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Research Briefs July 2018
A Path to Safer Opioids?
A “groundbreaking” study has uncovered important distinctions between the opioids the brain makes naturally and therapeutic opioids. National Institutes of Health (NIH) researchers tested the common wisdom that opioids act only on the same surface receptors as endogenous opioids. They discovered that manufactured opioids, such as morphine and oxycodone, bind to receptors inside neurons—which are not the targets of naturally occurring opioids. The difference in the actions could help guide the design of pain relievers that don’t produce addiction or other adverse opioid-related effects.
The researchers used a new type of antibody biosensor—a nanobody—that generates a fluorescent signal when certain proteins are activated. The signal allowed researchers to track chemicals as they moved through cells and responded to stimuli.
The first discovery was that the opioid receptors were activated not only on the surface, but in the endosome, where the mu-receptor remained activated over several minutes. The researchers also found that there are large differences across a range of opioid drugs in how strongly they induce receptor activation in the endosome. Yet another discovery was that the opioid drugs uniquely induce rapid nanobody signaling, within tens of seconds, in the Golgi apparatus.
Based on those findings, the researchers hypothesize that current medically used opioids distort the normal time and spatial sequence of mu-opioid receptor activating and signaling. That distortion may provide the mechanistic link, they say, that explains the undesired side effects of opioid medicines.
Source: NIH, May 2018
Helping to Heal Childhood Trauma
Nearly half (46%) of children in the U.S. report having experienced at least one traumatic event, according to a Substance Abuse and Mental Health Services Administration (SAMHSA) report.
The numbers support data from SAMHSA’s Children’s Mental Health Initiative (CMHI), which found 82% of children, youths, and young adults in systems of care have experienced at least one traumatic event before entering services.
The effects of the trauma can be catastrophic: 41% of children and young adults with a history of trauma have had suicidal thoughts and 23% have attempted suicide, compared with 24% and 13% of those without trauma history.
However, treatment through systems of care, such as CMHI, leads to significant improvement in behavioral and emotional health. Evaluation data after one year of treatment show that treatment reduces suicidal thoughts by 68% and suicide attempts by 78%. CMHI data also show that one year after intake into a system of care, 48% of children and youths had fewer school absences, 41% had improved school performance, and 15% improved competence in school and classroom tasks.
Source: SAMHSA, May 2018
Tobacco Screening Lags in Behavioral Health Facilities
People with mental and/or substance abuse disorders are more than twice as likely to smoke cigarettes as people without those disorders and are more likely to die from a smoking-related illness than from a behavioral health condition. Yet many are not screened for tobacco use in behavioral health facilities. According to the Centers for Disease Control and Prevention (CDC) and the Substance Abuse and Mental Health Services Administration, in 2016, only half of mental health treatment facilities and 64% of substance abuse treatment facilities reported screening patients for tobacco use.
And even fewer provide counseling and treatments. Only 38% of mental health facilities offer tobacco cessation counseling, 25% offer nicotine replacement therapy (NRT), and 22% offer non-nicotine cessation medications. Of substance abuse treatment facilities, 47% offer tobacco cessation counseling, 26% offer NRT, and 20% offer non-nicotine cessation medications. Oklahoma and New York had the highest percentage of programs.
On the other hand, 49% of mental health and one-third of substance abuse treatment facilities now have smoke-free campuses in the 50 states, Washington, D.C., and Puerto Rico. That number varies by state, ranging from 20% of mental health facilities in Idaho to 78% in Oklahoma, and 10% of substance abuse treatment facilities in Idaho to 83% in New York.
Practical steps can boost the availability of smoking cessation screening and programs. The CDC recommends integrating screening and treatment protocols into workflows and electronic health record systems. The CDC also advises offering outreach to behavioral health providers who reinforce the message that patients can benefit from evidence-based cessation treatment.
Source: CDC, May 2018
Managing Diabetes While Keeping Costs Down
A cost-effective community program at Pennsylvania State University helped most participants change their behavior and significantly improve their hemoglobin A1c (HbA1c) levels and blood pressure, according to a recent report.
The researchers for the extension program Dining with Diabetes collected data on 2,738 adults with type-2 diabetes or prediabetes and adult family members without diabetes. The program consisted of four weekly two-hour classes and a follow-up class conducted three months later. The classes included hands-on food preparation, food tastings, and physical activity.
At the follow-up class, participants who completed the program had significant improvements in diabetes-related biomarkers. A significantly greater percentage said they were confident they could keep their diabetes under control, compared with the number at baseline (67% versus 58%). At baseline, most participants were adhering to medications; the researchers found no significant change in adherence.
Participants also significantly increased the number of days per week on which they exercised for 20 minutes or more (from 2.9 to 3.4 days), and slightly increased the number of days on which they ate a variety of fruits and vegetables.
Nearly half of participants with baseline and follow-up measurements had a drop in HbA1c. At follow-up, 21% had a reduction large enough to lower their diabetes status. The changes translated to a 5.9% decrease in HbA1c for 27% of those who had uncontrolled diabetes at baseline. More than half (59%) had a drop in blood pressure, including 60% of those with uncontrolled diabetes.
The program, which was free to participants, cost Penn State Extension $407 per person. The researchers estimate that extending the program to half of the 1.3 million people with diabetes in Pennsylvania would save the state approximately $195 million at one year.
Source: Preventing Chronic Disease, May 2018
Falls Still a Danger for the Elderly
Falls have long been a major hazard for older adults—accounting for the largest percentage of deaths from unintentional injuries. Each year, about one in four older adults in the U.S. reports falling, and an estimated three million emergency department visits every year are related to falls.
According to the Centers for Disease Control and Prevention (CDC), things are getting worse, not better. Overall, deaths due to falls among older adults increased 31% from 2007 to 2016, a rate of 3% per year. The rate increased in every demographic category except among American Indians/Alaska Natives, with the largest increase (4%) among people 85 years of age and older. Nationwide, nearly 30,000 older adults died from fall-related causes in 2016.
But falls are not an inevitable part of aging, the CDC reminds. Advanced age is a well-known independent risk factor; other risk factors include reduced activity, chronic conditions (including incontinence), prescription medications (which may act synergistically on the central nervous system), and changes in gait and balance. The CDC says health care providers can address the problem by asking patients about falls, assessing gait and balance, reviewing medications, and prescribing interventions such as strength and balance exercises or physical therapy.
Source: Morbidity and Mortality Weekly Report, May 2018
Repurposing With a Purpose
Cryptococcal meningitis is one of the most common mycoses in patients with human immunodeficiency virus/acquired immunodeficiency syndrome. In developed countries, mortality rates due to the disease hover around 9%—in poor and underdeveloped regions, the number leaps to 70%. Many of those deaths are related to lack of access and difficulty in administering amphotericin B and flucytosine. That’s the most effective standard treatment, but it’s expensive and carries serious adverse effects, including nephrotoxicity, hepatotoxicity, and bone marrow suppression. Fluconazole, also commonly used, doesn’t effectively clear fungal burden and is associated with clinical relapse.
More antifungals are desperately needed. But it takes billions of dollars to get a drug to market, and it can be a slow process. Where are the new antifungals to come from?
Maybe from other drugs. Researchers have begun mining drug compound “libraries,” searching for existing drugs that can be repurposed. The drugs have already passed all the regulatory hurdles—it’s just a matter of finding out which ones could be turned to a new use. The antidepressant sertraline, for instance, has been found to be a potent antifungal that works synergistically with fluconazole and is now being repurposed for cryptococcal meningitis.
Researchers from the University of Technology Sydney screened the Screen-Well Enzo library of 640 compounds for candidates that phenotypically inhibited the growth of Cryptococcus deuterogattii. Their search turned up promising results for the anthelminthic agent flubendazole, as well as the L-type calcium channel-blockers nifedipine, nisoldipine, and felodipine. Flubendazole was very active against all pathogenic Cryptococcus species, and, importantly, was equally effective against isolates resistant to fluconazole. Nifedipine, nisoldipine, and felodipine inhibited Cryptococcus. Nisoldipine was also effective against Candida, Saccharomyces, and Aspergillus.
The researchers say flubendazole may be the best starting point for treating cryptococcal disease, both for its effectiveness and because research has not found serious adverse effects from antihelminthic treatment. Flubendazole interferes with normal cell growth as early as three hours post-treatment and continues to render treated Cryptococcus cells unviable. However, because flubendazole is formulated to treat gastrointestinal worms, it is not yet known whether it would be able to reach therapeutic concentrations in the brain required for an antifungal effect.
Overall, their findings, the researchers say, “validate repurposing as a rapid approach for finding new agents to treat neglected infectious diseases.”
Source: PeerJ, May 2018