To reduce diagnostic errors, providers told to start with radiology

There are plenty of places in the diagnostic process where things can go wrong. But radiology is a frequent source of medical error that is ripe for reform, according to a new report.

Coverys, a Boston-based medical liability insurer, reviewed more than 10,600 malpractice claims from between 2013 and 2017 and found that nearly 600 named a radiologist explicitly. These cases often related to significant patient harm and delayed diagnosis of serious conditions, according to the group’s report.

About 80% of claims involving radiology were related to misinterpretation of diagnostic reports, according to the study. There is a lot of variability in how different radiologists may read a report, which leaves the door wide open for a mistake, Robert Hanscom, vice president of business analytics at Coverys, said in an interview with FierceHealthcare.

“Radiology has done a lot over the last several years to try and see if they can become a safer discipline,” Hanscom said. “They need to continue to press on a number of fronts—they are still finding themselves very much connected to these poor outcomes.”

The report identifies several ways that radiology teams can address the risk of medical errors, including:

• Using clinical decision support
• Having a clear protocol for bringing in a second opinion on a reading
• Building templates for reports and using clear language in them
• Ensuring that incidental findings worthy of follow-up are highlighted so they aren’t missed

Peer review is a key strategy, Hanscom said, especially since the interpretation stage is the riskiest. Getting a second opinion can ensure that nothing on a test result is missed and can prevent communication gaps, such as getting crucial information to the physician that can best use it.

It doesn’t take much for one of these communications breakdowns to occur, Hanscom said. For example, if a patient were to undergo a chest x-ray in the emergency department that shows abnormal spotting, those results may not be taken care of if the only doctors who are made aware are in the ER. If that information doesn’t make it back to the primary care doctor or family doctor, that patient will learn too late that he or she has lung cancer.

Providers have begun to make strides on some of Coverys’ suggestions, however, Hanscom said. For example, many hospitals are building templates for radiology reports, he said—though the next step to really prevent patient harm would be to standardize those forms nationwide.

More providers are also working toward building clear guidelines on when second opinions are necessary, he said. But addressing the variability of interpretation still requires a lot of work.

“Radiology has to continue to really roll up their sleeves and figure out how they reduce that variation,” Hanscom said.

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Adding mental health options in clinical setting tough, with few ‘quick wins’

Though truly bringing mental health care into the fold with clinical care may ultimately require some major policy overhauls, there are “significant quick wins” key players can go after now, experts say.

When Rocky Mountain Health Plans refocused on connecting members with primary care—and community health centers in particular—they knew could either meet behavioral health needs with in-house specialists or connect them with the right provider, said Patrick Gordon, associate vice president of community integration.

There are plenty of opportunities for small change, Gordon said, that can improve outcomes for patients even though a significant reshaping of the delivery system is a ways off. “Broad system change will take a heavy lift, but we can start now,” Gordon said, speaking at a Bipartisan Policy Center event on Thursday on how to bridge the gap between behavioral health and clinical healthcare.

John Auerbach, CEO of Trust for America’s Health, said a good place for stakeholders to start is looking at the services patients use the most and where they’re the most comfortable. For example, his organization looked first at community health centers and mental or behavioral health clinics and used that as a baseline for where to reach the patients with the greatest need when looking for ways to plug away at smaller changes.

Other options may mean offering services outside of the traditional healthcare system entirely. Jill Bohnenkamp, Ph.D., assistant professor at the University of Maryland School of Medicine and core faculty at the university’s Center for School Mental Health, said a school is the “ideal place to serve students.”  Building strong behavioral health options into schools can be a crucial preventative measure, she said.

This is especially true in rural areas that may struggle with access to care generally, Gordon added.

Another starting step, Gordon said, is bringing leadership of behavioral health providers to the table. When they’re included in the dialogue, they’re more likely to get skin in the game.

Behavioral health providers should be offered a piece of the shared savings from these efforts in exchange, he said.

Though starting small can pay off, there are still major roadblocks for providers and payers looking to address this issue, Auerbach said. These obstacles can vary significantly from state to state and between types of insurers.

Technology investments are one of the biggest barriers, he said. Many behavioral health providers, in particular those in nontraditional settings such as schools, may not be sure how to use telemedicine and may not have access to the tools needed to succeed.

Licensing issues and contracting regulations can also make the process difficult, he said. In a review of Massachusetts regulations, Auerbach said he and his team identified 100 regulations that can get in the way of integrated care.

Payment models have also not quite caught up to these new approaches to care, he said. Reimbursement is also especially problematic for providers operating outside of traditional care settings.

“It’s one headache after another,” he said.

In Massachusetts, the team devised a workaround that could potentially be expanded to other states. They appointed a nurse who would field waiver requests from providers looking to get around some of these burdensome regulations, and she would connect with the needed regulators to see these requests through.

In the future, policymakers will have to consider ways to make it easier for providers to follow these rules, Gordon said. At present, it falls to them to simply find a way to navigate regulations.

“It’s the least efficient, most burdensome way to do this,” he said.

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New way to grow blood vessels

Formation of new blood vessels, a process also known as angiogenesis, is one of the major clinical challenges in wound healing and tissue implants. To address this issue, researchers from Texas A&M University have developed a clay-based platform to deliver therapeutic proteins to the body to assist with the formation of blood vessels.

The team is led by members of the Inspired Nanomaterials and Tissue Engineering Lab in the Department of Biomedical Engineering. They have developed technology that introduces a new type of two-dimensional clay, also known as nanosilicates, that delivers multiple specialized proteins called growth factors into the body to stimulate new blood vessel formation. To allow blood vessels time to form, the clay is designed to prolong the release through its high surface area and charged characteristics, according to biomedical engineering assistant professor Dr. Akhilesh K. Gaharwar.

“Clay nanoparticles work like tiny weak magnets that hold the growth factors within the polymeric hydrogels and release very slowly,” Gaharwar said. “Sustained and prolonged release of physiologically relevant doses of growth factors are important to avoid problems due to high doses, such as abrupt tissue formation.”

Co-investigator Dr. Kayla Bayless from the Department of Molecular and Cellular Medicine in the Texas A&M Health Science Center said the clay also keeps the growth factors organized, preventing abnormal growth and moderating activity of surrounding cells.

Gaharwar said by establishing clay nanoparticles as a platform technology for delivering the growth factors, the research will have a significant impact on designing the next generation of bioactive scaffolds and implants.

The research was recently published in Advanced Biosystems.

More information: David W. Howell et al, 2D Nanosilicates Loaded with Proangiogenic Factors Stimulate Endothelial Sprouting, Advanced Biosystems (2018). DOI: 10.1002/adbi.201800092

https://bit.ly/2MW0Yul

CDC: brucellosis in dogs remains a public health risk

Brucella canis is an under-recognized infection in dogs that poses a threat to human health, according to a report published in the August issue of the U.S. Centers for Disease Control and Prevention’s Emerging Infectious Diseases.

Noting that in humans, the infection can cause fever, chills, malaise, peripheral lymphadenomegaly, and splenomegaly, Martha E. Hensel, D.V.M., from Texas A&M University in College Station, and colleagues evaluated serologic data, transmission patterns, and regulations related to brucellosis in dogs, with a particular focus on the infection as an under-recognized zoonosis.

The researchers found that brucellosis in dogs remains endemic to many parts of the world and will probably remain a threat to human health and animal welfare unless stronger intervention measures are implemented. They propose implementation of mandatory testing of dogs before interstate or international movement as a first step for limiting disease spread.

“Future work is required to improve diagnostic assays for humans and animals and to generate policies to prevent the spread of disease,” the authors write.

 Explore further: Report warns of dog illness that can spread to owners

More information: Abstract/Full Text

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CRISPR technology targets mood-boosting receptors in brain

An estimated 13 percent of Americans take antidepressant drugs for depression, anxiety, chronic pain or sleep problems. For the 14 million Americans who have clinical depression, roughly one third don’t find relief with antidepressants.

But now, researchers at Washington University School of Medicine in St. Louis and Sage Therapeutics in Boston are trying a different approach to alleviate depression. Most antidepressant drugs target serotonin receptors, aiming to boost serotonin, a chemical thought to regulate mood and social behavior. Using CRISPR technology, the scientists have been able to target an altogether different type of receptor called delta-type GABA receptors. They think that natural mood-boosting substances in the brain can target these receptors.

The research is available online in The Journal of Neuroscience.

“There’s a real need to develop more effective antidepressants,” said principal investigator Steven Mennerick, professor of psychiatry. “The most commonly prescribed antidepressant drugs—such as Prozac, Paxil and Zoloft—were approved by the FDA more than 30 years ago, and there’s been a dearth of new antidepressants since then. A completely new approach is warranted.”

That new approach involves targeting GABA receptors with substances called neurosteroids, chemicals that occur naturally in the brain and are involved in emotional and motivational brain networks. The research was conducted through the university’s Taylor Family Institute for Innovative Psychiatric Research, which was established in 2013 to develop new drugs for depression and other psychiatric illnesses.

“Neurosteroids are thought to selectively interact with delta-type receptors, and there’s evidence that those drugs may help patients suffering from depression,” said Mennerick, who also is the scientific director of the Taylor Family Institute.

There is an “alphabet soup” of GABA receptor subtypes on brain cells. Targeting the delta-type GABA receptor could help alleviate depression because GABA, an inhibitory neurotransmitter, may help slow down some of the cognitive processes that lead to overwhelming and negative thoughts and feelings. Some types of GABA receptors have been linked to anxiety, but although many scientists have looked at the receptors as potential targets for depression, developing compounds that selectively bind to specific types of GABA receptors has complicated the search.

In the new research, Mennerick and his colleagues focused on GABA receptors located on neurons in the brain’s hippocampus, a part of the brain involved in learning and memory. Using CRISPR, they mutated the delta-type GABA receptors to isolate and test their role in brain functioning.

Earlier studies involving Taylor Family Institute scientists and carried forward in human trials by Sage Therapeutics suggested that targeting these receptors could alleviate symptoms of depression in women suffering from severe postpartum depression.

Last summer, The Lancet published results of a Sage-funded trial of the neurosteroid brexanolone as a treatment for postpartum depression. The study of 21 women showed that depression improved significantly in those given the drug.

Those drug trials did not take place in St. Louis, to avoid conflicts of interest because several Taylor Family Institute researchers serve as scientific advisers for Sage. In the current study, testing the same compound in cell cultures and mice, Mennerick’s team is exploring whether the drug works through delta-type GABA receptors.

“The drugs affect GABA receptors, but they also seem to have anti-inflammatory properties,” Mennerick said. “We think it may be that special mix of reducing inflammation while activating these receptors that contributes to antidepressant effects.”

First author Min-Yu Sun, PhD, a postdoctoral researcher in Mennerick’s lab, said the research team next plans to measure the actions of neurosteroids on various GABA receptor subtypes.

“It’s very difficult to differentiate among different types of GABA receptors because they share so many common properties,” Sun said. “Previously, scientists really had no way to isolate the subtypes, but we can do that with CRISPR/Cas9 gene editing technology to learn how particular drugs affect individual receptor subtypes.”

Mennerick explained that if further studies confirm that activating delta-type receptors has antidepressant effects, a next step would be to develop and test more compounds that activate those receptors. He said the mutant mice give them the tool they need to develop more potent drugs that also are more selective, with fewer side effects.

“We have a catalogue of neurosteroid compounds that our colleagues have been developing over the last 20 years, and any one of them could prove to be an effective antidepressant,” he said. “If brexanolone works in postpartum depression mainly through these delta-type receptors, then it may work in other types of depression, too. Eventually, the goal would be to develop ever more potent and selective drugs to interact with those same delta-type receptors.”

More information: Min-Yu Sun et al. Chemogenetic isolation reveals synaptic contribution of δ GABAAreceptors in mouse dentate granule neurons, The Journal of Neuroscience (2018). DOI: 10.1523/JNEUROSCI.0799-18.2018

Stephen Kanes et al. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial, The Lancet(2017). DOI: 10.1016/S0140-6736(17)31264-3

https://bit.ly/2KZXNjH

Links between fever and cancer incidence

Recurring patterns in patient accounts suggest the existence of an inverse relationship between personal history of infectious fever and cancer risk, and these patterns are documented throughout decades of medical literature. However, evidence supporting this correlation continues to be primarily anecdotal. In “Toward Antitumor Immunity and Febrile Infections: Gamma/Delta (γδ) T Cells Hypothesis” published in The Quarterly Review of Biology, Wieslaw Kozak, Tomasz Jedrzejewski, Malgorzata Pawlikowska, Jakub Piotrowski, and Sylwia Wrotek propose a mechanistic hypothesis that focuses on the potential impact infectious fever has on a particular subset of T cells, known as gamma/delta (gd) T cells.

Drawing upon previous research and experimental data, the authors argue that repeated exposure to fever enhances the ability of gd T cells to detect cellular abnormalities and to foster inhospitable environments that destroy malignant cells. This paper is the first to acknowledge the role that gd T cells may play as participants in this inverse relationship.

Infectious fever is the defensive and adaptive reaction that occurs when an organism’s immune system comes into contact with exogenous pyrogens, or pathogen-associated molecular pattern (PAMP). Upon recognition of these exogenous pyrogens, endogenous mediators — also known as endogenous pyrogens — engage the febrile system. According to previous work by Shephard et al., a febrile system is composed of all of the mechanisms responsible for facilitating a fever as well as the various systems the fever affects. Thermoregulatory mechanisms are activated, resulting in the elevation of an organism’s core body temperature.

The authors further elaborate on the function of endogenous mediators, like cytokines.

“In short, endogenous mediators of fever redirect metabolic substrates and energy to the immune system during fever. This markedly enhances the frequency of a vast range of immune effectors, including lymphocytes expressing gd heterodimer receptors, which possess a potent anti-infectious and antitumor competence,” the authors write.

Gamma/delta T cells possesses receptors (TCRs) comprised of gamma/delta chain heterodimer. In fact, the authors posit that the unique attributes of gd T lymphocytes — lower TCR variability, fewer gene segment rearrangements, and TCRs with older evolutionary memory — enable the cells to enact processes that aid in decreasing cancer risk, such as immune surveillance and attacking cancerous cells. Vg9Vd2 T cells are capable of responding to various types of cancer, such as carcinoma, lymphoma, prostate, myeloma, and sarcoma. Exposure to infection significantly expands the quantity of gd T cells. During infection, blood Vg9Vd2 T cells can increase in number until they constitute 60 percent of the total amount of lymphocytes.

While previous research and current cancer immunotherapy practices predominately focus on alpha/beta (ab) T cells, analysis of the interaction between fever and gd T cells may generate further inquiry into the larger impact and the clinical benefits of this relationship.

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Materials provided by University of Chicago Press Journals. Note: Content may be edited for style and length.

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Journal Reference:

1. Wieslaw Kozak, Tomasz Jedrzejewski, Malgorzata Pawlikowska, Jakub Piotrowski, Sylwia Wrotek. Toward Antitumor Immunity and Febrile Infections: Gamma/Delta (γδ) T Cells Hypothesis. The Quarterly Review of Biology, 2018; 93 (3): 187 DOI: 10.1086/699409

https://bit.ly/2whO9Um

Resistance training and exercise-motivation go hand-in-hand

A recent study conducted in the University of Jyväskylä suggests that resistance training improves exercise motivation and contributes to making exercise planning among older adults. Exercise motivation and exercise self-efficacy are key factors in continuing resistance training.

Resistance training can maintain and increase muscle strength and functional capacity when aging and it is recommended for older adults at least twice a week. However, only a few meet these recommendations. Sedentary lifestyle has unfavorable associations also with psychological functioning and mental health.

The study investigated the effects of a nine-month supervised resistance training intervention on exercise motivation, exercise planning and exercise self-efficacy. In addition, it was examined whether these factors predict the continuation of resistance training for the next year following the intervention. The study involved 104 healthy 65-75-year-olds who did not meet physical activity guidelines for endurance exercise at baseline and did not have previous resistance training experience.

– Nine months of regular resistance training increased the intrinsic motivation for both training and physical activity in general: the subjects started to enjoy exercising. Additionally, exercise planning increased, indicating that the subjects started to think about how to start and maintain a physically active lifestyle, says Tiia Kekäläinen, PhD student, from the University of Jyväskylä.

After completing the supervised resistance training intervention, nearly half of the participants (46%) continued resistance training independently. Approximately half of them participated in resistance training on average once-a-week during the following year and the other half twice-a-week. Participants who increased their intrinsic motivation for exercise and exercise self-efficacy during the intervention were more likely to continue resistance training twice-a-week.

– The results suggest that finding intrinsic motivation for exercise and increasing confidence to maintain a physically active lifestyle contribute to continuing resistance training independently. These factors should be taken into account in exercise interventions and exercise in general to promote continuance of behavior, Kekäläinen says.

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Materials provided by University of Jyväskylä. Note: Content may be edited for style and length.

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Journal Reference:

1. T. Kekäläinen, K. Kokko, T. Tammelin, S. Sipilä, S. Walker. Motivational characteristics and resistance training in older adults: A randomized controlled trial and 1-year follow-up. Scandinavian Journal of Medicine & Science in Sports, 2018; DOI: 10.1111/sms.13236

https://bit.ly/2vWairJ