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Thursday, May 10, 2018

Electroshock weighed for autism

Electroconvulsive therapy (ECT) may be a useful intervention for children with autism who have psychiatric comorbidities, a new systematic review suggests.
Results of a systematic literature review suggest that ECT has some benefit in patients with autism spectrum disorder (ASD) whose condition is refractory to multiple psychotropic medications.
These results contribute to the growing evidence of the benefits of ECT in young patients with severe ASD, study investigator Raul J. Poulsen, MD, Division of Child and Adolescent Psychiatry, Department of Psychiatry, University of Miami, Florida, told Medscape Medical News.
“It’s very important to be able to balance benefits and risks of any treatment we provide, and this is a step in the direction of gathering that information, to be able to provide the best treatment course for any single individual,” he said.
The results are especially notable given that ASD was significantly treatment resistant in these patients, said Poulsen.
The findings were presented here at the American Psychiatric Association (APA) 2018 annual meeting.

ECT Stigma

Patients with severe ASD typically engage in maladaptive or self-injurious behaviors. Many such patients suffer significant comorbid conditions, including catatonia, attention-deficit/hyperactivity disorder, and intellectual disabilities, said Poulsen.
Some of these patients also have mood disorders. Poulsen noted that ECT has had some success as a treatment for mood disorders, especially treatment-resistant depression.
The investigators researched the published literature in this area to “identify any gaps or any need for further study,” said Poulsen.
Another impetus for conducting the review, he said, was the “significant hesitance of physicians” to suggest ECT for patients “on the severe side of the spectrum” whose conditions are resistant to multiple psychotropic medications.
“Unfortunately,” he added, there is a general stigma about the use of ECT, largely because of negative portrayals of the therapy in the media.
After searching three databases (Cochrane, Embase, and PubMed), the researchers selected 17 articles involving 21 patients. The patients ranged in age from 8 years to 17 years (mean age, 14 years). Most were taking more than three psychotropic medications, said Poulsen.
Treatments for ASD include antipsychotics, antidepressants, stimulants, mood stabilizers, anticonvulsants, and often some form of behavioral therapy, including applied behavior analysis.
In about 76% of cases, treatment involved bitemporal stimulation; in 10%, treatment was unilateral; and in 14%, the type of stimulation was unclear.
Poulsen noted that unilateral stimulation is often used to reduce adverse events. In some studies, the therapy began with bilateral stimulation, and a switch to unilateral stimulation was made if there were side effects.
Patients received 10 to 156 ECT treatments. ECT-induced seizures, measured by EEG, lasted from 26 to 206 seconds.
Most of the studies assessed improvement in self-injurious behaviors, reversal of catatonia, being able to return to school, and being more engaged in day-to-day activities, said Poulsen.
All patients benefited from ECT treatment. The investigators note that there were reports on school attendance for 11 patients, all of whom attended school after ECT.
It is difficult to “tease out” exactly which symptoms ECT improved, because the patients had so many comorbid conditions, said Poulsen. However, he added, ECT releases neurotransmitters, so it helps boost serotonin and dopamine levels in the brain.
“Some of these chemical releases help improve mood,” said Poulsen.
He reported that the treatments were well tolerated by the patients in the studies. Rare side effects included fatigue, hunger, and postemergent agitation.
As with any treatment, the benefits must be weighed against the risks. Risks of ECT include retrograde and anterograde amnesia and headache, Poulsen said.

Not a “Magic Bullet”

Commenting on the study for Medscape Medical News, Neera Ghaziuddin, MD, associate professor of psychiatry, Child and Adolescent Section, University of Michigan, Ann Arbor, said the findings are in keeping with her own experience.
ECT, she said, is useful for children with autism or other developmental disorders who also have a psychiatric condition such as depression.
“It’s not for the autism itself but for this associated condition,” she said.
But children with autism, as well as those with Down syndrome or other intellectual disabilities of unknown cause, are at high risk for psychiatric disorders, said Ghaziuddin.
Ghaziuddin and her colleagues “do quite a bit of ECT in young people” and have found it to be “very helpful.”
“It’s not a magic bullet. It does not treat autism, and that’s an important distinction and thing to remember,” she said.
But it is an “extremely valuable treatment to have available” for young autism patients who have a severe mood disorder or catatonia or for those who engage in extremely severe, life-threatening, self-injurious behaviors or who have psychotic disorders.
Her youngest ECT patient was about 8 years of age, but she has provided consultations on younger patients.
“It’s really the severity of the illness and not age that should be the deciding factor,” she said.
Dr Poulsen has disclosed no relevant financial relationships. Dr Ghaziuddin is the primary author of the book, Electroconvulsive Therapy in Children and Adolescents (Oxford University Press, 2013).
American Psychiatric Association (APA) 2018. Abstract 1-047, presented May 5, 2018.

Vitamin D Supplementation May Help Ease Depression

Vitamin D supplementation may help reduce depressive symptoms, new results of an updated meta-analysis show.
“People who were vitamin D deficient and depressed seemed to respond best to supplementation, but there was some evidence that supplementation improved depressive symptoms in people who had a normal level of vitamin D,” Marissa Flaherty, MD, of the Department of Psychiatry, University of Maryland School of Medicine in Baltimore, told Medscape Medical News.
Globally, more than 300 million people suffer from depression. It’s the number one cause of years lost to disability worldwide. In the United States, the overall prevalence of vitamin D deficiency hovers around 42%, with the highest rate seen in blacks.
“In my third year of residency, I noticed that a lot of my depressed patients had very low vitamin D levels, and when I supplemented their vitamin D, their depressive symptoms, particularly their fatigue and energy levels, would improve,” Flaherty said.
To investigate further, Flaherty and her colleagues conducted a systematic review and meta-analysis of five randomized controlled trials published from 2011 to 2016 that examined the effect of vitamin D supplementation (vs no supplementation) on depressive symptoms, as measured by the Beck Depression Inventory and Hamilton Depression Rating Scale.
The number of participants in these studies ranged from 40 to 746. The type and route of vitamin D supplementation varied, as did the study length (from 3 to 52 weeks) and the results. For example:
  • 6-week study published in 2011 found no effect of daily supplementation with 5000 IU cholecalciferol on ratings of depression in a group of young healthy adults.
  • An 8-week study published in 2013 found that daily supplemention with 1500 IU vitamin D3 plus 20 mg fluoxetine was superior to fluoxetine alone in controlling depressive symptoms in patients with major depressive disorder (MDD).
  • 3-month study found that two single intramuscular injections of 150,000 or 300,000 IU vitamin D improved depression ratings in depressed adults with vitamin D deficiency.
  • An 8-week study found that weekly supplementation with 50,000 IU oral vitamin D improved depression scores in patients with MDD.
  • 52-week study found that weekly supplementation with 50,000 IU vitamin D3 did not significantly lower depressive symptoms in depressed dialysis patients.
In the pooled data analysis, Flaherty and her colleagues found that vitamin D supplementation improved depressive symptoms, with a medium overall effect size (SMD, 0.495; 95% confidence interval [CI], 0.190 – 0.801; P = 0001).
“There was some heterogeneity in some of the studies, but overall, the effect was there,” Flaherty told Medscape Medical News. “I think all doctors should check vitamin D levels and supplement when needed. There is no harm in supplementing vitamin D, and most people have low vitamin D,” she said.
Flaherty presented the results here May 6 at the American Psychiatric Association (APA) annual meeting.

Harmful on Many Fronts

Reached for comment, Gregory Dalack, MD, chair of the Department of Psychiatry, University of Michigan Medical School, Ann Arbor, said this is a “good update of the literature. In general, having low vitamin D is not helpful, not just for depression but for bones and all sorts of things.”
Dalack emphasized the importance of looking at the big picture for patients with depression.
“The way that I think about is, when I am looking to treat someone’s depression and trying to optimize their response, if they are not sufficient on their vitamin D level, if they are not taking their meds, if they are not active physically, those are all problems which would undermine their depression,” said Dalack.
He also noted that in most of the studies included in this analysis, vitamin D supplementation was not used as a primary treatment but rather to augment therapy with antidepressants, “which is important, because the evidence is not there that you could just use vitamin D as monotherapy and expect them to feel better.”
The study had no commercial funding. The authors and Dr Dalack have disclosed no relevant financial relationships.
American Psychiatric Association (APA) 2018. Poster P3-096, presented May 6, 2018.

Abiomed Q4 FY 2018 Revenue $174M, Up 40%; Full Year $594M, Up 33%

ABIOMED, Inc. (NASDAQ: ABMD), a leading provider of breakthrough heart recovery and support technologies, today reported fourth quarter fiscal 2018 revenue of $174.4 million, an increase of 40% compared to revenue of $124.7 million for the same period of fiscal 2017.
For fiscal year 2018, total revenue was $593.7 million, up 33% compared to revenue of $445.3 million and operating income was $157.1 million, up 74% compared to operating income of $90.1 million in fiscal year 2017.
Recent financial and operating highlights include: Worldwide Impella heart pump revenue for the quarter totaled $168.3 million, an increase of 42% compared to revenue of $118.9 million during the same period of the prior fiscal year. Full year worldwide Impella heart pump revenue totaled $570.9 million for fiscal 2018, an increase of 35% compared to revenue of $423.7 million for the prior year.
U.S. Impella heart pump revenue for the quarter totaled $146.2 million, an increase of 35% compared to revenue of $108.2 million during the same period in the prior fiscal year with U.S. patient usage of the Impella heart pumps up 35%. Full year U.S. Impella revenue totaled $505.1 million, up 30% compared to $387.5 million in the prior fiscal year with U.S. patient usage of the Impella heart pumps up 32%.
Outside the U.S., fourth quarter revenue from Impella heart pumps totaled $22.1 millionand was up 107% over prior year, predominantly from Germany, which recorded $15.0 million, up 95% over prior year. Full year revenue from Impella heart pumps outside of the U.S. totaled $65.7 million and was up 81% year over year, predominantly from Germany, which recorded $45.2 million, up 70%. Additionally, the Company began its commercial launch in Japan in September and recorded $2.9 million in revenue for the fiscal year 2018.
Gross margin for fourth quarter 2018 was 82.7% compared to 84.6% in the fourth quarter of prior fiscal year. For the full fiscal year 2018, gross margin was 83.4% compared to 84.1% in the prior year.
Operating income for the fourth quarter was $47.6 million, or 27.3% operating margin, compared to $29.0 million, or 23.3% operating margin in the prior year. For the full fiscal year 2018, operating income was $157.1 million, or 26.5% of revenue, compared to $90.1 million, or 20.2% of revenue in the prior fiscal year.
Fourth quarter fiscal 2018 GAAP net income was $36.8 million or $0.80 per diluted share compared to $14.9 million or $0.33 per diluted share for the prior fiscal year. Full fiscal year 2018 GAAP net income was $112.2 million or $2.45 per diluted share compared to $52.1 million or $1.17 per diluted share for the prior fiscal year.
The Company generated $49.1 million in cash, cash equivalents and marketable securities in the fourth quarter of fiscal 2018, bringing the total to $399.8 million as of March 31, 2018. The Company currently has no debt.
On February 13, 2018, the Company received approval for an expanded FDA indication for cardiomyopathy, including peripartum cardiomyopathy and myocarditis, with cardiogenic shock and announced Abiomed’s Women’s Initiative for Heart Recovery.
On February 14, 2018, the Company received approval for an expanded FDA indication for high risk percutaneous coronary intervention (PCI) procedures for severely complex patients with mild, moderate and severely depressed ejection fraction.
On March 30, 2018, the Company appointed new Vice President and Chief Financial Officer Todd A. Trapp.
On April 2, 2018, the Company received FDA approval for Impella CP with SmartAssist and Optical Sensor.
On April 4, 2018, the Company announced European Approval (CE Marking) for Impella 5.5 and first patient treated at University Heart Center Hamburg in Germany.
‘Abiomed delivered another record quarter and fiscal year. I am proud of our Patients First execution and operational discipline from research to manufacturing to customer support. We earned multiple global regulatory approvals in the US, Germany and Japanon new products, new indications and reimbursement,’ said Michael R. Minogue, Chairman, President and Chief Executive Officer, ABIOMED, Inc. ‘Fiscal 2019 is positioned to be another outstanding year and we appreciate the investment from our shareholders. I am also grateful to the dedicated employees and customers that have enabled us to serve our patients and achieve our corporate goals around heart recovery.’
FISCAL YEAR 2019 OUTLOOK
The Company is giving its fiscal year 2019 guidance for total revenues to be in the range of $740 million to $770 million, an increase of 25% to 30% over the prior year. The Company is also giving its fiscal year 2019 guidance for GAAP operating margin to be in the range of 28% to 30%.

Implanted Device Boosts Exercise, Quality of Life in Heart Failure Patients

A novel implanted electrical device to strengthen heart contractions improved exercise performance and other outcomes in heart failure patients in the 25% to 45% ejection fraction (EF) range, a confirmatory study showed.
The Optimizer device for cardiac contractility modulation (CCM) improved maximal aerobic capacity, with a significant 0.84-ml/kg/min greater VO2 max at 24 weeks than seen with medical management alone in the FIX-HF-5C trial.
That difference in these narrow, less than 130 ms QRS patients was on par with what has been seen with cardiac resynchronization therapy (CRT) in wide QRS intervals, and it was even greater in the group of patients with EF in the 35% to 45% for whom there are currently no guideline-directed therapies, William Abraham, MD, of Ohio State University Wexner Medical Center in Columbus, reported at a late-breaking clinical trial session here at the Heart Rhythm Society meeting.
The relative 11-point improvement in quality of life on the Minnesota Living with Heart Failure score was roughly twice what drug therapy can achieve and is on par with CRT, he added. The findings were simultaneously published in JACC: Heart Failure.
“It promises to meet a very large unmet need in the management of heart failure,” Abraham said at a press conference at the meeting. “About four million [Americans with symptomatic heart failure] have reduced ejection fraction — anything below 45%. At any time among those patients, about 30-40% are categorized in New York Heart Association [NYHA] functional class 3 or ambulatory class 4, and that’s despite all available guideline-directed drug and device therapies.”
Regulatory approval may be “in the hands of others,” but Sanjeev Saksena, MD, of Rutgers University Robert Wood Johnson Medical School in New Brunswick, NJ, and a past president of the Heart Rhythm Society, who was not involved with the study, told MedPage Today that the device is a treatment he wants available for his patients.
“These are groups of patients we have very little to offer at this point, beyond heroic measures like assist devices,” he said.
Previously, the FIX-HF-5 clinical trial showed the CCM strategy as safe but not meeting the primary efficacy endpoint of ventilatory anaerobic threshold on cardiopulmonary exercise stress testing in NYHA functional class III or IV symptoms and a site-determined EF of 35% or less.
The FDA required the new confirmatory trial under the agency’s expedited review process for the rechargeable device, which provides non-excitatory electrical signals via two leads in the right heart during the cardiac absolute refractory period. The mechanism of action is not heartbeat initiation, but rather a way to load the cells with calcium to induce a more forceful contraction.
The trial included 160 patients with heart failure, a QRS interval less than 130 ms, and an EF of 25-45%, randomized to CCM for 5 hours per day for 6 months or to medical therapy alone.
Notably, the trial’s primary endpoint shift from anaerobic to aerobic exercise capacity was a shift to a less subjective, more effort-dependent endpoint, noted the discussant for the study at the meeting, Lynne Stevenson, MD, of Vanderbilt University Medical Center in Nashville.
Abraham argued, though, for the “extensive efforts to avoid bias in exercise performance,” with onsite training for standardization of exercise testing, feedback to sites on study quality from the core lab, retest requests for inadequate studies, two tests performed at each time point, and blinded core lab reading.
When the two trials’ relevant patients were combined, there was a significant reduction in cardiovascular death and heart failure hospitalizations compared with controls, with a nearly 4-day advantage in days alive outside the hospital.
While the device outcomes met a “high bar,” Stevenson concluded, “I don’t think the CCM story is yet the CRT story.”
The complication rate of 10.3% met the primary safety performance criterion in the Bayesian analysis, which Abraham said generally included complications that would be anticipated with leads and pulse generators. “Taken in the context of risk-benefit, though, particularly to these patients — who I want to emphasize have no other options for treatment when they remain in class III-ambulatory IV despite current guideline-directed medical therapies — I would view [the complications] as acceptable.”
The study was supported by Impulse Dynamics.
Abraham disclosed consulting for Impulse Dynamics, and one of the other co-authors is an employee of Impulse Dynamics.
Stevenson disclosed relationships with Novartis, St. Jude, and Medtronic.

Medical device recalls hit historic high in 2018 with software as leading cause

Medical device recalls reached record highs in the first three months of 2018 thanks to software complications that are likely to continue with the proliferation of high-tech devices.
Device recalls increased 126% in the first quarter of 2018. At 343 recalls, it was the highest number in a single quarter since 2005, according to a report by Stericycle’s Recall Index (PDF), which tracks recall data across several industries.
Software was the biggest driver of medical device recalls in the first quarter, accounting for 23% of all recalls. Software issues have been the leading factor in device recalls each quarter since the beginning of 2016.
Bethany Hills, an attorney at Mintz Levin in New York who chairs the firm’s FDA practice, says the rapid increase is not totally unexpected. Medical device software is becoming increasingly complex, with analytics that provide a higher level of clinical decision support.
“The more complex the software, the more likely it is that the developers did not account for all variables in the clinical environment, increasing the risk of bugs and errors,” she told FierceHealthcare. “This risk increases further if the device manufacturer outsources software development because integration of outside software and the inability to quickly modify the code can lead to additional errors slipping through the cracks.”
All told, more than 208 million devices were recalled in the beginning of the year, more than the total number of recalled devices in all of 2017. There doesn’t appear to be one singular reason for the startling uptick, making it difficult to pinpoint an underlying trend.
Although it’s possible the first three months of 2018 were an anomaly, and recalls could dip back down to a level more consistent with past quarters, software challenges aren’t likely to recede. Device manufacturers are building more innovative devices with software that requires frequent updates and patches.
“[Manufacturers] don’t have this figured out yet and it’s going to continue to be a driver,” Mike Good, vice president of marketing and sales operations at Stericycle, told FierceHealthcare.

At the same time, medical device cybersecurity has emerged as a growing concern among industry leaders and lawmakers. Legacy devices are particularly susceptible to attacks, and a recent report from analysts at Symantec indicated a hacker group known as Orangeworm has been launching targeted attacks on the healthcare imaging suites where devices run on outdated operating systems.
Although there have been a limited number of cybersecurity recalls—the most notable being a firmware update for Abbott-manufactured cardiac devices last year—regulators appear acutely aware of the issue. Food and Drug Administration Commissioner Scott Gottlieb, M.D., has asked Congress for funding to create a cybersecurity “go-team” that would be housed in a new Center of Excellence on Digital Health.
Hills expects the medical device recall trend to continue, particularly now that the FDA is accepting devices with artificial intelligence and more complex clinical decision support algorithms.

Although the agency is in the process of updating regulatory guidance, the industry is currently relying on software validation requirements from the early 2000s. Gottlieb has signaled that overhauling the approval process for digital health devices and AI software is one of his top priorities, but manufacturers will still have to balance the time it takes to evaluate the potential hazards of complex software with a potential recall.
Minimizing the number of devices recalled from the market requires a joint effort by manufacturers and the FDA to minimize risks prior to approval, but doing so is a “delicate balance,” Hills says. Devices featuring complex algorithms that rely on large data sets may be particularly susceptible to recalls following widespread clinical use.
“Obviously, neither wants to see devices recalled from the market, but there needs to be a balance between constantly testing and validating software and the clinical benefits of using the software,” she said. “FDA’s job is to ensure that the manufacturer has done a reasonable job to identify and address any outstanding safety issues before the device goes on the market, but it would be an impossible task to resolve every possible issue since the testing environments for investigational devices are so limited.”

AHIP, others push back on stricter production limits for IV opioids

Numerous provider and insurer groups say proposed policy changes for opioid quotas could worsen current drug shortages.
proposed rule, released last month by the Drug Enforcement Administration, would limit drug makers’ annual production of opioids in some circumstances and require manufacturers to identify a need for controlled substances to justify their production.
Additionally, the agency is seeking to take greater control of production quotas and will consider how often a drug is diverted for misuse when setting production limits. The proposal is part of an effort by the Trump administration to “strengthen controls over diversion of controlled substances” during a time when the country is facing an opioid epidemic.
In a letter (PDF) to the agency, six major provider, service and payer groups, including America’s Health Insurance Plans, said the proposal could exacerbate drug shortages for vital opioid medications.
“Injectable opioids dispensed in clinical settings pose a far lower risk of diversion than other dosage forms dispensed directly to patients,” the groups said. “Having diminished supply of these critical drugs, or no supply at all, can cause suboptimal pain control or sedation for patients in addition to creating burdensome workarounds for healthcare staff.”

Intravenous opioids are used in hospitals and ambulatory surgical centers for the treatment of acute and chronic pain that cannot be managed because the patient has an addiction or contraindication for oral opioids, making the drugs vital for some patients.
The groups asked the agency to add drug shortages as a factor when determining quotas and added that shortages are unlikely to be resolved in the near future.
Individual insurers have made strides on in reducing prescriptions of opioids. Cigna announced in March that it had reduced opioid use among its customers by 25%.

UnitedHealth, AARP sued for diverting $400M a year to illegal rebates

The country’s largest Medigap insurer and an interest group for the elderly have been hit with a lawsuit accusing them of illegally diverting hundreds of millions of dollars a year.
class action lawsuit (PDF) was filed on Wednesday on behalf of “a nationwide class of Medicare-eligible individuals” who claim the insurer and AARP are diverting part of their Medigap payments to fund an illegal “rebating scheme.”
Led by Connecticut resident Mark Dane, who purchased AARP Medigap coverage in 2014, the suit alleged UnitedHealth allows AARP to take a 4.9% rebate from monthly beneficiary payments in exchange for AARP sponsoring UnitedHealth’s Medigap plan.
AARP then uses those rebates to pay for the monthly collective group plan premium in order to bind coverage, according to the complaint filed in a Connecticut U.S. District Court.
The suit claims an agreement between UnitedHealth and AARP violates Connecticut law by disguising the rebates as an “allowance” or “royalty” payment for AARP’s sponsorship of the plan to avoid paying taxes. The lawsuit claims the payments actually serve as inducements so AARP will continue using UnitedHealth as the carrier of Medigap Plans.

“The motive for terming the hundreds of millions of dollars a year reaped pursuant to this scheme as royalty payments is to assist AARP in avoiding taxation,” the suit alleged, adding that the scheme ultimately increases the cost of insurance for all beneficiaries.
The plaintiff is seeking an end to the alleged practices, and recoup all rebates, which is allegedly more than $400 million per year. In 2016, AARP earned nearly $600 million in royalty payments from UnitedHealth across all insurance products, up from 561.9 million in 2015, according to the complaint.