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Friday, June 8, 2018

Children with autism more likely to suffer from food allergy


A new study from the University of Iowa finds that children with autism spectrum disorder (ASD) are more than twice as likely to suffer from a food allergy than children who do not have ASD.
Wei Bao, assistant professor of epidemiology at the UI College of Public Health and the study’s corresponding author, says the finding adds to a growing body of research that suggests immunological dysfunction as a possible risk factor for the development of ASD.
“It is possible that the immunologic disruptions may have processes beginning early in life, which then influence brain development and social functioning, leading to the development of ASD,” says Bao.
The study is published in the Journal of the American Medical Association’s JAMA Network Open. It analyzed the health information of nearly 200,000 children gathered by the U.S. National Health Interview Survey (NHIS), an annual survey of American households conducted by the U.S. Centers for Disease Control and Prevention. The children were between the ages of 3 and 17 and the data were gathered between 1997 and 2016.
The study found that 11.25 percent of children reportedly diagnosed with ASD have a food allergy, significantly higher than the 4.25 percent of children who are not diagnosed with ASD and have a food allergy.
Bao says his study could not determine the causality of this relationship given its observational nature. But previous studies have suggested possible links–increased production of antibodies, immune system overreactions causing impaired brain function, neurodevelopmental abnormalities, and alterations in the gut biome. He says those connections warrant further investigation.
“We don’t know which comes first, food allergy or ASD,” says Bao, adding that another longitudinal follow-up study of children since birth would be needed to establish temporality.
He says previous studies on the association of allergic conditions with ASD have focused mainly on respiratory allergy and skin allergy, and those studies have yielded inconsistent and inconclusive results. The new study found 18.73 percent of children with ASD suffered from respiratory allergies, while 12.08 percent of children without ASD had such allergies; and 16.81 percent of children with ASD had skin allergies, well above the 9.84 percent of children without ASD.
“This indicates there could be a shared mechanism linking different types of allergic conditions to ASD,” says Bao.
Bao says the study is limited in that the NHIS depends on respondents to voluntarily self-report health conditions, so the number of children with ASD or allergies may be misreported by those taking the survey. But he says the large number of respondents and ethnic and gender cross-representation of the survey are major strengths.

Probing role of glutamate in age-associated cognitive disorders


As people around the world live longer, the prevalence of age-associated cognitive disorders is growing. Alzheimer’s disease (AD), for which advanced age is the most significant risk factor, currently defies all therapeutic efforts. Experts argue that identifying the onset of this progressive disease as early as possible will advance the fight against its devastating effects.
A research team at Wayne State University hopes to give clinicians tools for identifying the early signs of impending disease by measuring subtle deviations in the way the brain modulates its chemistry during the formation of new memories. Their research project, “Task-related modulation of hippocampal glutamate, subfield volumes and associative memory in younger and older adults: a longitudinal ¹H FMRS study,” was recently awarded a two-year, $423,500 grant from the National Institute on Aging of the National Institutes of Health.
The study, led by Jeffrey Stanley, Ph.D., professor of psychiatry and behavioral neurosciences in Wayne State’s School of Medicine, and by Naftali Raz, Ph.D., professor of psychology in Wayne State’s College of Liberal Arts and Sciences and director of the Lifespan Cognitive Neuroscience Program in the Institute of Gerontology at Wayne State, will use a noninvasive technique called functional magnetic resonance spectroscopy (fMRS) to characterize memory function based on the modulation of the brain’s most common neurotransmitter, glutamate, in real time, as study participants engage in a memory task.
Stanley and Raz will examine changes in glutamate within the hippocampus -; one of the brain regions that is critical for memory -; during creation of new associations between pictorial stimuli and their location.
“Studying glutamate, sometimes called the brain’s light switch, will help us better understand the brain chemistry behind basic memory processes,” said Raz. “Most of what we know about glutamate changes with age, and its relations to memory comes from animal models and measurements of stationary levels of glutamate in humans. The fMRS technique perfected by Dr. Stanley will allow us to examine age difference and age-related changes over time in task-related glutamate modulation, in intact human participants.”
The research team will acquire a structural MRI of the whole brain, a high-resolution scan of the hippocampal body, and a ¹H fMRS of the hippocampus during formation of associations between common objects and locations in healthy, young and older participants. An important feature of this study is a one-year follow-up that will help gauge the rate of change and individual differences in change over time in a fundamental memory-related brain process, while avoiding potentially misleading conclusions based on cross-sectional comparisons of age groups.
The investigators believe that the results of this study will lay the foundation for intervention aimed at mitigating cognitive decline.

Computerized brain shows how depressive episodes affect memory


It was already known that people who suffer an acute depressive episode are less likely to remember current events, but the new model suggests that older memories are also affected.
During a depressive episode, the brain’s ability to produce new brain cells is reduced. In major depressive disorder, patients can suffer from cognitive impairment so severe that it is sometimes referred to as pseudodementia.
Pseudodementia differs from the classic form of dementia in that the memory recovers once the depressive episode has ended.
Computational neuroscientists Professor Sen Cheng and colleagues investigated this process by developing a computational model that captures the characteristic features of the brain in patients with depression.
As occurs in patients with depression, the model alternated between depressive episodes and periods that were symptom-free.
As reported in the journal Plos One, the model showed that during a depressive episode, the brain formed fewer new brain cells.
Unlike previous simulations, memories were represented as a sequence of neural activity patterns rather than as static neural activity patterns.
“This allows us not only to store events in memory but also their temporal order,” explains Cheng.
The authors report that the model was able to recall memories more accurately if the brain region involved was able to form many new neurones, but if the region formed fewer new neurones, it was more difficult to distinguish similar memories and to recall them separately.
The model also showed that the impact of depressive episodes was stronger than previously thought.
Not only was there a reduced ability to recall current events, but there were also deficits in recalling memories that were collected prior to the depressive episode. The longer the duration of the depressive episode, the further the memory deficits reached back.
So far it was assumed that memory deficits only occur during a depressive episode,” says Cheng. “If our model is right, major depressive disorder could have consequences that are more far reaching. Once remote memories have been damaged, they do not recover, even after the depression has subsided.”
Professor Sen Cheng, Ruhr-Univesität Bochum

NYU Langone Health tests out Amazon Business programs


NYU Langone Health is a “strategic development partner” with Amazon Business, the online marketplace for institutions, said Chris Holt, leader of global health care at Amazon.
Holt spoke Thursday on the NYU Langone campus in Manhattan for the health system’s Health Tech Summit. He described how hospitals must adapt for the digital age and, of course, how Amazon could help them do it.
NYU Langone held the event in part to promote its health-tech hub, which conducts outreach to early stage companies that might partner with the system, said Dr. Christopher Morris, NYU Langone’s associate director for digital health innovation.
An NYU Langone spokeswoman said the health system was “in talks about partnership and participating in some pilot opportunities” with Amazon but declined to elaborate beyond that description.
One of Amazon Business’s major entries into health care has been as a supplier. Holt said that large organizations often spend 80% of their procurement budget with 20% of their suppliers, and the remaining 20% of spending is split between 80% of vendors. Amazon is looking to consolidate that share.
He said that NYU Langone is in “pilot mode” with Amazon Business, which allows organizations’ procurement offices to select certain products for employees to reorder.
Amazon Business said in July 2017 that its platform selling supplies to customers in health care, education, government and other business categories had more than 1 million U.S. customers.
Not all area health systems have jumped at the opportunity to work with Amazon. Northwell Health CEO Michael Dowling told Crain’s in April that Northwell had discussions with the company about its medical-supply business. It ultimately decided to continue using its internal group-purchasing organization and Acurity, the purchasing organization of the Greater New York Hospital Association.
Holt said Amazon’s interest in hospitals goes beyond medical and office supplies. He noted that Amazon’s Alexa device can help patients perform tasks such as adjusting the lights and lowering the shades. NYU Langone has begun using Alexa in some of its recovery rooms, he said. The company is also interested in remaking hospital cafeterias through its Amazon Fresh and Whole Foods brands.
Hospitals need to improve the patient experience if they are going to attract customers as more care moves online, Holt said.
He cited the example of his daughter’s emergency hospital visit. Several months afterward, Holt began receiving bills totaling $130,000. After his insurance company’s share, he was left to pay only about $2,600. But it was the billing experience, not the quality of care his daughter received, that lingered in his memory.
“This experience is unacceptable in any other industry on Earth except for health care,” Holt said.
With the rise in telehealth, proximity and a family’s history with a hospital won’t be enough to attract patients, he said.
“Probably in the next 10 years, I’m only going to interact with a person for the most acute care issues in my life. Everything else will be done digitally,” Holt said. “You’re going to have reinvent your brand in a digital setting with a new type of customer.”

Uncertainty could spook insurance markets as DOJ decides not to defend ACA


The Trump administration’s request Thursday that a Texas federal court invalidate three key Obamacare mandates for insurance coverage has jolted the healthcare industry as all eyes home in on a case that until now has drawn little national attention or interest.
The U.S. Justice Department on Thursday not only refused to defend the Affordable Care Act against a lawsuit filed by 20 Republican state attorneys general, but echoed the state litigators’ arguments that Congress rendered major provisions of the law invalid when it zeroed out the individual mandate penalty in the 2017 tax bill.
In particular, the Justice Department said the court should overturn the ACA’s individual mandate along with provisions requiring insurers to cover people with pre-existing conditions and to use a community rating to set premiums instead of basing rates on a person’s health condition because they were specifically tied to the mandate’s implementation.
The move shifts the defense of the law to Democratic state attorneys general who have already intervened.
The Justice Department pushed back on the plaintiffs’ request to immediately invalidate the ACA, since the tax penalty is still in effect until January 2019. Instead, the administration asked the court to nix the provisions when the tax cut begins. Paul Larkin of the conservative Heritage Foundation said he believes this request was made to set up the case for a Supreme Court hearing.
Legal scholars largely panned the Justice Department’s argument for lacking merit, but the industry and some analysts are already on alert for what the administration’s stated position on the Affordable Care Act’s most popular aspects could mean.
The legal questions boil down to the point of “severability,” an argument brought in Obama-era litigation against the ACA.
The Justice Department argued in its brief that most of the ACA could stand except the individual mandate, pre-existing conditions and community rating provisions. The Obama administration had said these measures go hand-in-hand and cannot survive without each other and the tax penalty.
“It’s pretty bad,” libertarian law professor Jonathan Adler said of the underlying case merits. “It reflects poor understanding of severability doctrine, you see that in the state’s brief, and you see it implicitly in the DOJ brief insofar as they accept those arguments.”
Abbe Gluck, a Yale University law professor, noted that the doctrine of severability is based on congressional intent, but the legal question in this case shouldn’t focus on Congress’ intent in 2010 when lawmakers passed the ACA. Instead, the court should focus on 2017 when Congress zeroed out the individual mandate penalty but did not touch the pre-existing condition and community rating provisions.
“A court doesn’t now have to guess whether Congress wanted the rest of the statute to remain standing,” Gluck said. “Congress told us that by leaving it intact. The intervening and dispositive action of the 2017 Congress itself is why the whole severability argument has no basis in law and also why the 2012 litigating position isn’t relevant any more.”
Melinda Hutton, general counsel for American Hospital Association, also weighed in on the severability issue, arguing that “as it stands today, the individual mandate is clearly severable from the rest of the (ACA).”
Hatton warned that a legal ruling otherwise “would devastate this nation’s hospitals and health systems and the patients they serve.”
“Nothing requires that catastrophic result,” Hatton said.
America’s Health Insurance Plans, the trade group representing a swath of carriers who offer plans on the exchanges, is planning to file an amicus brief against the plaintiffs’ request for a preliminary injunction—the first signal of stakeholder involvement in the lawsuit.
AHIP also issued a forceful statement against the Justice Department’s petition to invalidate the consumer protection clauses.
“Zeroing out the individual mandate penalty should not result in striking important consumer protections, such as guaranteed issue and community rating rules that help those with pre-existing conditions,” AHIP said Friday in a statement. “Removing those provisions will result in renewed uncertainty in the individual market, create a patchwork of requirements in the states, cause rates to go even higher for older Americans and sicker patients, and make it challenging to introduce products and rates for 2019.”
Ceci Connolly, president of the Alliance of Community Health Plans, called the legal position “troubling” and warned it could spark fresh market instability.
“At the very least it adds uncertainty at exactly the moment when plans are trying to set rates for next year,” Connolly said in a statement. “At the worst, it could strip away guaranteed coverage for those with pre-existing conditions. We don’t want to return to the days when people who needed the care the most could be turned away because of their health status.”
Insurers in Virginia and Maryland have already proposed 2019 rates showing high double-digit spikes, while insurers in Pennsylvania and Maine are showing minimal increases so far.
Jost also worried that as the case gets tangled in court, the Trump administration’s position could reverberate in HHS’ decisions as some states seek greater authority to skirt some ACA regulations.
Although he conceded it is unlikely, Jost wondered whether the Justice Department’s stated belief that the consumer protections are unconstitutional means the executive branch will stop enforcing them. He pointed to at least one outstanding case: HHS’ so-far delayed decision over Idaho’s request to offer exchange plans that don’t comply with the Obamacare requirements. The state is in discussions with the department over its proposal, with a decision expected later this month. Other states, including North Dakota, are watching how HHS responds before proposing their own coverage mandate changes.
For Jost, that leads to more complications for such major issues as setting tax credits that subsidize coverage for people with lower incomes.
“Once you start to invalidate those provisions, the problem is how does the rest of the statute work?” Jost said. “How do you set tax credits if everyone has different rate based on status?”
Gluck said, however, that the Justice Department brief shouldn’t affect HHS’ action.
“The guaranteed issue and community rating provisions are the law of the land until a court or Congress says otherwise,” Gluck said. “And in fact it was Congress that left those provisions on the books. For HHS to try to undermine those provisions before a court rules, which I wouldn’t expect it to do, would be unconstitutional sabotage.”
The case is being heard in a north Texas federal court by U.S. District Judge Reed O’Connor, who was appointed by President George W. Bush. Historically, O’Connor has been an outspoken opponent of Obamacare and observers expect him to skew in favor of the plaintiffs.
If O’Connor rules in Republicans’ favor, the case could move forward to the 5th U.S. Circuit Court of Appeals. Adler predicted the appellate judges won’t accept the merits of the plaintiffs’ case and that the litigation will end there rather than heading to the Supreme Court.
But Larkin, who has not yet studied the Justice Department’s severability argument, said he believes the case will get to the Supreme Court.

#ASCO18: Still Few Options for Advanced Cervical Cancer


Recent progress in the treatment of cancer has not had a major impact on outcomes in advanced forms of cervical cancer.
Increased emphasis on screening for human papillomavirus (HPV) — which causes almost all cervical cancers — has led to diagnosis of most cases of the disease at an early, curable stage. However, the prognosis remains grim for women with recurrent, persistent, or metastatic cervical cancer, associated with a 5-year survival rate of only 5-15%.
Of almost two dozen clinical trials conducted by the Gynecologic Oncology Group (GOG) since 1995, none surpassed a 1-year survival of 30%. The high-water marker occurred in GOG 240, which showed that adding bevacizumab (Avastin) to chemotherapy resulted in an almost 4-month improvement in median overall survival.
“We have an established first-line approach, based on the results of GOG 240,” said Don Dizon, MD, of Brown University and Rhode Island Hospital in Providence. “Every patient should receive either cisplatin or carboplatin, paclitaxel, and bevacizumab. However, for women who progress on that, that’s a real unmet need at this point. We don’t have good data on second-line therapies.”
Beyond GOG 240, the cooperative group trials collectively led to “pretty dismal results,” he said.
The demonstrated efficacy with the addition of bevacizumab to chemotherapy is the single most important development in management of recurrent/metastatic cervical cancer over the past several years, said Stephen C. Rubin, MD, of Fox Chase Cancer Center in Philadelphia. The regimen offers the best balance of efficacy and toxicity among other strategies that have been evaluated.
Several ongoing trials are evaluating vaccines and immunotherapeutic strategies, but none is far enough along to know whether one particular strategy will improve outcomes as compared with the chemotherapy-bevacizumab regimen, Rubin added.
Patients whose disease progresses on first-line chemotherapy-bevacizumab are candidates for clinical trials of novel therapies or combinations, said Charles A. Leith III, MD, of the University of Alabama at Birmingham. However, availability and access to those trials are limited. As a result, more attention should be paid to improved strategies for primary therapy to prevent recurrence.
“Specifically, patients found to have either intermediate- or high-risk pathologic findings following a radical hysterectomy may be eligible for clinical trials sponsored by the National Cancer Institute — GOG 263, or RTOG [Radiation Therapy Oncology Group]/GOG 0724 respectively — which may decrease their risk of cervical cancer recurrence,” said Leith. “In addition an ongoing upfront trial, GY006, is looking at the benefit of adding a ribonucleotide reductase inhibitor to the standard cisplatin chemoradiation backbone and is accruing patients with locally advanced cervical cancer who are not surgical candidates.”
A year ago at the Society of Gynecologic Oncology annual meeting, Leith reported initial results from a trial evaluating an HPV-directed immunotherapy for recurrent/metastatic cervical cancer. The data showed a 12-month survival rate of 38% in 50 heavily pretreated patients, including 44% and 41% in subgroups of patients whose tumors tested positive for HPV-16 and HPV-18. About half the patients in the trial had already received a bevacizumab-containing regimen.
A phase III evaluation of the immunotherapy — axalimogene filolisbac, or AXAL — has begun. The study will evaluate AXAL as consolidation therapy to eliminate residual disease and prevent recurrence in patients who received standard chemoradiation for locally advanced disease.
Evaluation of AXAL had a setback earlier this year when the FDA put a clinical hold on a trial evaluating the agent in combination with the immune checkpoint inhibitor durvalumab (Imfinzi) in patients with HPV-associated cancers. The hold occurred after a patient died of respiratory distress during treatment with the combination. Other clinical trials of AXAL, including the phase III study in cervical cancer, were not affected by the hold.
The 2018 American Society of Clinical Oncology (ASCO) annual meeting included several early-phase studies of candidate therapies for advanced cervical cancer. Key takeaways included:
  • Neoadjuvant chemotherapyprior to definitive chemoradiation (CRT) led to a lower objective response rate and worse progression-free survival as compared with CRT in patients with locally advanced cervical cancer
  • The PD-1 inhibitor pembrolizumab (Keytruda) led to objective responses in 12% of 98 patients with advanced cervical cancer, median PFS of 2.1 months, 6-month PFS of 25%, and median overall survival of 9.4 months
  • A 26-patient cohort with persistent cervical cancer fared even worse with the PD-1 inhibitor nivolumab (Opdivo), producing one objective response and a stable disease rate of 20%
  • phase II study of eribulin (Halaven) showed six partial responses in 30 evaluable patients with advanced disease and a median overall survival of 6.6 months
  • A trial of capecitabine in recurrent, platinum-pretreated disease showed an objective response rate of 41% and a clinical benefit rate of 62%
As an invited discussant for several of the presentations, Dizon noted that beyond surgery for low-risk early-stage disease, CRT for high-risk disease, and bevacizumab-containing therapy for advanced/metastatic disease, “there are no standards of care. We are pretty much out of options with known activity that I can cite data for.”
Dizon will chair a treatment planning committee for cervical cancer later this year, and the emphasis will be on strategies to exploit DNA damage-repair pathways. That does not mean that cervical cancer specialists have given up on immunotherapy, he added, noting that “a ton” of ongoing trials are evaluating checkpoint inhibitors and other immunotherapy-based strategies to improve outcomes for patients with advanced disease.
Liu disclosed relevant relationships with Acetylon; Agenus; AstraZeneca; Atara Biotherapeutics; Boston Biomedical; Bristol-Myers Squibb; CytomX Therapeutics; Genentech/Roche; Merrimack and Tesaro.
Hasan disclosed relevant relationships with Inovio Pharmaceuticals.
Tewari disclosed relevant relationships with AstraZeneca; Merck; Roche/Genentech

Antibiotics Still Widely Prescribed for Viral Acute Respiratory Infections


Antibiotic overuse remains common in the treatment of outpatient acute respiratory infections (ARIs) during flu season, even among patients with laboratory-confirmed influenza, new research suggests.
When researchers reviewed data on patients attending outpatient clinics participating in the Influenza Vaccine Effectiveness Network during the 2013-2014 and 2014-2015 influenza seasons, they found that 41% of patients prescribed an antibiotic had diagnoses for which antibiotics were not indicated.
Just under one-third of patients with influenza confirmed through research testing were prescribed antibiotics, Fiona Havers, MD, of the CDC’s Division of Bacterial Diseases, and colleagues wrote in the online journal JAMA Network Open.
“Antibiotics don’t treat viruses, but many, many patients are still receiving antibiotics inappropriately for common things like sore throats and sinusitis,” Havers told MedPage Today. “There are pretty strict clinical criteria for when it is appropriate to treat people with sore throats with an antibiotic, but doctors in this study weren’t necessarily following those criteria.”
ARIs remain the conditions for which antibiotics are most often prescribed, even though these infections are most often viral, Havers explained.
Inappropriate antibiotic use leads to antibiotic resistance, which is responsible for an estimated 2 million illnesses and 23,000 deaths each year in the United States, according to the CDC.
Most previous studies examining antibiotic overuse have relied on national survey data, which often lacks clinical and laboratory testing results, Havers said.
The newly published study included detailed patient data, such as illness onset date, laboratory testing for influenza self-reported fever and results of clinician-ordered group A streptococcal (GAS) testing.
The researchers also used three approaches to assess antibiotic prescribing among outpatients: they examined antibiotic prescribing by age group, antibiotic type and diagnosis; they characterized antibiotic prescribing among patients with laboratory-confirmed influenza, excluding syndromes for which antibiotics are indicated, such as pneumonia; and they examined appropriateness of antibiotic prescribing for those with pharyngitis, sinusitis, and otitis media diagnoses based on symptom duration, presence of fever, prescription of recommended first-line antibiotics, and GAS testing results.
The study included outpatients 6 months of age or older with ARIs evaluated at outpatient clinics associated with five US Influenza Vaccine Effectiveness Network sites during the 2013-2014 and 2014-2015 influenza seasons.
All patients received influenza testing by real-time reverse transcriptase–polymerase chain reaction for research purposes only.
Antibiotic prescriptions, medical history, and ICD-9 diagnosis codes were collected from medical and pharmacy records, as were GAS testing results in a patient subset.
Antibiotic prescription within seven days of enrollment was the main outcome, and appropriateness of antibiotic prescribing was based on diagnosis codes, clinical information, and influenza and GAS testing results.
Some 15,000 patients with ARIs were included in the analysis. Mean age was 32 (SD 24); about 60% were women and 80% were white. Abpout 40% received an antibiotic.
The analysis revealed that:
  • Of the 2,522 with diagnoses for which antibiotics are not indicated, 2,106 (84%) were diagnosed with viral upper respiratory tract infection or bronchitis (acute or not otherwise specified).
  • Among the 3,306 patients (22%) not diagnosed as having pneumonia and who had laboratory confirmed influenza, 945 (29%) were prescribed an antibiotic, accounting for 17% of all antibiotic prescriptions among patients with non-pneumonia ARI.
  • Among 1,248 patients with pharyngitis, 1,137 (91%) had GAS testing; 440 of the 1,248 patients (35%) were prescribed antibiotics, among whom 168 (38%) had negative results on GAS testing.
  • Of 1,200 patients with sinusitis and no other indication for antibiotic treatment who received an antibiotic, 454 (38%) had symptoms for 3 days or less prior to the outpatient visit, suggesting acute viral sinusitis not requiring antibiotics.
“Our study adds to evidence that misuse of antibiotics, characterized by antibiotic overuse and inappropriate antibiotic selection, is widespread in the treatment of outpatient ARIs,” the researchers wrote. “The study indicates a number of potential targets to achieve the goal of the National Action Plan for Combating Antibiotic-Resistant Bacteria of reducing inappropriate outpatient antibiotic use by 50% by 2020.”
Havers and colleagues called for the strengthening of outpatient antibiotic stewardship efforts aimed at eliminating antibiotic treatment for viral upper respiratory infections and acute bronchitis and improving adherence to guidelines for antibiotic prescribing.
“In addition, our findings indicate that improved point-of-care influenza diagnostics and increased recognition and appropriate treatment of influenza virus infection may also aid in decreasing unnecessary antibiotic use for ARIs,” they wrote.
This research was funded by the CDC.
  • Reviewed by F. Perry Wilson, MD, MSCEAssistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner
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