Body

Medicaid expansion dramatically reduced the numbers of low-income residents without insurance in the Diabetes Belt, a swath of 644 counties across 15 southeastern states (including Virginia) that are stricken with high diabetes rates, a new study has found.

The increase in people with insurance helps address the lack of access to care that is a key contributor to the diabetes epidemic. Prior to the Affordable Care Act, the Diabetes Belt counties had higher uninsured rates than other areas, but that was erased by 2014 through Medicaid expansion.

"With increased access to care, patients are more likely to receive the care they need to prevent diabetes or at least slow the progression of the disease," said Jennifer M. Lobo, PhD, of the University of Virginia School of Medicine's Department of Public Health Sciences. "Addressing complications of diabetes as early as possible through regular preventive care can greatly improve quality of life."

Alarming Diabetes Rates

More than 11% of adults in the Diabetes Belt have the condition, compared with 8.5% elsewhere. The disease is believed to be a significant contributor to the shortened life expectancy seen in the Diabetes Belt.

To get a sense of the impact of Medicaid expansion both in and outside the Belt, the researchers looked at uninsured rates among adults age 64 or younger with household incomes equal to or less than 138% percent of the federal poverty line. In 2012, 39.3% of those in the Diabetes Belt were uninsured, compared with 33.9% outside the belt. Those numbers fell to 13.1% and 15.1%, respectively, in 2016.

By 2016, uninsured rates were 15% higher in states that had not expanded Medicaid, the researchers report. "States that expanded Medicaid achieved an absolute reduction of 20 percentage points in uninsured rates, while states that did not achieved 13% reduction," the researchers write in a new paper outlining their findings.

Broadening their scope to look at all income levels, the researchers found that Medicaid expansion led to a 4.8% overall reduction of the uninsured rate in the Diabetes Belt.

While additional research is needed to determine if Medicaid expansion led to improved care and outcomes, the researchers conclude: "Medicaid expansion has had its intended effect of increasing insurance coverage among the low-income populations." They note, "Eight states that contain Diabetes Belt counties are not expanding Medicaid at this time. Medicaid expansion may help realize more equity in insurance coverage between Belt and non-Belt areas in these states."

"We hope that our findings encourage policy makers to maintain and expand policies that increase health insurance coverage, particularly in areas like the Diabetes Belt which have a greater prevalence of the disease," Lobo said. "Whether increased insurance coverage is enough to narrow the gaps in diabetes prevalence between the Diabetes Belt and the rest of the country is yet to be seen, but one thing is clear: The Diabetes Belt is an area that needs more attention by policy makers."

Ann Arbor, February 4, 2020 - Dentists are among top prescribers of opioids in the US, however, whether their opioid prescribing exceeds guidance had not been investigated. A new study in the American Journal of Preventive Medicine, published by Elsevier, indicates that more than half of opioid prescriptions issued by dentists exceed the three-day supply recommended by the US Centers for Disease Control and Prevention (CDC) for acute dental pain management. The findings also show that 29 percent of dental patients received more powerful opioids than needed for expected post-procedure pain.

"Unlike national trends, opioid overprescribing by dentists is increasing. Our results should initiate a call to action to professional organizations and public health and advocacy groups to improve the guidelines for prescribing opioids for oral pain. As high prescribers of opioids writing prescriptions for a tenth of the opioids dispensed in the US, dentists should be included as part of the multi-faceted solution needed for the opioid epidemic," explained lead investigator Katie J. Suda, PharmD, MS, Professor, University of Pittsburgh School of Medicine, Division of General Internal Medicine, Pittsburgh, PA, USA.

The study used Truven Health MarketScan Research Databases to assess close to 550,000 dental visits by adult patients between 2011 and 2015, prior to the implementation of the 2016 CDC guidelines for pain management. These guidelines recommend first-line treatment using non-opioid analgesics for oral pain when possible. If stronger analgesics are needed after dental surgery, low-potency opioids (e.g., acetaminophen with codeine) are recommended instead of high-potency opioids (e.g., oxycodone). Moreover, three days or less of treatment is considered sufficient for typical oral pain. It is also a best practice for dentists to check their local prescription drug monitoring program (PDMP) before they write a prescription for any opioid to identify patients at risk of opioid abuse.

Investigators also found that the proportion of prescribed opioids that exceeded the recommended morphine equivalents increased in 2015. This was likely due to an increase in the quantity of hydrocodone tablets dispensed after the Food and Drug Administration's (FDA) rescheduling of hydrocodone from a schedule III to a schedule II drug in 2014. While hydrocodone rescheduling was associated with a decrease in hydrocodone prescribing nationally, this study's results suggest that this change resulted in an average increase of two tablets dispensed per hydrocodone prescription prescribed by dentists. Nationally, this increase translates to more than14 million additional hydrocodone tablets dispensed to patients after rescheduling hydrocodone to a schedule II drug.

"Similar to medical providers, dentists need to be provided resources to aid in their prescribing decisions for pain medications," commented Dr. Suda. "This should include clinical guidelines specific to oral pain and education on how to talk to their patients about treating their oral pain."

Co-investigator Susan A. Rowan, DDS, College of Dentistry, University of Illinois at Chicago, Chicago, IL, USA, emphasized that the demographic groups most impacted by overprescribing (patients aged 18 to 34 years, men, those living in the Southern US, and those receiving oxycodone) also carry a higher risk of addiction and overdose. She suggested that "additional studies are needed to evaluate the efficacy of the CDC 2016 prescribing guidelines subsequent to their introduction."

"Future studies and targeted efforts to reduce overprescribing would also be well motivated among older patients and others taking multiple other high risk medications such as benzodiazepines," added Gregory S. Calip, PharmD, MPH, PhD, College of, Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.

Dr. Suda and co-investigators invite professional organizations and public health and advocacy groups to use the study's data to inform future efforts. In the interim, they recommend that individual dentists implement their own practice-specific guidelines, favoring ibuprofen plus acetaminophen and low-potency opioids for post-extraction pain management.

Using statistical modeling, investigators predict that overprescribing would decrease by more than 20 percent if oxycodone prescriptions were substituted with lower potency opioids (such as hydrocodone).

Researchers at the University of Turku, Turku University Central Hospital, and Western Cancer Center (FICAN West) have discovered a new RNA molecule, PRECSIT, which regulates the growth and invasion of squamous cell carcinoma of the skin. In the future, PRECSIT could potentially serve as a new marker for the detection of rapidly advancing or spreading squamous cell carcinoma and as a target for new therapies.

Skin cancers are the most common cancers in the world and their incidence is increasing. Squamous cell carcinoma is the most common metastatic skin cancer and its incidence is increasing worldwide. Long-term exposure to the sun's ultraviolet radiation is the most important risk factor for the development of this type of cancer.

- Squamous cell carcinoma of the skin is characterized by a significant gene mutation burden of cancer cells resulting from long-term exposure to the sun's ultraviolet radiation. Several gene mutations predisposing to skin cancer are known, but the importance of non-coding RNA molecules of the so-called dark side of the genome in the development of squamous cell carcinoma is still unclear, says Professor Veli-Matti Kähäri from the Department of Dermatology at the University of Turku.

- The majority of the human genome contains genes that do not produce protein, but their role as regulators of cellular functions is still essential. Long non-coding RNAs are a largely unknown set of RNAs and recent studies have found that they play a role in regulating signaling pathways, particularly in cancer, says researcher Minna Piipponen, one of the authors of the study.

Thus, RNA molecules could be utilized in cancer diagnostics as specific marker molecules and as targets for new therapies.

PRECSIT regulates the growth and spread of squamous cell carcinoma

The study found that expression of a new long non-coding RNA in cancer cells of squamous cell carcinoma was elevated compared to healthy skin. The study also showed that expression of PRECSIT is regulated by the tumor suppressor gene p53, which is inactivated by mutations in most squamous cell carcinomas. The researchers also discovered that PRECSIT promotes the invasion of cancer cells by increasing the production of extracellular matrix cleaving proteolytic enzymes via the STAT3 signaling pathway.

Based on its expression and mechanism of action, this long non-coding RNA was named PRECSIT (p53 regulated carcinoma-associated STAT3-activating long intergenic non-protein coding transcript).

- Long non-coding RNAs are currently a hot topic in cancer research worldwide as they could potentially be used as new biomarkers and specific therapeutic targets in different cancers. PRECSIT provides new insight into the role of long non-coding RNA molecules in the progression of squamous cell carcinoma, Piipponen concludes.

Some diseases are like black swans. They occur so rarely that many physicians never encounter them in their clinical practice, complicating efforts to treat them.

How many rare diseases are there? According to a new study co-led by University of New Mexico data scientist Tudor Oprea, MD, PhD, no one really knows - and that's a problem, because it's likely that many rare disease patients do not receive appropriate medical care.

In a commentary published in Nature Reviews Drug Discovery, a high-impact research journal, Oprea and colleagues from the U.S., Australia, France and Germany point out that as much as 10 percent of the world's population suffers from a rare disease, which translates into hundreds of millions of people.

"You have thousands and thousands of papers a year related to rare diseases, yet very few translate into cures," says Oprea, professor and chief of the Translational Informatics Division in UNM's Department of Internal Medicine.

A big part of the problem has to do with definitions, the authors argue, because the inability to reliably diagnose a rare disease hinders researchers' ability to develop treatments for it.

In the U.S., the Orphan Drug Act of 1983 defines a rare disease as one affecting fewer than 200,000 people. In the European Union, legislation introduced in 2000 defines it differently: when fewer than one in 2,000 people is affected.

And, the authors point out, a disease that is considered "rare" in the general population might be relatively common within a subgroup - examples include Tay-Sachs disease among Ashkenazi Jews and sickle cell disease among people of sub-Saharan African descent.

Another complicating factor is that the terms used to define diseases are often inconsistent and imprecise, and they sometimes vary from country to country. For example, "breast cancer" actually encompasses a variety of tumor sub-types with unique genetic signatures and different optimal treatments, Oprea says. Should it be classified as one disease or many?

Estimates of the number of rare diseases usually settle in the range of 7,000, the authors report. But their recent analysis of an international disease classification database known as the Monarch Disease Ontology - or Mondo - suggests it could be as much as 50 percent higher.

"The Mondo project is the first computer-assisted human curation process to bring together separate efforts in the rare disease community in order to catalog and annotate all rare diseases, regardless of country or disease type," Oprea says.

Improving care for patients with rare diseases requires reaching consensus on the physical, genetic and environmental characteristics of each condition, but overlapping terminologies and models makes that difficult. The authors are calling upon the World Health Organization, the U.S. Food and Drug Administration, the European Medicines Agency, the National Academy of Medicine and other entities, to adopt a unified definition of rare diseases.

"We encourage the community to get together and come up with more precise rare disease definitions," Oprea says. "There needs to be a forum to discuss this and dedicated funding mechanisms to address it."

Many people experience peace of mind from getting their children vaccinated, according to new research from the University of Bristol. However, this benefit is currently being ignored when health bodies weigh up vaccine benefits to make decisions about whether or not to introduce vaccines or expand their coverage.

The qualitative study, published in Vaccine, found that peace of mind should be considered in the health economic framework used by decision makers, but that more research is required to further define and quantify peace of mind.

Many different factors are considered by the Joint Committee on Vaccination and Immunisation (JCVI), who advise UK government on vaccines, but peace of mind is not currently one of them.

Researchers found that whether a person experienced peace of mind from vaccination depended on their knowledge of the benefits of having a jab. The reassurance they experienced was from knowing that when an individual was vaccinated it would offer some level of protection against a disease.

While peace of mind from vaccinating their children was important to some participants of the study, it wasn't for others. Parents who benefitted tended to think that vaccination was intrinsically beneficial, but people who simply considered vaccination as a routine health intervention said that they did not receive peace of mind benefits.

Even though these peace of mind benefits are only experienced by some parents, the added value to their health could still influence decisions on whether or not a government should fund a vaccine. The research suggests decision makers need to consider these benefits.

The researchers also found that peace of mind varies over time. Reassurance from the knowledge of benefits, or from healthcare providers, could be diminished by short-term unease about believing a child could be in pain or distress when receiving a jab. Certain vaccines brought less peace of mind if an individual either hadn't experienced the disease or if they had experienced of a mild form of the disease as a child but without complications.

Discussion from one focus group reported the longer a vaccine had been introduced, the more safe it felt to them. Participants were more cautious about vaccinations that they considered to be 'newer' or vaccinations that they had little personal experience with. There were exceptions to this for severe illnesses such as meningitis. The MenB vaccine, although considered relatively 'new' by some participants, provided increased reassurance because of the perceived severity of the disease.

Dr Gemma Lasseter, lead author, Research Fellow and Programme Manager at the National Institute for Health Research Health Protection Research Unit in Evaluation of Interventions at the University of Bristol, said: "Our research, funded by the Meningitis Research Foundation, shows that vaccine associated peace of mind was important to some members of the UK general public when making vaccination decisions for themselves or their children. This peace of mind varied in magnitude, duration and over time. These findings are important because they indicate that the current economic approach used to make funding decisions about healthcare interventions in the UK may need to be refined to take peace of mind into consideration in the future."

Dr Hannah Christensen, co-author and Senior Lecturer at the University of Bristol, said: "When policy makers decide which health interventions are made available free at the point of use in the NHS they consider the benefits and costs, to assess whether the intervention provides value for money. This research shows us there is a benefit, in terms of peace of mind after vaccination, that could contribute to these policy decisions. Given the benefit appeared quite variable between people, and was influenced by a person's attitudes and beliefs about vaccinations, the challenge now is to work out how we can appropriately capture the 'value' of this peace of mind benefit so that it can contribute meaningfully to the vaccine decision-making process."

Vinny Smith, Chief Executive at Meningitis Research Foundation, the charity that funded the research, said: "This study now highlights that current government vaccine decisions miss some important benefits of immunisation. When considering the introduction of new vaccines, we want the government to take into account important health benefits, such as the reassurance that comes from knowing that your child is protected from death and disability."

"Parents know how dangerous and concerning meningitis is, and consistently rate it as a more serious illness than other preventable diseases. When the MenB vaccine was first introduced in September 2015 it was provided to young babies, but older children were not eligible for the vaccine on the analysis at the time of cost against benefits. Subsequently, the tragic death of a two year old from MenB in 2016, led to a surge in demand for the vaccine and an online petition calling for wider access. We have been calling for government to address the unfairness of the vaccine rules, which, if addressed, may have made the vaccine accessible to all children under the age of five."

"This study also gives us an insight into beliefs about vaccines can change. More time for conversations between healthcare professionals and parents could help address incorrect beliefs about vaccines and increase knowledge of the benefits."

Plants have been harnessing the sun’s energy for hundreds of millions of years.

Algae and photosynthetic bacteria have been doing the same for even longer, all with remarkable efficiency and resiliency.

It’s no wonder, then, that scientists have long sought to understand exactly how they do this, hoping to use this knowledge to improve human-made devices such as solar panels and sensors.

“We have a tremendous opportunity here to open up completely new disciplines of light-driven biochemical reactions, ones that haven’t been envisioned by nature. If we can do that, that’s huge.” — Argonne biophysicist Philip Laible

Scientists from the U.S. Department of Energy’s (DOE) Argonne National Laboratory, working closely with collaborators at Washington University in St. Louis, recently solved a critical part of this age-old mystery, homing in on the initial, ultrafast events through which photosynthetic proteins capture light and use it to initiate a series of electron transfer reactions.

“In order to understand how biology fuels all of its engrained activities, you must understand electron transfer,” said Argonne biophysicist Philip Laible. “The movement of electrons is crucial: it’s how work is accomplished inside a cell.”

In photosynthetic organisms, these processes begin with the absorption of a photon of light by pigments localized in proteins.

Each photon propels an electron across a membrane located inside specialized compartments within the cell.

“The separation of charge across a membrane — and stabilization of it — is critical as it generates energy that fuels cell growth,” said Argonne biochemist Deborah Hanson.

The Argonne and Washington University research team has gained valuable insight on the initial steps in this process: the electron’s journey.

Nearly 35 years ago, when the first structure of these types of complexes was unveiled, scientists were surprised to discover that after the absorption of light, the electron transfer processes faced a dilemma: there are two possible pathways for the electron to travel.

In nature, plants, algae and photosynthetic bacteria use just one of them — and scientists had no idea why.

What they did know was that the propulsion of the electron across the membrane — effectively harvesting the energy of the photon — required multiple steps.

Argonne and Washington University scientists have managed to interfere with each one of them to change the electron’s trajectory.

“We’ve been on this trail for more than three decades, and it is a great accomplishment that opens up many opportunities,” said Dewey Holten, a chemist at Washington University.

The scientists’ recent article, "Switching sides—Reengineered primary charge separation in the bacterial photosynthetic reaction center," published in the Proceedings of the National Academy of Sciences, shows how they discovered an engineered version of this protein complex that switched the utilization of the pathways, enabling the one that was inactive while disabling the other.

“It is remarkable that we have managed to switch the direction of initial electron transfer,” said Christine Kirmaier, Washington University chemist and project leader. “In nature, the electron chose one path 100 percent of the time. But through our efforts, we have been able to make the electron switch to an alternate path 90 percent of the time. These discoveries pose exciting questions for future research.”

As a result of their efforts, the scientists are now closer than ever to being able to design electron transfer systems in which they can send an electron down a pathway of their choosing.

“This is important because we are gaining the ability to harness the flow of energy to understand design principles that will lead to new applications of abiotic systems,” Laible said. “This would allow us to greatly improve the efficiency of many solar-powered devices, potentially making them far smaller. We have a tremendous opportunity here to open up completely new disciplines of light-driven biochemical reactions, ones that haven’t been envisioned by nature. If we can do that, that’s huge.”

The first ever treatment for preventing a group of viruses from causing potentially lethal infections has been tested in a phase I clinical trial, and was found to be safe and able to neutralise the viruses, according to results from 40 patients published in The Lancet Infectious Diseases journal. The trial was conducted in healthy participants and further trials will be needed to demonstrate its efficacy in infected patients.

Hendra virus and Nipah virus are two closely related RNA henipaviruses that emerged in 1994 and 1998 respectively. Flying foxes, a type of fruit bat, appear to be the major natural reservoir hosts for henipaviruses. A mortality rate of 57% has been observed from seven known cases of Hendra virus in Australia, while 373 fatalities from Nipah virus have been reported in south and southeast Asia between 1998 and 2018.

Although the number of outbreaks has been small so far, Henipavirus diseases have been placed on the WHO list of diseases with epidemic potential that are a priority for research because there are no, or insufficient, countermeasures. Nipah virus has the potential to mutate rapidly, and human-to-human transmission is possible, raising concerns of pandemic potential.

"Given the high death rate from infection by henipaviruses, their ability to cause infection in multiple organs including the brain, and their unique ability to spread to humans from bats via a wide range of animal species including horses and dogs, doctors need a safe way to neutralise them," says Dr Elliott Geoffrey Playford from Princess Alexandra Hospital, Australia. "Our results are the first to confirm that administering an antibody that binds to the virus is safe, making it the most promising therapeutic option to date for addressing this unmet medical need." [1]

The monoclonal antibody m102.4 has successfully neutralised henipaviruses in previous experiments with non-human primates. It binds to proteins on the surface of virus cells that would normally allow the virus to gain access to host cells and cause infection. The antibody has been available since 2010 for compassionate emergency use in Australia for people exposed to Hendra virus, but the current study is the world's first clinical trial to assess its safety in humans and to determine its fate as it travels through the body. Laboratory experiments were also used to test the ability of the antibody to neutralise the viruses after it had been circulating in the body.

The study was randomised, double blinded and placebo-controlled. Forty eligible adults aged 18 to 50 were randomly assigned to five different groups: four groups receiving the antibody in single doses that escalated from 1mg/kg in the first group to 20mg/kg for the fourth group, and the fifth group receiving two doses of 20mg/kg. In each group, six participants received the antibody and two received a saline placebo.

The safety and tolerability of m102.4 was assessed using a combination of tests including physical examinations, clinical laboratory tests, electrocardiogram (ECG), and records of adverse events. Blood samples were taken from volunteers to test for any immune reactions and for the ability of the body to eliminate the antibody. The samples were also used to test the circulating antibody's ability to neutralise the viruses 12 hours, 24 hours, four days, and eight days after injection.

Overall, the doses of m102.4 used in the study were found to be safe and well tolerated. The researchers recorded no serious adverse events related to treatment. The most common treatment-related adverse events were headaches, which were reported by 12 out of 30 volunteers in those receiving the antibody and three out of 10 volunteers who received the placebo. Volunteers who received the double dose did not report an increase in headaches.

In tests on the blood samples, the body's ability to eliminate the antibody was found to be similar between participants receiving the single or repeated dose. At no time point during the study did the antibody generate an immune reaction against the antibody itself. Tests on the circulating antibody's ability to neutralise the viruses found neutralisation activity against both Hendra and Nipah viruses in all samples and at all the time points tested. The authors conclude that the antibody remained active for at least eight days after intravenous injection.

"When there's a possible case of henipavirus infection, or people suspect they might have been exposed to one of the viruses, there often isn't time to confirm a diagnosis before it could be become too late to do anything about it," says Dr Heidi Carroll from Queensland Health, Australia. "Based on the results of our trial, we suggest offering a single dose of 20mg/kg of m102.4 to people likely to have been exposed to one of the viruses, or two doses separated by 48 hours to patients with clinical signs of infection." [1]

The authors note that the main limitation of the study is the small number of participants, which is common in phase I studies. They also note that at the moment there is no evidence of viral mutants able to escape m102.4, and that escape is unlikely, but the potential for this with RNA viruses cannot be ruled out. Future studies will be needed to demonstrate the efficacy of the antibody against different strains of Nipah and Hendra viruses and it might be necessary to consider a cocktail of monoclonal antibodies to reduce the chances of m102.4 decreasing in efficacy.

Writing in a linked Comment, Dr Hossain Sazzad from the University of New South Wales, Australia, says: "The safety profile of both single and repeated dosing of m102.4 and the standard pharmacokinetic profile presented by Playford and colleagues make m102.4 a potential candidate for post-exposure prophylaxis against henipavirus infection. m102.4 prophylaxis will be crucial for accidental laboratory exposure or healthcare workers working in a high-risk setting. However, in real-world outbreak settings, such as Bangladesh, the situation might be different." He continues: "Further evaluation of efficacy of m102.4 in established clinical infection-- which was beyond the scope of the small-scale phase 1 trial done by Playford and colleagues--will be crucial."

Army scientists working with partners from industry and academia have developed an experimental treatment that protects animals from Sudan virus, which is closely related to Ebola. Their work is published online today in the journal Proceedings of the National Academy of Sciences.

There are six distinct species of ebolaviruses, which collectively pose a significant threat to the global community, particularly in areas of equatorial and West Africa. While Ebola virus was the causative agent of the 2013-2016 outbreak that developed into the largest epidemic in recorded history, Sudan virus also presents a significant health threat, according to the authors.

One promising approach to treating ebolavirus infection involves the development of immunotherapies--drugs that boost the body's own immune system to fight infection. Scientists can design proteins, called antibodies, and combine them into "cocktails" to treat a particular type of infectious disease. Until now, however, there has been no such cocktail specific for Sudan virus.

Led by John M. Dye, Ph.D. of the U.S. Army Medical Research Institute of Infectious Diseases, the team produced a panel of monoclonal antibodies that are specifically designed to attach to the Sudan virus glycoprotein and block the virus from entering cells. They tested them in cell culture, and further evaluated the most promising candidates in a mouse model of Sudan virus infection.

Based on the results of the rodent testing, the team then selected a mixture of two Sudan-specific monoclonal antibodies for assessment in rhesus macaques. This mixture, called RIID F6-H2, provided protection from Sudan virus in rhesus macaques when administered on days 4 and 6 post-infection.

"We are excited to offer a potential treatment option against one of the most deadly human pathogens known," said Dye. "Being prepared by having countermeasures against emerging infectious diseases allows the global community to try to stay one step ahead, rather than play 'catch-up' against potential pandemic viruses."

According to COL E. Darrin Cox, commander of USAMRIID, the work highlights the impact of USAMRIID research on warfighter health and public health.

"In addition, the sheer number of collaborators is a testament to the importance of government, academic and commercial laboratories working together to advance medical countermeasure development," said Cox.

Co-investigators on the study included Albert Einstein College of Medicine, Mapp Biopharmaceutical, Inc., Fraunhofer, BioFactura, and The Geneva Foundation.

"Our team is extremely proud that this cocktail of antibodies is now being considered for advancement into phase 1 clinical studies," said Dr. Andrew Herbert of USAMRIID, the paper's first author. "We have the opportunity to make a real impact on global health."

PHILADELPHIA - Uveal melanoma - a cancer found in the eye - is rare, comprising less than 5% of all melanomas. Despite successful treatment of the primary tumor in the eye, up to 50% of patients will develop systemic spread (metastasis), most commonly in the liver. A recent study from Massachusetts Eye and Ear Infirmary reported that prognosis of uveal melanoma patients with metastasis is very poor with a median survival of 3.9 months after diagnosis. They also suggested there has been no improvement in care over decades of treatment of metastatic disease. In contrast, new research from The Sidney Kimmel Cancer Center (SKCC) - Jefferson Health investigating uveal melanoma patients with liver metastasis treated at Jefferson showed that outcomes of these patients significantly improved with changes in treatment.

Currently, there is no FDA-approved treatment for metastatic uveal melanoma. Systemic chemotherapy rarely induces a response in patients with metastatic disease. Likewise, while developments in new immunotherapy have improved outcomes of metastatic skin melanoma, a similar benefit has not been seen in metastatic uveal melanoma. In response, physician researchers at Jefferson have been experimenting with treatments directed to the liver. Rather than exposing the entire body to the treatment, localized therapy targeting one organ, the liver, allows the delivery of higher doses of medication to tumors. Furthermore, cutting blood supply to the liver metastasis after delivering the medications by the technique called "embolization" gives additional damage to the tumors.

"We recognized the poor prognosis associated with liver metastasis and we shifted from systemic chemotherapies to the use of various liver-directed treatments,' says Takami Sato, MD, PhD, Director of the Metastatic Uveal Melanoma Program at SKCC. "We wanted to analyze patient outcomes before and after this shift." The study was published in Cancers on Jan 1st, 2020.

The researchers performed a retrospective review on uveal melanoma patients with liver metastasis who were treated at Thomas Jefferson University Hospital during three time periods over five decades: 1971-1993 (Cohort 1), 1998-2007 (Cohort 2), and 2008-2017 (Cohort 3). 70% of patients in Cohort 1 received only systemic chemotherapy, while 98% of patients in Cohort 2 and 3 received liver-directed treatments either alone or in combination with systemic therapy. The study found that overall survival was shortest in Cohort 1 (5.3 months), longer in Cohort 2 (13.6 months) and longest in the more recent Cohort 3 (17.8 months). The researchers suggest that the shift of treatment modalities from systemic chemotherapy (Cohort 1) to liver-directed treatments (Cohorts 2 and 3) improved the survivals of uveal melanoma patients with liver metastasis.

"Approximately 650 liver-directed treatments annually have been given to metastatic uveal melanoma patients at Thomas Jefferson University Hospital", says David Eschelman, MD, Co-Director of Interventional Radiology at Jefferson and co-author of the study.

The researchers also suggest potential benefits of combining liver-directed therapies with newly emerging systemic therapies.

"We believe that our study is one of the largest studies showing extended survival in uveal melanoma patients with liver metastasis," says Dr. Sato. "We are also hoping that the addition of newly developed systemic therapies, especially immunotherapy, to liver-directed treatments will further increase the survival of patients with this devastating disease."

BIRMINGHAM, Ala. - People with chronic kidney disease have a higher risk for heart disease and heart-disease death. Now, for the first time in humans, research led by Navkaranbir Bajaj, M.D., of the University of Alabama at Birmingham, has identified a pathological change that appears to link kidney disease to progressive heart disease.

This offers a potential treatment target, which could have wide benefit because 14 percent of the U.S. adult population has chronic kidney disease. The research is published in the journal Circulation, with Bajaj -- a UAB assistant professor in the Division of Cardiovascular Disease, Department of Medicine and Department of Radiology -- as first author.

"I am now collaborating with other UAB researchers to figure out how we can target therapeutics to help these patients," Bajaj said.

The pathological change identified is coronary microvascular dysfunction, or CMD, say Bajaj and research colleagues at Harvard Medical School. CMD is decreased blood flow in the small blood vessels inside the heart muscle that provide oxygen and fuel to feed the pumping heart.

In healthy hearts, visualized postmortem, these blood vessels look like a tight filigree network that fills the heart muscle tissue. A diseased postmortem heart has lost much of this network. In living patients, however, those small blood vessels inside the heart muscle cannot be visualized; blood flow scans of living patients visualize only the larger, exterior coronary arteries. So Bajaj and colleagues needed an indirect way to gauge CMD.

That measure is coronary flow reserve, or CFR, which Bajaj and colleagues measured via positron emission tomography. CFR is the maximum increase in blood flow through the coronary arteries above the normal resting volume. Bajaj, a cardiologist who trained at UAB, did his advanced imaging fellowship at Brigham and Women's Hospital in Boston, before returning to UAB in 2018.

In a longitudinal study of 352 patients with chronic kidney disease, all with healthy heart function as measured by ejection fraction and none with signs of overt coronary artery disease, the researchers measured CFR and also measured signs of subclinical heart dysfunction via deformation analysis with echocardiograms. The patients were then followed a median of 4.4 years for major adverse cardiac events. A total of 108 patients had such major events, including death and hospitalization for non-fatal heart attack or heart failure.

The researchers found that CMD was a significant predictor of abnormal mechanics of the left ventricle -- the heart's major pumping chamber -- and a significant predictor of clinical risk of adverse cardiovascular outcomes.

A statistical model called mediation analysis examined the relationship between impaired kidney function and heart disease. It showed that CMD accounted for 19 to 24 percent of left ventricle diastolic dysfunction, 19 to 42 percent of left ventricle systolic dysfunction and 32 percent of major adverse cardiovascular events.

These significant associations "provide important new evidence that the development of severe microvascular dysfunction likely signals the transition from physiological to pathological left ventricle remodeling that increases the risk of heart failure and death in patients with chronic kidney disease," the study said. "To the best of our knowledge, our study is the first and largest to comprehensively explore these associations and to suggest a possible pathway to the development of uremic cardiomyopathy in individuals without overt ischemic heart disease."

New Rochelle, NY, February 3, 2020--A new study shows that women have many medical questions about the use of cannabis both before and during pregnancy, and during the postpartum period while breastfeeding. While more than half of licensed U.S. healthcare providers responded by saying that perinatal cannabis use was harmful, and nearly half discouraged perinatal cannabis use, many providers missed the opportunity to educate on safety or discourage cannabis use during pregnancy and breastfeeding. These findings are published in Journal of Women's Health, a peer-reviewed publication from Mary Ann Liebert, Inc., publishers. Click here to read the full-text article on the Journal of Women's Health website through March 3, 2020.

The article entitled "Women's Questions about Perinatal Cannabis Use and Healthcare Providers' Responses" was coauthored by Kelly Young-Wolff, PhD, MPH, Kaiser Permanente Northern California (Oakland) and colleagues from Stanford University and HealthTap. HealthTap is an open online platform in which anyone, anywhere can ask a free question. HealthTap's healthcare providers are licensed in the U.S.

The researchers categorized the women's questions about cannabis use into themes that spanned the time period of preconception, prenatal, and postpartum. The most prevalent questions were those concerning detection of cannabis in pregnant women or at delivery, effects on the ability to conceive, potential harms of a mother's prenatal use to the fetus, and risks of baby exposure and health effects via breastmilk. The provider responses regarding the safety of perinatal cannabis were denoted as 55.6% harmful, 8.8% safe, 8.8% mixed/unsure, and 26.8% not addressed.

Susan G. Kornstein, MD, Editor-in-Chief of Journal of Women's Health and Executive Director of the Virginia Commonwealth University Institute for Women's Health, Richmond, VA, states: "While nearly half (49.6%) of the providers discouraged perinatal cannabis use, 49.9% neither encouraged nor discouraged its use. This represents a missed opportunity to counsel women on the potentially harmful effects of cannabis use during conception, fetal growth and development, and breastfeeding."

A review of recent clinical trials paints a sobering picture of the usefulness of first-line psychotherapies in treating active duty military personnel and veterans with Post-Traumatic Stress Disorder (PTSD).

Led by researchers at NYU Grossman School of Medicine and recently published in the Journal of the American Medical Association (JAMA) Insights, the article summarizes findings of recently conducted clinical trials of two well-established, first-line cognitive-behavioral psychotherapies - Prolonged Exposure Therapy (PE) and Cognitive Processing Therapy (CPT) -- to treat PTSD.

The researchers conclude that clinical trials of these treatment modalities show limited effectiveness for treating PTSD in active duty military personnel and veterans.

The review also reports that for military service related PTSD, more emotionally demanding therapies like PE and CPT, which repeatedly activate and process memories of traumatic experiences, were not more beneficial than interventions which do not require patients to focus on their traumatic events, including present-centered therapy (a supportive, problem-solving treatment), transcendental meditation and biological treatments such as anti-depressants.

"Cognitive behavioral therapy's limited value for treating military service related PTSD suggests the need to go beyond the one-size-fits-all approaches rolled out in most VA and DoD healthcare settings and personalize treatment, accounting for pre-service vulnerabilities and complex, repeated exposures to warzone stressors," says senior author Charles R. Marmar, MD, the Lucius Littauer Professor and Chair of Psychiatry at NYU Grossman School of Medicine.

Lead author Maria M. Steenkamp, PhD, clinical assistant professor of Psychiatry at NYU Grossman School of Medicine, also points out that more attention should focus on managing non-response to treatment. "Research in this field needs to shift from confirmatory trials to studies that explore more flexible, multifaceted and long-term treatments, including biological therapies," she says.

This retrospective review comes just months following the publication of a seminal study - led by researchers at Stanford University and published in April 2019 in Science Translational Medicine -- of civilians with PTSD and why a sub-group did not respond to prolonged exposure therapy. The Stanford study, using functional brain imaging, found that civilian PTSD patients with altered neural circuit activity in the ventral attention network (VAN) in the brain had poor outcomes to prolonged exposure therapy. Whether this pattern of brain circuit abnormality is over-represented in those suffering from military service related PTSD remains to be studied.

"In the meantime, current clinical trials strongly suggest that treating military-related PTSD involves significant clinical complexity and heterogeneity. For many who have served in the military, a course of standardized, trauma-focused cognitive behavioral therapy for PTSD is emotionally demanding and likely to result in only modest clinical improvement," Marmar concludes.

Homicide is a leading cause of death among pregnant and postpartum women in Louisiana, according to an analysis of birth and death records from 2016 and 2017. The study, appearing as a research letter in JAMA Pediatrics, was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health. The research team was led by Maeve E. Wallace, Ph.D., of Tulane University School of Public Health and Tropical Medicine in New Orleans.

The authors wrote that they undertook their analysis because few studies have looked at non-obstetric causes of death during pregnancy and the year after birth. They analyzed maternal death data from the Louisiana Department of Health and homicide data for women and girls of reproductive age from a U.S. Centers for Disease Control and Prevention database.

Of the 119 pregnancy-associated deaths for 2016 and 2017 in the state, 13.4% (16) were homicides. They estimated that, for every 100,000 women who were pregnant or postpartum, there were 12.9 homicide deaths, which outnumbered deaths from any single obstetric cause, including hypertensive disorders (3.2) and amniotic fluid entering the bloodstream (4.8). The risk of homicide death was twice as high for women and girls during pregnancy and the postpartum period, compared to women and girls who were not pregnant. Pregnancy and postpartum deaths were highest for women and girls ages 10 to 29.

The authors said that women's increased contact with the health care system during pregnancy provides clinicians with an opportunity to offer violence prevention services and interventions. They do not know whether the high maternal homicide rate they found--among the highest reported, compared to other jurisdictions--is a function of better reporting or reflects an actual spike of maternal homicides in Louisiana.

Pregnant women diagnosed with diabetes who have elevated fasting (pre-meal) blood sugar levels are more likely to face complications than those who have only elevated post-meal glucose levels, according to a new study by a University of Alberta research team.

"The women who had elevated fasting glucose, adjusted for all other risk factors, were almost three times more likely to have a big baby than women who had normal fasting glucose levels but elevated postprandial sugar levels," said cardiology professor Padma Kaul, who is also an adjunct professor in the School of Public Health.

The women with high fasting blood sugars were also found to be at 1.5 times higher risk for high blood pressure during pregnancy, and had a higher likelihood of needing an induced labour, having a caesarean section or having a preterm birth.

Kaul said large babies are at risk for complications during birth and obesity later in life, and high blood pressure during pregnancy can place extra stress on the heart and kidneys of a mother.

The researchers found that the adverse outcomes for women with high fasting blood sugars persisted even when the women were given diabetes drug treatments such as insulin or metformin.

"Why the women who have fasting glucose are less responsive to treatment is a very important question," Kaul said. "It may indicate some other mechanism that requires further study."

Kaul said further research is needed to determine whether earlier or more aggressive diabetes treatment for women with high fasting glucose levels would reduce or prevent the adverse outcomes.

The researchers examined health records for more than 250,000 pregnancies in Alberta between 2008 and 2014. Nearly 13,000 of the mothers were diagnosed with gestational diabetes. Four thousand had elevated fasting blood sugars of 5.3 mmol/L or higher, whereas the others had normal blood sugars while fasting but showed elevated levels following an oral glucose tolerance test.

Kaul explained that nearly all pregnant women in Alberta undergo a two-step screening process for gestational diabetes. The first test, done between 20 and 24 weeks of gestation, is a 50 gram oral glucose tolerance test, taken at any time of the day. If the woman's blood sugar is found to be higher than 7.8 mmol/L one hour later, she is sent for the second test, which involves giving a blood sample after 12 hours of fasting, usually first thing in the morning, then ingesting 75 grams of glucose and giving more samples one and two hours later.

Kaul said that about 15 per cent of pregnant women in Alberta receive the second test and about one-third of those tested are diagnosed with gestational diabetes. As trends in older maternal age and higher weight in pregnancy continue, rates of gestational diabetes are also on the rise.

SPOKANE, Wash. -- English proficiency shouldn't be a barrier to health care. That's why the federal government requires hospitals to make translated documents and interpreters available to patients.

But a patient who needs language services would have to navigate through one to four web pages in English to find information on such services at most hospitals in Washington, according to a new study led by Associate Professor Janessa Graves of the Washington State University College of Nursing. The research was published recently in the Journal of Immigrant and Minority Health.

The study examined the website of each of Washington's 93 licensed hospitals.

Graves said her team decided to focus on websites because many patients consult them for information ranging from what to expect during a medical procedure to the availability of financial assistance. Patients also might look at a hospital website to learn about language translation services in preparation for an appointment.

Only 20% of the hospital websites listed language services on their homepage, and in many cases that information was listed in English.

"The hospitals are telling people, 'Yes, we'll translate for you,' but they're telling people that in English, which seems counterintuitive," said Graves, who's also associate dean of undergraduate and community research.

Research has shown that patients who aren't fluent in English receive poorer quality of care, have lower comprehension of health care encounters and are less likely to follow provider recommendations, which can contribute to health disparities. 

Hospitals and other organizations that receive federal funds are required to provide meaningful access to their programs and services for patients whose primary language is not English.

About 7.6% of Washington residents over age 5 speak English less than "very well," a status referred to as having limited English proficiency (LEP). Nationally, the number of people in that category more than doubled from 1980 to 2015. In Washington, the most common languages spoken at home other than English are Spanish, Chinese, Russian, Tagalog, Korean and Vietnamese.

Despite federal requirements to provide language services, such as in-person or telephone interpreters and translated websites, "few details are known about the actual language assistance services provided to patients with LEP" by hospitals, the study noted.

Just 10 hospitals provided a translated version of their website, with the most common languages being Spanish, Japanese, Korean and Russian. No hospital offered translation into Chinese "despite it being a commonly spoken language in the state," the study said.

Large hospitals and those with higher revenue included language service information on their websites more often than smaller hospitals did, the study found. However, there was no significant association between the size of a county's LEP population and whether a hospital included those services on its website.

Graves said the study is a snapshot in time, with researchers evaluating websites in February 2018. The study didn't look at what kinds of services are available at the hospitals, just whether those services are listed on the website. That will be the topic of a subsequent study, she said.

"We can't advocate to improve services if we don't know what's there currently," she said. "This paper is a call to action to ask hospitals to keep up-to-date websites."

Besides Graves, other investigators on the study, titled "Too Little Information: Accessibility of Information about Language Services on Hospital Websites," were Megan Moore, Carmen Gonzalez, Joana Ramos, Lilian Nguyen and Monica S. Vavilala. Nguyen was a WSU College of Nursing undergraduate student at the time the research was conducted.

The study was carried out through a collaboration with the Language Access Research for Community Health (LARCH), whose members include universities and community advocates. Funding was provided in part by a grant from the Health Equity Research Center, a strategic research initiative of Washington State University.