerides. These reductions were conserved at the end of week 26 in patients who had to reduce their dosing to biweekly (62%) and patients who maintained weekly dosing treatments (78%). Overall, a greater than 40% reduction of fasting triglyceride levels after 3 months of treatment was achieved in 87% of volanesorsen-treated patients, compared to 13% of placebo-treated patients (P < 0.0001).
Serious adverse events (SAEs) occurred in nine patients (8%). In the placebo group, two patients (5%) reported acute pancreatitis. Apart from the bouts of pancreatitis, some of the most common AEs were decreased platelet count, thrombocytopenia, and nasopharyngitis.
APPROACH OPEN LABEL
The open label portion of the APPROACH study is ongoing and was designed to assess the safety and efficacy of extended treatment with volanesorsen in patients with FCS who had previously completed APPROACH or COMPASS studies or had never received volanesorsen treatment. Patients received 300 mg of volanesorsen once weekly for 52 weeks. Patients who completed the trial were eligible to continue treatment for an additional 52 weeks or until a product is available. As of August 31, 2017, after the data cutoff, 60 patients were enrolled.
The results of this open label portion of the APPROACH trial were similar to that of the APPROACH trial itself. Patients who transitioned from APPROACH or COMPASS showed decreases in their open label extension (OLE) baseline triglyceride measurements to OLE month 3 of 48.1% and 52.1%, respectively. Treatment-naive patients displayed a nearly 60% decrease in their triglyceride levels 3 months.
Of the 60 patients who started the study, 12 have discontinued the study prematurely. The majority of patients, eight, who discontinued did so because of adverse events and four withdrew voluntarily.
Adverse events were not uncommon, with 56 patients (93%) experiencing an AE during the course of the study. Some of the most common AEs were decreased platelet count, thrombocytopenia, and nasopharyngitis.
Akcea has developed a Risk Evaluation and Mitigation program to mitigate the risk of serious bleeding related to severe thrombocytopenia with volanesorsen use in patients with FCS.
Panelist Susan Z. Yanovksi, MD, of the National Institutes of Health, said she voted no over safety concerns, but felt conflicted.
“There’s no question that volanesorsen is effective in dramatically reducing triglycerides, but I had a lot of concerns whether the data presented by the sponsor actually established favorable risk-benefit ratio.”
The FDA is expected to decide on the application by August 30. The FDA usually follows the recommendations of its advisory panels, which are not binding.
REPORTING FROM an fda advisory committee meeting
Managing agitation in outpatient dementia
NEW ORLEANS – A reasonable stepwise approach to pharmacotherapy for agitation in outpatient dementia begins with a judiciously chosen SSRI as first-line therapy, with the second-line consisting of augmentation with a benzodiazepine, M. Philip Luber, MD, said at the annual meeting of the American College of Physicians.
If this combination doesn’t provide satisfactory improvement after adequate dosing for sufficient duration, only then is it time to turn to an atypical antipsychotic agent as a higher-risk/higher-reward third-line therapy, added Dr. Luber, professor of psychiatry and associate dean for graduate medical education at the University of Texas, San Antonio.
He emphasized, however, that medications are not the first-line therapy for agitation in outpatients with dementia. That distinction belongs to psychosocial interventions.
“Utilize a social worker to assist the family in modifying the environment: family settings and people, regular routines, consistently orienting the patient, keeping stimulation at a low to moderate level. When that’s done right, it can really dampen down a lot of agitation,” he said.
Dr. Luber noted that the formal randomized trial evidence base for SSRIs as first-line pharmacotherapy and benzodiazepines as second-line is quite limited. But in conversations with geriatric psychiatrists and other health care professionals around the country who are working in this area, he has found broad agreement that this is a good strategy.
“A lot of folks don’t realize that [SSRIs] are actually very useful in the treatment of agitation in dementia. But you want to choose one with fewer side effects and drug-drug interactions,” Dr. Luber said.
Two SSRIs that fit the bill are escitalopram (Lexapro) and sertraline (Zoloft). Start low and increase the dose slowly, provided circumstances allow. Expect a therapeutic response to emerge in weeks, not days. And, in this elderly population, be sure to monitor for hyponatremia.
When considering augmentation, remember that “using benzodiazepines in the elderly is controversial, particularly with agitation in dementia. There is very little randomized clinical trial data on benzodiazepines in dementia. Actually, though, there are lots of clinical trials of benzodiazepines in dementia that feature benzodiazepines as rescue medication. So, clinically, there’s an awareness that the drugs work, but they haven’t been studied except as rescue medication,” he explained.
The phenomenon of paradoxical agitation occurring in elderly patients on benzodiazepines “is something to be careful about, but in fact it’s pretty uncommon. Just watch for it,” he added.
Dr. Luber is among many geriatric psychiatrists who preferentially turn to clonazepam (Klonopin) because its relatively long half-life allows for twice-daily administration.
“Think about using it regularly rather than PRN. You want to stay ahead of the agitation rather than behind it,” he advised.
Patients with liver disease are better served by a shorter-acting benzodiazepine such as lorazepam (Ativan), which is not oxidized in the liver.
Also controversial is use of atypical antipsychotics as third-line pharmacotherapy, “but many geriatric psychiatrists would agree with me that the next step if the patient is still agitated despite an SSRI augmented with a benzodiazepine is to consider a trial of an atypical antipsychotic,” Dr. Luber said.
He pointed to risperidone (Risperdal) and aripiprazole (Abilify) as agents with a good track record for treatment of agitation in dementia. He urged primary care physicians to be familiar with the risk of serious and even potentially fatal side effects as described in the black box warning.
“There are tough choices involved in treating patients with this disorder. Use shared decision making with the patient or family,” Dr. Luber said.
He reported having no financial conflicts of interest regarding his presentation.
NEW ORLEANS – A reasonable stepwise approach to pharmacotherapy for agitation in outpatient dementia begins with a judiciously chosen SSRI as first-line therapy, with the second-line consisting of augmentation with a benzodiazepine, M. Philip Luber, MD, said at the annual meeting of the American College of Physicians.
If this combination doesn’t provide satisfactory improvement after adequate dosing for sufficient duration, only then is it time to turn to an atypical antipsychotic agent as a higher-risk/higher-reward third-line therapy, added Dr. Luber, professor of psychiatry and associate dean for graduate medical education at the University of Texas, San Antonio.
He emphasized, however, that medications are not the first-line therapy for agitation in outpatients with dementia. That distinction belongs to psychosocial interventions.
“Utilize a social worker to assist the family in modifying the environment: family settings and people, regular routines, consistently orienting the patient, keeping stimulation at a low to moderate level. When that’s done right, it can really dampen down a lot of agitation,” he said.
Dr. Luber noted that the formal randomized trial evidence base for SSRIs as first-line pharmacotherapy and benzodiazepines as second-line is quite limited. But in conversations with geriatric psychiatrists and other health care professionals around the country who are working in this area, he has found broad agreement that this is a good strategy.
“A lot of folks don’t realize that [SSRIs] are actually very useful in the treatment of agitation in dementia. But you want to choose one with fewer side effects and drug-drug interactions,” Dr. Luber said.
Two SSRIs that fit the bill are escitalopram (Lexapro) and sertraline (Zoloft). Start low and increase the dose slowly, provided circumstances allow. Expect a therapeutic response to emerge in weeks, not days. And, in this elderly population, be sure to monitor for hyponatremia.
When considering augmentation, remember that “using benzodiazepines in the elderly is controversial, particularly with agitation in dementia. There is very little randomized clinical trial data on benzodiazepines in dementia. Actually, though, there are lots of clinical trials of benzodiazepines in dementia that feature benzodiazepines as rescue medication. So, clinically, there’s an awareness that the drugs work, but they haven’t been studied except as rescue medication,” he explained.
The phenomenon of paradoxical agitation occurring in elderly patients on benzodiazepines “is something to be careful about, but in fact it’s pretty uncommon. Just watch for it,” he added.
Dr. Luber is among many geriatric psychiatrists who preferentially turn to clonazepam (Klonopin) because its relatively long half-life allows for twice-daily administration.
“Think about using it regularly rather than PRN. You want to stay ahead of the agitation rather than behind it,” he advised.
Patients with liver disease are better served by a shorter-acting benzodiazepine such as lorazepam (Ativan), which is not oxidized in the liver.
Also controversial is use of atypical antipsychotics as third-line pharmacotherapy, “but many geriatric psychiatrists would agree with me that the next step if the patient is still agitated despite an SSRI augmented with a benzodiazepine is to consider a trial of an atypical antipsychotic,” Dr. Luber said.
He pointed to risperidone (Risperdal) and aripiprazole (Abilify) as agents with a good track record for treatment of agitation in dementia. He urged primary care physicians to be familiar with the risk of serious and even potentially fatal side effects as described in the black box warning.
“There are tough choices involved in treating patients with this disorder. Use shared decision making with the patient or family,” Dr. Luber said.
He reported having no financial conflicts of interest regarding his presentation.
NEW ORLEANS – A reasonable stepwise approach to pharmacotherapy for agitation in outpatient dementia begins with a judiciously chosen SSRI as first-line therapy, with the second-line consisting of augmentation with a benzodiazepine, M. Philip Luber, MD, said at the annual meeting of the American College of Physicians.
If this combination doesn’t provide satisfactory improvement after adequate dosing for sufficient duration, only then is it time to turn to an atypical antipsychotic agent as a higher-risk/higher-reward third-line therapy, added Dr. Luber, professor of psychiatry and associate dean for graduate medical education at the University of Texas, San Antonio.
He emphasized, however, that medications are not the first-line therapy for agitation in outpatients with dementia. That distinction belongs to psychosocial interventions.
“Utilize a social worker to assist the family in modifying the environment: family settings and people, regular routines, consistently orienting the patient, keeping stimulation at a low to moderate level. When that’s done right, it can really dampen down a lot of agitation,” he said.
Dr. Luber noted that the formal randomized trial evidence base for SSRIs as first-line pharmacotherapy and benzodiazepines as second-line is quite limited. But in conversations with geriatric psychiatrists and other health care professionals around the country who are working in this area, he has found broad agreement that this is a good strategy.
“A lot of folks don’t realize that [SSRIs] are actually very useful in the treatment of agitation in dementia. But you want to choose one with fewer side effects and drug-drug interactions,” Dr. Luber said.
Two SSRIs that fit the bill are escitalopram (Lexapro) and sertraline (Zoloft). Start low and increase the dose slowly, provided circumstances allow. Expect a therapeutic response to emerge in weeks, not days. And, in this elderly population, be sure to monitor for hyponatremia.
When considering augmentation, remember that “using benzodiazepines in the elderly is controversial, particularly with agitation in dementia. There is very little randomized clinical trial data on benzodiazepines in dementia. Actually, though, there are lots of clinical trials of benzodiazepines in dementia that feature benzodiazepines as rescue medication. So, clinically, there’s an awareness that the drugs work, but they haven’t been studied except as rescue medication,” he explained.
The phenomenon of paradoxical agitation occurring in elderly patients on benzodiazepines “is something to be careful about, but in fact it’s pretty uncommon. Just watch for it,” he added.
Dr. Luber is among many geriatric psychiatrists who preferentially turn to clonazepam (Klonopin) because its relatively long half-life allows for twice-daily administration.
“Think about using it regularly rather than PRN. You want to stay ahead of the agitation rather than behind it,” he advised.
Patients with liver disease are better served by a shorter-acting benzodiazepine such as lorazepam (Ativan), which is not oxidized in the liver.
Also controversial is use of atypical antipsychotics as third-line pharmacotherapy, “but many geriatric psychiatrists would agree with me that the next step if the patient is still agitated despite an SSRI augmented with a benzodiazepine is to consider a trial of an atypical antipsychotic,” Dr. Luber said.
He pointed to risperidone (Risperdal) and aripiprazole (Abilify) as agents with a good track record for treatment of agitation in dementia. He urged primary care physicians to be familiar with the risk of serious and even potentially fatal side effects as described in the black box warning.
“There are tough choices involved in treating patients with this disorder. Use shared decision making with the patient or family,” Dr. Luber said.
He reported having no financial conflicts of interest regarding his presentation.
REPORTING FROM ACP INTERNAL MEDICINE
Implanted pulse generator ups exercise tolerance in HF
BOSTON – Cardiac contractility modulation (CCM), an electrical device–based modality, may improve exercise tolerance and quality of life in heart failure patients with ejection fraction between 25% and 45%, results of a randomized, controlled trial suggested.
Notably, clinical effectiveness appeared to be even greater in the subset of patient with ejection fractions between 35% and 45%, according to results presented at the annual scientific sessions of the Heart Rhythm Society.
The CCM approach was designed to treat chronic heart failure patients with reduced and midrange ejection fractions. It involves the delivery of electrical signals during the cardiac absolute refractory period to enhance contraction strength. Key components include an atrial lead used for sensing and two ventricular leads used for sensing local electrical activity and delivery of CCM signals.
The device was previously evaluated in FIX-HF-5, a 428-patient randomized trial of CCM in patients with New York Heart Association functional class III/IV and reduced ejection fraction. That study failed to meet its primary efficacy end point, but a subgroup analysis showed significant treatment effects in patients with ejection fractions between 25% and 45%.
Consequently, Dr. Abraham initiated the FIX-HF-5 confirmatory study (FIX-HF-5C) to prospectively evaluate CCM in patients with ejection fractions in that range.
The study included 160 with NYHA class III/IV heart failure, QRS duration less than 130 ms, and ejection fractions of 25%-45% who were randomized either to CCM or to continued optimal medical therapy. The control arm included 86 patients, and the CCM arm included 74 patients, of whom 68 received device implantation.
For evaluating peak VO2, the primary end point of this confirmatory study, investigators used a Bayesian model that allowed them incorporate some data from the corresponding subgroup of patients with ejection fractions between 25% and 45% in the previous FIX-HF-5 randomized trial.
Using this model, they found the mean difference between CCM and medical therapy groups at week 24 was 0.836 mL O2/kg per minute (95% Bayesian credible interval, 0.123-1.552). The probability of CCM treatment’s superiority to control was 0.989, according to investigators, which exceeded the 0.975 threshold for statistical significance.
Dr. Abraham and his coinvestigators found that CCM implantation was safe, with a 90% complication-free rate, and that it improved both quality of life and functional status.
All efficacy endpoints were better in patients with ejection fractions of 35% or greater, confirming the subgroup analysis findings of the previous randomized trial, according to Dr. Abraham and his coinvestigators.
Survival free of cardiac death and heart failure hospitalization at 24 weeks was 97.1% in the CCM arm versus 89.2% in controls, which was a secondary finding that reached statistical significance in favor of CCM (P = .048) in one analysis of Kaplan-Meier estimates, investigators said in their report.
The CCM device could fulfill an unmet need for patients who have persistent heart failure despite optimal, guideline-based medical therapy, according to the investigators.
“Although ICDs are applicable to the broad population of patients with ejection fraction [at least] 35%, they do not deliver a therapy for improving exercise tolerance or quality of life,” they said in their report.
Research grant support for the study came from Impulse Dynamics. Dr. Abraham and several coauthors reported serving as consultants to the company.
SOURCE: Abraham WT et al. JACC Heart Fail. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010.
BOSTON – Cardiac contractility modulation (CCM), an electrical device–based modality, may improve exercise tolerance and quality of life in heart failure patients with ejection fraction between 25% and 45%, results of a randomized, controlled trial suggested.
Notably, clinical effectiveness appeared to be even greater in the subset of patient with ejection fractions between 35% and 45%, according to results presented at the annual scientific sessions of the Heart Rhythm Society.
The CCM approach was designed to treat chronic heart failure patients with reduced and midrange ejection fractions. It involves the delivery of electrical signals during the cardiac absolute refractory period to enhance contraction strength. Key components include an atrial lead used for sensing and two ventricular leads used for sensing local electrical activity and delivery of CCM signals.
The device was previously evaluated in FIX-HF-5, a 428-patient randomized trial of CCM in patients with New York Heart Association functional class III/IV and reduced ejection fraction. That study failed to meet its primary efficacy end point, but a subgroup analysis showed significant treatment effects in patients with ejection fractions between 25% and 45%.
Consequently, Dr. Abraham initiated the FIX-HF-5 confirmatory study (FIX-HF-5C) to prospectively evaluate CCM in patients with ejection fractions in that range.
The study included 160 with NYHA class III/IV heart failure, QRS duration less than 130 ms, and ejection fractions of 25%-45% who were randomized either to CCM or to continued optimal medical therapy. The control arm included 86 patients, and the CCM arm included 74 patients, of whom 68 received device implantation.
For evaluating peak VO2, the primary end point of this confirmatory study, investigators used a Bayesian model that allowed them incorporate some data from the corresponding subgroup of patients with ejection fractions between 25% and 45% in the previous FIX-HF-5 randomized trial.
Using this model, they found the mean difference between CCM and medical therapy groups at week 24 was 0.836 mL O2/kg per minute (95% Bayesian credible interval, 0.123-1.552). The probability of CCM treatment’s superiority to control was 0.989, according to investigators, which exceeded the 0.975 threshold for statistical significance.
Dr. Abraham and his coinvestigators found that CCM implantation was safe, with a 90% complication-free rate, and that it improved both quality of life and functional status.
All efficacy endpoints were better in patients with ejection fractions of 35% or greater, confirming the subgroup analysis findings of the previous randomized trial, according to Dr. Abraham and his coinvestigators.
Survival free of cardiac death and heart failure hospitalization at 24 weeks was 97.1% in the CCM arm versus 89.2% in controls, which was a secondary finding that reached statistical significance in favor of CCM (P = .048) in one analysis of Kaplan-Meier estimates, investigators said in their report.
The CCM device could fulfill an unmet need for patients who have persistent heart failure despite optimal, guideline-based medical therapy, according to the investigators.
“Although ICDs are applicable to the broad population of patients with ejection fraction [at least] 35%, they do not deliver a therapy for improving exercise tolerance or quality of life,” they said in their report.
Research grant support for the study came from Impulse Dynamics. Dr. Abraham and several coauthors reported serving as consultants to the company.
SOURCE: Abraham WT et al. JACC Heart Fail. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010.
BOSTON – Cardiac contractility modulation (CCM), an electrical device–based modality, may improve exercise tolerance and quality of life in heart failure patients with ejection fraction between 25% and 45%, results of a randomized, controlled trial suggested.
Notably, clinical effectiveness appeared to be even greater in the subset of patient with ejection fractions between 35% and 45%, according to results presented at the annual scientific sessions of the Heart Rhythm Society.
The CCM approach was designed to treat chronic heart failure patients with reduced and midrange ejection fractions. It involves the delivery of electrical signals during the cardiac absolute refractory period to enhance contraction strength. Key components include an atrial lead used for sensing and two ventricular leads used for sensing local electrical activity and delivery of CCM signals.
The device was previously evaluated in FIX-HF-5, a 428-patient randomized trial of CCM in patients with New York Heart Association functional class III/IV and reduced ejection fraction. That study failed to meet its primary efficacy end point, but a subgroup analysis showed significant treatment effects in patients with ejection fractions between 25% and 45%.
Consequently, Dr. Abraham initiated the FIX-HF-5 confirmatory study (FIX-HF-5C) to prospectively evaluate CCM in patients with ejection fractions in that range.
The study included 160 with NYHA class III/IV heart failure, QRS duration less than 130 ms, and ejection fractions of 25%-45% who were randomized either to CCM or to continued optimal medical therapy. The control arm included 86 patients, and the CCM arm included 74 patients, of whom 68 received device implantation.
For evaluating peak VO2, the primary end point of this confirmatory study, investigators used a Bayesian model that allowed them incorporate some data from the corresponding subgroup of patients with ejection fractions between 25% and 45% in the previous FIX-HF-5 randomized trial.
Using this model, they found the mean difference between CCM and medical therapy groups at week 24 was 0.836 mL O2/kg per minute (95% Bayesian credible interval, 0.123-1.552). The probability of CCM treatment’s superiority to control was 0.989, according to investigators, which exceeded the 0.975 threshold for statistical significance.
Dr. Abraham and his coinvestigators found that CCM implantation was safe, with a 90% complication-free rate, and that it improved both quality of life and functional status.
All efficacy endpoints were better in patients with ejection fractions of 35% or greater, confirming the subgroup analysis findings of the previous randomized trial, according to Dr. Abraham and his coinvestigators.
Survival free of cardiac death and heart failure hospitalization at 24 weeks was 97.1% in the CCM arm versus 89.2% in controls, which was a secondary finding that reached statistical significance in favor of CCM (P = .048) in one analysis of Kaplan-Meier estimates, investigators said in their report.
The CCM device could fulfill an unmet need for patients who have persistent heart failure despite optimal, guideline-based medical therapy, according to the investigators.
“Although ICDs are applicable to the broad population of patients with ejection fraction [at least] 35%, they do not deliver a therapy for improving exercise tolerance or quality of life,” they said in their report.
Research grant support for the study came from Impulse Dynamics. Dr. Abraham and several coauthors reported serving as consultants to the company.
SOURCE: Abraham WT et al. JACC Heart Fail. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010.
REPORTING FROM HEART RHYTHM 2018
Key clinical point: Compared with continued medical therapy, cardiac contractility modulation (CCM) improved exercise tolerance and quality of life in heart failure patients with ejection fraction between 25% and 45%.
Major finding: The difference in peak VO2 between study arms was 0.836 mL O2/kg per minute (95% Bayesian credible interval, 0.123-1.552).
Study details: A randomized controlled trial including 160 patients with NYHA class III/IV heart failure and ejection fraction between 25% and 45%.
Disclosures: Research grant support for the study came from Impulse Dynamics. Several study authors reported serving as consultants to Impulse Dynamics.
Source: Abraham WT et al. JACC Heart Fail. 2018 May 10. doi: 10.1016/j.jchf.2018.04.010.
Pain relievers, bed rest may be sufficient to manage PEH
Although skin biopsy and the “presence of deep dermal mixed infiltrate with abundant neutrophils surrounding eccrine sweat glands” is considered the preferred method for diagnosing palmoplantar eccrine hidradenitis (PEH), Paola Piccini, MD, and her colleagues at the University of Florence (Italy) caution that biopsy frequently is not needed.
In the days prior to the appearance of erythematous and painful nodules on the soles of his feet, a healthy 8-year-old boy sustained “thermal and mechanical trauma playing football and cycling,” that made walking difficult. The week prior to the injury, he had complained of diarrhea in the absence of fever.
Given results of testing and the patient’s overall good health, he received a diagnosis of PEH. Dr. Piccini and her colleagues chose not to biopsy the nodules because they typically resolve on their own within a few weeks. Instead, he was prescribed pain relievers and bed rest. Within 2 weeks, the nodules were completely healed, and no further relapse was reported, the authors noted in the Journal of Pediatrics.
All previous case studies cited in the literature reported complete resolution without treatment within 4 weeks, said Dr. Piccini and her colleagues. They added that correct diagnosis is key to avoiding inappropriate medical treatments given the benign course of PEH.
Common presenting risk factors tend to include local thermal and mechanical trauma plus intense physical activity and recent infection. It is these risk factors that cause rupture of the eccrine gland and resulting infiltration of neutrophils to the site.
Conditions that share common symptoms with PEH include erythema multiforme, nodular erythema, cellulitis, and viral infections.
No disclosures were noted.
SOURCE: Piccini, P et al. J. Pediatr. 2018. doi: 10.1016/j.peds.2018.03.017.
Although skin biopsy and the “presence of deep dermal mixed infiltrate with abundant neutrophils surrounding eccrine sweat glands” is considered the preferred method for diagnosing palmoplantar eccrine hidradenitis (PEH), Paola Piccini, MD, and her colleagues at the University of Florence (Italy) caution that biopsy frequently is not needed.
In the days prior to the appearance of erythematous and painful nodules on the soles of his feet, a healthy 8-year-old boy sustained “thermal and mechanical trauma playing football and cycling,” that made walking difficult. The week prior to the injury, he had complained of diarrhea in the absence of fever.
Given results of testing and the patient’s overall good health, he received a diagnosis of PEH. Dr. Piccini and her colleagues chose not to biopsy the nodules because they typically resolve on their own within a few weeks. Instead, he was prescribed pain relievers and bed rest. Within 2 weeks, the nodules were completely healed, and no further relapse was reported, the authors noted in the Journal of Pediatrics.
All previous case studies cited in the literature reported complete resolution without treatment within 4 weeks, said Dr. Piccini and her colleagues. They added that correct diagnosis is key to avoiding inappropriate medical treatments given the benign course of PEH.
Common presenting risk factors tend to include local thermal and mechanical trauma plus intense physical activity and recent infection. It is these risk factors that cause rupture of the eccrine gland and resulting infiltration of neutrophils to the site.
Conditions that share common symptoms with PEH include erythema multiforme, nodular erythema, cellulitis, and viral infections.
No disclosures were noted.
SOURCE: Piccini, P et al. J. Pediatr. 2018. doi: 10.1016/j.peds.2018.03.017.
Although skin biopsy and the “presence of deep dermal mixed infiltrate with abundant neutrophils surrounding eccrine sweat glands” is considered the preferred method for diagnosing palmoplantar eccrine hidradenitis (PEH), Paola Piccini, MD, and her colleagues at the University of Florence (Italy) caution that biopsy frequently is not needed.
In the days prior to the appearance of erythematous and painful nodules on the soles of his feet, a healthy 8-year-old boy sustained “thermal and mechanical trauma playing football and cycling,” that made walking difficult. The week prior to the injury, he had complained of diarrhea in the absence of fever.
Given results of testing and the patient’s overall good health, he received a diagnosis of PEH. Dr. Piccini and her colleagues chose not to biopsy the nodules because they typically resolve on their own within a few weeks. Instead, he was prescribed pain relievers and bed rest. Within 2 weeks, the nodules were completely healed, and no further relapse was reported, the authors noted in the Journal of Pediatrics.
All previous case studies cited in the literature reported complete resolution without treatment within 4 weeks, said Dr. Piccini and her colleagues. They added that correct diagnosis is key to avoiding inappropriate medical treatments given the benign course of PEH.
Common presenting risk factors tend to include local thermal and mechanical trauma plus intense physical activity and recent infection. It is these risk factors that cause rupture of the eccrine gland and resulting infiltration of neutrophils to the site.
Conditions that share common symptoms with PEH include erythema multiforme, nodular erythema, cellulitis, and viral infections.
No disclosures were noted.
SOURCE: Piccini, P et al. J. Pediatr. 2018. doi: 10.1016/j.peds.2018.03.017.
FROM THE JOURNAL OF PEDIATRICS
Key clinical point: Complete resolution within 4 weeks is common without treatment.
Major finding: .
Study details: Case study.
Disclosures: No disclosures were noted.
Source: Lund, E et al. Ped. Dermatol. 2018. doi: 10.1111/pde.13508.
Delay of NSCLC surgery can lead to worse prognosis
SAN DIEGO – Delaying
“There is significant upstaging with time from completion of clinical staging to surgical resection, with a 4% increase of upstaging per week for the overall study population,” said study coauthor Harmik J. Soukiasian, MD, FACS, of Cedars-Sinai Medical Center, Los Angeles, in an interview. “Upstaging impacts lung cancer prognosis as more advanced stages portend to a poorer prognosis.”
An estimated 80%-85% of lung cancer patients have NSCLC, according to the American Cancer Society, and Dr. Soukiasian said surgery offers a chance at a cure for those diagnosed at stage I.
“National Cancer Comprehensive Network (NCCN) Guidelines recommend surgery within 8 weeks of completed clinical staging for NSCLC to limit cancer progression or upstaging,” Dr. Soukiasian said. “Although these guidelines are well established and widely adopted, our study performs a more granular analysis, studying time as a predictor of upstaging for those patients diagnosed with stage I NSCLC.”
For the new study, Dr. Soukiasian and colleagues tracked 52,406 patients in a cancer database who had stage I NSCLC but had not undergone preoperative chemotherapy. The researchers tracked their clinical stages for up to 12 weeks from initial staging.
Researchers found that, while staging levels rose with each successive week, just 25% of patients underwent surgery by 1 week, and only 79% had surgery in accordance with NSCLC guidelines by week 8. At 12 weeks, 9% had still not undergone surgery.
Upstaging was common: 22% at 1 week, 32% after 8 weeks, and 33% after 12 weeks.
“We demonstrate that patients diagnosed with stage I NSCLC benefit from surgery sooner than the 8-week window recommended by the NCCN guidelines,” Dr. Soukiasian said. “Exclusive of the rate of progression and in addition to time to surgery, our study also demonstrated academic centers, higher lymph node yield during surgery, and left-sided tumors to be independent predictors of upstaging.”
The study design doesn’t provide insight into why surgery is often delayed. However, “we can theorize factors associated with delays to surgery may be due to patient factors (personal scheduling, availability of support systems, etc.), delays in follow up, operating room availability or scheduling, and issues with insurance approval,” Dr. Soukiasian said.
In his presentation, Dr. Soukiasian emphasized the role of the mediastinum. “Given the clinical impact of stage III disease, we analyzed upstaging rates of stage I NSCLC to stage IIIA and revealed a 1.3% increase per week of upstaging specifically to stage IIIA. Additionally, almost 5% of patients initially diagnosed with stage I NSCLC upstaged to IIIA disease. The significant rate of upstaging to IIIA disease makes the case for more accurate and aggressive mediastinal staging prior to surgical resection.”
No disclosures and no study funding are reported.
SOURCE: Soukiasian HJ et al. AATS 2018, Abstract 67.
SAN DIEGO – Delaying
“There is significant upstaging with time from completion of clinical staging to surgical resection, with a 4% increase of upstaging per week for the overall study population,” said study coauthor Harmik J. Soukiasian, MD, FACS, of Cedars-Sinai Medical Center, Los Angeles, in an interview. “Upstaging impacts lung cancer prognosis as more advanced stages portend to a poorer prognosis.”
An estimated 80%-85% of lung cancer patients have NSCLC, according to the American Cancer Society, and Dr. Soukiasian said surgery offers a chance at a cure for those diagnosed at stage I.
“National Cancer Comprehensive Network (NCCN) Guidelines recommend surgery within 8 weeks of completed clinical staging for NSCLC to limit cancer progression or upstaging,” Dr. Soukiasian said. “Although these guidelines are well established and widely adopted, our study performs a more granular analysis, studying time as a predictor of upstaging for those patients diagnosed with stage I NSCLC.”
For the new study, Dr. Soukiasian and colleagues tracked 52,406 patients in a cancer database who had stage I NSCLC but had not undergone preoperative chemotherapy. The researchers tracked their clinical stages for up to 12 weeks from initial staging.
Researchers found that, while staging levels rose with each successive week, just 25% of patients underwent surgery by 1 week, and only 79% had surgery in accordance with NSCLC guidelines by week 8. At 12 weeks, 9% had still not undergone surgery.
Upstaging was common: 22% at 1 week, 32% after 8 weeks, and 33% after 12 weeks.
“We demonstrate that patients diagnosed with stage I NSCLC benefit from surgery sooner than the 8-week window recommended by the NCCN guidelines,” Dr. Soukiasian said. “Exclusive of the rate of progression and in addition to time to surgery, our study also demonstrated academic centers, higher lymph node yield during surgery, and left-sided tumors to be independent predictors of upstaging.”
The study design doesn’t provide insight into why surgery is often delayed. However, “we can theorize factors associated with delays to surgery may be due to patient factors (personal scheduling, availability of support systems, etc.), delays in follow up, operating room availability or scheduling, and issues with insurance approval,” Dr. Soukiasian said.
In his presentation, Dr. Soukiasian emphasized the role of the mediastinum. “Given the clinical impact of stage III disease, we analyzed upstaging rates of stage I NSCLC to stage IIIA and revealed a 1.3% increase per week of upstaging specifically to stage IIIA. Additionally, almost 5% of patients initially diagnosed with stage I NSCLC upstaged to IIIA disease. The significant rate of upstaging to IIIA disease makes the case for more accurate and aggressive mediastinal staging prior to surgical resection.”
No disclosures and no study funding are reported.
SOURCE: Soukiasian HJ et al. AATS 2018, Abstract 67.
SAN DIEGO – Delaying
“There is significant upstaging with time from completion of clinical staging to surgical resection, with a 4% increase of upstaging per week for the overall study population,” said study coauthor Harmik J. Soukiasian, MD, FACS, of Cedars-Sinai Medical Center, Los Angeles, in an interview. “Upstaging impacts lung cancer prognosis as more advanced stages portend to a poorer prognosis.”
An estimated 80%-85% of lung cancer patients have NSCLC, according to the American Cancer Society, and Dr. Soukiasian said surgery offers a chance at a cure for those diagnosed at stage I.
“National Cancer Comprehensive Network (NCCN) Guidelines recommend surgery within 8 weeks of completed clinical staging for NSCLC to limit cancer progression or upstaging,” Dr. Soukiasian said. “Although these guidelines are well established and widely adopted, our study performs a more granular analysis, studying time as a predictor of upstaging for those patients diagnosed with stage I NSCLC.”
For the new study, Dr. Soukiasian and colleagues tracked 52,406 patients in a cancer database who had stage I NSCLC but had not undergone preoperative chemotherapy. The researchers tracked their clinical stages for up to 12 weeks from initial staging.
Researchers found that, while staging levels rose with each successive week, just 25% of patients underwent surgery by 1 week, and only 79% had surgery in accordance with NSCLC guidelines by week 8. At 12 weeks, 9% had still not undergone surgery.
Upstaging was common: 22% at 1 week, 32% after 8 weeks, and 33% after 12 weeks.
“We demonstrate that patients diagnosed with stage I NSCLC benefit from surgery sooner than the 8-week window recommended by the NCCN guidelines,” Dr. Soukiasian said. “Exclusive of the rate of progression and in addition to time to surgery, our study also demonstrated academic centers, higher lymph node yield during surgery, and left-sided tumors to be independent predictors of upstaging.”
The study design doesn’t provide insight into why surgery is often delayed. However, “we can theorize factors associated with delays to surgery may be due to patient factors (personal scheduling, availability of support systems, etc.), delays in follow up, operating room availability or scheduling, and issues with insurance approval,” Dr. Soukiasian said.
In his presentation, Dr. Soukiasian emphasized the role of the mediastinum. “Given the clinical impact of stage III disease, we analyzed upstaging rates of stage I NSCLC to stage IIIA and revealed a 1.3% increase per week of upstaging specifically to stage IIIA. Additionally, almost 5% of patients initially diagnosed with stage I NSCLC upstaged to IIIA disease. The significant rate of upstaging to IIIA disease makes the case for more accurate and aggressive mediastinal staging prior to surgical resection.”
No disclosures and no study funding are reported.
SOURCE: Soukiasian HJ et al. AATS 2018, Abstract 67.
AT THE AATS ANNUAL MEETING
Key clinical point: Clinical staging levels worsen in each successive surgery-free week after initial staging in certain NSCLC patients.
Major finding: There was a 1.3% increase per week of upstaging to stage IIIA.
Study details: Analysis of 52,406 patients with stage I NSCLC who were tracked for up to 12 weeks.
Disclosures: No disclosures and no funding were reported.
Source: Soukiasian HJ et al. AATS 2018, Abstract 67.
White House targets CHIP, CMMI for budget cuts
The package also includes an $800 million cut to the Centers for Medicare & Medicaid Innovation (CMMI), a policy incubator that the Centers for Medicare & Medicaid Services uses to test innovative payment approaches.
These funds were a one-time, additional appropriation “to reimburse states for eligible CHIP expenses.” According to the rescission request, the authority “to obligate these funds to states expired on Sept. 30, 2017, and the remaining funding is no longer needed.”
A second request would rescind nearly $1.9 billion from the Child Enrollment Contingency Fund, which provides payments to states that experience shortfalls from higher-than-expected enrollment. The White House notes that there were $2.4 billion available as of March 23, 2018, and that CMS “does not expect that any state would require a contingency fund payment in fiscal year 2018; therefore, this funding is not needed.”
If enacted, these rescissions “would have no programmatic impact,” according to the White House.
A broad coalition of physicians’ organizations and other advocates protested the proposed cuts in a May 9 letter to Congress.
“While White House officials insist that the CHIP cuts would not harm access to care for children and families, that is simply not the case,” according to the letter signed by more than 500 organizations. “Our nation is facing an increasing number of natural disasters ... [and] each catastrophe leaves families more vulnerable and more likely to qualify for CHIP. In addition to natural disasters, the Child Enrollment Contingency Fund provides states needed protection and security should their CHIP enrollment suddenly spike due to an economic recession or a public health crisis.”
Regarding the CMMI cut, the $800,000 would be rescinded from funds appropriated through fiscal year 2019. The White House notes that $3.5 billion was available as of Oct. 1, 2017.
The rescission represents funds that “are in excess of amounts needed to carry out the Innovation Center’s planned activities in fiscal 2018 and fiscal 2019, and the Innovation Center will receive new mandatory appropriation in fiscal 2020. Enacting this rescission would allow the Innovation Center to continue its current activity, initiate new activity, and continue to pay for its administrative costs,” according to the rescission request.
CMMI “is our best hope to innovate & achieve better health outcomes at lower costs,” Patrick Conway, MD, former deputy administrator and chief medical officer at CMS said in a May 8 tweet. “Cutting $800M or any amount would be a bad decision. CMS spends over $1 trillion per year; over $100M/hour. CMMI is key to better system.”
American Academy of Family Physicians President Michael Munger, MD, agreed.
“We’re also concerned about the $800 million rescission in funding for the CMS Innovation Center,” he said. “This initiative has been at the forefront of innovative demonstrations that can pave the way for a health care system that improves the quality of care and cuts health care spending.”
Congress has 45 days to act on the White House’s rescission proposal. If it takes no action, the proposal expires and the funds cannot be targeted by the same mechanism in the future. If Congress addresses the rescission request, it would need just a simple majority to pass each chamber.
Despite slashing more than $15 billion from the budget, the White House notes that the rescission request would reduce spending by only $3 billion.
The package also includes an $800 million cut to the Centers for Medicare & Medicaid Innovation (CMMI), a policy incubator that the Centers for Medicare & Medicaid Services uses to test innovative payment approaches.
These funds were a one-time, additional appropriation “to reimburse states for eligible CHIP expenses.” According to the rescission request, the authority “to obligate these funds to states expired on Sept. 30, 2017, and the remaining funding is no longer needed.”
A second request would rescind nearly $1.9 billion from the Child Enrollment Contingency Fund, which provides payments to states that experience shortfalls from higher-than-expected enrollment. The White House notes that there were $2.4 billion available as of March 23, 2018, and that CMS “does not expect that any state would require a contingency fund payment in fiscal year 2018; therefore, this funding is not needed.”
If enacted, these rescissions “would have no programmatic impact,” according to the White House.
A broad coalition of physicians’ organizations and other advocates protested the proposed cuts in a May 9 letter to Congress.
“While White House officials insist that the CHIP cuts would not harm access to care for children and families, that is simply not the case,” according to the letter signed by more than 500 organizations. “Our nation is facing an increasing number of natural disasters ... [and] each catastrophe leaves families more vulnerable and more likely to qualify for CHIP. In addition to natural disasters, the Child Enrollment Contingency Fund provides states needed protection and security should their CHIP enrollment suddenly spike due to an economic recession or a public health crisis.”
Regarding the CMMI cut, the $800,000 would be rescinded from funds appropriated through fiscal year 2019. The White House notes that $3.5 billion was available as of Oct. 1, 2017.
The rescission represents funds that “are in excess of amounts needed to carry out the Innovation Center’s planned activities in fiscal 2018 and fiscal 2019, and the Innovation Center will receive new mandatory appropriation in fiscal 2020. Enacting this rescission would allow the Innovation Center to continue its current activity, initiate new activity, and continue to pay for its administrative costs,” according to the rescission request.
CMMI “is our best hope to innovate & achieve better health outcomes at lower costs,” Patrick Conway, MD, former deputy administrator and chief medical officer at CMS said in a May 8 tweet. “Cutting $800M or any amount would be a bad decision. CMS spends over $1 trillion per year; over $100M/hour. CMMI is key to better system.”
American Academy of Family Physicians President Michael Munger, MD, agreed.
“We’re also concerned about the $800 million rescission in funding for the CMS Innovation Center,” he said. “This initiative has been at the forefront of innovative demonstrations that can pave the way for a health care system that improves the quality of care and cuts health care spending.”
Congress has 45 days to act on the White House’s rescission proposal. If it takes no action, the proposal expires and the funds cannot be targeted by the same mechanism in the future. If Congress addresses the rescission request, it would need just a simple majority to pass each chamber.
Despite slashing more than $15 billion from the budget, the White House notes that the rescission request would reduce spending by only $3 billion.
The package also includes an $800 million cut to the Centers for Medicare & Medicaid Innovation (CMMI), a policy incubator that the Centers for Medicare & Medicaid Services uses to test innovative payment approaches.
These funds were a one-time, additional appropriation “to reimburse states for eligible CHIP expenses.” According to the rescission request, the authority “to obligate these funds to states expired on Sept. 30, 2017, and the remaining funding is no longer needed.”
A second request would rescind nearly $1.9 billion from the Child Enrollment Contingency Fund, which provides payments to states that experience shortfalls from higher-than-expected enrollment. The White House notes that there were $2.4 billion available as of March 23, 2018, and that CMS “does not expect that any state would require a contingency fund payment in fiscal year 2018; therefore, this funding is not needed.”
If enacted, these rescissions “would have no programmatic impact,” according to the White House.
A broad coalition of physicians’ organizations and other advocates protested the proposed cuts in a May 9 letter to Congress.
“While White House officials insist that the CHIP cuts would not harm access to care for children and families, that is simply not the case,” according to the letter signed by more than 500 organizations. “Our nation is facing an increasing number of natural disasters ... [and] each catastrophe leaves families more vulnerable and more likely to qualify for CHIP. In addition to natural disasters, the Child Enrollment Contingency Fund provides states needed protection and security should their CHIP enrollment suddenly spike due to an economic recession or a public health crisis.”
Regarding the CMMI cut, the $800,000 would be rescinded from funds appropriated through fiscal year 2019. The White House notes that $3.5 billion was available as of Oct. 1, 2017.
The rescission represents funds that “are in excess of amounts needed to carry out the Innovation Center’s planned activities in fiscal 2018 and fiscal 2019, and the Innovation Center will receive new mandatory appropriation in fiscal 2020. Enacting this rescission would allow the Innovation Center to continue its current activity, initiate new activity, and continue to pay for its administrative costs,” according to the rescission request.
CMMI “is our best hope to innovate & achieve better health outcomes at lower costs,” Patrick Conway, MD, former deputy administrator and chief medical officer at CMS said in a May 8 tweet. “Cutting $800M or any amount would be a bad decision. CMS spends over $1 trillion per year; over $100M/hour. CMMI is key to better system.”
American Academy of Family Physicians President Michael Munger, MD, agreed.
“We’re also concerned about the $800 million rescission in funding for the CMS Innovation Center,” he said. “This initiative has been at the forefront of innovative demonstrations that can pave the way for a health care system that improves the quality of care and cuts health care spending.”
Congress has 45 days to act on the White House’s rescission proposal. If it takes no action, the proposal expires and the funds cannot be targeted by the same mechanism in the future. If Congress addresses the rescission request, it would need just a simple majority to pass each chamber.
Despite slashing more than $15 billion from the budget, the White House notes that the rescission request would reduce spending by only $3 billion.
Marijuana: Most oncologists are having the conversation
The vast majority of oncologists discuss medical marijuana use with their patients, and around one-half recommend it to patients, yet many also say they do not feel equipped to make clinical recommendations on its use, new research has found.
A survey on medical marijuana was mailed to a nationally-representative, random sample of 400 medical oncologists and had a response rate of 63%; results from the 237 responders revealed that 79.8% had discussed medical marijuana use with patients or their families and 45.9% had recommended medical marijuana for cancer-related issues to at least one patient in the previous year.
Oncologists in the western United States were significantly more likely to recommend medical marijuana use, compared with those in the south of the country (84.2% vs. 34.7%, respectively; P less than .001), Ilana M. Braun, MD, and her associates reported in Journal of Clinical Oncology.
Doctors who practiced outside a hospital setting were also significantly more likely to recommend medical marijuana to their patients, as were medical oncologists with higher practice volumes.
Among the oncologists who reported discussing medical marijuana use with patients, 78% said these conversations were more likely to be initiated by the patient and their family than by the oncologist themselves.
However only 29.4% of oncologists surveyed said they felt “sufficiently knowledgeable” to make recommendations to patients about medical marijuana. Even among those who said they had recommended medical marijuana to a patient in the past year, 56.2% said they didn’t feel they had enough knowledge to make a recommendation.
Overall, oncologists had mixed views about medical marijuana. About one-third viewed it as equal to or more effective than standard pain treatments, one-third viewed it as less effective, and one-third said they did not know. However two-thirds viewed medical marijuana as a useful adjunct to standard pain therapies.
Two-thirds of oncologists surveyed believed medical marijuana was as good as or better than standard treatments for poor appetite or cachexia, but less than half felt it was equal to or better than standard antinausea therapies.
The data revealed a “clinically problematic discrepancy” between medical oncologists’ their perceived knowledge about medical marijuana use and their actual beliefs and practices, said Dr. Braun of the Dana-Farber Cancer Institute and her associates.
“Although our survey could not determine why oncologists recommend medical marijuana, it may be because they regard medical marijuana as an alternative therapy that is difficult to evaluate given sparse randomized, controlled trial data,” they wrote.
“[The results] highlight a crucial need for expedited clinical trials exploring marijuana’s potential medicinal effects in oncology (e.g. as an adjunctive pain management strategy or as a treatment of anorexia/cachexia) and the need for educational programs about medical marijuana to inform oncologists who frequently confront questions regarding medical marijuana in daily practice.”
No funding was declared. Two authors declared royalties and honoraria from medical publishing and a research institute, and one declared fees for expert testimony.
SOURCE: Braun I et al. J Clin Oncol. 2018 May 10. doi: 10.1200/JCO.2017.76.1221.
The vast majority of oncologists discuss medical marijuana use with their patients, and around one-half recommend it to patients, yet many also say they do not feel equipped to make clinical recommendations on its use, new research has found.
A survey on medical marijuana was mailed to a nationally-representative, random sample of 400 medical oncologists and had a response rate of 63%; results from the 237 responders revealed that 79.8% had discussed medical marijuana use with patients or their families and 45.9% had recommended medical marijuana for cancer-related issues to at least one patient in the previous year.
Oncologists in the western United States were significantly more likely to recommend medical marijuana use, compared with those in the south of the country (84.2% vs. 34.7%, respectively; P less than .001), Ilana M. Braun, MD, and her associates reported in Journal of Clinical Oncology.
Doctors who practiced outside a hospital setting were also significantly more likely to recommend medical marijuana to their patients, as were medical oncologists with higher practice volumes.
Among the oncologists who reported discussing medical marijuana use with patients, 78% said these conversations were more likely to be initiated by the patient and their family than by the oncologist themselves.
However only 29.4% of oncologists surveyed said they felt “sufficiently knowledgeable” to make recommendations to patients about medical marijuana. Even among those who said they had recommended medical marijuana to a patient in the past year, 56.2% said they didn’t feel they had enough knowledge to make a recommendation.
Overall, oncologists had mixed views about medical marijuana. About one-third viewed it as equal to or more effective than standard pain treatments, one-third viewed it as less effective, and one-third said they did not know. However two-thirds viewed medical marijuana as a useful adjunct to standard pain therapies.
Two-thirds of oncologists surveyed believed medical marijuana was as good as or better than standard treatments for poor appetite or cachexia, but less than half felt it was equal to or better than standard antinausea therapies.
The data revealed a “clinically problematic discrepancy” between medical oncologists’ their perceived knowledge about medical marijuana use and their actual beliefs and practices, said Dr. Braun of the Dana-Farber Cancer Institute and her associates.
“Although our survey could not determine why oncologists recommend medical marijuana, it may be because they regard medical marijuana as an alternative therapy that is difficult to evaluate given sparse randomized, controlled trial data,” they wrote.
“[The results] highlight a crucial need for expedited clinical trials exploring marijuana’s potential medicinal effects in oncology (e.g. as an adjunctive pain management strategy or as a treatment of anorexia/cachexia) and the need for educational programs about medical marijuana to inform oncologists who frequently confront questions regarding medical marijuana in daily practice.”
No funding was declared. Two authors declared royalties and honoraria from medical publishing and a research institute, and one declared fees for expert testimony.
SOURCE: Braun I et al. J Clin Oncol. 2018 May 10. doi: 10.1200/JCO.2017.76.1221.
The vast majority of oncologists discuss medical marijuana use with their patients, and around one-half recommend it to patients, yet many also say they do not feel equipped to make clinical recommendations on its use, new research has found.
A survey on medical marijuana was mailed to a nationally-representative, random sample of 400 medical oncologists and had a response rate of 63%; results from the 237 responders revealed that 79.8% had discussed medical marijuana use with patients or their families and 45.9% had recommended medical marijuana for cancer-related issues to at least one patient in the previous year.
Oncologists in the western United States were significantly more likely to recommend medical marijuana use, compared with those in the south of the country (84.2% vs. 34.7%, respectively; P less than .001), Ilana M. Braun, MD, and her associates reported in Journal of Clinical Oncology.
Doctors who practiced outside a hospital setting were also significantly more likely to recommend medical marijuana to their patients, as were medical oncologists with higher practice volumes.
Among the oncologists who reported discussing medical marijuana use with patients, 78% said these conversations were more likely to be initiated by the patient and their family than by the oncologist themselves.
However only 29.4% of oncologists surveyed said they felt “sufficiently knowledgeable” to make recommendations to patients about medical marijuana. Even among those who said they had recommended medical marijuana to a patient in the past year, 56.2% said they didn’t feel they had enough knowledge to make a recommendation.
Overall, oncologists had mixed views about medical marijuana. About one-third viewed it as equal to or more effective than standard pain treatments, one-third viewed it as less effective, and one-third said they did not know. However two-thirds viewed medical marijuana as a useful adjunct to standard pain therapies.
Two-thirds of oncologists surveyed believed medical marijuana was as good as or better than standard treatments for poor appetite or cachexia, but less than half felt it was equal to or better than standard antinausea therapies.
The data revealed a “clinically problematic discrepancy” between medical oncologists’ their perceived knowledge about medical marijuana use and their actual beliefs and practices, said Dr. Braun of the Dana-Farber Cancer Institute and her associates.
“Although our survey could not determine why oncologists recommend medical marijuana, it may be because they regard medical marijuana as an alternative therapy that is difficult to evaluate given sparse randomized, controlled trial data,” they wrote.
“[The results] highlight a crucial need for expedited clinical trials exploring marijuana’s potential medicinal effects in oncology (e.g. as an adjunctive pain management strategy or as a treatment of anorexia/cachexia) and the need for educational programs about medical marijuana to inform oncologists who frequently confront questions regarding medical marijuana in daily practice.”
No funding was declared. Two authors declared royalties and honoraria from medical publishing and a research institute, and one declared fees for expert testimony.
SOURCE: Braun I et al. J Clin Oncol. 2018 May 10. doi: 10.1200/JCO.2017.76.1221.
FROM THE JOURNAL OF CLINICAL ONCOLOGY
Key clinical point: The majority of medical oncologists discuss medical marijuana use with their patients, though few feel knowledgeable on the subject.
Major finding: Nearly 80% of medical oncologists have discussed medical marijuana use with their patients, but only 29.4% of those surveyed felt sufficiently knowledgeable.
Study details: Survey of 237 medical oncologists.
Disclosures: No funding was declared. Two authors declared royalties and honoraria from medical publishing and a research institute, and one declared fees for expert testimony.
Source: Braun I et al. J Clin Oncol. 2018 May 10. doi: 10.1200/JCO.2017.76.1221.
Pursuing violators seen as way to achieving mental health parity
NEW YORK – The Mental Health Parity and Addiction Equity Act, passed in 2008 and strengthened within the Affordable Care Act, continues to be routinely violated, but there are avenues for complaint that can help keep pressure on third-party payers, according to an update on this topic presented at the annual meeting of the American Psychiatric Association.
“There are basically two approaches: One is the top-down approach, which is actual government enforcement; the other is the bottom-up approach, which is to work through the courts with class action suits,” reported Daniel Knoepflmacher, MD, assistant professor of clinical psychiatry at Cornell University, New York.
Some of the enforcement falls to the Employment Benefits Security Administration (EBSA), which is an agency within the Department of Labor. EBSA, which recently published a report on mental health parity violations spanning 2016-2017, steps in because health insurance is commonly an employee benefit, Dr. Knoepflmacher explained.
In the EBSA report, 136 mental health parity violations were documented, said Dr. Knoepflmacher, who summarized the findings. These were not single denials of coverage but 136 cases of insurance company policy violations that covered thousands or even hundreds of thousands of participants.
For example, one denial of coverage occurred for chronic behavioral disorders. This is a violation of parity, because there are no such restrictions on coverage of chronic physical disorders. In another example, coverage of mental health disorders was provided only when a treatment plan had been submitted.
“Requiring a treatment plan is one of the ways often used to create more onerous requirements for mental health or substance use providers,” Dr. Knoepflmacher said. “What makes this a parity violation is that there is no equivalent restriction for providing medical or surgical benefits.”
Both of these examples, which were found in insurance plans each covering about 300,000 individuals, represented nonquantitative treatment limitations, which Dr. Knoepflmacher said are often more difficult to identify than quantitative limitations, such as a cap on patient consultations or access to medications.
Another example of a nonquantitative limitation is low reimbursement when different types of services make parity difficult to establish. Recently, a firm that evaluates employee benefits compared the reimbursement received by psychiatrists with that received by primary care physicians for CPT code 99213 claims. This is a code applied for behavioral assessment. Based on national data, the report found that primary care clinicians received a 20% higher reimbursement on average than did mental health specialists. The disparity was greatest in Connecticut, and Nebraska was the only state offering similar reimbursement. In all other states, psychiatrists received less.
“This is an apples-to-apples comparison,” Dr. Knoepflmacher said. “What does this difference create? This leads to a reality that is familiar to many of us, which is that a large number of psychiatrists are working out of network.”
This is highly relevant to parity for mental health services: Reduced numbers of mental health specialists working in network mean patients face greater barriers to finding a clinician at an affordable cost.
EBSA provides a hotline (866-444-3722) for reporting parity violations. It also provides information on its website for steps to take when violations occur, Dr. Knoepflmacher said. However, Dr. Knoepflmacher conceded that establishing parity is a moving target because third-party payers alter policies and use their own criteria to establish which mental health services represent necessary care.
“Most psychiatrists I have spoken to have experienced some sort of denial of coverage,” Dr. Knoepflmacher noted. Not all may be a violation of parity, but Dr. Knoepflmacher suggested that psychiatrists should be proactive in order to preserve mental health and substance use services for those who need them.
NEW YORK – The Mental Health Parity and Addiction Equity Act, passed in 2008 and strengthened within the Affordable Care Act, continues to be routinely violated, but there are avenues for complaint that can help keep pressure on third-party payers, according to an update on this topic presented at the annual meeting of the American Psychiatric Association.
“There are basically two approaches: One is the top-down approach, which is actual government enforcement; the other is the bottom-up approach, which is to work through the courts with class action suits,” reported Daniel Knoepflmacher, MD, assistant professor of clinical psychiatry at Cornell University, New York.
Some of the enforcement falls to the Employment Benefits Security Administration (EBSA), which is an agency within the Department of Labor. EBSA, which recently published a report on mental health parity violations spanning 2016-2017, steps in because health insurance is commonly an employee benefit, Dr. Knoepflmacher explained.
In the EBSA report, 136 mental health parity violations were documented, said Dr. Knoepflmacher, who summarized the findings. These were not single denials of coverage but 136 cases of insurance company policy violations that covered thousands or even hundreds of thousands of participants.
For example, one denial of coverage occurred for chronic behavioral disorders. This is a violation of parity, because there are no such restrictions on coverage of chronic physical disorders. In another example, coverage of mental health disorders was provided only when a treatment plan had been submitted.
“Requiring a treatment plan is one of the ways often used to create more onerous requirements for mental health or substance use providers,” Dr. Knoepflmacher said. “What makes this a parity violation is that there is no equivalent restriction for providing medical or surgical benefits.”
Both of these examples, which were found in insurance plans each covering about 300,000 individuals, represented nonquantitative treatment limitations, which Dr. Knoepflmacher said are often more difficult to identify than quantitative limitations, such as a cap on patient consultations or access to medications.
Another example of a nonquantitative limitation is low reimbursement when different types of services make parity difficult to establish. Recently, a firm that evaluates employee benefits compared the reimbursement received by psychiatrists with that received by primary care physicians for CPT code 99213 claims. This is a code applied for behavioral assessment. Based on national data, the report found that primary care clinicians received a 20% higher reimbursement on average than did mental health specialists. The disparity was greatest in Connecticut, and Nebraska was the only state offering similar reimbursement. In all other states, psychiatrists received less.
“This is an apples-to-apples comparison,” Dr. Knoepflmacher said. “What does this difference create? This leads to a reality that is familiar to many of us, which is that a large number of psychiatrists are working out of network.”
This is highly relevant to parity for mental health services: Reduced numbers of mental health specialists working in network mean patients face greater barriers to finding a clinician at an affordable cost.
EBSA provides a hotline (866-444-3722) for reporting parity violations. It also provides information on its website for steps to take when violations occur, Dr. Knoepflmacher said. However, Dr. Knoepflmacher conceded that establishing parity is a moving target because third-party payers alter policies and use their own criteria to establish which mental health services represent necessary care.
“Most psychiatrists I have spoken to have experienced some sort of denial of coverage,” Dr. Knoepflmacher noted. Not all may be a violation of parity, but Dr. Knoepflmacher suggested that psychiatrists should be proactive in order to preserve mental health and substance use services for those who need them.
NEW YORK – The Mental Health Parity and Addiction Equity Act, passed in 2008 and strengthened within the Affordable Care Act, continues to be routinely violated, but there are avenues for complaint that can help keep pressure on third-party payers, according to an update on this topic presented at the annual meeting of the American Psychiatric Association.
“There are basically two approaches: One is the top-down approach, which is actual government enforcement; the other is the bottom-up approach, which is to work through the courts with class action suits,” reported Daniel Knoepflmacher, MD, assistant professor of clinical psychiatry at Cornell University, New York.
Some of the enforcement falls to the Employment Benefits Security Administration (EBSA), which is an agency within the Department of Labor. EBSA, which recently published a report on mental health parity violations spanning 2016-2017, steps in because health insurance is commonly an employee benefit, Dr. Knoepflmacher explained.
In the EBSA report, 136 mental health parity violations were documented, said Dr. Knoepflmacher, who summarized the findings. These were not single denials of coverage but 136 cases of insurance company policy violations that covered thousands or even hundreds of thousands of participants.
For example, one denial of coverage occurred for chronic behavioral disorders. This is a violation of parity, because there are no such restrictions on coverage of chronic physical disorders. In another example, coverage of mental health disorders was provided only when a treatment plan had been submitted.
“Requiring a treatment plan is one of the ways often used to create more onerous requirements for mental health or substance use providers,” Dr. Knoepflmacher said. “What makes this a parity violation is that there is no equivalent restriction for providing medical or surgical benefits.”
Both of these examples, which were found in insurance plans each covering about 300,000 individuals, represented nonquantitative treatment limitations, which Dr. Knoepflmacher said are often more difficult to identify than quantitative limitations, such as a cap on patient consultations or access to medications.
Another example of a nonquantitative limitation is low reimbursement when different types of services make parity difficult to establish. Recently, a firm that evaluates employee benefits compared the reimbursement received by psychiatrists with that received by primary care physicians for CPT code 99213 claims. This is a code applied for behavioral assessment. Based on national data, the report found that primary care clinicians received a 20% higher reimbursement on average than did mental health specialists. The disparity was greatest in Connecticut, and Nebraska was the only state offering similar reimbursement. In all other states, psychiatrists received less.
“This is an apples-to-apples comparison,” Dr. Knoepflmacher said. “What does this difference create? This leads to a reality that is familiar to many of us, which is that a large number of psychiatrists are working out of network.”
This is highly relevant to parity for mental health services: Reduced numbers of mental health specialists working in network mean patients face greater barriers to finding a clinician at an affordable cost.
EBSA provides a hotline (866-444-3722) for reporting parity violations. It also provides information on its website for steps to take when violations occur, Dr. Knoepflmacher said. However, Dr. Knoepflmacher conceded that establishing parity is a moving target because third-party payers alter policies and use their own criteria to establish which mental health services represent necessary care.
“Most psychiatrists I have spoken to have experienced some sort of denial of coverage,” Dr. Knoepflmacher noted. Not all may be a violation of parity, but Dr. Knoepflmacher suggested that psychiatrists should be proactive in order to preserve mental health and substance use services for those who need them.
REPORTING FROM APA
Texas pharmacies restrict access to morning-after pill
TORONTO – Despite federal legislation making emergency contraception available without age limits or a prescription, Texas adolescents may be denied or hindered in their attempts to obtain it, according to a study presented at the Pediatric Academic Societies.
When researchers queried 768 Texas pharmacy employees (97% of whom were pharmacists or pharmacy techs) about the availability of levonorgestrel at their stores, the drug was available in only 76% of pharmacies. However, contrary to federal law, 6% of stores required a prescription to obtain it.
Almost half (47%) of the pharmacies who stocked the drug reported an age requirement for purchase; this rose to 81% in the panhandle of the state, which is considered a more socially conservative region. The researchers divided the pharmacies into six geographic regions and 25% of pharmacies in each region were randomly selected for inclusion.
“Typically, the age limit these pharmacies picked was 17, which is what the most recent federal law said too, but in 2013, that was changed such that there is not supposed to be an age limit,” said Mr. Goff. “But it really varied – some told us 18, some said 21, and some said, ‘I don’t know the age limit, but I would give it out without checking their ID.’ ”
As well, 52% required some degree of interaction or consultation with pharmacy staff to obtain the drug – either it was behind the counter or on the shelf, but maybe in a locked cabinet.
Turns out, pharmacy staff also aren’t well versed in the use of levonorgestrel. Only 10% of those surveyed recognized that there may be a weight limitation with use of levonorgestrel and only 2% knew that the medication could be used up to 120 hours after unprotected intercourse.
“Texas has the fifth highest rate of teen pregnancy and the highest rate of repeat teen pregnancy in the United States, and we think these barriers are a big contributor to this,” Mr. Goff said in an interview.
Senior author, Maria C. Monge, MD, of the university, added in a press release that comprehensive sex education and contraception services also are not readily available to all adolescents across the state, which likely increases the use of emergency contraception.
In the United States, levonorgestrel 1.5 mg oral tablet has been available over the counter for more than 10 years and without an age limit since 2013.
TORONTO – Despite federal legislation making emergency contraception available without age limits or a prescription, Texas adolescents may be denied or hindered in their attempts to obtain it, according to a study presented at the Pediatric Academic Societies.
When researchers queried 768 Texas pharmacy employees (97% of whom were pharmacists or pharmacy techs) about the availability of levonorgestrel at their stores, the drug was available in only 76% of pharmacies. However, contrary to federal law, 6% of stores required a prescription to obtain it.
Almost half (47%) of the pharmacies who stocked the drug reported an age requirement for purchase; this rose to 81% in the panhandle of the state, which is considered a more socially conservative region. The researchers divided the pharmacies into six geographic regions and 25% of pharmacies in each region were randomly selected for inclusion.
“Typically, the age limit these pharmacies picked was 17, which is what the most recent federal law said too, but in 2013, that was changed such that there is not supposed to be an age limit,” said Mr. Goff. “But it really varied – some told us 18, some said 21, and some said, ‘I don’t know the age limit, but I would give it out without checking their ID.’ ”
As well, 52% required some degree of interaction or consultation with pharmacy staff to obtain the drug – either it was behind the counter or on the shelf, but maybe in a locked cabinet.
Turns out, pharmacy staff also aren’t well versed in the use of levonorgestrel. Only 10% of those surveyed recognized that there may be a weight limitation with use of levonorgestrel and only 2% knew that the medication could be used up to 120 hours after unprotected intercourse.
“Texas has the fifth highest rate of teen pregnancy and the highest rate of repeat teen pregnancy in the United States, and we think these barriers are a big contributor to this,” Mr. Goff said in an interview.
Senior author, Maria C. Monge, MD, of the university, added in a press release that comprehensive sex education and contraception services also are not readily available to all adolescents across the state, which likely increases the use of emergency contraception.
In the United States, levonorgestrel 1.5 mg oral tablet has been available over the counter for more than 10 years and without an age limit since 2013.
TORONTO – Despite federal legislation making emergency contraception available without age limits or a prescription, Texas adolescents may be denied or hindered in their attempts to obtain it, according to a study presented at the Pediatric Academic Societies.
When researchers queried 768 Texas pharmacy employees (97% of whom were pharmacists or pharmacy techs) about the availability of levonorgestrel at their stores, the drug was available in only 76% of pharmacies. However, contrary to federal law, 6% of stores required a prescription to obtain it.
Almost half (47%) of the pharmacies who stocked the drug reported an age requirement for purchase; this rose to 81% in the panhandle of the state, which is considered a more socially conservative region. The researchers divided the pharmacies into six geographic regions and 25% of pharmacies in each region were randomly selected for inclusion.
“Typically, the age limit these pharmacies picked was 17, which is what the most recent federal law said too, but in 2013, that was changed such that there is not supposed to be an age limit,” said Mr. Goff. “But it really varied – some told us 18, some said 21, and some said, ‘I don’t know the age limit, but I would give it out without checking their ID.’ ”
As well, 52% required some degree of interaction or consultation with pharmacy staff to obtain the drug – either it was behind the counter or on the shelf, but maybe in a locked cabinet.
Turns out, pharmacy staff also aren’t well versed in the use of levonorgestrel. Only 10% of those surveyed recognized that there may be a weight limitation with use of levonorgestrel and only 2% knew that the medication could be used up to 120 hours after unprotected intercourse.
“Texas has the fifth highest rate of teen pregnancy and the highest rate of repeat teen pregnancy in the United States, and we think these barriers are a big contributor to this,” Mr. Goff said in an interview.
Senior author, Maria C. Monge, MD, of the university, added in a press release that comprehensive sex education and contraception services also are not readily available to all adolescents across the state, which likely increases the use of emergency contraception.
In the United States, levonorgestrel 1.5 mg oral tablet has been available over the counter for more than 10 years and without an age limit since 2013.
AT PAS 2018
Key clinical point:
Major finding: 76% of pharmacies carried levonorgestrel, but 6% required a prescription, and 47% set an age requirement on its purchase.
Study details: A survey of 768 Texas pharmacy employees from randomly sampled pharmacies, 97% pharmacists or pharmacy technicians.
Disclosures: The author reported no financial conflict of interest.
Patients with CF at increased risk for GI cancers
Patients with cystic fibrosis have a significantly greater risk for developing cancers of the gastrointestinal tract compared with the general population, results of a systematic review and meta-analysis indicate.
Among persons with cystic fibrosis (CF) the standardized incidence ratio (SIR) for any gastrointestinal cancer compared with the general population was 8.13 (P less than .0001). Patients with CF were at significantly elevated risk for cancers of the small bowel, colon, biliary tract, and pancreas, reported Atsushi Sakuraba, MD, PhD, of the University of Chicago, and his colleagues.
“Additionally, our findings suggest that patients who had an organ transplant have a higher risk of developing gastrointestinal cancer than those who did not. Although further studies are needed to monitor gastrointestinal cancer incidence over time in patients with cystic fibrosis, the development of a screening strategy for gastrointestinal cancer in these patients is warranted,” they wrote in Lancet Oncology.
As patients with CF live longer because of improvements in therapies and management of comorbidities, their risks for cancer and other diseases will increase, the authors noted.
To get a more accurate estimate of the degree of risk than what smaller cohort studies could provide, the investigators conducted a systematic review and meta-analysis. They narrowed their search to six cohort studies including 99,925 patients with CF followed for a total of 5,444,695 person-years.
As noted, patients with CF overall had an eightfold higher risk for gastrointestinal cancers compared with the general population, and for the subgroup of patients who had undergone a lung transplant, the SIR was 21.13 compared with 4.18 for those with CF but no lung transplant (P less than .0001).
- The SIRs for site-specific gastrointestinal cancers were as follows:
- Small bowel: SIR= 18.94 (P less than .0001).
- Colon: SIR = 10.91 (P less than .0001).
- Biliary tract: SIR = 17.87 (P less than .0001).
- Pancreas: SIR = 6.18 (P = .022).
The investigators recommend screening for gastrointestinal cancers in patients with CF in general, and especially for patients who have undergone lung transplantation and are receiving immunosuppressive therapies.
Because of the elevated risk of pancreatic and biliary tract cancers, the authors propose a screening program including magnetic resonance cholangiopancreatography, endoscopic ultrasound, or abdominal ultrasound and measurement of cancer antigen 19-9.
The authors reported that the study had no funding source, and they declared no competing interests.
SOURCE: Yamada A et al. Lancet Oncol. 2018 Apr 26. doi: 10.1016/S1470-2045(18)30188-8.
The emergence of gastrointestinal cancer as a clinical complication in adults with cystic fibrosis is a consequence of the substantial improvement in life expectancy. Novel CFTR modulator therapies, which correct the malfunctioning protein and increase its expression at the apical surface, might decrease the incidence of gastrointestinal cancers in patients with cystic fibrosis.
In conclusion, the meta-analysis by Yamada and colleagues shows that cystic fibrosis can be considered a gastrointestinal cancer syndrome, for which screening and surveillance protocols should be implemented. Oncologists and gastroenterologists managing patients with cystic fibrosis should consider the best methods for screening of the small bowel, biliary tract, pancreas, and colon to prevent gastrointestinal malignancies in these patients.
Mordechai Slae, MD, and Michael Wilschanski, MD, are with the Hadassah Medical Center in Jerusalem. These comments are condensed from their editorial in The Lancet Oncology.
The emergence of gastrointestinal cancer as a clinical complication in adults with cystic fibrosis is a consequence of the substantial improvement in life expectancy. Novel CFTR modulator therapies, which correct the malfunctioning protein and increase its expression at the apical surface, might decrease the incidence of gastrointestinal cancers in patients with cystic fibrosis.
In conclusion, the meta-analysis by Yamada and colleagues shows that cystic fibrosis can be considered a gastrointestinal cancer syndrome, for which screening and surveillance protocols should be implemented. Oncologists and gastroenterologists managing patients with cystic fibrosis should consider the best methods for screening of the small bowel, biliary tract, pancreas, and colon to prevent gastrointestinal malignancies in these patients.
Mordechai Slae, MD, and Michael Wilschanski, MD, are with the Hadassah Medical Center in Jerusalem. These comments are condensed from their editorial in The Lancet Oncology.
The emergence of gastrointestinal cancer as a clinical complication in adults with cystic fibrosis is a consequence of the substantial improvement in life expectancy. Novel CFTR modulator therapies, which correct the malfunctioning protein and increase its expression at the apical surface, might decrease the incidence of gastrointestinal cancers in patients with cystic fibrosis.
In conclusion, the meta-analysis by Yamada and colleagues shows that cystic fibrosis can be considered a gastrointestinal cancer syndrome, for which screening and surveillance protocols should be implemented. Oncologists and gastroenterologists managing patients with cystic fibrosis should consider the best methods for screening of the small bowel, biliary tract, pancreas, and colon to prevent gastrointestinal malignancies in these patients.
Mordechai Slae, MD, and Michael Wilschanski, MD, are with the Hadassah Medical Center in Jerusalem. These comments are condensed from their editorial in The Lancet Oncology.
Patients with cystic fibrosis have a significantly greater risk for developing cancers of the gastrointestinal tract compared with the general population, results of a systematic review and meta-analysis indicate.
Among persons with cystic fibrosis (CF) the standardized incidence ratio (SIR) for any gastrointestinal cancer compared with the general population was 8.13 (P less than .0001). Patients with CF were at significantly elevated risk for cancers of the small bowel, colon, biliary tract, and pancreas, reported Atsushi Sakuraba, MD, PhD, of the University of Chicago, and his colleagues.
“Additionally, our findings suggest that patients who had an organ transplant have a higher risk of developing gastrointestinal cancer than those who did not. Although further studies are needed to monitor gastrointestinal cancer incidence over time in patients with cystic fibrosis, the development of a screening strategy for gastrointestinal cancer in these patients is warranted,” they wrote in Lancet Oncology.
As patients with CF live longer because of improvements in therapies and management of comorbidities, their risks for cancer and other diseases will increase, the authors noted.
To get a more accurate estimate of the degree of risk than what smaller cohort studies could provide, the investigators conducted a systematic review and meta-analysis. They narrowed their search to six cohort studies including 99,925 patients with CF followed for a total of 5,444,695 person-years.
As noted, patients with CF overall had an eightfold higher risk for gastrointestinal cancers compared with the general population, and for the subgroup of patients who had undergone a lung transplant, the SIR was 21.13 compared with 4.18 for those with CF but no lung transplant (P less than .0001).
- The SIRs for site-specific gastrointestinal cancers were as follows:
- Small bowel: SIR= 18.94 (P less than .0001).
- Colon: SIR = 10.91 (P less than .0001).
- Biliary tract: SIR = 17.87 (P less than .0001).
- Pancreas: SIR = 6.18 (P = .022).
The investigators recommend screening for gastrointestinal cancers in patients with CF in general, and especially for patients who have undergone lung transplantation and are receiving immunosuppressive therapies.
Because of the elevated risk of pancreatic and biliary tract cancers, the authors propose a screening program including magnetic resonance cholangiopancreatography, endoscopic ultrasound, or abdominal ultrasound and measurement of cancer antigen 19-9.
The authors reported that the study had no funding source, and they declared no competing interests.
SOURCE: Yamada A et al. Lancet Oncol. 2018 Apr 26. doi: 10.1016/S1470-2045(18)30188-8.
Patients with cystic fibrosis have a significantly greater risk for developing cancers of the gastrointestinal tract compared with the general population, results of a systematic review and meta-analysis indicate.
Among persons with cystic fibrosis (CF) the standardized incidence ratio (SIR) for any gastrointestinal cancer compared with the general population was 8.13 (P less than .0001). Patients with CF were at significantly elevated risk for cancers of the small bowel, colon, biliary tract, and pancreas, reported Atsushi Sakuraba, MD, PhD, of the University of Chicago, and his colleagues.
“Additionally, our findings suggest that patients who had an organ transplant have a higher risk of developing gastrointestinal cancer than those who did not. Although further studies are needed to monitor gastrointestinal cancer incidence over time in patients with cystic fibrosis, the development of a screening strategy for gastrointestinal cancer in these patients is warranted,” they wrote in Lancet Oncology.
As patients with CF live longer because of improvements in therapies and management of comorbidities, their risks for cancer and other diseases will increase, the authors noted.
To get a more accurate estimate of the degree of risk than what smaller cohort studies could provide, the investigators conducted a systematic review and meta-analysis. They narrowed their search to six cohort studies including 99,925 patients with CF followed for a total of 5,444,695 person-years.
As noted, patients with CF overall had an eightfold higher risk for gastrointestinal cancers compared with the general population, and for the subgroup of patients who had undergone a lung transplant, the SIR was 21.13 compared with 4.18 for those with CF but no lung transplant (P less than .0001).
- The SIRs for site-specific gastrointestinal cancers were as follows:
- Small bowel: SIR= 18.94 (P less than .0001).
- Colon: SIR = 10.91 (P less than .0001).
- Biliary tract: SIR = 17.87 (P less than .0001).
- Pancreas: SIR = 6.18 (P = .022).
The investigators recommend screening for gastrointestinal cancers in patients with CF in general, and especially for patients who have undergone lung transplantation and are receiving immunosuppressive therapies.
Because of the elevated risk of pancreatic and biliary tract cancers, the authors propose a screening program including magnetic resonance cholangiopancreatography, endoscopic ultrasound, or abdominal ultrasound and measurement of cancer antigen 19-9.
The authors reported that the study had no funding source, and they declared no competing interests.
SOURCE: Yamada A et al. Lancet Oncol. 2018 Apr 26. doi: 10.1016/S1470-2045(18)30188-8.
FROM THE LANCET ONCOLOGY
Key clinical point: Patients with cystic fibrosis, especially those who have received a lung transplant, are at increased risk for gastrointestinal tract cancers.
Major finding: The standard incidence ratio for GI cancers among patients with CF was 8.13 compared with the general population.
Study details: Systematic review and meta-analysis of published studies including 99,925 patients with CF followed for 5,444,695 person-years.
Disclosures: The authors reported that the study had no funding source, and they declared no competing interests.
Source: Yamada A et al. Lancet Oncol 2018 Apr 26. doi: 10.1016/S1470-2045(18)30188-8.