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FDA approves Reyvow for acute migraine treatment
The Food and Drug Administration has approved lasmiditan (Reyvow) for acute treatment of migraines with and without auras in adults.
The agency’s Oct. 11 announcement said the approval is based on results from a pair of randomized, double-blind, placebo-controlled trials that included 3,177 adult patients with a history of migraine with and without aura. The percentage of patients whose pain and most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved after 2 hours was higher in patients receiving lasmiditan than in patients receiving placebo.
Lasmiditan is a serotonin 5-hydroxytryptamine1F–receptor agonist, giving it a unique mechanism of action as compared with other migraine treatments.
The most common adverse events associated with lasmiditan include dizziness, fatigue, paresthesia, and sedation. There is a risk of driving impairment while taking the medication, and patients are advised not to operate or drive machinery for 8 hours after taking lasmiditan.
“Reyvow is a new option for the acute treatment of migraine, a painful condition that affects one in seven Americans. We know that the migraine community is keenly interested in additional treatment options, and we remain committed to continuing to work with stakeholders to promote the development of new therapies for the acute and preventive treatment of migraine,” said Nick Kozauer, MD, acting deputy director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research.
Eli Lilly, the drug’s manufacturer, said in a news release that “the recommended controlled substance classification for Reyvow is currently under review by the Drug Enforcement Administration and is expected within 90 days of today’s FDA approval, after which Reyvow will be available to patients in retail pharmacies” in oral doses of 50 mg, 100 mg, and 200 mg.
The Food and Drug Administration has approved lasmiditan (Reyvow) for acute treatment of migraines with and without auras in adults.
The agency’s Oct. 11 announcement said the approval is based on results from a pair of randomized, double-blind, placebo-controlled trials that included 3,177 adult patients with a history of migraine with and without aura. The percentage of patients whose pain and most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved after 2 hours was higher in patients receiving lasmiditan than in patients receiving placebo.
Lasmiditan is a serotonin 5-hydroxytryptamine1F–receptor agonist, giving it a unique mechanism of action as compared with other migraine treatments.
The most common adverse events associated with lasmiditan include dizziness, fatigue, paresthesia, and sedation. There is a risk of driving impairment while taking the medication, and patients are advised not to operate or drive machinery for 8 hours after taking lasmiditan.
“Reyvow is a new option for the acute treatment of migraine, a painful condition that affects one in seven Americans. We know that the migraine community is keenly interested in additional treatment options, and we remain committed to continuing to work with stakeholders to promote the development of new therapies for the acute and preventive treatment of migraine,” said Nick Kozauer, MD, acting deputy director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research.
Eli Lilly, the drug’s manufacturer, said in a news release that “the recommended controlled substance classification for Reyvow is currently under review by the Drug Enforcement Administration and is expected within 90 days of today’s FDA approval, after which Reyvow will be available to patients in retail pharmacies” in oral doses of 50 mg, 100 mg, and 200 mg.
The Food and Drug Administration has approved lasmiditan (Reyvow) for acute treatment of migraines with and without auras in adults.
The agency’s Oct. 11 announcement said the approval is based on results from a pair of randomized, double-blind, placebo-controlled trials that included 3,177 adult patients with a history of migraine with and without aura. The percentage of patients whose pain and most bothersome migraine symptom (nausea, light sensitivity, or sound sensitivity) resolved after 2 hours was higher in patients receiving lasmiditan than in patients receiving placebo.
Lasmiditan is a serotonin 5-hydroxytryptamine1F–receptor agonist, giving it a unique mechanism of action as compared with other migraine treatments.
The most common adverse events associated with lasmiditan include dizziness, fatigue, paresthesia, and sedation. There is a risk of driving impairment while taking the medication, and patients are advised not to operate or drive machinery for 8 hours after taking lasmiditan.
“Reyvow is a new option for the acute treatment of migraine, a painful condition that affects one in seven Americans. We know that the migraine community is keenly interested in additional treatment options, and we remain committed to continuing to work with stakeholders to promote the development of new therapies for the acute and preventive treatment of migraine,” said Nick Kozauer, MD, acting deputy director of the division of neurology products in the FDA’s Center for Drug Evaluation and Research.
Eli Lilly, the drug’s manufacturer, said in a news release that “the recommended controlled substance classification for Reyvow is currently under review by the Drug Enforcement Administration and is expected within 90 days of today’s FDA approval, after which Reyvow will be available to patients in retail pharmacies” in oral doses of 50 mg, 100 mg, and 200 mg.
Pediatric stroke thrombectomy study sheds light on off-label procedure
based on data from a retrospective, multicenter study of 73 patients.
Children with high scores on the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) or large-vessel occlusion in the anterior or posterior circulation are at increased risk for morbidity and mortality, but the safety of thrombectomy in children has not been well studied. Several randomized trials have showed its safety and efficacy in adults, wrote Peter Sporns, MD, of the Institute of Clinical Radiology at Universitätsklinikum Muenster (Germany), and colleagues.
In a study published in JAMA Neurology, Dr. Sporns and coauthors reviewed data from pediatric patients aged younger than 18 years who underwent endovascular recanalization between Jan. 1, 2000, and Dec. 31, 2018, at 25 stroke centers in Europe and 2 in the United States.
The primary outcome was change in the PedNIHSS scores and the endovascular recanalization involved “a combination of techniques using distal thrombaspiration and/or clot retrievers,” the researchers wrote.
Neurologic outcomes improved from a median PedNIHSS score of 14.0 at hospital admission to 4.0 at day 7. The average time from stroke onset to hospital admission was 3 hours, and the median time from stroke onset to recanalization was 4 hours.
“The rapidity of recanalization across the large number of centers in the Save ChildS study is a commendable achievement, establishing feasibility for acute pediatric stroke treatment within the short window of time for embolectomy at centers prepared for this event,” wrote Christine Fox, MD, of the University of California, San Francisco, and Nomazulu Dlamini, MBBS, PhD, of the Hospital for Sick Children, Toronto, in an accompanying editorial.
In addition, the median modified Rankin Scale score was 1.0 at discharge and at 6 and 24 months, and the median Pediatric Stroke Outcome Measure score was 1.0 at discharge and 0.5 at 6 and 24 months.
The median age of the patients was 11 years, and approximately half were boys (51%). A total of 63 children (86%) were treated for anterior circulation occlusion, and 10 (14%) were treated for posterior circulation occlusion; (22%) received concomitant intravenous thrombolysis.
Transient vasospasm was the only observed periprocedural complication, seen in four patients, and all cases resolved without clinical sequelae. One patient with a history of a heart anomaly died of cardiac arrest after recanalization. No vascular complications were reported, and the proportion of symptomatic intracerebral hemorrhage events was 1.37 per 100 observations, compared with 2.79 in a meta-analysis of adult studies.
The main limitation of the study was its retrospective design, as well as the absence of a control group, the researchers noted. However, the results “may support clinicians’ practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.”
The editorial authors emphasized that safety concerns remain despite the relatively low level of complications observed in the current study. “The safety of thrombectomy in children with suspected focal cerebral arteriopathy or bilateral arteriopathies is a particular concern because of the potential to further injure an acutely inflamed or chronically diseased vessel,” they wrote.
“We should be cautious about the interpretation of long-term outcome measures in the Save ChildS study,” Dr. Fox and Dr. Dlamini added, noting that additional multicenter studies are needed “to advance our knowledge of pediatric stroke and inform best practices.”
Dr. Sporns had no financial conflicts to disclose; several coauthors disclosed relationships with multiple pharmaceutical companies. Dr. Fox and Dr. Dlamini had no financial conflicts to disclose.
SOURCES: Sporns P et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3403; Fox C, Dlamini N. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3412.
based on data from a retrospective, multicenter study of 73 patients.
Children with high scores on the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) or large-vessel occlusion in the anterior or posterior circulation are at increased risk for morbidity and mortality, but the safety of thrombectomy in children has not been well studied. Several randomized trials have showed its safety and efficacy in adults, wrote Peter Sporns, MD, of the Institute of Clinical Radiology at Universitätsklinikum Muenster (Germany), and colleagues.
In a study published in JAMA Neurology, Dr. Sporns and coauthors reviewed data from pediatric patients aged younger than 18 years who underwent endovascular recanalization between Jan. 1, 2000, and Dec. 31, 2018, at 25 stroke centers in Europe and 2 in the United States.
The primary outcome was change in the PedNIHSS scores and the endovascular recanalization involved “a combination of techniques using distal thrombaspiration and/or clot retrievers,” the researchers wrote.
Neurologic outcomes improved from a median PedNIHSS score of 14.0 at hospital admission to 4.0 at day 7. The average time from stroke onset to hospital admission was 3 hours, and the median time from stroke onset to recanalization was 4 hours.
“The rapidity of recanalization across the large number of centers in the Save ChildS study is a commendable achievement, establishing feasibility for acute pediatric stroke treatment within the short window of time for embolectomy at centers prepared for this event,” wrote Christine Fox, MD, of the University of California, San Francisco, and Nomazulu Dlamini, MBBS, PhD, of the Hospital for Sick Children, Toronto, in an accompanying editorial.
In addition, the median modified Rankin Scale score was 1.0 at discharge and at 6 and 24 months, and the median Pediatric Stroke Outcome Measure score was 1.0 at discharge and 0.5 at 6 and 24 months.
The median age of the patients was 11 years, and approximately half were boys (51%). A total of 63 children (86%) were treated for anterior circulation occlusion, and 10 (14%) were treated for posterior circulation occlusion; (22%) received concomitant intravenous thrombolysis.
Transient vasospasm was the only observed periprocedural complication, seen in four patients, and all cases resolved without clinical sequelae. One patient with a history of a heart anomaly died of cardiac arrest after recanalization. No vascular complications were reported, and the proportion of symptomatic intracerebral hemorrhage events was 1.37 per 100 observations, compared with 2.79 in a meta-analysis of adult studies.
The main limitation of the study was its retrospective design, as well as the absence of a control group, the researchers noted. However, the results “may support clinicians’ practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.”
The editorial authors emphasized that safety concerns remain despite the relatively low level of complications observed in the current study. “The safety of thrombectomy in children with suspected focal cerebral arteriopathy or bilateral arteriopathies is a particular concern because of the potential to further injure an acutely inflamed or chronically diseased vessel,” they wrote.
“We should be cautious about the interpretation of long-term outcome measures in the Save ChildS study,” Dr. Fox and Dr. Dlamini added, noting that additional multicenter studies are needed “to advance our knowledge of pediatric stroke and inform best practices.”
Dr. Sporns had no financial conflicts to disclose; several coauthors disclosed relationships with multiple pharmaceutical companies. Dr. Fox and Dr. Dlamini had no financial conflicts to disclose.
SOURCES: Sporns P et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3403; Fox C, Dlamini N. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3412.
based on data from a retrospective, multicenter study of 73 patients.
Children with high scores on the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) or large-vessel occlusion in the anterior or posterior circulation are at increased risk for morbidity and mortality, but the safety of thrombectomy in children has not been well studied. Several randomized trials have showed its safety and efficacy in adults, wrote Peter Sporns, MD, of the Institute of Clinical Radiology at Universitätsklinikum Muenster (Germany), and colleagues.
In a study published in JAMA Neurology, Dr. Sporns and coauthors reviewed data from pediatric patients aged younger than 18 years who underwent endovascular recanalization between Jan. 1, 2000, and Dec. 31, 2018, at 25 stroke centers in Europe and 2 in the United States.
The primary outcome was change in the PedNIHSS scores and the endovascular recanalization involved “a combination of techniques using distal thrombaspiration and/or clot retrievers,” the researchers wrote.
Neurologic outcomes improved from a median PedNIHSS score of 14.0 at hospital admission to 4.0 at day 7. The average time from stroke onset to hospital admission was 3 hours, and the median time from stroke onset to recanalization was 4 hours.
“The rapidity of recanalization across the large number of centers in the Save ChildS study is a commendable achievement, establishing feasibility for acute pediatric stroke treatment within the short window of time for embolectomy at centers prepared for this event,” wrote Christine Fox, MD, of the University of California, San Francisco, and Nomazulu Dlamini, MBBS, PhD, of the Hospital for Sick Children, Toronto, in an accompanying editorial.
In addition, the median modified Rankin Scale score was 1.0 at discharge and at 6 and 24 months, and the median Pediatric Stroke Outcome Measure score was 1.0 at discharge and 0.5 at 6 and 24 months.
The median age of the patients was 11 years, and approximately half were boys (51%). A total of 63 children (86%) were treated for anterior circulation occlusion, and 10 (14%) were treated for posterior circulation occlusion; (22%) received concomitant intravenous thrombolysis.
Transient vasospasm was the only observed periprocedural complication, seen in four patients, and all cases resolved without clinical sequelae. One patient with a history of a heart anomaly died of cardiac arrest after recanalization. No vascular complications were reported, and the proportion of symptomatic intracerebral hemorrhage events was 1.37 per 100 observations, compared with 2.79 in a meta-analysis of adult studies.
The main limitation of the study was its retrospective design, as well as the absence of a control group, the researchers noted. However, the results “may support clinicians’ practice of off-label thrombectomy in childhood stroke in the absence of high-level evidence.”
The editorial authors emphasized that safety concerns remain despite the relatively low level of complications observed in the current study. “The safety of thrombectomy in children with suspected focal cerebral arteriopathy or bilateral arteriopathies is a particular concern because of the potential to further injure an acutely inflamed or chronically diseased vessel,” they wrote.
“We should be cautious about the interpretation of long-term outcome measures in the Save ChildS study,” Dr. Fox and Dr. Dlamini added, noting that additional multicenter studies are needed “to advance our knowledge of pediatric stroke and inform best practices.”
Dr. Sporns had no financial conflicts to disclose; several coauthors disclosed relationships with multiple pharmaceutical companies. Dr. Fox and Dr. Dlamini had no financial conflicts to disclose.
SOURCES: Sporns P et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3403; Fox C, Dlamini N. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3412.
FROM JAMA NEUROLOGY
Increased Parkinson’s disease risk seen with bipolar disorder
Patients with bipolar disorder may be at increased risk of Parkinson’s disease in later life, according to a systematic review and meta-analysis published in JAMA Neurology.
Patrícia R. Faustino, MD, from the faculty of medicine at the University of Lisboa (Portgual), and coauthors reviewed and analyzed seven articles – four cohort studies and three cross-sectional studies – that reported data on idiopathic Parkinson’s disease in patients with bipolar disorder, compared with those without. The meta-analysis found that individuals with a previous diagnosis of bipolar disorder had a 235% higher risk of being later diagnosed with Parkinson’s disease. Even after removing studies with a high risk of bias, the risk was still 3.21 times higher in those with bipolar disorder, compared with those without.
“The pathophysiological rationale between bipolar disorder and Parkinson’s disease might be explained by the dopamine dysregulation hypothesis, which states that the cyclical process of bipolar disorder in manic states leads to a down-regulation of dopamine receptor sensitivity (depression phase), which is later compensated by up-regulation (manic state),” the authors wrote. “Over time, this phenomenon may lead to an overall reduction of dopaminergic activity, the prototypical Parkinson’s disease state.”
Subgroup analysis revealed that subgroups with shorter follow-up periods – less than 9 years – had a greater increase in the risk of a later Parkinson’s disease diagnosis. The authors noted that this could represent misdiagnosis of parkinsonism – possibly drug induced – as Parkinson’s disease. The researchers also raised the possibility that the increased risk of Parkinson’s disease in patients with bipolar disorder could relate to long-term lithium use, rather than being a causal relationship. “However, treatment with lithium is foundational in bipolar disorder, and so to separate the causal effect from a potential confounder would be particularly difficult,” they wrote.
One of the studies included did explore the use of lithium, and found that lithium monotherapy was associated with a significant increase in the risk of being diagnosed with Parkinson’s disease or taking antiparkinsonism medication, compared with antidepressant therapy. However the authors commented that the diagnostic code may not differentiate Parkinson’s disease from other causes of parkinsonism.
Given their findings, the authors suggested that, if patients with bipolar disorder present with parkinsonism features, it may not necessarily be drug induced. In these patients, they recommended an investigation for Parkinson’s disease, perhaps using functional neuroimaging “as Parkinson’s disease classically presents with nigrostriatal degeneration while drug-induced parkinsonism does not.”
Two authors declared grants and personal fees from the pharmaceutical sector. No other conflicts of interest were reported.
SOURCE: Faustino PR et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3446.
Patients with bipolar disorder may be at increased risk of Parkinson’s disease in later life, according to a systematic review and meta-analysis published in JAMA Neurology.
Patrícia R. Faustino, MD, from the faculty of medicine at the University of Lisboa (Portgual), and coauthors reviewed and analyzed seven articles – four cohort studies and three cross-sectional studies – that reported data on idiopathic Parkinson’s disease in patients with bipolar disorder, compared with those without. The meta-analysis found that individuals with a previous diagnosis of bipolar disorder had a 235% higher risk of being later diagnosed with Parkinson’s disease. Even after removing studies with a high risk of bias, the risk was still 3.21 times higher in those with bipolar disorder, compared with those without.
“The pathophysiological rationale between bipolar disorder and Parkinson’s disease might be explained by the dopamine dysregulation hypothesis, which states that the cyclical process of bipolar disorder in manic states leads to a down-regulation of dopamine receptor sensitivity (depression phase), which is later compensated by up-regulation (manic state),” the authors wrote. “Over time, this phenomenon may lead to an overall reduction of dopaminergic activity, the prototypical Parkinson’s disease state.”
Subgroup analysis revealed that subgroups with shorter follow-up periods – less than 9 years – had a greater increase in the risk of a later Parkinson’s disease diagnosis. The authors noted that this could represent misdiagnosis of parkinsonism – possibly drug induced – as Parkinson’s disease. The researchers also raised the possibility that the increased risk of Parkinson’s disease in patients with bipolar disorder could relate to long-term lithium use, rather than being a causal relationship. “However, treatment with lithium is foundational in bipolar disorder, and so to separate the causal effect from a potential confounder would be particularly difficult,” they wrote.
One of the studies included did explore the use of lithium, and found that lithium monotherapy was associated with a significant increase in the risk of being diagnosed with Parkinson’s disease or taking antiparkinsonism medication, compared with antidepressant therapy. However the authors commented that the diagnostic code may not differentiate Parkinson’s disease from other causes of parkinsonism.
Given their findings, the authors suggested that, if patients with bipolar disorder present with parkinsonism features, it may not necessarily be drug induced. In these patients, they recommended an investigation for Parkinson’s disease, perhaps using functional neuroimaging “as Parkinson’s disease classically presents with nigrostriatal degeneration while drug-induced parkinsonism does not.”
Two authors declared grants and personal fees from the pharmaceutical sector. No other conflicts of interest were reported.
SOURCE: Faustino PR et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3446.
Patients with bipolar disorder may be at increased risk of Parkinson’s disease in later life, according to a systematic review and meta-analysis published in JAMA Neurology.
Patrícia R. Faustino, MD, from the faculty of medicine at the University of Lisboa (Portgual), and coauthors reviewed and analyzed seven articles – four cohort studies and three cross-sectional studies – that reported data on idiopathic Parkinson’s disease in patients with bipolar disorder, compared with those without. The meta-analysis found that individuals with a previous diagnosis of bipolar disorder had a 235% higher risk of being later diagnosed with Parkinson’s disease. Even after removing studies with a high risk of bias, the risk was still 3.21 times higher in those with bipolar disorder, compared with those without.
“The pathophysiological rationale between bipolar disorder and Parkinson’s disease might be explained by the dopamine dysregulation hypothesis, which states that the cyclical process of bipolar disorder in manic states leads to a down-regulation of dopamine receptor sensitivity (depression phase), which is later compensated by up-regulation (manic state),” the authors wrote. “Over time, this phenomenon may lead to an overall reduction of dopaminergic activity, the prototypical Parkinson’s disease state.”
Subgroup analysis revealed that subgroups with shorter follow-up periods – less than 9 years – had a greater increase in the risk of a later Parkinson’s disease diagnosis. The authors noted that this could represent misdiagnosis of parkinsonism – possibly drug induced – as Parkinson’s disease. The researchers also raised the possibility that the increased risk of Parkinson’s disease in patients with bipolar disorder could relate to long-term lithium use, rather than being a causal relationship. “However, treatment with lithium is foundational in bipolar disorder, and so to separate the causal effect from a potential confounder would be particularly difficult,” they wrote.
One of the studies included did explore the use of lithium, and found that lithium monotherapy was associated with a significant increase in the risk of being diagnosed with Parkinson’s disease or taking antiparkinsonism medication, compared with antidepressant therapy. However the authors commented that the diagnostic code may not differentiate Parkinson’s disease from other causes of parkinsonism.
Given their findings, the authors suggested that, if patients with bipolar disorder present with parkinsonism features, it may not necessarily be drug induced. In these patients, they recommended an investigation for Parkinson’s disease, perhaps using functional neuroimaging “as Parkinson’s disease classically presents with nigrostriatal degeneration while drug-induced parkinsonism does not.”
Two authors declared grants and personal fees from the pharmaceutical sector. No other conflicts of interest were reported.
SOURCE: Faustino PR et al. JAMA Neurol. 2019 Oct 14. doi: 10.1001/jamaneurol.2019.3446.
FROM JAMA NEUROLOGY
Accounting for sex may improve diagnosis of amnestic MCI
, according to an investigation published Oct. 9 in Neurology. Using sex-specific cut scores to define verbal memory impairment improves diagnostic accuracy and “may result in earlier detection of memory impairment in women and avoid false diagnoses in men,” wrote Erin E. Sundermann, PhD, assistant project scientist in psychiatry at the University of California, San Diego, and colleagues.
A diagnosis of aMCI generally requires a verbal memory deficit. Ample research demonstrates a female advantage on verbal memory tests, but normative data for these tests usually do not adjust for sex. Dr. Sundermann and colleagues previously showed that among men and women with aMCI and similar disease burden, women perform better on tests of verbal memory. Given these results, the investigators initiated a new study to test the hypothesis that using sex-specific norms and cut scores to identify memory impairment improves the accuracy of aMCI diagnosis, compared with non–sex-specific norms and cut scores.
An examination of ADNI data
Dr. Sundermann’s group extracted cross-sectional data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database in October 2016. They included participants without dementia for whom neuropsychologic and Alzheimer’s disease pathologic marker data were available at baseline. They excluded patients with a non-aMCI diagnosis based on typical and sex-specific criteria.
The researchers’ primary outcome was the Rey Auditory Verbal Learning Test (RAVLT). They also determined the presence or absence of the APOE e4 allele for each participant. Biomarker outcomes included the CSF ratio of hyperphosphorylated tau (p-tau) to beta-amyloid (A-beta), and cortical A-beta deposition.
Dr. Sundermann and colleagues applied the Jak/Bondi actuarial neuropsychologic diagnostic method to baseline data. This method relies on six neuropsychologic tests, including the RAVLT Learning and Delayed Recall. They subsequently derived two sets of normative data for the RAVLT outcomes in a normative sample of 1,620 patients enrolled in the Mayo Clinic Study of Aging (MCSA). The latter patients were considered normal controls at baseline and at least two follow-up visits at 15 months apart. One set of normative data was specific for age and education, and the other was specific for age, education, and sex. Dr. Sundermann’s group next applied the typical Jak/Bondi method and the sex-specific Jak/Bondi method to all ADNI participants’ data.
Biomarker analysis supported the hypothesis
The researchers included 985 participants (453 women) in their final sample. Approximately 94% of the population was white. Mean age was 72.9 years, and mean education duration was 16.3 years. Overall, women had a significantly lower mean age (71.9 years vs. 73.6 years), significantly fewer mean years of education (15.7 years vs. 16.7 years), and a significantly higher mean Mini-Mental State Examination score (28 vs. 28.1) compared with men. Compared with men’s scores, women’s scores on the RAVLT Learning (mean 42.3 vs. mean 35.6) and Delayed Recall (mean 6.2 vs. mean 4.5) were significantly higher.
When Dr. Sundermann and colleagues used typical cut scores, the frequency of aMCI diagnosis was significantly higher in men. Using sex-specific cut scores eliminated this sex difference, however. Among men, 184 (35%) were categorized as true positive, 293 (55%) as true negative, and 55 (10%) as false positive. No men were categorized as false negative. Among women, 120 (26%) were categorized as true positive, 288 (64%) as true negative, and 45 (10%) as false negative. No women were categorized as false positive.
The likelihood of cortical amyloid positivity in false negative women was 3.6 times greater than in true negative women but did not differ from that in true positive women. The likelihood of positivity for the CSF p-tau/A-beta ratio in false negative women was more than two times higher than in true negative women but did not differ from that in true positive women. The likelihood of having an APOE e4 allele in false negative women was almost fivefold higher than in true negative women but did not differ from that in true positive women.
The likelihood of cortical amyloid positivity in false positive men was less than that in true positive men (odds ratio [OR], 0.45) but did not differ from that in true negative men. The likelihood of positivity for CSF p-tau/A-beta ratio in false positive men was significantly less than in true positive men (OR, 0.47) but did not differ from that in true negative men. The likelihood of having the APOE e4 allele in false positive men was lower than that in true positive men (OR, 0.63) and higher than that in true negative men (OR, 1.50), but not significantly.
Results have implications for treatment
“If these results are confirmed, they have vital implications,” Dr. Sundermann said in a press release. “If women are inaccurately identified as having no problems with memory and thinking skills when they actually have MCI, then treatments are not being started, and they and their families are not planning ahead for their care or their financial or legal situations. And for men who are inaccurately diagnosed with MCI, they can be exposed to unneeded medications along with undue stress for them and their families.”
Among the limitations that the investigators acknowledged was the study’s cross-sectional, rather than longitudinal, design. In addition, the ADNI population that the researchers examined is a convenience sample of predominantly white and well-educated volunteers. The results therefore may not be generalizable to the broader U.S. population, wrote the authors.
Grants from the National Institutes of Health funded the study. Several of the investigators reported receiving honoraria from various pharmaceutical companies such as Mylan. One investigator sits on the editorial board for Neurology.
, according to an investigation published Oct. 9 in Neurology. Using sex-specific cut scores to define verbal memory impairment improves diagnostic accuracy and “may result in earlier detection of memory impairment in women and avoid false diagnoses in men,” wrote Erin E. Sundermann, PhD, assistant project scientist in psychiatry at the University of California, San Diego, and colleagues.
A diagnosis of aMCI generally requires a verbal memory deficit. Ample research demonstrates a female advantage on verbal memory tests, but normative data for these tests usually do not adjust for sex. Dr. Sundermann and colleagues previously showed that among men and women with aMCI and similar disease burden, women perform better on tests of verbal memory. Given these results, the investigators initiated a new study to test the hypothesis that using sex-specific norms and cut scores to identify memory impairment improves the accuracy of aMCI diagnosis, compared with non–sex-specific norms and cut scores.
An examination of ADNI data
Dr. Sundermann’s group extracted cross-sectional data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database in October 2016. They included participants without dementia for whom neuropsychologic and Alzheimer’s disease pathologic marker data were available at baseline. They excluded patients with a non-aMCI diagnosis based on typical and sex-specific criteria.
The researchers’ primary outcome was the Rey Auditory Verbal Learning Test (RAVLT). They also determined the presence or absence of the APOE e4 allele for each participant. Biomarker outcomes included the CSF ratio of hyperphosphorylated tau (p-tau) to beta-amyloid (A-beta), and cortical A-beta deposition.
Dr. Sundermann and colleagues applied the Jak/Bondi actuarial neuropsychologic diagnostic method to baseline data. This method relies on six neuropsychologic tests, including the RAVLT Learning and Delayed Recall. They subsequently derived two sets of normative data for the RAVLT outcomes in a normative sample of 1,620 patients enrolled in the Mayo Clinic Study of Aging (MCSA). The latter patients were considered normal controls at baseline and at least two follow-up visits at 15 months apart. One set of normative data was specific for age and education, and the other was specific for age, education, and sex. Dr. Sundermann’s group next applied the typical Jak/Bondi method and the sex-specific Jak/Bondi method to all ADNI participants’ data.
Biomarker analysis supported the hypothesis
The researchers included 985 participants (453 women) in their final sample. Approximately 94% of the population was white. Mean age was 72.9 years, and mean education duration was 16.3 years. Overall, women had a significantly lower mean age (71.9 years vs. 73.6 years), significantly fewer mean years of education (15.7 years vs. 16.7 years), and a significantly higher mean Mini-Mental State Examination score (28 vs. 28.1) compared with men. Compared with men’s scores, women’s scores on the RAVLT Learning (mean 42.3 vs. mean 35.6) and Delayed Recall (mean 6.2 vs. mean 4.5) were significantly higher.
When Dr. Sundermann and colleagues used typical cut scores, the frequency of aMCI diagnosis was significantly higher in men. Using sex-specific cut scores eliminated this sex difference, however. Among men, 184 (35%) were categorized as true positive, 293 (55%) as true negative, and 55 (10%) as false positive. No men were categorized as false negative. Among women, 120 (26%) were categorized as true positive, 288 (64%) as true negative, and 45 (10%) as false negative. No women were categorized as false positive.
The likelihood of cortical amyloid positivity in false negative women was 3.6 times greater than in true negative women but did not differ from that in true positive women. The likelihood of positivity for the CSF p-tau/A-beta ratio in false negative women was more than two times higher than in true negative women but did not differ from that in true positive women. The likelihood of having an APOE e4 allele in false negative women was almost fivefold higher than in true negative women but did not differ from that in true positive women.
The likelihood of cortical amyloid positivity in false positive men was less than that in true positive men (odds ratio [OR], 0.45) but did not differ from that in true negative men. The likelihood of positivity for CSF p-tau/A-beta ratio in false positive men was significantly less than in true positive men (OR, 0.47) but did not differ from that in true negative men. The likelihood of having the APOE e4 allele in false positive men was lower than that in true positive men (OR, 0.63) and higher than that in true negative men (OR, 1.50), but not significantly.
Results have implications for treatment
“If these results are confirmed, they have vital implications,” Dr. Sundermann said in a press release. “If women are inaccurately identified as having no problems with memory and thinking skills when they actually have MCI, then treatments are not being started, and they and their families are not planning ahead for their care or their financial or legal situations. And for men who are inaccurately diagnosed with MCI, they can be exposed to unneeded medications along with undue stress for them and their families.”
Among the limitations that the investigators acknowledged was the study’s cross-sectional, rather than longitudinal, design. In addition, the ADNI population that the researchers examined is a convenience sample of predominantly white and well-educated volunteers. The results therefore may not be generalizable to the broader U.S. population, wrote the authors.
Grants from the National Institutes of Health funded the study. Several of the investigators reported receiving honoraria from various pharmaceutical companies such as Mylan. One investigator sits on the editorial board for Neurology.
, according to an investigation published Oct. 9 in Neurology. Using sex-specific cut scores to define verbal memory impairment improves diagnostic accuracy and “may result in earlier detection of memory impairment in women and avoid false diagnoses in men,” wrote Erin E. Sundermann, PhD, assistant project scientist in psychiatry at the University of California, San Diego, and colleagues.
A diagnosis of aMCI generally requires a verbal memory deficit. Ample research demonstrates a female advantage on verbal memory tests, but normative data for these tests usually do not adjust for sex. Dr. Sundermann and colleagues previously showed that among men and women with aMCI and similar disease burden, women perform better on tests of verbal memory. Given these results, the investigators initiated a new study to test the hypothesis that using sex-specific norms and cut scores to identify memory impairment improves the accuracy of aMCI diagnosis, compared with non–sex-specific norms and cut scores.
An examination of ADNI data
Dr. Sundermann’s group extracted cross-sectional data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database in October 2016. They included participants without dementia for whom neuropsychologic and Alzheimer’s disease pathologic marker data were available at baseline. They excluded patients with a non-aMCI diagnosis based on typical and sex-specific criteria.
The researchers’ primary outcome was the Rey Auditory Verbal Learning Test (RAVLT). They also determined the presence or absence of the APOE e4 allele for each participant. Biomarker outcomes included the CSF ratio of hyperphosphorylated tau (p-tau) to beta-amyloid (A-beta), and cortical A-beta deposition.
Dr. Sundermann and colleagues applied the Jak/Bondi actuarial neuropsychologic diagnostic method to baseline data. This method relies on six neuropsychologic tests, including the RAVLT Learning and Delayed Recall. They subsequently derived two sets of normative data for the RAVLT outcomes in a normative sample of 1,620 patients enrolled in the Mayo Clinic Study of Aging (MCSA). The latter patients were considered normal controls at baseline and at least two follow-up visits at 15 months apart. One set of normative data was specific for age and education, and the other was specific for age, education, and sex. Dr. Sundermann’s group next applied the typical Jak/Bondi method and the sex-specific Jak/Bondi method to all ADNI participants’ data.
Biomarker analysis supported the hypothesis
The researchers included 985 participants (453 women) in their final sample. Approximately 94% of the population was white. Mean age was 72.9 years, and mean education duration was 16.3 years. Overall, women had a significantly lower mean age (71.9 years vs. 73.6 years), significantly fewer mean years of education (15.7 years vs. 16.7 years), and a significantly higher mean Mini-Mental State Examination score (28 vs. 28.1) compared with men. Compared with men’s scores, women’s scores on the RAVLT Learning (mean 42.3 vs. mean 35.6) and Delayed Recall (mean 6.2 vs. mean 4.5) were significantly higher.
When Dr. Sundermann and colleagues used typical cut scores, the frequency of aMCI diagnosis was significantly higher in men. Using sex-specific cut scores eliminated this sex difference, however. Among men, 184 (35%) were categorized as true positive, 293 (55%) as true negative, and 55 (10%) as false positive. No men were categorized as false negative. Among women, 120 (26%) were categorized as true positive, 288 (64%) as true negative, and 45 (10%) as false negative. No women were categorized as false positive.
The likelihood of cortical amyloid positivity in false negative women was 3.6 times greater than in true negative women but did not differ from that in true positive women. The likelihood of positivity for the CSF p-tau/A-beta ratio in false negative women was more than two times higher than in true negative women but did not differ from that in true positive women. The likelihood of having an APOE e4 allele in false negative women was almost fivefold higher than in true negative women but did not differ from that in true positive women.
The likelihood of cortical amyloid positivity in false positive men was less than that in true positive men (odds ratio [OR], 0.45) but did not differ from that in true negative men. The likelihood of positivity for CSF p-tau/A-beta ratio in false positive men was significantly less than in true positive men (OR, 0.47) but did not differ from that in true negative men. The likelihood of having the APOE e4 allele in false positive men was lower than that in true positive men (OR, 0.63) and higher than that in true negative men (OR, 1.50), but not significantly.
Results have implications for treatment
“If these results are confirmed, they have vital implications,” Dr. Sundermann said in a press release. “If women are inaccurately identified as having no problems with memory and thinking skills when they actually have MCI, then treatments are not being started, and they and their families are not planning ahead for their care or their financial or legal situations. And for men who are inaccurately diagnosed with MCI, they can be exposed to unneeded medications along with undue stress for them and their families.”
Among the limitations that the investigators acknowledged was the study’s cross-sectional, rather than longitudinal, design. In addition, the ADNI population that the researchers examined is a convenience sample of predominantly white and well-educated volunteers. The results therefore may not be generalizable to the broader U.S. population, wrote the authors.
Grants from the National Institutes of Health funded the study. Several of the investigators reported receiving honoraria from various pharmaceutical companies such as Mylan. One investigator sits on the editorial board for Neurology.
FROM NEUROLOGY
HHS floats Stark/anti-kickback revisions to support value-based care
The long-awaited reforms would create permanent exemptions and safe harbors to protect doctors participating in legitimate value-based arrangements. If finalized, the proposals also would offer flexibility for innovation and improved care coordination, while easing the compliance burden for health care professionals and maintaining safeguards against actual fraud and abuse, according to the U.S. Department of Health & Human Services.
The proposals acknowledge that the Stark Law has been an unintentional roadblock to value-based programs in part because it circumscribed parties’ exchanges of rewards for good behavior, said Donna K. Thiel, a Washington-based health law attorney.
“This should be helpful to doctors in that it removes some of the risk in such arrangements under the existing law,” she said in an interview. “If finalized, the new regulations will alleviate some roadblocks created by the Stark Law with respect to hospital-physician and other arrangements designed to enhance care coordination, improve quality, and reduce waste. Likewise, the changes to the [Anti-Kickback Statute] and Beneficiary Inducement laws loosen the reins on compensation arrangements that might be technical violations of those laws where the arrangement fosters [value-based payments] or efficiency, transparency, or innovation in the provision of health care.”
“These proposed rules would be a historic reform of how healthcare is regulated in America,” HHS Deputy Secretary Eric Hargan said in a statement. “They are part of a much broader effort to update, reform, and cut back our regulations to allow innovation toward a more affordable, higher quality, value-based health care system, while maintaining the important protections patients need.”
The two proposed measures – one rule by the Centers for Medicare and Medicaid Services and the other rule by the Office of Inspector General – include safe harbors for certain remuneration exchanged among participants in a value-based arrangement that fosters better coordinated and managed patient care. This includes care arrangements that improve quality, health outcomes, and efficiency, value-based arrangements with substantial downside financial risk, and value-based arrangements with full financial risk.
In addition, the proposals would protect certain tools and supports shared or delivered under patient engagement and support arrangements to improve quality, health outcomes, and efficiency. For example, a specialty physician practice could share data analytics services with a primary care physician practice in an effort to coordinate care and better manage shared patients, according to the HHS.
If finalized, the changes would modify existing safe harbor for personal services and management contracts to add flexibility with respect to outcomes-based payments and part-time arrangements, according to a fact sheet by the OIG. The rule would also modify existing safe harbors for local transportation to expand and modify mileage limits for rural areas and for transportation for discharged patients.
The proposals include guidance on several requirements that must be met for physicians and health care providers to comply with the Stark Law. For example, compensation provided to a doctor by another health care provider generally must be at fair-market value. As part of the proposals, the HHS offers guidance on how to determine if compensation meets this requirement and provides clarity on a range of other technical compliance requirements.
If the rules are approved, more physicians may be encouraged to become part of value-based arrangements, according to Anjali N.C. Downs, a health law attorney based in Washington.
“As stakeholders have long known, physicians are key components to achieving value-based health care delivery and payment systems,” Ms. Downs said in an interview. “The proposed rules remove regulatory barriers that chill physician’s willingness and ability to participate in or even consider participating in integrated care delivery models, alternative payment models, and incentive based arrangements based on outcomes and reductions in cost.”
However, Ms. Thiel noted the proposed rules do not scale back the affected laws as comprehensively as some stakeholders hoped.
“Some would like to see the Stark law repealed completely, opining that the Stark Law has become too complex, creating obstacles in the transition from the fee-for-service model,” Ms. Thiel said. “Because Stark is a strict liability law, meaning no proof of specific intent to violate is required, providers and doctors can violate Stark even when there is no corrupt intent involved. This new regulation purports to fix some of those issues, but others will remain. Some in the industry believe full repeal is necessary to allow the health industry to move forward with pay-for-performance initiatives.”
The agency is also proposing a safe harbor for donations of cybersecurity technology and services between aligned providers in both the fee-for-service and the value-based settings. For example, a local hospital looking to improve its cybersecurity and that of nearby providers could donate cybersecurity software to each physician that refers patients to its hospital, according to the HHS. In addition, the proposals would add protections for certain cybersecurity technology included as part of an electronic health records (EHR) arrangement.
Physician organizations expressed cautious optimism about the proposed changes.
“While the [American Medical Association] is assessing the full scope of today’s proposals, we are pleased to see that the administration has acknowledged a need for policy revisions in response to potential barriers that impede the delivery of patient-centric care,” AMA President Patrice A. Harris, MD, said in a statement. “Currently, the Stark Law and Anti-Kickback Statute can have a negative impact on the ability of physicians to assist with coordination because they inhibit collaborative partnerships, care continuity, and the engagement of patients in their care. These obstacles can hinder the health care system’s movement to value-based care.”
The proposed rules have been submitted to the Federal Registry and are not yet published. The HHS will accept mail and electronic comments about the proposals up to 75 days after publication in the registry.
The long-awaited reforms would create permanent exemptions and safe harbors to protect doctors participating in legitimate value-based arrangements. If finalized, the proposals also would offer flexibility for innovation and improved care coordination, while easing the compliance burden for health care professionals and maintaining safeguards against actual fraud and abuse, according to the U.S. Department of Health & Human Services.
The proposals acknowledge that the Stark Law has been an unintentional roadblock to value-based programs in part because it circumscribed parties’ exchanges of rewards for good behavior, said Donna K. Thiel, a Washington-based health law attorney.
“This should be helpful to doctors in that it removes some of the risk in such arrangements under the existing law,” she said in an interview. “If finalized, the new regulations will alleviate some roadblocks created by the Stark Law with respect to hospital-physician and other arrangements designed to enhance care coordination, improve quality, and reduce waste. Likewise, the changes to the [Anti-Kickback Statute] and Beneficiary Inducement laws loosen the reins on compensation arrangements that might be technical violations of those laws where the arrangement fosters [value-based payments] or efficiency, transparency, or innovation in the provision of health care.”
“These proposed rules would be a historic reform of how healthcare is regulated in America,” HHS Deputy Secretary Eric Hargan said in a statement. “They are part of a much broader effort to update, reform, and cut back our regulations to allow innovation toward a more affordable, higher quality, value-based health care system, while maintaining the important protections patients need.”
The two proposed measures – one rule by the Centers for Medicare and Medicaid Services and the other rule by the Office of Inspector General – include safe harbors for certain remuneration exchanged among participants in a value-based arrangement that fosters better coordinated and managed patient care. This includes care arrangements that improve quality, health outcomes, and efficiency, value-based arrangements with substantial downside financial risk, and value-based arrangements with full financial risk.
In addition, the proposals would protect certain tools and supports shared or delivered under patient engagement and support arrangements to improve quality, health outcomes, and efficiency. For example, a specialty physician practice could share data analytics services with a primary care physician practice in an effort to coordinate care and better manage shared patients, according to the HHS.
If finalized, the changes would modify existing safe harbor for personal services and management contracts to add flexibility with respect to outcomes-based payments and part-time arrangements, according to a fact sheet by the OIG. The rule would also modify existing safe harbors for local transportation to expand and modify mileage limits for rural areas and for transportation for discharged patients.
The proposals include guidance on several requirements that must be met for physicians and health care providers to comply with the Stark Law. For example, compensation provided to a doctor by another health care provider generally must be at fair-market value. As part of the proposals, the HHS offers guidance on how to determine if compensation meets this requirement and provides clarity on a range of other technical compliance requirements.
If the rules are approved, more physicians may be encouraged to become part of value-based arrangements, according to Anjali N.C. Downs, a health law attorney based in Washington.
“As stakeholders have long known, physicians are key components to achieving value-based health care delivery and payment systems,” Ms. Downs said in an interview. “The proposed rules remove regulatory barriers that chill physician’s willingness and ability to participate in or even consider participating in integrated care delivery models, alternative payment models, and incentive based arrangements based on outcomes and reductions in cost.”
However, Ms. Thiel noted the proposed rules do not scale back the affected laws as comprehensively as some stakeholders hoped.
“Some would like to see the Stark law repealed completely, opining that the Stark Law has become too complex, creating obstacles in the transition from the fee-for-service model,” Ms. Thiel said. “Because Stark is a strict liability law, meaning no proof of specific intent to violate is required, providers and doctors can violate Stark even when there is no corrupt intent involved. This new regulation purports to fix some of those issues, but others will remain. Some in the industry believe full repeal is necessary to allow the health industry to move forward with pay-for-performance initiatives.”
The agency is also proposing a safe harbor for donations of cybersecurity technology and services between aligned providers in both the fee-for-service and the value-based settings. For example, a local hospital looking to improve its cybersecurity and that of nearby providers could donate cybersecurity software to each physician that refers patients to its hospital, according to the HHS. In addition, the proposals would add protections for certain cybersecurity technology included as part of an electronic health records (EHR) arrangement.
Physician organizations expressed cautious optimism about the proposed changes.
“While the [American Medical Association] is assessing the full scope of today’s proposals, we are pleased to see that the administration has acknowledged a need for policy revisions in response to potential barriers that impede the delivery of patient-centric care,” AMA President Patrice A. Harris, MD, said in a statement. “Currently, the Stark Law and Anti-Kickback Statute can have a negative impact on the ability of physicians to assist with coordination because they inhibit collaborative partnerships, care continuity, and the engagement of patients in their care. These obstacles can hinder the health care system’s movement to value-based care.”
The proposed rules have been submitted to the Federal Registry and are not yet published. The HHS will accept mail and electronic comments about the proposals up to 75 days after publication in the registry.
The long-awaited reforms would create permanent exemptions and safe harbors to protect doctors participating in legitimate value-based arrangements. If finalized, the proposals also would offer flexibility for innovation and improved care coordination, while easing the compliance burden for health care professionals and maintaining safeguards against actual fraud and abuse, according to the U.S. Department of Health & Human Services.
The proposals acknowledge that the Stark Law has been an unintentional roadblock to value-based programs in part because it circumscribed parties’ exchanges of rewards for good behavior, said Donna K. Thiel, a Washington-based health law attorney.
“This should be helpful to doctors in that it removes some of the risk in such arrangements under the existing law,” she said in an interview. “If finalized, the new regulations will alleviate some roadblocks created by the Stark Law with respect to hospital-physician and other arrangements designed to enhance care coordination, improve quality, and reduce waste. Likewise, the changes to the [Anti-Kickback Statute] and Beneficiary Inducement laws loosen the reins on compensation arrangements that might be technical violations of those laws where the arrangement fosters [value-based payments] or efficiency, transparency, or innovation in the provision of health care.”
“These proposed rules would be a historic reform of how healthcare is regulated in America,” HHS Deputy Secretary Eric Hargan said in a statement. “They are part of a much broader effort to update, reform, and cut back our regulations to allow innovation toward a more affordable, higher quality, value-based health care system, while maintaining the important protections patients need.”
The two proposed measures – one rule by the Centers for Medicare and Medicaid Services and the other rule by the Office of Inspector General – include safe harbors for certain remuneration exchanged among participants in a value-based arrangement that fosters better coordinated and managed patient care. This includes care arrangements that improve quality, health outcomes, and efficiency, value-based arrangements with substantial downside financial risk, and value-based arrangements with full financial risk.
In addition, the proposals would protect certain tools and supports shared or delivered under patient engagement and support arrangements to improve quality, health outcomes, and efficiency. For example, a specialty physician practice could share data analytics services with a primary care physician practice in an effort to coordinate care and better manage shared patients, according to the HHS.
If finalized, the changes would modify existing safe harbor for personal services and management contracts to add flexibility with respect to outcomes-based payments and part-time arrangements, according to a fact sheet by the OIG. The rule would also modify existing safe harbors for local transportation to expand and modify mileage limits for rural areas and for transportation for discharged patients.
The proposals include guidance on several requirements that must be met for physicians and health care providers to comply with the Stark Law. For example, compensation provided to a doctor by another health care provider generally must be at fair-market value. As part of the proposals, the HHS offers guidance on how to determine if compensation meets this requirement and provides clarity on a range of other technical compliance requirements.
If the rules are approved, more physicians may be encouraged to become part of value-based arrangements, according to Anjali N.C. Downs, a health law attorney based in Washington.
“As stakeholders have long known, physicians are key components to achieving value-based health care delivery and payment systems,” Ms. Downs said in an interview. “The proposed rules remove regulatory barriers that chill physician’s willingness and ability to participate in or even consider participating in integrated care delivery models, alternative payment models, and incentive based arrangements based on outcomes and reductions in cost.”
However, Ms. Thiel noted the proposed rules do not scale back the affected laws as comprehensively as some stakeholders hoped.
“Some would like to see the Stark law repealed completely, opining that the Stark Law has become too complex, creating obstacles in the transition from the fee-for-service model,” Ms. Thiel said. “Because Stark is a strict liability law, meaning no proof of specific intent to violate is required, providers and doctors can violate Stark even when there is no corrupt intent involved. This new regulation purports to fix some of those issues, but others will remain. Some in the industry believe full repeal is necessary to allow the health industry to move forward with pay-for-performance initiatives.”
The agency is also proposing a safe harbor for donations of cybersecurity technology and services between aligned providers in both the fee-for-service and the value-based settings. For example, a local hospital looking to improve its cybersecurity and that of nearby providers could donate cybersecurity software to each physician that refers patients to its hospital, according to the HHS. In addition, the proposals would add protections for certain cybersecurity technology included as part of an electronic health records (EHR) arrangement.
Physician organizations expressed cautious optimism about the proposed changes.
“While the [American Medical Association] is assessing the full scope of today’s proposals, we are pleased to see that the administration has acknowledged a need for policy revisions in response to potential barriers that impede the delivery of patient-centric care,” AMA President Patrice A. Harris, MD, said in a statement. “Currently, the Stark Law and Anti-Kickback Statute can have a negative impact on the ability of physicians to assist with coordination because they inhibit collaborative partnerships, care continuity, and the engagement of patients in their care. These obstacles can hinder the health care system’s movement to value-based care.”
The proposed rules have been submitted to the Federal Registry and are not yet published. The HHS will accept mail and electronic comments about the proposals up to 75 days after publication in the registry.
Trump: No health insurance, no U.S. entry
Health insurance or the ability to pay for care soon will be a requirement for immigrants seeking U.S. visas, under a proclamation from President Trump.
Effective Nov. 3, 2019, visa applicants must demonstrate to immigration authorities that they can obtain coverage by an approved health insurer within 30 days of entering the United States or show evidence they possess the financial resources to pay for foreseeable medical costs. Approved coverage includes, but is not limited to, an employer-sponsored plan, an unsubsidized health plan offered in the individual market, a family member’s plan, or a visitor health insurance plan that provides coverage for at least 364 days, according to the proclamation.
President Trump said that the restriction protects Americans from bearing the burden of uncompensated health care costs generated by immigrants.
“While our health care system grapples with the challenges caused by uncompensated care, the United States government is making the problem worse by admitting thousands of aliens who have not demonstrated any ability to pay for their health care costs,” President Trump said in the proclamation. “Notably, data show that lawful immigrants are about three times more likely than United States citizens to lack health insurance. Immigrants who enter this country should not further saddle our health care system, and subsequently American taxpayers, with higher costs.”
The rule does not apply to refugees or asylum seekers, immigrants holding valid visas prior to Nov. 3, noncitizen children of U.S. citizens, unaccompanied minors, or permanent residents returning to the country after less than a year overseas.
The rule is the latest in a series of immigration restrictions by President Trump. Most recently in August 2019, the Trump administration amended the federal public charge rule, a longstanding policy that allows authorities to refuse to admit immigrants into the United States – or to adjust their legal status – if they are deemed likely to become a public charge. The revised regulation allows officials to consider previously excluded programs in their determination, including nonemergency Medicaid for nonpregnant adults, the Supplemental Nutrition Assistance Program, and several housing programs.
The proclamation is consistent with the President’s recent public charge rule, and it is sound immigration policy, said Dale Wilcox, executive director and general counsel for the Immigration Reform Law Institute.
“If U.S. citizens are responsible for the health care costs of the world, then the world will show up at our doorstep for free health care,” Mr. Wilcox said in an interview. “That is unfair to American citizens and would financially devastate health care providers. The impact of this proclamation would be a more manageable immigration policy that welcomes immigrants who will contribute to our country as well as benefit from it.”
J. Wesley Boyd, MD, of the Center for Bioethics at Harvard University, Boston, said he was saddened to learn about the proclamation, adding that the Trump administration is relying on inaccurate information and falsified facts to justify the new restriction. Dr. Boyd, cofounder of the Human Rights and Asylum Clinic at Cambridge Health Alliance in Cambridge, Mass., coauthored a 2018 study finding that immigrants pay more into the U.S. health care system than they use.
That analysis, which examined 188 peer-reviewed studies related to immigrants and U.S. health care expenditures, found that per capita expenditures from private and public insurance sources were about 40% lower for immigrants, compared with native-born Americans. Expenditures for undocumented immigrants were even lower. Immigrants also made a greater contribution to Medicare’s trust fund than they withdrew, the study found (Int J Health Serv. 2018 Aug. 8 doi: 10.1177/0020731418791963).
Immigrants use less health care resources because they are generally younger and healthier than native-born Americans, and they are less likely to access health care services – regardless of health status, Dr. Boyd said in an interview. In addition, many immigrants who contribute to Medicare through payroll and/or taxes are no longer in the U.S. when they reach Medicare age.
“The Trump administration, in this case, is making yet another set of excuses for why they are trying to keep immigrants out of the country,” Dr. Boyd said. “The potential impact of this restriction is devastating. Obviously, the Trump administration is doing anything that it possibly can to try to limit immigrants from coming into our country and seeking a better life for themselves.”
The proclamation also could have a chilling effect on immigrants currently in the United States who are in need of medical treatment, Dr. Boyd noted.
“The real effect is you’re going to have immigrants who are already here, not [accessing] health care when they need it, for fear they somehow become known to the government,” he said.
Health insurance or the ability to pay for care soon will be a requirement for immigrants seeking U.S. visas, under a proclamation from President Trump.
Effective Nov. 3, 2019, visa applicants must demonstrate to immigration authorities that they can obtain coverage by an approved health insurer within 30 days of entering the United States or show evidence they possess the financial resources to pay for foreseeable medical costs. Approved coverage includes, but is not limited to, an employer-sponsored plan, an unsubsidized health plan offered in the individual market, a family member’s plan, or a visitor health insurance plan that provides coverage for at least 364 days, according to the proclamation.
President Trump said that the restriction protects Americans from bearing the burden of uncompensated health care costs generated by immigrants.
“While our health care system grapples with the challenges caused by uncompensated care, the United States government is making the problem worse by admitting thousands of aliens who have not demonstrated any ability to pay for their health care costs,” President Trump said in the proclamation. “Notably, data show that lawful immigrants are about three times more likely than United States citizens to lack health insurance. Immigrants who enter this country should not further saddle our health care system, and subsequently American taxpayers, with higher costs.”
The rule does not apply to refugees or asylum seekers, immigrants holding valid visas prior to Nov. 3, noncitizen children of U.S. citizens, unaccompanied minors, or permanent residents returning to the country after less than a year overseas.
The rule is the latest in a series of immigration restrictions by President Trump. Most recently in August 2019, the Trump administration amended the federal public charge rule, a longstanding policy that allows authorities to refuse to admit immigrants into the United States – or to adjust their legal status – if they are deemed likely to become a public charge. The revised regulation allows officials to consider previously excluded programs in their determination, including nonemergency Medicaid for nonpregnant adults, the Supplemental Nutrition Assistance Program, and several housing programs.
The proclamation is consistent with the President’s recent public charge rule, and it is sound immigration policy, said Dale Wilcox, executive director and general counsel for the Immigration Reform Law Institute.
“If U.S. citizens are responsible for the health care costs of the world, then the world will show up at our doorstep for free health care,” Mr. Wilcox said in an interview. “That is unfair to American citizens and would financially devastate health care providers. The impact of this proclamation would be a more manageable immigration policy that welcomes immigrants who will contribute to our country as well as benefit from it.”
J. Wesley Boyd, MD, of the Center for Bioethics at Harvard University, Boston, said he was saddened to learn about the proclamation, adding that the Trump administration is relying on inaccurate information and falsified facts to justify the new restriction. Dr. Boyd, cofounder of the Human Rights and Asylum Clinic at Cambridge Health Alliance in Cambridge, Mass., coauthored a 2018 study finding that immigrants pay more into the U.S. health care system than they use.
That analysis, which examined 188 peer-reviewed studies related to immigrants and U.S. health care expenditures, found that per capita expenditures from private and public insurance sources were about 40% lower for immigrants, compared with native-born Americans. Expenditures for undocumented immigrants were even lower. Immigrants also made a greater contribution to Medicare’s trust fund than they withdrew, the study found (Int J Health Serv. 2018 Aug. 8 doi: 10.1177/0020731418791963).
Immigrants use less health care resources because they are generally younger and healthier than native-born Americans, and they are less likely to access health care services – regardless of health status, Dr. Boyd said in an interview. In addition, many immigrants who contribute to Medicare through payroll and/or taxes are no longer in the U.S. when they reach Medicare age.
“The Trump administration, in this case, is making yet another set of excuses for why they are trying to keep immigrants out of the country,” Dr. Boyd said. “The potential impact of this restriction is devastating. Obviously, the Trump administration is doing anything that it possibly can to try to limit immigrants from coming into our country and seeking a better life for themselves.”
The proclamation also could have a chilling effect on immigrants currently in the United States who are in need of medical treatment, Dr. Boyd noted.
“The real effect is you’re going to have immigrants who are already here, not [accessing] health care when they need it, for fear they somehow become known to the government,” he said.
Health insurance or the ability to pay for care soon will be a requirement for immigrants seeking U.S. visas, under a proclamation from President Trump.
Effective Nov. 3, 2019, visa applicants must demonstrate to immigration authorities that they can obtain coverage by an approved health insurer within 30 days of entering the United States or show evidence they possess the financial resources to pay for foreseeable medical costs. Approved coverage includes, but is not limited to, an employer-sponsored plan, an unsubsidized health plan offered in the individual market, a family member’s plan, or a visitor health insurance plan that provides coverage for at least 364 days, according to the proclamation.
President Trump said that the restriction protects Americans from bearing the burden of uncompensated health care costs generated by immigrants.
“While our health care system grapples with the challenges caused by uncompensated care, the United States government is making the problem worse by admitting thousands of aliens who have not demonstrated any ability to pay for their health care costs,” President Trump said in the proclamation. “Notably, data show that lawful immigrants are about three times more likely than United States citizens to lack health insurance. Immigrants who enter this country should not further saddle our health care system, and subsequently American taxpayers, with higher costs.”
The rule does not apply to refugees or asylum seekers, immigrants holding valid visas prior to Nov. 3, noncitizen children of U.S. citizens, unaccompanied minors, or permanent residents returning to the country after less than a year overseas.
The rule is the latest in a series of immigration restrictions by President Trump. Most recently in August 2019, the Trump administration amended the federal public charge rule, a longstanding policy that allows authorities to refuse to admit immigrants into the United States – or to adjust their legal status – if they are deemed likely to become a public charge. The revised regulation allows officials to consider previously excluded programs in their determination, including nonemergency Medicaid for nonpregnant adults, the Supplemental Nutrition Assistance Program, and several housing programs.
The proclamation is consistent with the President’s recent public charge rule, and it is sound immigration policy, said Dale Wilcox, executive director and general counsel for the Immigration Reform Law Institute.
“If U.S. citizens are responsible for the health care costs of the world, then the world will show up at our doorstep for free health care,” Mr. Wilcox said in an interview. “That is unfair to American citizens and would financially devastate health care providers. The impact of this proclamation would be a more manageable immigration policy that welcomes immigrants who will contribute to our country as well as benefit from it.”
J. Wesley Boyd, MD, of the Center for Bioethics at Harvard University, Boston, said he was saddened to learn about the proclamation, adding that the Trump administration is relying on inaccurate information and falsified facts to justify the new restriction. Dr. Boyd, cofounder of the Human Rights and Asylum Clinic at Cambridge Health Alliance in Cambridge, Mass., coauthored a 2018 study finding that immigrants pay more into the U.S. health care system than they use.
That analysis, which examined 188 peer-reviewed studies related to immigrants and U.S. health care expenditures, found that per capita expenditures from private and public insurance sources were about 40% lower for immigrants, compared with native-born Americans. Expenditures for undocumented immigrants were even lower. Immigrants also made a greater contribution to Medicare’s trust fund than they withdrew, the study found (Int J Health Serv. 2018 Aug. 8 doi: 10.1177/0020731418791963).
Immigrants use less health care resources because they are generally younger and healthier than native-born Americans, and they are less likely to access health care services – regardless of health status, Dr. Boyd said in an interview. In addition, many immigrants who contribute to Medicare through payroll and/or taxes are no longer in the U.S. when they reach Medicare age.
“The Trump administration, in this case, is making yet another set of excuses for why they are trying to keep immigrants out of the country,” Dr. Boyd said. “The potential impact of this restriction is devastating. Obviously, the Trump administration is doing anything that it possibly can to try to limit immigrants from coming into our country and seeking a better life for themselves.”
The proclamation also could have a chilling effect on immigrants currently in the United States who are in need of medical treatment, Dr. Boyd noted.
“The real effect is you’re going to have immigrants who are already here, not [accessing] health care when they need it, for fear they somehow become known to the government,” he said.
Congenital heart disease in children linked to increased autism risk
A new study of children who were born with congenital heart disease (CHD) has found that they have increased odds of developing autism spectrum disorder.
“To our knowledge, this is the only study in which there has been a comparison between [autism spectrum disorder] and multiple CHD subtypes,” wrote Eric R. Sigmon, MD, of Emory University, Atlanta, and coauthors. “Our findings are consistent with previous studies of CHD developmental outcomes, which have shown an increased risk of developmental and academic delay after CHD diagnosis and treatment.” The study was published in Pediatrics.
To further investigate the association between CHD and autism, the researchers performed a case-control study using the Military Health System administrative database. They uncovered 8,760 cases of children with autism spectrum disorder and matched each one with three controls (n = 26,280). From that sample size, they identified 1,063 children with CHD: 401 in the autism spectrum disorder group and 662 in the control group.
Before analysis, children with autism spectrum disorder had an odds ratio of 1.85 of having any form of CHD, compared with controls (95% confidence interval, 1.63-2.10). After adjustment for covariates – including genetic syndromes, maternal age and morbidity, perinatal morbidity, and neonatal complications – the OR was 1.33 (95% CI, 1.16-1.52).
In the sensitivity analysis – which included only 593 children with CHD – the OR was a similar 1.32 (95% CI, 1.10-1.59).
Left heart obstructive lesion was significantly associated with autism spectrum disorder after covariate adjustment (OR, 1.42; 95% CI, 1.04-1.93), but the finding was no longer significant in the sensitivity analysis.
The authors noted the potential limitations of their study, including the general weaknesses of administrative data, which they attempted to counter with the sensitive analysis. In addition, they recognized that children with either autism spectrum disorder or CHD “tend to present for care more frequently,” which could have created an ascertainment bias.
In an accompanying editorial, Johanna Calderon, PhD, David C. Bellinger, PhD, and Jane W. Newburger, MD, MPH, stated that more work needs to be done to further quantify the relationship between CHD and autism spectrum disorder (Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2019-2752). The three authors – all affiliated with Boston Children’s Hospital and Harvard Medical School, also in Boston – reiterated the acknowledgment from Dr. Sigmon and coauthors that the “etiologic pathways that might explain” the link between the two remains unknown. They also noted their surprise that autism spectrum disorder risk appears to be increased in children with modestly severe forms of CHD, stating that this finding required additional investigation.
“Despite the strengths of this study,” they wrote, “it raises more questions than answers.”
The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
SOURCE: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
A new study of children who were born with congenital heart disease (CHD) has found that they have increased odds of developing autism spectrum disorder.
“To our knowledge, this is the only study in which there has been a comparison between [autism spectrum disorder] and multiple CHD subtypes,” wrote Eric R. Sigmon, MD, of Emory University, Atlanta, and coauthors. “Our findings are consistent with previous studies of CHD developmental outcomes, which have shown an increased risk of developmental and academic delay after CHD diagnosis and treatment.” The study was published in Pediatrics.
To further investigate the association between CHD and autism, the researchers performed a case-control study using the Military Health System administrative database. They uncovered 8,760 cases of children with autism spectrum disorder and matched each one with three controls (n = 26,280). From that sample size, they identified 1,063 children with CHD: 401 in the autism spectrum disorder group and 662 in the control group.
Before analysis, children with autism spectrum disorder had an odds ratio of 1.85 of having any form of CHD, compared with controls (95% confidence interval, 1.63-2.10). After adjustment for covariates – including genetic syndromes, maternal age and morbidity, perinatal morbidity, and neonatal complications – the OR was 1.33 (95% CI, 1.16-1.52).
In the sensitivity analysis – which included only 593 children with CHD – the OR was a similar 1.32 (95% CI, 1.10-1.59).
Left heart obstructive lesion was significantly associated with autism spectrum disorder after covariate adjustment (OR, 1.42; 95% CI, 1.04-1.93), but the finding was no longer significant in the sensitivity analysis.
The authors noted the potential limitations of their study, including the general weaknesses of administrative data, which they attempted to counter with the sensitive analysis. In addition, they recognized that children with either autism spectrum disorder or CHD “tend to present for care more frequently,” which could have created an ascertainment bias.
In an accompanying editorial, Johanna Calderon, PhD, David C. Bellinger, PhD, and Jane W. Newburger, MD, MPH, stated that more work needs to be done to further quantify the relationship between CHD and autism spectrum disorder (Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2019-2752). The three authors – all affiliated with Boston Children’s Hospital and Harvard Medical School, also in Boston – reiterated the acknowledgment from Dr. Sigmon and coauthors that the “etiologic pathways that might explain” the link between the two remains unknown. They also noted their surprise that autism spectrum disorder risk appears to be increased in children with modestly severe forms of CHD, stating that this finding required additional investigation.
“Despite the strengths of this study,” they wrote, “it raises more questions than answers.”
The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
SOURCE: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
A new study of children who were born with congenital heart disease (CHD) has found that they have increased odds of developing autism spectrum disorder.
“To our knowledge, this is the only study in which there has been a comparison between [autism spectrum disorder] and multiple CHD subtypes,” wrote Eric R. Sigmon, MD, of Emory University, Atlanta, and coauthors. “Our findings are consistent with previous studies of CHD developmental outcomes, which have shown an increased risk of developmental and academic delay after CHD diagnosis and treatment.” The study was published in Pediatrics.
To further investigate the association between CHD and autism, the researchers performed a case-control study using the Military Health System administrative database. They uncovered 8,760 cases of children with autism spectrum disorder and matched each one with three controls (n = 26,280). From that sample size, they identified 1,063 children with CHD: 401 in the autism spectrum disorder group and 662 in the control group.
Before analysis, children with autism spectrum disorder had an odds ratio of 1.85 of having any form of CHD, compared with controls (95% confidence interval, 1.63-2.10). After adjustment for covariates – including genetic syndromes, maternal age and morbidity, perinatal morbidity, and neonatal complications – the OR was 1.33 (95% CI, 1.16-1.52).
In the sensitivity analysis – which included only 593 children with CHD – the OR was a similar 1.32 (95% CI, 1.10-1.59).
Left heart obstructive lesion was significantly associated with autism spectrum disorder after covariate adjustment (OR, 1.42; 95% CI, 1.04-1.93), but the finding was no longer significant in the sensitivity analysis.
The authors noted the potential limitations of their study, including the general weaknesses of administrative data, which they attempted to counter with the sensitive analysis. In addition, they recognized that children with either autism spectrum disorder or CHD “tend to present for care more frequently,” which could have created an ascertainment bias.
In an accompanying editorial, Johanna Calderon, PhD, David C. Bellinger, PhD, and Jane W. Newburger, MD, MPH, stated that more work needs to be done to further quantify the relationship between CHD and autism spectrum disorder (Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2019-2752). The three authors – all affiliated with Boston Children’s Hospital and Harvard Medical School, also in Boston – reiterated the acknowledgment from Dr. Sigmon and coauthors that the “etiologic pathways that might explain” the link between the two remains unknown. They also noted their surprise that autism spectrum disorder risk appears to be increased in children with modestly severe forms of CHD, stating that this finding required additional investigation.
“Despite the strengths of this study,” they wrote, “it raises more questions than answers.”
The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
SOURCE: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
FROM PEDIATRICS
Key clinical point: Children born with congenital heart disease have higher odds of developing autism, especially with certain forms of CHD, such as atrial and ventricular septal defects.
Major finding: After sensitivity analysis, children with congenital heart disease had increased odds of autism, compared with controls (odds ratio, 1.32; 95% confidence interval, 1.10-1.59).
Study details: A case-control study of children enrolled in the U.S. Military Health System from 2001 to 2013.
Disclosures: The study was funded by the Congressional Directed Medical Research Programs Autism Research Award. The authors reported no conflicts of interest.
Source: Sigmon ER at al. Pediatrics. 2019 Oct 10. doi: 10.1542/peds.2018-4114.
Appeals court to hear prescription drug privacy rights case
An appeals court may soon decide whether federal authorities can access a patient’s medical records through a statewide prescription drug monitoring database without a warrant or if such searches infringe upon privacy rights.
On Oct. 10, the 1st U.S. Circuit Court of Appeals will hear arguments in U.S. Department of Justice v. Jonas, which centers on an investigatory subpoena issued by the U.S. Drug Enforcement Agency in 2018 that sought records about a certain patient from New Hampshire’s Prescription Drug Monitoring Program (PDMP). The subpoena’s recipient, PDMP program manager Michelle Ricco-Jonas, refused to comply, citing state law that prohibits law enforcement from accessing the database without a court order based on probable cause. Releasing PDMP records to authorities without cause violate patients’ privacy protections under the Fourth Amendment, Ms. Jonas and the New Hampshire Attorney General’s Office argued.
The U.S. Department of Justice sued to enforce the subpoena, contending that the DEA’s authority to investigate suspected criminal drug activity preempts New Hampshire’s law under the Supremacy Clause. In November 2018, U.S. Magistrate Judge Andrea K. Johnstone agreed with the DOJ and recommended the district judge grant the government’s motion to enforce the subpoena, a decision affirmed by the U.S. District Court for the District of New Hampshire in January 2019. The court ruled the government met its burden to satisfy the modest requirements for enforcement of the subpoena. Attorneys for New Hampshire appealed to the 1st Circuit.
The case is being closely watched by states, physician groups, pharmacies, and patient advocacy groups. In a joint court brief by the New Hampshire Medical Society and the American Civil Liberties Union, the organizations urged the appeals court to protect patient privacy by finding in favor of New Hampshire.
“The DEA has sought to enforce a subpoena that both injures Jonas and threatens to invade the Fourth Amendment privacy rights of individuals whose private medical information resides in the database, and whose privacy and confidentiality Jonas is statutorily charged with protecting. ... but who have no ability to challenge that impending harm,” the groups wrote in the brief. “The prescription records at issue in this case reveal intimate, private, and potentially stigmatizing details about patients’ health, including details of those patients’ underlying medical conditions. For that reason, as with other medical records, people have a reasonable expectation of privacy in them.”
Oregon’s PDMP faced a similar legal challenge in 2012. In that case, the DEA attempted to access the records of one patient and two prescribing physicians from Oregon’s prescription database. The state sued to prevent release of the records, and the ACLU intervened as a plaintiff on behalf of several unnamed patients and a doctor. A district court ruled in favor of the plaintiffs, finding that the DEA’s actions constituted a Fourth Amendment violation. However, the 9th U.S. Circuit Court in 2017 overturned the decision, ruling that federal law regarding administrative subpoenas trumps Oregon law. In addition, the appeals court ruled that the ACLU lacked standing to intervene and seek relief different from that sought by Oregon. By invalidating ACLU from the suit, the Fourth Amendment argument was never resolved by the 9th Circuit.
New Hampshire is one of 49 states that have Prescription Drug Monitoring Programs in addition to the District of Columbia. The programs collect, monitor, and analyze electronically transmitted prescribing and dispensing data submitted by physicians and pharmacies with the aim of reducing prescription drug abuse and diversion.
An appeals court may soon decide whether federal authorities can access a patient’s medical records through a statewide prescription drug monitoring database without a warrant or if such searches infringe upon privacy rights.
On Oct. 10, the 1st U.S. Circuit Court of Appeals will hear arguments in U.S. Department of Justice v. Jonas, which centers on an investigatory subpoena issued by the U.S. Drug Enforcement Agency in 2018 that sought records about a certain patient from New Hampshire’s Prescription Drug Monitoring Program (PDMP). The subpoena’s recipient, PDMP program manager Michelle Ricco-Jonas, refused to comply, citing state law that prohibits law enforcement from accessing the database without a court order based on probable cause. Releasing PDMP records to authorities without cause violate patients’ privacy protections under the Fourth Amendment, Ms. Jonas and the New Hampshire Attorney General’s Office argued.
The U.S. Department of Justice sued to enforce the subpoena, contending that the DEA’s authority to investigate suspected criminal drug activity preempts New Hampshire’s law under the Supremacy Clause. In November 2018, U.S. Magistrate Judge Andrea K. Johnstone agreed with the DOJ and recommended the district judge grant the government’s motion to enforce the subpoena, a decision affirmed by the U.S. District Court for the District of New Hampshire in January 2019. The court ruled the government met its burden to satisfy the modest requirements for enforcement of the subpoena. Attorneys for New Hampshire appealed to the 1st Circuit.
The case is being closely watched by states, physician groups, pharmacies, and patient advocacy groups. In a joint court brief by the New Hampshire Medical Society and the American Civil Liberties Union, the organizations urged the appeals court to protect patient privacy by finding in favor of New Hampshire.
“The DEA has sought to enforce a subpoena that both injures Jonas and threatens to invade the Fourth Amendment privacy rights of individuals whose private medical information resides in the database, and whose privacy and confidentiality Jonas is statutorily charged with protecting. ... but who have no ability to challenge that impending harm,” the groups wrote in the brief. “The prescription records at issue in this case reveal intimate, private, and potentially stigmatizing details about patients’ health, including details of those patients’ underlying medical conditions. For that reason, as with other medical records, people have a reasonable expectation of privacy in them.”
Oregon’s PDMP faced a similar legal challenge in 2012. In that case, the DEA attempted to access the records of one patient and two prescribing physicians from Oregon’s prescription database. The state sued to prevent release of the records, and the ACLU intervened as a plaintiff on behalf of several unnamed patients and a doctor. A district court ruled in favor of the plaintiffs, finding that the DEA’s actions constituted a Fourth Amendment violation. However, the 9th U.S. Circuit Court in 2017 overturned the decision, ruling that federal law regarding administrative subpoenas trumps Oregon law. In addition, the appeals court ruled that the ACLU lacked standing to intervene and seek relief different from that sought by Oregon. By invalidating ACLU from the suit, the Fourth Amendment argument was never resolved by the 9th Circuit.
New Hampshire is one of 49 states that have Prescription Drug Monitoring Programs in addition to the District of Columbia. The programs collect, monitor, and analyze electronically transmitted prescribing and dispensing data submitted by physicians and pharmacies with the aim of reducing prescription drug abuse and diversion.
An appeals court may soon decide whether federal authorities can access a patient’s medical records through a statewide prescription drug monitoring database without a warrant or if such searches infringe upon privacy rights.
On Oct. 10, the 1st U.S. Circuit Court of Appeals will hear arguments in U.S. Department of Justice v. Jonas, which centers on an investigatory subpoena issued by the U.S. Drug Enforcement Agency in 2018 that sought records about a certain patient from New Hampshire’s Prescription Drug Monitoring Program (PDMP). The subpoena’s recipient, PDMP program manager Michelle Ricco-Jonas, refused to comply, citing state law that prohibits law enforcement from accessing the database without a court order based on probable cause. Releasing PDMP records to authorities without cause violate patients’ privacy protections under the Fourth Amendment, Ms. Jonas and the New Hampshire Attorney General’s Office argued.
The U.S. Department of Justice sued to enforce the subpoena, contending that the DEA’s authority to investigate suspected criminal drug activity preempts New Hampshire’s law under the Supremacy Clause. In November 2018, U.S. Magistrate Judge Andrea K. Johnstone agreed with the DOJ and recommended the district judge grant the government’s motion to enforce the subpoena, a decision affirmed by the U.S. District Court for the District of New Hampshire in January 2019. The court ruled the government met its burden to satisfy the modest requirements for enforcement of the subpoena. Attorneys for New Hampshire appealed to the 1st Circuit.
The case is being closely watched by states, physician groups, pharmacies, and patient advocacy groups. In a joint court brief by the New Hampshire Medical Society and the American Civil Liberties Union, the organizations urged the appeals court to protect patient privacy by finding in favor of New Hampshire.
“The DEA has sought to enforce a subpoena that both injures Jonas and threatens to invade the Fourth Amendment privacy rights of individuals whose private medical information resides in the database, and whose privacy and confidentiality Jonas is statutorily charged with protecting. ... but who have no ability to challenge that impending harm,” the groups wrote in the brief. “The prescription records at issue in this case reveal intimate, private, and potentially stigmatizing details about patients’ health, including details of those patients’ underlying medical conditions. For that reason, as with other medical records, people have a reasonable expectation of privacy in them.”
Oregon’s PDMP faced a similar legal challenge in 2012. In that case, the DEA attempted to access the records of one patient and two prescribing physicians from Oregon’s prescription database. The state sued to prevent release of the records, and the ACLU intervened as a plaintiff on behalf of several unnamed patients and a doctor. A district court ruled in favor of the plaintiffs, finding that the DEA’s actions constituted a Fourth Amendment violation. However, the 9th U.S. Circuit Court in 2017 overturned the decision, ruling that federal law regarding administrative subpoenas trumps Oregon law. In addition, the appeals court ruled that the ACLU lacked standing to intervene and seek relief different from that sought by Oregon. By invalidating ACLU from the suit, the Fourth Amendment argument was never resolved by the 9th Circuit.
New Hampshire is one of 49 states that have Prescription Drug Monitoring Programs in addition to the District of Columbia. The programs collect, monitor, and analyze electronically transmitted prescribing and dispensing data submitted by physicians and pharmacies with the aim of reducing prescription drug abuse and diversion.
Investigators use ARMSS score to predict future MS-related disability
STOCKHOLM – , according to research presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. The resulting measurement is stable, not highly sensitive to age, and appropriate for research applications. “It could give a clinician an earlier indication of the potential disease course of a patient,” said Ryan Ramanujam, PhD, assistant professor of translational neuroepidemiology at Karolinska Institutet in Stockholm.
Researchers who study MS use various scores to measure disease severity, including the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). These scores cannot predict a patient’s future status, however, and they do not remain stable throughout the course of a patient’s disease. Fitting a linear model over a series of scores over time can provide a misleading impression of a patient’s disease progression. “What we need is a metric to give a holistic overview of disease course, regardless of when it’s measured in a patient’s disease progression,” said Dr. Ramanujam. Such a measurement could aid the search for genes that affect MS severity, he added.
Examining disability by patient age
Dr. Ramanujam and colleagues constructed their measure using the ARMSS score, which ranks EDSS score by age instead of by disease duration. The ARMSS score ranges from 0 to 10, and the median value is 5 for all patients at a given age. Investigators can calculate the score using a previously published global matrix of values for ARMSS and MSSS available in the R package ms.sev.
The investigators found that the ARMSS score is slightly superior to the MSSS in detecting small increases in EDSS. One benefit of the ARMSS score, compared with the MSSS, is that it allows investigators to study patients for whom time of disease onset is unknown. The ARMSS score also removes potential systematic bias that might result from a neurologist’s retrospective assignment of date of disease onset, said Dr. Ramanujam.
He and his colleagues used ARMSS to compare patients’ disease course with what is expected for that patient (i.e., an ARMSS that remains stable at 5). They extracted data for 15,831 patients participating in the Swedish MS registry, including age and EDSS score at each neurological visit. Eligible patients had serial EDSS scores for 10 years. Dr. Ramanujam and colleagues included 4,514 patients in their analysis.
Measures at 2 years correlated with those at 10 years
The researchers created what they called the ARMSS integral by calculating the ARMSS score’s change from 5 at each examination (e.g., −0.5 or 1). “The ARMSS integral can be thought of as the cumulative disability that a patient accrues over his or her disease course, relative to the average patient, who had the disease for the same ages,” said Dr. Ramanujam. At 2 years of follow-up and at 10 years of follow-up, the distribution of ARMSS integrals for the study population followed a normal pattern.
Next, the investigators sought to compare patients by standardizing their follow-up time. To do this, they calculated what they called the ARMSS-rate by dividing each patient’s ARMSS integral by the number of years of follow-up. The ARMSS-rate offers a “snapshot of disease severity and progression,” said Dr. Ramanujam. When the researchers compared ARMSS-rates at 2 years and 10 years for each patient, they found that the measure was “extremely stable over time and strongly correlated with future disability.” The correlation improved slightly when the researchers compared ARMSS-rates at 4 years and 10 years.
The investigators then categorized patients based on their ARMSS-rate at 2 years (e.g., 0 to 1, 1 to 2, 2 to 3). When they compared the values in these categories with the median ARMSS-rates for the same individuals over the subsequent 8 years, they found strong group-level correlations.
To analyze correlations on an individual level, Dr. Ramanujam and colleagues examined the ability of different metrics at the time closest to 2 years of follow-up to predict those measured at 10 years. They assigned the value 1 to the most severe quartile of outcomes and the value 0 to all other quartiles. For predictors and outcomes, the investigators examined ARMSS-rate and the integral of progression index, which they calculated using the integral of EDSS. They also included EDSS at 10 years as an outcome for progression index.
For predicting the subsequent 8 years of ARMSS-rates, ARMSS-rate at 2 years had an area under the curve (AUC) of 0.921. When the investigators performed the same analysis using a cohort of patients with MS from British Columbia, Canada, they obtained an AUC of 0.887. Progression index at 2 years had an AUC of 0.61 for predicting the most severe quartile of the next 8 years. Compared with this result, ARMSS integral up to 2 years was slightly better at predicting EDSS at 10 years, said Dr. Ramanujam. The progression index poorly predicted the most severe quartile of EDSS at 10 years.
The main limitation of the ARMSS integral and ARMSS-rate is that they are based on EDSS, he added. The EDSS gives great weight to mobility and largely does not measure cognitive disability. “Future metrics could therefore include additional data such as MRI, Symbol Digit Modalities Test, or neurofilament light levels,” said Dr. Ramanujam. “Also, self-assessment could be one area to improve in the future.”
Dr. Ramanujam had no conflicts of interest to disclose. He receives funding from the MultipleMS Project, which is part of the EU Horizon 2020 Framework.
STOCKHOLM – , according to research presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. The resulting measurement is stable, not highly sensitive to age, and appropriate for research applications. “It could give a clinician an earlier indication of the potential disease course of a patient,” said Ryan Ramanujam, PhD, assistant professor of translational neuroepidemiology at Karolinska Institutet in Stockholm.
Researchers who study MS use various scores to measure disease severity, including the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). These scores cannot predict a patient’s future status, however, and they do not remain stable throughout the course of a patient’s disease. Fitting a linear model over a series of scores over time can provide a misleading impression of a patient’s disease progression. “What we need is a metric to give a holistic overview of disease course, regardless of when it’s measured in a patient’s disease progression,” said Dr. Ramanujam. Such a measurement could aid the search for genes that affect MS severity, he added.
Examining disability by patient age
Dr. Ramanujam and colleagues constructed their measure using the ARMSS score, which ranks EDSS score by age instead of by disease duration. The ARMSS score ranges from 0 to 10, and the median value is 5 for all patients at a given age. Investigators can calculate the score using a previously published global matrix of values for ARMSS and MSSS available in the R package ms.sev.
The investigators found that the ARMSS score is slightly superior to the MSSS in detecting small increases in EDSS. One benefit of the ARMSS score, compared with the MSSS, is that it allows investigators to study patients for whom time of disease onset is unknown. The ARMSS score also removes potential systematic bias that might result from a neurologist’s retrospective assignment of date of disease onset, said Dr. Ramanujam.
He and his colleagues used ARMSS to compare patients’ disease course with what is expected for that patient (i.e., an ARMSS that remains stable at 5). They extracted data for 15,831 patients participating in the Swedish MS registry, including age and EDSS score at each neurological visit. Eligible patients had serial EDSS scores for 10 years. Dr. Ramanujam and colleagues included 4,514 patients in their analysis.
Measures at 2 years correlated with those at 10 years
The researchers created what they called the ARMSS integral by calculating the ARMSS score’s change from 5 at each examination (e.g., −0.5 or 1). “The ARMSS integral can be thought of as the cumulative disability that a patient accrues over his or her disease course, relative to the average patient, who had the disease for the same ages,” said Dr. Ramanujam. At 2 years of follow-up and at 10 years of follow-up, the distribution of ARMSS integrals for the study population followed a normal pattern.
Next, the investigators sought to compare patients by standardizing their follow-up time. To do this, they calculated what they called the ARMSS-rate by dividing each patient’s ARMSS integral by the number of years of follow-up. The ARMSS-rate offers a “snapshot of disease severity and progression,” said Dr. Ramanujam. When the researchers compared ARMSS-rates at 2 years and 10 years for each patient, they found that the measure was “extremely stable over time and strongly correlated with future disability.” The correlation improved slightly when the researchers compared ARMSS-rates at 4 years and 10 years.
The investigators then categorized patients based on their ARMSS-rate at 2 years (e.g., 0 to 1, 1 to 2, 2 to 3). When they compared the values in these categories with the median ARMSS-rates for the same individuals over the subsequent 8 years, they found strong group-level correlations.
To analyze correlations on an individual level, Dr. Ramanujam and colleagues examined the ability of different metrics at the time closest to 2 years of follow-up to predict those measured at 10 years. They assigned the value 1 to the most severe quartile of outcomes and the value 0 to all other quartiles. For predictors and outcomes, the investigators examined ARMSS-rate and the integral of progression index, which they calculated using the integral of EDSS. They also included EDSS at 10 years as an outcome for progression index.
For predicting the subsequent 8 years of ARMSS-rates, ARMSS-rate at 2 years had an area under the curve (AUC) of 0.921. When the investigators performed the same analysis using a cohort of patients with MS from British Columbia, Canada, they obtained an AUC of 0.887. Progression index at 2 years had an AUC of 0.61 for predicting the most severe quartile of the next 8 years. Compared with this result, ARMSS integral up to 2 years was slightly better at predicting EDSS at 10 years, said Dr. Ramanujam. The progression index poorly predicted the most severe quartile of EDSS at 10 years.
The main limitation of the ARMSS integral and ARMSS-rate is that they are based on EDSS, he added. The EDSS gives great weight to mobility and largely does not measure cognitive disability. “Future metrics could therefore include additional data such as MRI, Symbol Digit Modalities Test, or neurofilament light levels,” said Dr. Ramanujam. “Also, self-assessment could be one area to improve in the future.”
Dr. Ramanujam had no conflicts of interest to disclose. He receives funding from the MultipleMS Project, which is part of the EU Horizon 2020 Framework.
STOCKHOLM – , according to research presented at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis. The resulting measurement is stable, not highly sensitive to age, and appropriate for research applications. “It could give a clinician an earlier indication of the potential disease course of a patient,” said Ryan Ramanujam, PhD, assistant professor of translational neuroepidemiology at Karolinska Institutet in Stockholm.
Researchers who study MS use various scores to measure disease severity, including the Expanded Disability Status Scale (EDSS) and the MS Severity Scale (MSSS). These scores cannot predict a patient’s future status, however, and they do not remain stable throughout the course of a patient’s disease. Fitting a linear model over a series of scores over time can provide a misleading impression of a patient’s disease progression. “What we need is a metric to give a holistic overview of disease course, regardless of when it’s measured in a patient’s disease progression,” said Dr. Ramanujam. Such a measurement could aid the search for genes that affect MS severity, he added.
Examining disability by patient age
Dr. Ramanujam and colleagues constructed their measure using the ARMSS score, which ranks EDSS score by age instead of by disease duration. The ARMSS score ranges from 0 to 10, and the median value is 5 for all patients at a given age. Investigators can calculate the score using a previously published global matrix of values for ARMSS and MSSS available in the R package ms.sev.
The investigators found that the ARMSS score is slightly superior to the MSSS in detecting small increases in EDSS. One benefit of the ARMSS score, compared with the MSSS, is that it allows investigators to study patients for whom time of disease onset is unknown. The ARMSS score also removes potential systematic bias that might result from a neurologist’s retrospective assignment of date of disease onset, said Dr. Ramanujam.
He and his colleagues used ARMSS to compare patients’ disease course with what is expected for that patient (i.e., an ARMSS that remains stable at 5). They extracted data for 15,831 patients participating in the Swedish MS registry, including age and EDSS score at each neurological visit. Eligible patients had serial EDSS scores for 10 years. Dr. Ramanujam and colleagues included 4,514 patients in their analysis.
Measures at 2 years correlated with those at 10 years
The researchers created what they called the ARMSS integral by calculating the ARMSS score’s change from 5 at each examination (e.g., −0.5 or 1). “The ARMSS integral can be thought of as the cumulative disability that a patient accrues over his or her disease course, relative to the average patient, who had the disease for the same ages,” said Dr. Ramanujam. At 2 years of follow-up and at 10 years of follow-up, the distribution of ARMSS integrals for the study population followed a normal pattern.
Next, the investigators sought to compare patients by standardizing their follow-up time. To do this, they calculated what they called the ARMSS-rate by dividing each patient’s ARMSS integral by the number of years of follow-up. The ARMSS-rate offers a “snapshot of disease severity and progression,” said Dr. Ramanujam. When the researchers compared ARMSS-rates at 2 years and 10 years for each patient, they found that the measure was “extremely stable over time and strongly correlated with future disability.” The correlation improved slightly when the researchers compared ARMSS-rates at 4 years and 10 years.
The investigators then categorized patients based on their ARMSS-rate at 2 years (e.g., 0 to 1, 1 to 2, 2 to 3). When they compared the values in these categories with the median ARMSS-rates for the same individuals over the subsequent 8 years, they found strong group-level correlations.
To analyze correlations on an individual level, Dr. Ramanujam and colleagues examined the ability of different metrics at the time closest to 2 years of follow-up to predict those measured at 10 years. They assigned the value 1 to the most severe quartile of outcomes and the value 0 to all other quartiles. For predictors and outcomes, the investigators examined ARMSS-rate and the integral of progression index, which they calculated using the integral of EDSS. They also included EDSS at 10 years as an outcome for progression index.
For predicting the subsequent 8 years of ARMSS-rates, ARMSS-rate at 2 years had an area under the curve (AUC) of 0.921. When the investigators performed the same analysis using a cohort of patients with MS from British Columbia, Canada, they obtained an AUC of 0.887. Progression index at 2 years had an AUC of 0.61 for predicting the most severe quartile of the next 8 years. Compared with this result, ARMSS integral up to 2 years was slightly better at predicting EDSS at 10 years, said Dr. Ramanujam. The progression index poorly predicted the most severe quartile of EDSS at 10 years.
The main limitation of the ARMSS integral and ARMSS-rate is that they are based on EDSS, he added. The EDSS gives great weight to mobility and largely does not measure cognitive disability. “Future metrics could therefore include additional data such as MRI, Symbol Digit Modalities Test, or neurofilament light levels,” said Dr. Ramanujam. “Also, self-assessment could be one area to improve in the future.”
Dr. Ramanujam had no conflicts of interest to disclose. He receives funding from the MultipleMS Project, which is part of the EU Horizon 2020 Framework.
REPORTING FROM ECTRIMS 2019
Intensive cognitive training may be needed for memory gains in MS
STOCKHOLM – Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.
in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.
To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.
Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.
After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.
To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.
Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.
Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.
Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.
“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.
Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.
Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.
STOCKHOLM – Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.
in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.
To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.
Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.
After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.
To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.
Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.
Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.
Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.
“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.
Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.
Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.
STOCKHOLM – Cognitive rehabilitation to address memory deficits in multiple sclerosis (MS) can take a page from efforts to help those with other conditions, but practitioners and patients should realize that more intensive interventions are likely to be of greater benefit in MS.
in addressing the memory problems frequently seen in MS, Piet Bouman reported at the annual congress of the European Committee for Treatment and Research in Multiple Sclerosis.
Hippocampal pathology can underlie the high-impact memory deficits that are seen frequently in patients with MS, noted Mr. Bouman, a doctoral student at Amsterdam University Medical Centers, and his collaborators. However, they observed, which strategies might best ameliorate hippocampal memory loss for those with MS is an open question.
To address this knowledge gap, Mr. Bouman and his coauthors conducted a systematic review and meta-analysis that aimed to determine which memory interventions in current use most help hippocampal memory functioning. The authors did not limit the review to MS, but included other conditions where hippocampal lesions, atrophy, or changes in connection or functioning may affect memory. These include healthy aging, mild cognitive impairment, and Alzheimer’s disease.
Included in the search for studies were those that used either cognitive or exercise interventions and also evaluated both visuospatial and verbal memory using validated measures, such as the Brief Visuospatial Memory Test or the California Verbal Learning Test.
After reviewing an initial 6,697 articles, the authors used Cochrane criteria to eliminate studies that were at high risk of bias. In the end, 141 studies were selected for the final review, and 82 of these were included in the meta-analysis. Eighteen studies involving 895 individuals addressed healthy aging; 39 studies enrolled 2,256 patients with mild cognitive impairment; 8 studies enrolled 223 patients with Alzheimer’s disease; and 26 studies involving 1,174 patients looked at cognitive impairment in the MS population.
To express the efficacy of the interventions across the various studies, Mr. Bouman and collaborators used the ratio of the difference in mean outcomes between groups and the standard deviation in outcome among participants. This ratio, commonly used to harmonize data in meta-analyses, is termed standardized mean difference.
Individuals representing the healthy aging population saw the most benefit from interventions to address memory loss, with a standardized mean difference of 0.48. Patients with mild cognitive impairment saw a standardized mean difference of 0.46, followed by patients with Alzheimer’s disease with a standardized mean difference of 0.43. Patients with MS lagged far behind in their response to interventions to improve memory, with a standardized mean difference of 0.34.
Looking at the different kinds of interventions, exercise interventions showed moderate effectiveness, with a standardized mean difference of 0.46. By contrast, high intensity cognitive training working on memory strategies was the most effective intervention, said Mr. Bouman and his coauthors: This intervention showed a standardized mean difference of 1.03.
Among the varying conditions associated with hippocampal memory loss, MS-related memory problems saw the least response to intervention, “which might be a result of a more widespread pattern of cognitive decline in MS,” noted Mr. Bouman and coauthors.
“Future studies should work from the realization that memory rehabilitation in MS might require a different approach” than that used in healthy aging, mild cognitive impairment, and Alzheimer’s disease, wrote the authors.
Their review revealed “persistent methodological flaws” in the literature, they noted. These included small sample sizes and selection bias.
Mr. Bouman reported that he had no disclosures. One coauthor reported financial relationships with Sanofi Genzyme, Merck-Serono and Biogen Idec. Another reported financial relationships with Merck-Serono, Bogen, Novartis, Genzyme, and Teva Pharmaceuticals.
SOURCE: Bouman P et al. ECTRIMS 2019. Abstract P1439.
REPORTING FROM ECTRIMS 2019