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Monday, August 27, 2018

Tetraphase reports FDA approval of med for intra-abdominal infections


Tetraphase Pharmaceuticals, Inc. (NASDAQ: TTPH), a biopharmaceutical company focused on developing and commercializing novel antibiotics to treat life-threatening multidrug-resistant (MDR) infections, today announced that the U.S. Food and Drug Administration (FDA) has granted approval of XERAVA™ (eravacycline) for the treatment of complicated intra-abdominal infections (cIAI). In clinical trials, XERAVA was well-tolerated and achieved high clinical cure rates in patients with cIAI, demonstrating statistical non-inferiority to two widely used comparators – ertapenem and meropenem.
XERAVA is indicated for the treatment of complicated intra-abdominal infections in patients 18 years of age and older. To reduce the development of drug-resistant bacteria and maintain the effectiveness of XERAVA and other antibacterial drugs, XERAVA should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria.
“The approval of XERAVA is an extraordinary achievement, one for which we thank the patients who have participated in our clinical studies, study investigators and physicians as well as our dedicated employees,” said Guy Macdonald, President and Chief Executive Officer of Tetraphase. “We are thrilled to have received FDA approval, and a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) in Europe all within the same quarter. Each milestone is a significant accomplishment on its own and achieving both underscores the potential for Tetraphase and the medical need for XERAVA.”
Mr. Macdonald added, “We will now turn our efforts towards delivering XERAVA to patients suffering from cIAI in the United States, an important goal we expect to begin executing on in the fourth quarter of this year. We look forward to a successful launch and commercialization moving forward.”
“Complicated intra-abdominal infections are the second-most prevalent infection site in intensive care units (ICUs), as well as the second leading cause of infection-related mortality in ICUs,” said Philip S. Barie, MD, MBA, Professor of Surgery and Professor of Public Health in Medicine at Weill Cornell Medicine, and an attending surgeon at New York-Presbyterian/Weill Cornell Medical Center in New York City. “With the growing crisis of antibiotic resistance, treatment options for these polymicrobial infections are limited following surgery or percutaneous drainage, and the causative pathogens may be multi-drug resistant. Current empiric treatments for cIAI have limitations, and there is a need for new and novel treatments. Eravacycline has a broad spectrum of antibacterial activity and a clinical profile that addresses this unmet medical need.”
Dr. Barie added, “Eravacycline also has a favorable safety profile as observed in clinical trials, and no dose adjustment is required when given to patients with renal impairment, which is advantageous for seriously ill patients who may have impaired kidney function. Additionally, the drug may be given safely to patients who are allergic to penicillin. This new and novel treatment may be of great benefit to patients with complicated intra-abdominal infections.”

Cancer’s Last Gasp? Could Be, If Hypoxia Pathway Is Blocked


A proteomics study has identified a novel hypoxia-activated signaling axis that facilitates the adaptation of tumor cells to low-oxygen conditions. Hypoxia-inducible factors (HIFs) directly induce the expression of orphan receptor GPRC5A, which signals via Hippo pathway effector YAP to protect hypoxic tumor cells from apoptosis. GPRC5A, then, is a potentially druggable target to exploit tumor-associated hypoxia for cancer therapy. [EMBO Molecular Medicine]
  • Low-oxygen conditions ought to suffocate cells, but somehow cancer cells survive. They even progress and spread more aggressively, thanks to a newly identified signaling pathway, the HIF-GPRC5A-YAP axis. Blocking this pathway, scientists suggest, could choke cancer. The pathway appears to be “druggable” because it depends on a G protein-coupled receptor (GPCR), a type of receptor commonly targeted by drugs. Also, the receptor does not appear to be useful to normal cells, so interfering with it could stifle cancer cells without harming healthy tissue.
    The pathway was identified by University of Bristol scientists who worked with cancer cells grown in dishes, mouse models, and with a molecular biology technique called proteomics. Essentially, the scientists determined which proteins are present at elevated levels in cancer cells that are subjected to hypoxia, or oxygen-deficient conditions—conditions of the sort that arise when rumors grow faster than their blood supply.
    The results of this work appeared in the journal EMBO Molecular Medicine, in an article titled, “Cancer cell adaptation to hypoxia involves a HIF-GPRC5A-YAP axis.”
    “Using genetic approaches in vitro and in vivo, we reveal HIFs as direct activators of GPRC5A transcription,” wrote the article’s authors. “Furthermore, we find that GPRC5A is upregulated in the colonic epithelium of patients with mesenteric ischemia, and in colorectal cancers high GPRC5A correlates with hypoxia gene signatures and poor clinical outcomes.”
    Previous studies had shown that tumor cells in hypoxic regions switch on an adaptive transcriptional response mediated primarily by hypoxia-inducible factors (HIFs) that help them survive and continue to grow. Transcriptional regulators, however, are considered difficult therapeutic targets. Could more attractive, more druggable, mediators of hypoxic cancer cell survival be identified?
    That was the task facing the Bristol scientists, who were led by Alexander Greenhough, Ph.D., a researcher at Bristol’s School of Cellular and Molecular Medicine.
    “Hypoxia is considered an excellent target for cancer therapy because it generally features in cancers rather than healthy tissues,” Dr. Greenhough explains. “However, finding ways to effectively exploit this difference in the clinic is a major challenge.”
    “This work,” he continues “advances our knowledge of hypoxic cancer cell behavior and take us a step closer toward developing novel therapies that could achieve this goal.”
    In the current study, Dr. Greenhough’s team showed that GPRC5A (G Protein-coupled Receptor Class C, Group 5, Member A)—an orphan GPCR of poorly understood regulation and function—is a bona fide transcriptional target of HIFs both in vitro and in vivo.
    “Mechanistically, we show that GPRC5A enables hypoxic cell survival by activating the Hippo pathway effector YAP and its anti-apoptotic target gene BCL2L1,” the EMBO Molecular Medicine article detailed. “Importantly, we show that the apoptosis induced by GPRC5A depletion in hypoxia can be rescued by constitutively active YAP.”
    “This type of receptor is a GPCR, which are considered to be among the best drug targets for many diseases,” Dr. Greenhough points out. “We would like to know whether this receptor serves as a biomarker for more aggressive cancers that are resistant to therapy, and whether it has roles in other diseases where hypoxia or inflammation is implicated, which could lead to advances in regenerative medicine as well as oncology.”

Cutting higher payments to long-term care hospitals could save $4.6 billion


A trio of economists has a suggestion it says will save taxpayers about $4.6 billion per year with no harm to patients: get rid of higher payments to long-term care hospitals.
A National Bureau of Economic Research study released Monday found that despite being reimbursed at much higher rates than skilled nursing facilities and home healthcare providers, long-term care hospitals don’t produce better outcomes in three important areas: They don’t reduce mortality or length of stay and they leave patients with higher out-of-pocket costs.
The CMS has taken a number of steps over the years to rein in long-term care hospital spending, including a dual payment system under which such facilities only receive higher payments if their patients meet certain criteria. But Liran Einav, one of the paper’s authors and an economics professor at Stanford University, said those restrictions probably cut the facilities’ growth in half, but they’ve still been able to generate significant profit.
When the government created long-term care hospitals in the early 1980s, they created an “unintended monster,” Einav said.
“Since then, the government, CMS didn’t try to kill the monster, they tried to just stop it from growing arms and legs,” he said. “They created freezes on new beds, new facilities … Part of our point is maybe instead of trying to curb it from growing arms and legs, just kill the monster.”
Einav’s report suggests paying long-term care hospitals the same rate as skilled nursing facilities would cut 1% of Medicare’s total spending.
More than 70% of long-term care hospitals are for-profit, and the report said the largest such providers, Kindred Healthcare and Select Medical, have reported profit margins between 16% and 29%.
A spokesman for Select said the study mistakenly reports its earnings before interest, taxes, depreciation and amortization margin of 13.7% as profit, but the company does not report profit margins as part of financial disclosures.
“Select’s critical illness recovery hospital segment has never achieved EBITDA margins of 29%,” Jeffrey Birnbaum wrote in an email. “In addition, the margins on Medicare reimbursed stays, for both cash flow or profits, have consistently been lower than overall margins.”
Long-term care hospitals were created in the 1980s to protect 40 chronic disease hospitals from the prospective payment system. At the time, regulators feared the fixed payments wouldn’t be enough to cover those hospitals’ costs. That small group has since grown to more than 400 hospitals with $5.4 billion in annual Medicare spending as of 2014, the report found.
Both Select and the American Hospital Association called the study’s findings outdated and said they don’t account for a law implemented in 2015 that changed how such facilities are paid and caused up to 7% of them to close.
“Moreover, I would say it’s written from a purely economic perspective and ignores the fact that LTCHs are needed to provide extended, specialized hospital care to the very sickest of patients,” said Ashley Thompson, the AHA’s senior vice president of policy.
Thompson said long-term care hospitals are required to report patient outcomes measures such as changes in mobility, Clostridium difficile infections and catheter-associated urinary tract infections, which are posted on a publicly accessible website.
Neale Mahoney, an author of the report and professor of economics at the University of Chicago Booth School of Business conceded it’s possible some patients owe their recoveries or even survival to long-term care hospitals, and that there may be other outcomes measures their study didn’t track. But he emphasized the burden of proof is on those facilities to justify the higher cost, especially as taxpayers pay $950 more per day for long-term care hospital stays compared with stays in skilled nursing facilities, per the new report.
“If we could look at data and see better outcomes and see whether they’re worth the extra $950 a day, that’s the way that research and policymaking is supposed to progress, and we’d love to see it,” Mahoney said.
The average stay in a long-term care hospital lasted 26 days and cost Medicare $36,000 in 2014, according to the report. The average skilled nursing facility stay, by contrast, lasted 25 days and cost $12,000, the study found.
“At the end of the day, the question is at what point do we say, ‘Taxpayers should not pay for extra benefits unless you prove these benefits exist?'” Einav said. “My sense is that the burden of proof is on the industry.”

Pediatricians: Counsel Pregnant, Lactating Women Against Marijuana Use


Clinicians should counsel women who are considering becoming pregnant or are of childbearing age about the potential negative effects of maternal marijuana use on pregnancy outcomes, as well as on fetal, infant, and child neurodevelopment, according to a clinical report from the American Academy of Pediatrics (AAP).
Prompted in part by the increasing prevalence of marijuana use among reproductive-aged women, the guidance is informed by a small but growing body of data showing that cannabis compounds quickly cross the placenta and can be transferred through breast milk. Those data suggest marijuana use can potentially influence obstetrical outcomes and embryonic development, write Sheryl A. Ryan, MD, from the Department of Pediatrics at Penn State Health Milton S. Hershey Medical Center in Pennsylvania, and colleagues write in the report, published online today in Pediatrics.
To help clinicians address the issue with their patients, the clinical report provides specific recommendations and summarizes available data on the pharmacokinetics of cannabinoids during pregnancy and lactation. Data link  maternal marijuana use to a range of adverse pregnancy outcomes, including low birth weight, premature birth, small head circumference, small length, and stillbirth, as well as to poor pediatric outcomes, such as trouble with memory, attention, impulse control, and school performance.
While Ryan and colleagues acknowledge that the evidence for adverse effects of marijuana are limited — particularly because women who use marijuana are also more likely to use substances such as alcoholtobacco, and other drugs — “the evidence from the available research studies indicates reason for concern, particularly in fetal growth and early neonatal behaviors.”

Cannabinoids in Breast Milk

study published in the same issue of Pediatrics, quantifying cannabinoid concentrations in breast milk, validates the concern and supports the recommendation that clinicians advise mothers to abstain from marijuana use while breastfeeding.
In the study, Kerri A. Bertrand, MPH, from the Department of Pediatrics at the University of California, San Diego, and colleagues, analyzed breast milk samples from 50 women who reported using marijuana while breastfeeding between 2014 and 2017. The investigators used mass spectrometry to identify concentrations of several cannabinoids, including Δ-9-tetrahydrocannabinol (∆9-THC), the primary psychoactive ingredient in marijuana, and 11-hydroxy-Δ-9-tetrahydrocannabinol, cannabidiol, and cannabinol.
Of 54 samples analyzed (four women provided samples at two time points), ∆9-THC, 11-OH-THC, and cannabidiol were detected at 1 ng/mL or higher in at least one sample, and ∆9-THC was detected in 34 (63%) samples, the authors report. Significant  predictors of ∆9-THC concentrations included the number of times a women used marijuana per day, as well as hours since last use.
“[W]e estimated the mean infant plasma concentration of ∆9-THC obtained from breastfeeding to be ∼1000 times lower than the concentration in an adult after a single dose of 10 mg of ∆9-THC,” the authors state. “If a child is exposed to low levels of Δ9-THC in milk daily, there is a concern for accumulation of the various cannabinoids in the nursing infant because of slow elimination from body fat stores and continuous daily exposure.‍”
This exposure, they hypothesize, may alter brain development  because the    brain develops rapidly during the first 2 years of life — the period when infants’ main source of nutrition is likely human milk.
The findings by Bertrand and colleagues are “extremely important in documenting the ability of cannabinoids, including cannabidiol, which is increasingly being used for medicinal purposes, to be transferred from a cannabis-using lactating mother into her breast milk,” Ryan writes in an accompanying commentary.
Ryan suggests that legalization has led people to think marijuana is safe, despite accumulating evidence that its use has harmful side effects. “Up to 36% of women report having used marijuana at some point in their pregnancy, and 18% report having used it while breastfeeding,” she explains. “These high rates of reported use raise important issues for those medical providers who provide care to infants and children or who may be asked by parents about the safety of marijuana use during lactation.”
Ryan notes that more context is needed to fully understand the implications of the findings from Bertrand and colleagues. For example, it’s not clear yet how or how quickly the compounds are metabolized or what the short- and long-term developmental effects are.
Acknowledging limitations, the study authors call for further research into the oral absorption of cannabinoids in breastfeeding infants as well as metabolic and accumulation patterns and pharmacologic effects on neurodevelopment. “Because marijuana is the most commonly used recreational drug among breastfeeding women, information regarding risks to breastfeeding infants is urgently needed,” they write.
Some of this research has already begun, according to Christina D. Chambers, PhD, MPH, professor and director of clinical research in the Department of Pediatrics at the University of California in San Diego, senior author on the breastfeeding study. “We have in process collection of long term follow up data for the mothers and children enrolled in this study, including growth and neurodevelopmental testing, and we continue to enroll new mothers in the UCSD Human Milk Biorepository,” she said in an interview with Medscape Medical News. “While this work will help answer the key question of whether or not the exposure does affect infant brain development, additional work is also needed to determine the actual dose of cannabis the breastfed infant is receiving.”
Limitations notwithstanding, the AAP urges clinicians to discuss what is currently known about adverse consequences of marijuana use during pregnancy and breastfeeding at prenatal visits to promote optimal health outcomes for mother and child.
“Legalization of marijuana may give the false impression that marijuana is safe,” the authors write in the AAP clinical report. Although ethical concerns preclude randomized controlled studies to definitively prove otherwise, the current pool of data provides “theoretical justification” for this conclusion.
Whether legalization of marijuana has led to its increased use among pregnant/lactating women or whether it is a function of the increasingly common perception that the substance’s medicinal properties are benign “is hard for me to say,” Chambers said. “But recent national survey data do suggest that a high proportion of women think that occasional use is harmless.” For this reason, she stressed, the AAP’s clinical guidance is timely and necessary.
Bertrand et al and the authors of the AAP clinical report have disclosed no relevant financial relationships.
Pediatrics. Published online August 27, 2018. AAP clinical report,  Bertrand et al abstractCommentary

Cutting home lead levels may not aid neurobehavioral outcomes for children


Reducing lead levels in the home may not affect neurobehavioral outcomes for children, according to a new study.
In the Health Outcomes and Measures of the Environment (HOME) Study, interventions aimed at reducing lead in the households of pregnant women were effective at reducing lead levels in various surfaces throughout the home and were sustained for 2 years, reported Joseph Braun, PhD, of Brown University in Providence, and colleagues.
According to the study in JAMA Pediatricsthe reductions were as follows:
  • Dust lead loadings for the floor: 24% reduction (95% CI -43% to 1%)
  • Windowsill: 40% reduction (95% CI -60% to -11%)
  • Window trough: 47% reduction (95% CI -68% to -10%)
“This finding offers clinicians and public health practitioners with an opportunity to prevent childhood lead exposure and is directly relevant to a recent court order mandating the U.S. Environmental Protection Agency to promulgate a lower residential dust lead standard,” the researchers wrote.
However, this intervention to reduce lead throughout the home did not have any significant impact on blood lead concentrations among young children compared with children whose homes did not receive any household cleaning interventions (-6%, 95% CI -17% to 6%, P=0.29). Interestingly, non-Hispanic black children alone did see a 31% drop (95% CI -50% to -5%, P=0.02) in blood lead concentrations — the only group of children to see any significant benefit with this intervention. This also included a 40% reduction in risk (95% CI 0.4-1.0) of blood lead concentration greater than 2.5 μg/dL only seen in black children.
This lead-reducing intervention in the homes of pregnant women also had no significant impact on neurobehavioral outcomes in children throughout the total 8-year follow-up period, except for an improvement in anxiety levels in kids whose homes were cleaned (β = -1.6, 95% CI, -3.2 to -0.1, P=0.04).
While most other neurobehavioral outcomes measured on several scales — the Bayley Scales of Infant Development, Wechsler Preschool and Primary Scale of Intelligence/Wechsler Intelligence Scale for Children, Behavior Assessment System for Children, Behavior Rating Inventory of Executive Function, and Conners’ Continuous Performance Test — tended to favor the intervention, none of these outcomes actually reached statistically significant benefits.
The longitudinal study included 355 pregnant women, half of whom were randomized into the lead-reducing intervention group while the other half served as the control population. The lead-reducing intervention was introduced into the homes between 32 weeks of gestation and delivery.
“These interventions included covering bare lead-contaminated soil with ground cover, installing a tap-water filter if the lead concentration in drinking water exceeded 2 μg/L, repairing and repainting peeling or deteriorating lead-based paint, creating smooth and cleanable floors and windows, installing window trough liners, replacing windows that have lead-based paint or show more than 10% deterioration, and undertaking extensive dust control and cleanup,” Braun and co-authors explained.
Following these interventions, the researchers tested several household surfaces and ordered additional cleaning if necessary. Prior to this intervention, the baseline household levels of lead were similar between both study groups. These levels were measured again when the child was 1 to 2 years old, while blood concentrations were assessed six times until the child reached age 8.
In an accompanying editorial, Jessica Wolpaw Reyes, PhD, of Amherst College in Massachusetts, wrote that although the study may not answer all the lingering questions surrounding the implications of having lead in the home, the results do “sharpen what we know about home-centered primary prevention, showing that such intervention can be effective and safe,” and that finding these “substantial” reductions in household lead levels was “both new and promising.”
However, she critiqued the study for its smaller sample size, and posed that this may have limited the researchers from finding any statistically significant differences in neurobehavioral outcomes in the children. “It seems possible that the authors may have sized only for the first step,” she suggested, recommending that future studies employ “more aggressive econometric methods … testing each stage directly, testing more nuanced hypotheses, or testing the omnibus hypothesis that lead has adverse behavioral effects (rather than testing each behavior individually).”
Nonetheless, Reyes suggested that the findings should be used for addressing top-priority locations where children spend most of their time, such as schools, playgrounds, and housing.
The study was funded by grants from the National Institutes of Environmental Health Sciences, the U.S. Environmental Protection Agency, and the U.S. Department of Housing and Urban Development.
Braun reported being financially compensated for conducting a re-analysis of a child lead exposure study for the plaintiffs in a public nuisance childhood lead poisoning case.
Reyes reported serving as chair of the Advisory Committee for the Lead Poisoning Prevention Program in the Office of Governor Charles Baker for the Commonwealth of Massachusetts.
  • Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner
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3 Notable Leaps in Sepsis Care


Sepsis is deadly, it’s expensive, and there are abundant initiatives under way that could lead to earlier detection, lowering costs, and saving lives.
In May 2016, the Healthcare Cost and Utilization Project and the Agency for Healthcare Research and Quality released a report about the impact of sepsis on U.S. inpatient hospital costs. The study, which analyzed billings from 2013, revealed the following:
  • Sepsis accounts for nearly $24 billion in annual costs, making it the most expensive condition to treat in the U.S. healthcare system
  • Sepsis was responsible for 6.2% of all hospital costs across the country
  • Sepsis also was the most expensive hospital condition billed to Medicare, accounting for 8.2% of all Medicare costs
  • The condition accounted for nearly 1.3 million hospital stays
The Sepsis Alliance estimates that 258,000 patients die from the condition each year in the U.S. To save lives and improve the bottom line, hospitals across the nation are trying different approaches to reduce sepsis morbidity and mortality. At the same time, innovators strive to create ways to identify the condition earlier.
Here is a look at best practices from Nemours Children’s Hospital in Orlando, Fla., which instituted a program that reduced its pediatric morality rate to zero, as well as two promising innovations on the horizon.
Remote Monitoring at Nemours
In 2015 Nemours decided to take an aggressive, multifaceted approach to sepsis that dropped sepsis mortality rates from 12.5% in 2016 to zero during the first 6 months of 2018. While there were numerous factors that contributed to the decrease, remote monitoring was one of the primary drivers behind the improvement, according to one of the physicians involved in the project.
Jennifer Setlik, MD, a pediatric emergency physician, explained: “The way we have improved our sepsis results is through a bundle of care. We’ve educated nurses on administering IV fluids in a faster way. We also worked on pharmacy processes to have antibiotics delivered faster to a patient with sepsis. There are many different mechanisms we have used to help this process, but the key starting point — or the gun that starts the race — is [remote monitoring from] the Logistic Center. Logistics really gives us a head start in the race to treat patients with sepsis.”
The initiative began in November 2015 in the emergency department, and was then rolled out to the rest of the hospital. Nemours also participates in a national collaborative with the Children’s Hospital Association, which is working to reach consensus on appropriate mechanisms of action related to sepsis.
How It Works
  • The Nemours Clinical Logistics Center, a facility located in the hospital, provides 24/7 remote monitoring by paramedics who observe all patients in the emergency department and every bed in the hospital, except the neonatal intensive care unit, which uses separate protocols
  • Vital signs and other data are aggregated into a shock/sepsis score
  • Nemours designed the scoring system, which contains a unique feature that gives greater weight to blood pressure changes
  • The team tweaks the scoring system over time to further improve its sensitivity
  • If the score reaches a threshold value of 25 or more points, paramedics receive a visual cue and prompt a bedside nurse (who also receives the score on her monitor) to gather additional information
  • Additional inputs include assessments for a shock/sepsis state, which may raise the score
  • If the child has a score of 45 points or higher, a rapid response team is deployed, since there is an elevated risk of shock, a precursor to sepsis
Results
  • The average length of stay dropped from 10 days in 2016 to 7 days throughout 2017 and the first 6 months of 2018
  • Mortality rates decreased from 12.5% in 2016, to 4.5% in 2017, to zero through June 2018 (However, physicians note that figures can be artificially inflated due to the small size of the 100-bed hospital)
  • Mortality rates for medically complex children saw a similar decline — from 21% in 2016, to 6% in 2017, and zero in 2018 through June
There are numerous innovative approaches to sepsis now in development. Here’s a look at two:
Artificial Intelligence Tool
Predictive analytics already play a role in early sepsis detection in models introduced by Mayo Clinic, Penn Medicine, and other places. But it’s only a matter of time before artificial intelligence speeds up the detection process even further.
Using real-time data, innovators at Emory University in Atlanta are testing their Artificial Intelligence Sepsis Expert. It already can accurately predict the onset of sepsis in an intensive care unit patient 4 to 12 hours prior to clinical recognition, according to a 2018 study in Critical Care Medicine.
The accuracy rate is 85%-90%, reported the study’s senior author, Timothy Buchman, MD, PhD, director of the Emory Critical Care Center and chief of critical care services at Emory Healthcare. In addition to predicting sepsis, the developers want the model, which is still in development, to explain why the patient is likely to become septic.
“The novelty of this algorithm is that it [will tell clinicians] that among hundreds of tests, you need to pay attention to these five labs right now,” said another of the co-authors, Shamim Nemati, PhD. “This information will not only help providers build trust in the device, but will also offer more precise opportunities for action.”
It may be up to 5 years before the device is commercially available, although initial forms of the Sepsis Expert may be available for testing in academic health environments as soon as next year.
Test Immune Response, Not Pathogens
Seattle-based Immunexpress has taken a different approach to the sepsis battle. Currently, no definitive test exists to diagnose sepsis.
Clinicians rely on detecting pathogens in blood cultures, a process that takes time and still doesn’t offer a conclusive diagnosis. Minutes are precious in the sepsis battle: each hour without treatment increases mortality by 8%, said the company’s CEO, Rolland Carlson, PhD. He explained that rather than passively chasing pathogens, Immunexpress developed a test to measure the body’s specific immune response to infection by examining biomarkers in the patient’s blood.
These biomarkers may hold the key to the early and accurate detection of infection, as well as assist in guiding the use and timing of drugs and other therapies, he said. “SeptiCyte is the first FDA-cleared diagnostic to test for a gene signature that differentiates between positive systemic inflammation, which would be sepsis, or negative systemic inflammation, which would be indicative of SIRS [systemic inflammatory response syndrome].”
The latter diagnosis is treated much differently from sepsis and usually doesn’t require admission to the intensive care unit. Up to 43% of patients treated for sepsis were unlikely to have had a sepsis infection, according to a 2015 study in Critical Care.
SeptiCyte has received FDA approval and conducted some of its clinical trials at Seattle Children’s Hospital. The company is now testing SeptiCyte on a different platform that could produce results in less than 90 minutes, and expects to have a product commercially available during 2019.
Learn More
  • Hospital sepsis scores are now publicly available on Medicare’s Hospital Compare website (select a hospital, then “Timely & Effective Care,” then “Sepsis Care”).
  • Learn how the U.S. Department of Health and Human Services aims to accelerate sepsis innovation.
  • Preliminary findings from an Intermountain Healthcare study found no difference in 30-day mortality among sepsis patients treated as inpatients versus outpatients.
This report is brought to you by HealthLeaders Media.
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NIH: Some Foreign Researchers May Be Spies


At the request of members of the Senate, the head of the National Institutes of Health explored current threats to biomedical research and intellectual property diversion and his agency’s efforts to address them, at a hearing of the Senate Health, Education, Labor and Pensions Committee on Thursday.
NIH Director Francis Collins, MD, PhD, briefed the committee on the agency’s investigation of NIH-funded scientists who may be smuggling intellectual property or unpublished scientific information to foreign governments. Some of these researchers are foreign nationals.
In July, Business Insider reported that a Chinese billionaire and former Duke University student was accused of stealing his American mentor’s research on a certain “invisibility technology” and then duplicating it.
Collins noted that security threats in biomedical research have long been a concern, but the magnitude of these threats is increasing.
He said he wrote letters shortly before the hearing to more than 10,000 NIH-grantee institutions, asking them to review their researchers’ records for “evidence of malfeasance” across three core areas of concern:
  • Failure by some investigators to disclose “substantial contributions of resources from other organizations including foreign governments”
  • Diversion of intellectual property to other entities or to other countries
  • Failure by peer reviewers to ensure that information on grant applications is kept confidential (i.e., not being shared with foreign countries)
After the hearing, Collins told reporters that besides that general letter, he had also written more targeted letters to a half-dozen institutions noting concerns about specific investigators on their faculty.
“We have evidence [in these cases] that somebody who has an NIH grant is getting a lot of money from a foreign government and did not inform us of that… and we’re asking them to look into it,” he said.
Collins acknowledged that some of these may have been innocent lapses: “Like, ‘Oops, I knew that and I should have told you, and I forgot.'” In such cases, he said, the researcher would simply be told not to do it again.
“But we are concerned about circumstances where people have intentionally been deceptive about those connections, with an intention then to divert intellectual property or perhaps to use their access to peer-review materials to ship them overseas, which would be a very bad thing to do.”
While any intentional “bad behavior” is the fault of the scientist, NIH doesn’t fund scientists, it funds institutions, Collins explained. So, with these letters, the agency is reminding institutions that it’s their responsibility to ensure that researchers follow the rules.
Penalties “can be anything from losing your ability to have your grant, to being debarred from ever getting grants, to, if it’s actually criminal activity, then potentially somebody bringing a charge — all depending on the severity of the infraction,” Collins said.
Sen. Lamar Alexander (R-Tenn.), the HELP committee’s chairman, emphasized that most foreign researchers are completely legitimate. “But if there’s some bad actors who are attempting to influence NIH-funded research, we want to know about it,” he said. “And we want to know what authorities you need, or others need, to deal with it.”
Collins said he is setting up a new working group tasked with identifying new ways to enhance the accuracy of research support funding and its sources; reducing the risk to intellectual property security; identifying new approaches to “protect the integrity of peer review,” and do so in a way that underscores “the compelling value of ongoing honorable participation by foreign nationals in the American scientific enterprise.”
Roy Wilson, MD, president of Wayne State University, and Lawrence Tabak, PhD, principal deputy for the NIH, will co-chair this working group. Other members hail from Vanderbilt University, the University of Washington, Ohio State University, the University of Maryland, Stony Brook University, and MIT.
“We must move effectively to root out examples where our system is being exploited, but make sure to preserve the vibrancy of the diverse workforce that has played a major role in the American biomedical research success story,” Collins said.