New assay may lead to a cure for debilitating inflammatory joint disease

Current treatments for rheumatoid arthritis relieve the inflammation that leads to joint destruction, but the immunologic defect that triggers the inflammation persists to cause relapses. Known as autoantibodies and produced by the immune system’s B cells, these defective molecules mistakenly attack the body’s own proteins in an example of autoimmune disease.
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Sleeping for 9+ Hours May Be Early Sign of Dementia

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  • Note that this observational study found that self-reported longer sleep duration (when duration increased over a 13-year timeframe) was associated with dementia.
  • The authors suggest that prolonged sleep duration may be a sign of neurodegeneration, rather than that long sleep duration is injurious to the brain.

Sleeping for extended amounts of time may be an early indicator of cognitive decline in older people, especially among those with lower education levels, researchers report.

Elderly participants who consistently slept more than 9 hours a night had double the dementia risk over a decade of follow-up in an analysis of data from the Framingham Heart Study.

Longer sleepers also had smaller brain volumes in the study of close to 2,500 older men and women, now online in Neurology.

Study participants without high school degrees who slept more than 9 hours a night had six times the risk of developing dementia over the decade-long follow-up, compared with participants who slept less than 9 hours a night.

The findings suggest that longer sleep duration may be a marker of early neurodegeneration, wrote Sudha Seshadri, MD, of the Boston University School of Medicine Alzheimer’s Disease Center, and colleagues.

Another co-author, Matthew Pase, PhD, also of Boston University, told MedPage Today that several previously reported studies examining self-reported sleep duration and dementia risk in older populations have had mixed findings: some suggested that it is actually sleeping for shorter periods that has the association with increased dementia risk, while others found long-duration (>9 hours) sleep to be associated with the greater risk.

The newly reported analysis of Framingham Heart Study data is the first to span two generations of participants asked about their sleep patterns twice during their participation in the study, Pace explained.

“Participants were asked about their sleep duration 13 years apart. We did not see an increased risk in people who said they were excessive sleepers at both time points. People who reported excessive sleep duration on the second inquiry, but not the first, showed the higher risk.”

The analysis included 2,457 Framingham Heart Study participants (mean age 72±6; 57% women) who self-reported total hours of sleep as a three-level variable: 6 hours was categorized as short, 6 to 9 hours was considered the reference point, and more than 9 hours was categorized as long.

During the 10 years of follow-up, 234 cases of all-cause dementia were observed, and 181 cases (8% of total cohort) were clinically consistent with Alzheimer’s disease. The analysis revealed that:

  • On multivariable analyses, prolonged sleep duration was associated with an increased risk of incident dementia (HR 2.01; 95% CI 1.24-3.26)
  • The findings were driven by individuals with baseline mild cognitive impairment (HR 2.83; 95% CI 1.06-7.55) and those without a high school degree (HR 6.05; 95% CI 3.00-12.18)
  • Transitioning to sleeping more than 9 hours over a mean period of 13 years before baseline was associated with an increased risk of all-cause dementia (HR 2.43; 95% CI 1.44–4.11) and clinical Alzheimer disease (HR 2.20; 95% CI 1.17-4.13)

Long sleep duration was also associated on cross-sectional analysis with smaller total cerebral brain volume (TCBV) (β±SE, -1.08±0.41 mean units of TCBV difference) and poorer executive function.

“Collectively, these results suggest that long sleep duration serves as an early biological marker of neurodegeneration, especially in those with low educational attainment,” the researchers wrote.

Study limitations cited by the authors included possible confounding due to unrecognized mild cognitive impairment at baseline and the assessment of sleep duration through self-reporting, which may not be reliable. Still, self-reported sleep duration “is easy to collect, thus increasing the applicability of our results to general practice,” the researchers said.

“Patients reporting long sleep duration and cognitive complaints to their primary care provider could be triaged for further dementia screening, without the need for overnight sleep studies. As our findings were driven by those with low educational attainment, we identified a rather select subgroup that may warrant further screening for dementia. Thus, self-reported sleep duration may be a useful clinical tool to help predict persons at risk of progressing to clinical dementia within 10 years.”

Funding for the study was provided by the National Institute of Aging, the National Institute of Neurological Disorders and Stroke, and the National Heart, Lung and Blood Institute.

The principal researchers reported having no relevant relationships with industry related to the study.

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    F. Perry Wilson, MD, MSCE Assistant Professor, Section of Nephrology, Yale School of Medicine and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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Pitt study sheds light on shared roots of schizophrenia and rheumatoid arthritis

February 24, 2017 at 7:33 PM

An in-depth computational analysis of genetic variants implicated in both schizophrenia and rheumatoid arthritis by researchers at the University of Pittsburgh points to eight genes that may explain why susceptibility to one of the disorders could place individuals at lower risk for the other, according to the results of a study published today in the journal npj Schizophrenia.

“There is a wealth of genomic data on both schizophrenia and rheumatoid arthritis. Analyzing it jointly with known protein interaction information could provide invaluable clues to the relationship between the diseases and also shed light on their shared roots,” said Madhavi Ganapathiraju Ph.D., associate professor of biomedical informatics at the University of Pittsburgh School of Medicine and senior author of the study.

While schizophrenia is a psychiatric disorder of unknown origin and rheumatoid arthritis is an autoimmune disease of the joints that occurs as a result of the body’s immune system attacking its own cells, both disorders are thought to be influenced by multiple genetic risk factors modified by the environment.

“Several previous research studies have hinted at a potential inverse relationship in the prevalence and risk for the two disorders, so we wondered if individual genetic variants may exist that could have opposing effects on the risk of schizophrenia and rheumatoid arthritis,” said co-senior author Vishwajit Nimgaonkar M.D., Ph.D., professor of psychiatry at Pitt’s School of Medicine and human genetics at Pitt’s Graduate School of Public Health.

The researchers first analyzed two large databases of genetic variants significantly associated with either schizophrenia or rheumatoid arthritis. They identified 18 unique variants, also known as single nucleotide polymorphisms (SNPs) that were located in the HLA region of the genome that harbors genes associated with immune function. The variants appeared to confer different risk for schizophrenia or rheumatoid arthritis. As the SNPs were located near eight known genes in this region, the authors suggested those genes might lead to dysfunction in both schizophrenia and rheumatoid arthritis. Proteins encoded by two of these eight genes, HLA-B and HLA-C, are present in both brain and immune cells.

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Analysis of proteins that interact with these eight genes using a computational model developed last year by Ganapathiraju’s team called High-Precision Protein Interaction Prediction found more than 25 signaling pathways with proteins common to both rheumatoid arthritis and schizophrenia signaling. Moreover, several of these pathways were associated with immune system function and inflammation.

The findings are encouraging because they support associations of the HLA gene region and immune function with schizophrenia and rheumatoid arthritis that were known over four decades ago, said Ganapathiraju. Increasing evidence also suggests that a dysfunctional immune system could play a role in the development of schizophrenia.

“We believe that the research community studying these two disorders will find our results extremely helpful,” Nimgaonkar said.

The authors note that the study only focused on SNPs in known gene regions, and other mechanisms apart from the ones they described may also contribute to the diseases. However, the study has significantly narrowed the list of potential genes for examining the schizophrenia/rheumatoid arthritis relationship. Studying the functional relevance of the gene candidates in cells and tissues will provide insights into the two disorders, according to the researchers.

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http://www.upmc.com/media/NewsReleases/2017/Pages/bioinformatics-study.aspx

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Researchers discover promising target for treatment of leishmaniasis

February 24, 2017 at 7:07 PM

Each year, about 2 million people contract leishmaniasis, a parasitic disease transmitted by the bite of a sand fly. The cutaneous form of the disease results in disfiguring skin ulcers that may take months or years to heal and in rare cases can become metastatic, causing major tissue damage.

Though anti-parasitic drugs can speed healing, some patients’ ulcers persist even when the parasite is nearly undetectable in their bodies.

Now a team led by University of Pennsylvania School of Veterinary Medicine researchers understand why, and they have a promising target for treatment.

In a new publication in the journal PLOS Pathogens, they report that the immune system’s T cells trigger the activation of a signaling pathway that leads to chronic inflammation. Blocking either of two major players in this pathway with drugs that are already FDA-approved for other conditions led to significant reductions in lesions in an animal model.

“This is a neglected tropical disease, so it can be difficult to get the investment needed to develop new therapies,” said Phillip Scott, senior author on the study and vice dean for research and academic resources at Penn Vet. “Our discoveries implicate the use of drugs in leishmaniasis that are already in use for other inflammatory diseases. This will be the foundation for clinical trials moving forward.”

Fernanda O. Novais, a research associate at Penn Vet, led the work. She and Scott collaborated with coauthors Megan L. Clark, Daniel P. Beiting and Ian E. Brodsky of Penn Vet and Augusto M. Carvalho, Lucas P. Carvalho and Edgar M. Carvalho of the Oswaldo Cruz Foundation in Salvador, Brazil.

Scott’s work on leishmania in Brazil goes back 30 years. Along with colleagues, he’s determined that the the skin damage associated with the disease owes less to the direct effects of the Leishmania parasite than to an immune response gone awry. The culprits are CD8 T cells, which in some modes can protect the body from infections but in other cases can promote increased disease.

“In earlier work, we found that CD8 T cells lead to inflammation, but what we didn’t know was what was downstream from the CD8 T cells,” Novais said, “Here we discover the pathway by which they cause inflammation.”

The research team did have a suspicion of a molecule that might be involved. In a previous study, they had found that expression levels of the IL-1 gene, which encodes a cytokine known for contributing to inflammation in other conditions, were elevated in tissue samples of the lesions of leishmania-infected people.

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To test whether the IL-1 protein was indeed responsible for the tissue damage, the researchers turned to mice. In infected animals bred to lack mature T cells that then had CD8 T cells added back, the team found higher levels of IL-1 compared to infected mice lacking those T cells. The latter animals also developed skin lesions, while the former group failed to.

Treating the mice that had CD8 T cell added with an inhibitor of IL-1 greatly reduced the severity of their disease. Notably, treatment with an inhibitor of a related molecule, IL-1, was not nearly as effective.

A drug called anakinra, which blocks the IL-1 receptor, is FDA-approved to treat rheumatoid arthritis. The researchers were pleased to see that this, too, reduced skin pathology in the mice.

Because Scott, Novais and colleagues knew that IL-1 needs to be processed by an enzyme in order to become active, they wanted to see if that enzyme might also be a potential therapeutic target. One of the types of enzymes that can process IL-1 are caspases, and data from previous experiments had implicated caspase-1 as requisite for the CD8-induced pathology in leishmaniasis.

Caspase-1 itself requires processing, and further investigation revealed that the NLRP3 inflammasome — a protein complex responsible for processing caspase — 1was required in this case for mice to develop leishmania-related skin lesions.

Testing two inhibitors of the NLRP3 inflammasome, including one that is an approved diabetes drug, glyburide, prevented mice from developing severe disease.

To assess the relevance of these findings in humans, the research team went back to the skin biopsies from leishmaniasis patients. They found that the lesion biopsies in culture produced more IL-1 than normal skin cells. Furthermore, treating the lesion biopsy with glyburide significantly decreased the amount of IL-1 the cultured cells released.

“What we found was that drugs blocking either the inflammasome or IL-1 have the same effect in controlling disease,” says Novais.

“At this point,” Scott said, “we have solid evidence in the mouse that blocking these pathways with a couple of different drugs blocks the pathology, and we have data from patients that this pathway is operating in humans. What we don’t have is information on whether blocking these pathways will clear up pathology in patients.”

Clinical trials testing the efficacy of drugs currently on the market, such as anakinra, glyburide or a humanized inhibitor of IL-1, are something the researchers hope to be involved in soon.

Source:

https://news.upenn.edu/news/penn-vet-team-identifies-new-therapeutic-targets-tropical-disease-leishmaniasis

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Depression puts psoriasis patients at significantly greater risk of psoriatic arthritis

Psoriasis is a lifelong disease that is associated with significant cosmetic and physical disability and puts patients at increased risk for many major medical disorders. A multidisciplinary team of researchers has found that psoriasis patients who developed depression were at a 37 percent greater risk of subsequently developing psoriatic arthritis, compared with psoriasis patients who did not develop depression.
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Support For Health Law Grows, Leaving Republicans In A Bind

Republican members of Congress are at home this week, with many of them getting an earful from anxious constituents about their plans to “repeal and replace” the Affordable Care Act. A poll out Friday gives those lawmakers something to be anxious about, too.

The monthly tracking poll from the Kaiser Family Foundation finds overall support for the health law ticked up to 48 percent in February, the highest point since shortly after it passed in 2010. That was a 5-point increase since the last poll in December. (Kaiser Health News is an editorially independent project of the foundation.)

In addition, 6 in 10 people said they did not favor current GOP proposals for turning control of Medicaid, the federal-state program for low-income residents, over to the states or changing the federal funding method. More than half said Medicaid is important to them or family members.

kff-022417-medicaid_small

The increase in the law’s popularity is almost entirely due to a spike in support among independents, whose approval of the law has risen to 50 percent, compared with 39 percent unfavorable. Continuing a trend that dates to the passage of the law, the vast majority of Democrats approve of it (73 percent), while the vast majority of Republicans disapprove (74 percent).

Poll respondents are also concerned about the way Republicans say they will overhaul the measure. While they are almost evenly divided between wanting to see the law repealed (47 percent) or not repealed (48 percent), very few (18 percent) of those favoring repeal support the idea of working out replacement details later. More than half of the repeal supporters (28 percent of the sample) say the repeal and the ACA’s replacement should come simultaneously.

Interestingly, even among Republicans, fewer than a third (31 percent) favor an immediate repeal, while 48 percent support simultaneous repeal and replacement, and 16 percent don’t want the law repealed at all.

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This KHN story can be republished for free (details).

Simultaneous repeal and replacement, which is what President Donald Trump has promised, could prove difficult since Republicans have not agreed to a plan. They are using a special budget procedure, called reconciliation, that allows them to move legislation with only a simple majority in the Senate, but that bill is limited in what it can remove from the law and what can be added to it. Other bills would likely have to overcome a filibuster by Democrats in the Senate, which requires 60 votes. Republicans currently have a 52-48 majority in that chamber.

When asked about the Republican plans to overhaul the Medicaid program, nearly two-thirds of those polled prefer the current Medicaid program to either a “block grant” that gives states more flexibility but would limit Medicaid’s currently unlimited budget, or a “per capita cap,” which would also limit spending to states but would allow federal funding to rise with enrollment increases.

Respondents also strongly favor letting states that expanded Medicaid under the Affordable Care Act continue to receive federal funding. The Supreme Court in 2012 made that expansion optional; 31 states (plus Washington, D.C.) adopted it. Eighty-four percent said letting the federal funds continue was very or somewhat important, including 69 percent of Republicans, and 80 percent of respondents in states that did not expand the program.

Republicans are counting on savings from capping Medicaid to pay for other health care options they are advocating.

The national telephone poll was conducted Feb. 13-19 with a sample of 1,160 adults. The margin of error is plus or minus 3 percentage points for the full sample.

Categories: Medicaid, Repeal And Replace Watch, Syndicate, The Health Law

Tags: KFF, Legislation, Polls

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Threat Of Obamacare Repeal Leaves Community Health Centers In Limbo

Treating people for free or for very little money has been the role of community health centers across the U.S. for decades. In 2015, 1 in 12 Americans sought care at one of these clinics; nearly 6 in 10 were women, and hundreds of thousands were veterans.

The community clinics — now roughly 1,300-strong — have also expanded in recent years to serve people who gained insurance under the Affordable Care Act. In 2015, community health centers served 24.3 million people — up from 19.5 million in 2010. Most of the centers are nonprofits with deep roots in their communities and they meet the criteria to be a federally qualified health center. That means they can qualify for federal grants and a higher payment rate from Medicaid and Medicare.

The ACA was a game changer for these clinics — it has enabled them to get reimbursement for much more of the care they provided, because more of their patients now had private insurance or were on Medicaid. Revenue at many clinics went up overall, and many of the health centers used federal funding available under the law to expand their physical facilities and add more services, such as dentistry, urgent care or mental health care.

With repeal of the ACA looming, clinic directors said they stay up at night wondering what’s next. We spoke with four, who all say their clinics are in a holding pattern as Congress debates the health law’s future.

Saban Community Clinic, Los Angeles

Julie Hudman, the CEO of Saban Community Clinic in Los Angeles, Calif., said there’s a lot at stake for her patients.

“A lot of the folks that we see are single adults,” she explained. “They’re maybe more transitional. They’re homeless patients. They have behavioral health challenges. They’re really, to be honest, some of the most vulnerable and poorest patients of all.”

Before the ACA went into effect, eligibility for Medi-Cal, as Medicaid is known in California, depended on a variety of factors, including income, household size, family status, disability and others. Under Obamacare, according to the California Department of Health Care Services, people can now qualify for Medi-Cal on the basis of income alone if their household makes less than 138 percent of the federal poverty level — that’s $16,395 for an individual and $33,534 for a family of four.

Prior the ACA, about half of the Saban clinic’s 18,000 patients were uninsured, Hudman said. They paid little for treatment — maybe a copay of $5 or $10. Almost all of those patients qualified for Medi-Cal after the health law expanded eligibility, she said, and that’s made a big difference for the clinic’s bottom line: Medi-Cal pays the clinic around $200 per patient visit.

These days, more than half of Saban’s revenue comes from health insurance. The possibility of losing some of that money, Hudman said, is forcing some hard decisions. She had been looking to lease or buy a fourth facility, she said, but now that plan is on hold; as are her hopes of expanding free help for the homeless.

“I’m not willing to move forward and take some of those risks,” she said. “I need to make sure that we’re able to pay our bills and pay our staff.”

Before the last election, Hudman said, “we had a lot of momentum moving forward. And now we’ve just sort of stalled.” — Rebecca Plevin, KPCC, Los Angeles

Jordan Health, Rochester, N.Y.

In the last few years, funding has been on the rise at Jordan Health, in Rochester, N.Y., and so has the extent of the clinic’s services.

The boost in funding has partly come from higher reimbursement rates the ACA authorizes, and from the increased number of patients at the clinic who have insurance. But Jordan Health, which has 10 locations in the area, has also benefited from the federal government’s pumping of more money into what are known as section 330 grants that enable expansion of services and facilities.

Janice Harbin, CEO of Jordan Health in Rochester, N.Y. says section 330 grants have allowed Jordan Health to hire more health practitioners. (Karen Shakerdge/WXXI)

Janice Harbin, CEO of Jordan Health in Rochester, N.Y. says section 330 grants have allowed Jordan Health to hire more health practitioners. (Karen Shakerdge/WXXI)

The 330 grant money gives qualified clinics the option of offering services that aren’t billable to insurance plans. At Jordan Health, the funds enabled the hiring of some different types of health practitioners who were not previously part of the team — dietitians, behavioral health specialists and care coordinators. And that, in turn, said Janice Harbin, president and CEO of Jordan Health, means patients can increasingly get the different kinds of care they need in one place.

Almost 90 percent of Jordan’s patients are considered a racial or ethnic minority, and over 97 percent live at or below 200 percent of the federal poverty line, according to data gathered by the federal Health Resources & Services Administration.

“When you’re dealing with a situation of concentrated poverty,” Harbin said, “your patient needs more than just ‘OK, let me give you a checkup, and pat you on the back and say now go out and do all these things I told you to do.’”

Jordan Health received an increase of about $1 million since 2013, according to its grant coordinator, Deborah Tschappat.

Tschappat said she expects Jordan will get about the same annual award in 2017, assuming federal funding for the 330 program stays about the same. If federal funding is cut significantly, they would potentially lose some services.

For now, Jordan Health plans to “expand services judiciously, while increasing efficiency and productivity,” Tschappat said.

In the coming months Harbin and her colleagues will be lobbying lawmakers in Albany and Washington, D.C., to renew Jordan’s funding — including the 330 grant, which is set to end in September.

“We’re used to doing a lot with a little, but we increasingly know that we do need to have financial support,” Harban said. “And that’s keeping us up at night.” — Karen Shakerdge, WXXI, Rochester

Adelante Healthcare, Phoenix

Adelante Healthcare has been part of the health safety net in Phoenix for nearly four decades — when its doctors began helping farm workers in the city’s surrounding fields. But the Affordable Care Act enabled Adelante to expand like a brand new business.

“Adelante has grown by 35 percent in the last 12 months,” said Dr. Robert Babyar, Adelante’s assistant chief medical officer. “We’ve increased our provider staffing — almost doubled our providers. And the number of services we provide has doubled.”

Adelante operates nine clinics throughout the Phoenix metro area. The one where Babyar met with me includes play areas for children and a dental office.

Most of their 70,000 patients are low-income and about half are covered by either Medicaid or KidsCare — Arizona’s version of the Children Health Insurance Program. In 2014, Arizona became one of the Republican-led states that expanded Medicaid under the ACA. That brought more than 400,000 people onto the state’s Medicaid rolls and created big demand for Adelante. Low-income patients who did not have insurance before the expansion had relied on Adelante’s sliding fee schedule. Much of that population now has health coverage, either through the ACA marketplace or the state.

“That opened up more options for our patients, more specialists they could see, procedures they could have done,” Babyar said.

As Congress moves to repeal and replace the health care law, Adelante is in a holding pattern. It has delayed the groundbreaking of a new site until later this year because of the uncertainty. A full repeal of the ACA — without a replacement that keeps its patients covered — would limit any future growth, and strain the new staff and resources it has added. It wouldn’t be the first time Adelante had to scale back its services because of changes to Medicaid. In 2010 and 2011, Arizona lawmakers froze enrollment for its CHIP program and for childless adults in Medicaid. Then, in 2012, Adelante lost more than a million dollars.

Babyar said it has taken several years to get their new patients into the system and working with doctors consistently to manage their conditions.

“All the progress we made with those patients to stay and be healthy — that can fall apart really quick,” said Babyar. — Will Stone, KJZZ, Phoenix

Denver Health, Denver

Denver’s Federico F. Peña Southwest Family Health Center is part of Denver Health — the safety-net system that takes care of low-income people.

“Definitely this clinic has benefited from Obamacare,” said Dr. Michael Russum, who practices family medicine for Denver Health and helps lead the clinic. “And this population has benefited from Obamacare by the expansion of Medicaid.”

That’s what helped make the economics work as Denver Health put a new $26 million clinic in a high poverty neighborhood in 2016, said Dr. Simon Hambidge, Denver Health’s CEO of Community Health Services. With the ACA in place, he said, the health system was able to count on the new clinic having a population of paying patients with insurance that could help support it.

Hambidge predicted the hospital will weather the storm if Obamacare is repealed and there are serious cuts to safety-net programs, like Medicaid and Medicare, as some Republicans have suggested. But it will probably be harder to open new clinics in other high-need neighborhoods, he conceded.

“We’ll survive,” Hambidge said. “We may not be able to be as expansive, because we would be back to less secure times.” — John Daley, Colorado Public Radio

This story is part of NPR’s reporting partnership with local member stations and Kaiser Health News.

Categories: Medicaid, Public Radio Partnership, Repeal And Replace Watch, States, Syndicate, The Health Law

Tags: Clinics, Community Health, Disparities, Medi-Cal

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