General, pediatric ‘Treat All’ policies spur antiretrovirus therapy in youth

A new study published as “Editor’s Choice” in The Journal of Infectious Diseases found that expansion of HIV treatment eligibility to include those under age 15 led to large and significant increases in initiation of antiretroviral therapy (ART) within 30 days of enrollment in care among 10- to 14-year-olds living with HIV.

Led by Olga Tymejczyk and Ellen Brazier of the Institute for Implementation Science in Population Health (ISPH) at the CUNY Graduate School of Public Health and Health Policy, the study used real-world longitudinal service delivery data from HIV clinics in seven countries in sub-Saharan Africa, all members of the global IeDEA research consortium: Burundi, Democratic Republic of the Congo (DRC), Rwanda, Kenya, Uganda, Malawi, and Zambia. All of the countries in the study adopted general universal test and treat, or Treat All, policies in 2016–policies that made all people living with HIV eligible for immediate treatment, regardless of CD4 count or clinical symptoms. Prior to adopting general Treat All policies in 2016, Uganda and Zambia had also adopted pediatric-specific Treat All policies in 2013, which extended treatment eligibility to all children younger than 15 years.

Using a regression discontinuity design, the study found large increases in rapid ART initiation among young adolescents following the adoption of Treat All policies. In Burundi, Democratic Republic of the Congo, Kenya, Malawi, and Rwanda, where “Treat All” policies were adopted in 2016, there was a 23.4 percentage point increase in rapid ART initiation among young adolescents. In Uganda and Zambia in 2013, there was a 11.2 percentage point increase in rapid ART initiation following the adoption of pediatric Treat All policies.

Given the study design, these increases in rapid ART initiation can be interpreted as the effect of expanded treatment eligibility guidelines for a population that has proven hard to reach with HIV care.

“Our findings are clinically important because young adolescents living with HIV in these settings often do not initiate ART until they are at advanced stages of HIV disease,” said Tymejczyk. “Getting them on treatment faster after they enroll in HIV care could help lower disproportionately high HIV mortality rates in this age group.”

The researchers emphasize, however, that as more follow-up data become available, it will be important to assess whether these young adolescent patients remain on treatment and achieve viral suppression.

“We also need to do more to shorten the time from HIV infection to diagnosis and enrollment in HIV care,” said Brazier. “Most of those enrolling into HIV care between the ages of 10-14 years are thought to have acquired the infection perinatally. While it is encouraging that Treat All has improved their access to HIV treatment, we need to understand and address barriers to timely diagnosis and enrollment in HIV among this age group.”

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Funding

NIAID award numbers U01AI096299 and U01AI069924, and NICHHD, NIDA, NCI, and NIMH award number U01AI069911

https://www.eurekalert.org/pub_releases/2019-12/cgso-gap120319.php

Common drug could help restore limb function after spinal cord injury

Long-term treatment with gabapentin, a commonly prescribed drug for nerve pain, could help restore upper limb function after a spinal cord injury, new research in mice suggests.

In the study, mice treated with gabapentin regained roughly 60 percent of forelimb function in a skilled walking test, compared to restoration of approximately 30 percent of forelimb function in mice that received a placebo.

The drug blocks activity of a protein that has a key role in the growth process of axons, the long, slender extensions of nerve cell bodies that transmit messages. The protein stops axon growth at times when synapses form, allowing transmission of information to another nerve cell.

The research showed that gabapentin blocks the protein from putting on its brakes, which effectively allowed axons to grow longer after injury.

“There is some spontaneous recovery in untreated mice, but it’s never complete. The treated mice still have deficits, but they are significantly better,” said senior author Andrea Tedeschi, assistant professor of neuroscience at The Ohio State University.

“This research has translational implications because the drug is clinically approved and already prescribed to patients,” he said. “I think there’s enough evidence here to reconsider how we use this drug in the clinic. The implication of our finding may also impact other neurological conditions such as brain injury and stroke.”

The regained function in mice occurred after four months of treatment – the equivalent of about nine years in adult humans.

“We really have to consider that rebuilding neuronal circuits, especially in an adult central nervous system, takes time. But it can happen,” said Wenjing Sun, research assistant professor of neuroscience at Ohio State and first author of the publication.

The study is published in the Journal of Clinical Investigation.

The spinal cord injury in these mice is located near the top of the spine. Humans with this type of injury generally lose enough sensation and movement to require assistance with daily living tasks.

After receiving gabapentin for four months, the treated mice were better able to move across a horizontal ladder and spread their forelimb toes than untreated mice. When the researchers used a special technique to silence neurons in the repair pathway they had targeted, there was no difference in functional recovery between treated and untreated mice.

“Now we can comfortably say that whatever we see in terms of structural and functional alterations of this motor pathway is really meaningful in promoting recovery in these mice,” Tedeschi said.

Tedeschi noted that in this study, treatment with gabapentin occurred much earlier than is typical in human medicine, when it is prescribed to treat existing neuropathic pain and other neurological conditions.

“Gabapentin is given when the nervous system is already having issues associated with maladaptive plasticity that hinders normal function. We are giving it much, much earlier, when the nervous system may be more responsive to programming an adaptive repair process,” he said.

A retrospective study of European medical data published in 2017 showed that individuals who had received anticonvulsants – gabapentin or a similar drug – early after spinal cord injury regained motor function. It was not a clinical trial, but the analysis showed an association between taking a class of drugs called gabapentinoids and regaining muscle strength.

Plenty of questions remain: how and when to adjust the amount of gabapentin used for treatment, and whether the drug could be combined with other interventions used to promote repair of an injured spinal cord at chronic stages. But testing the effectiveness of the drug in larger animal models is a logical next step prior to embarking on clinical trials, Tedeschi said.

“With all the evidence and mechanistic insight we provide, I feel like we are in a better situation to start planning a more translational type of research,” he said. “It’s the right time to try.”

Tedeschi’s research focuses on neurons in the corticospinal tract – specifically motor neurons that carry signals from the central nervous system to the body telling muscles to move. These cells are particularly important in controlling voluntary movement, which is impaired in cervical spinal cord injuries modeled in the study.

This work builds upon the recent discovery of the regulatory role of a neuronal receptor called alpha2delta2 in controlling axon growth ability. Tedeschi and colleagues have determined that alpha2delta2 facilitates synapse formation by putting on the brake for axon growth, an essential step during the development of the central nervous system.

The researchers discovered in the current study that after a cervical spinal cord injury, affected motor neurons above the spine increased the expression of this receptor, interfering with axons’ ability to regrow. If axon repair doesn’t go as expected and neuronal circuits are reorganized improperly, individuals with spinal cord injury may experience uncontrolled movement and pain.

“When neuronal circuits need to be rebuilt after injury, we need to down-regulate the expression of the receptor so axons can re-engage in an active growth program. And we found that it’s doing exactly the opposite,” said Tedeschi, also a member of Ohio State’s Chronic Brain Injury Discovery Theme.

“Because this receptor can be pharmacologically blocked through administration of clinically approved drugs called gabapentinoids – for example, gabapentin and pregabalin – that’s a very powerful target that you can modulate as long as you take the drug.”

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This research was funded by the Craig H. Neilsen Foundation, the Marina Romoli Onlus Association, the Ohio State University Neuroscience Research Institute, and grants from the National Institute of Neurological Disorders and the National Institutes of Health.

Additional Ohio State co-authors are Molly J. E. Larson, Conrad M. Kiyoshi, Alexander J. Annett, William A. Stalker and Juan Peng.

https://www.eurekalert.org/pub_releases/2019-12/osu-acd120319.php

Diabetes drug has unexpected, broad implications for healthy aging

Metformin is the most commonly prescribed type 2 diabetes drug, yet scientists still do not fully know how it works to control blood sugar levels. In a collaborative effort, researchers from the Salk Institute, The Scripps Research Institute and Weill Cornell Medical College have used a novel technology to investigate why it functions so well. The findings, which identified a surprising number of biochemical “switches” for various cellular processes, could also explain why metformin has been shown to extend health span and life span in recent studies. The work was published in Cell Reports on December 3, 2019.

“These results provide us with new avenues to explore in order to understand how metformin works as a diabetes drug, along with its health-span-extending effects,” says Professor Reuben Shaw, co-corresponding author of the paper and the director of Salk’s NCI-designated Cancer Center. “These are pathways that neither we, nor anyone else, would have imagined.”

Previously, the only biochemical pathway that was known to be activated by metformin was the AMPK pathway, which Shaw discovered stalls cell growth and changes metabolism when nutrients are scarce, as can occur in cancer. But the scientists believed more pathways than AMPK might be involved.

The scientists developed a novel screening platform to examine kinases, the proteins that transfer phosphate groups, which are critical on/off switches in cells and can be rapidly flipped by metformin. Using this technology, the researchers were able to decode hundreds of regulatory “switch-flipping” events that could affect healthy aging.

“Being mentored by John Yates, one of the top mass spectrometry investigators in the world, and Reuben Shaw, an expert in the field of metabolism, enabled me to both develop and apply a novel technology to a critical biological question: What pathways are regulated by metformin in the liver?” says Ben Stein, first author and postdoctoral associate at Weill Cornell Medical College.

The results revealed that metformin turns on unexpected kinases and pathways, many independent of AMPK. Two of the activated kinases are called Protein Kinase D and MAPKAPK2. These kinases are poorly understood, but are known to have some relation to cellular stress, which could connect them to the health-span- and life-span-extending effects observed in other studies. In fact, metformin is currently being tested in multiple large-scale clinical trials as a health-span- and life-span-extending drug, but the mechanism for how metformin could affect health and aging has not been clear. The current study indicates that Protein Kinase D and MAPKAPK2 may be two players in providing these therapeutic effects, and identifies new targets and cellular processes regulated by AMPK that may also be critical to metformin’s beneficial effects.

“We never imagined these two kinases would have anything to do with metformin,” says Shaw, holder of the William R. Brody Chair. “The results broaden our understanding of how metformin induces a mild stress that triggers sensors to restore metabolic balance, explaining some of the benefits previously reported such as extended healthy aging in model organisms taking metformin. The big questions now are what targets of metformin can benefit the health of all individuals, not just type 2 diabetics.”

Next, the researchers plan to examine the new signaling pathways they discovered in more detail to better understand the beneficial effects of metformin.

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Other authors included Kristina Hellberg, Ying S. Hu, Chien-Min Hung, Erin Q. Toyama, Debbie S. Ross and Björn F. Lillemeier of Salk; Diego Calzolari, Lin He and John R. Yates III of The Scripps Research Institute; and Lewis C. Cantley of Weill Cornell Medical College.

The work was funded by NIH grants (R01-DK080425, R35-CA220538, P01-CA120964, R35 CA197588, P41-GM103533, R01-MH068770 and 1DP2GM105455-01), the NOMIS Foundation, the Waitt Foundation, the James B. Pendleton Charitable Trust, the George E. Hewitt Foundation for Medical Research and the American Cancer Society (122123-PF-12-029-01-TBE).

https://www.eurekalert.org/pub_releases/2019-12/si-ddh120219.php

Implant Survival Poor for Converted ‘Partial’ Knee Replacements

Total knee arthroplasty (TKA) converted from medial unicompartmental (or “partial”) knee arthroplasty (UKA) has a risk for revision that is threefold higher than that for primary TKA, according to a study published online Nov. 20 in The Journal of Bone & Joint Surgery.

Anders El-Galaly, M.D., from Aalborg University Hospital in Denmark, and colleagues used data from the Danish Knee Arthroplasty Registry (1997 to 2017) to assess survival of 1,012 TKAs converted from UKAs versus 73,819 primary TKAs and 2,572 revision TKAs.

The researchers found that the survival of TKAs converted from UKAs was comparable with that of revision TKAs (P = 0.42) and significantly inferior to the survival of primary TKAs (P < 0.001). Differences between the groups did not alter this relationship compared with revision TKAs (adjusted hazard ratio, 0.94; 95 percent confidence interval, 0.74 to 1.19) and primary TKAs (adjusted hazard ratio, 3.00; 95 percent confidence interval, 2.47 to 3.66). Differences in the conversion implants (all P ≥ 0.47), experience with revision surgery (all P ≥ 0.06), and the indications for the UKA-to-TKA conversion (all P ≥ 0.27) did not affect survival of TKA converted from UKA. Frequent indications for revisions of TKA converted from UKA (P < 0.001) included instability (26 percent) and unexplained pain (13 percent).

“On the basis of this study, we believe that careful consideration is necessary before using medial UKA as treatment for knee osteoarthritis, as a potential conversion to a TKA decreased implant survival when compared with that following primary TKA,” the authors write.

Abstract/Full Text (subscription or payment may be required)

https://www.physiciansbriefing.com/orthopedics-14/artificial-knees-news-45/implant-survival-poor-for-converted-partial-knee-replacements-752538.html

JNJ says no asbestos found in baby powder

Tests conducted by two third-party labs show asbestos was not present in the single bottle that the FDA’s contracted lab tested, nor was it present in retained samples of the finished lot from which the bottle was produced.

Further, JNJ’s (NYSE:JNJ) investigation showed the testing protocol at said lab deviated from standard practice.

Shares are up 0.6% after hours.

Source: Press Release

https://seekingalpha.com/news/3523522-jnj-says-no-asbestos-found-in-baby-powder

Migraine headaches? Consider aspirin for treatment and prevention

Migraine headache is the third most common disease in the world affecting about 1 in 7 people. More prevalent than diabetes, epilepsy and asthma combined, migraine headaches are among the most common and potentially debilitating disorders encountered by primary health care providers. Migraines also are associated with an increased risk of stroke.

There are effective prescription medications available to treat acute migraine headaches as well as to prevent recurrent attacks. Nonetheless, in the United States many patients are not adequately treated for reasons that include limited access to health care providers and lack of health insurance or high co-pays, which make expensive medications of proven benefit unaffordable. The rates of uninsured or underinsured individuals have been estimated to be 8.5 percent nationwide and 13 percent in Florida. Furthermore, for all patients, the prescription drugs may be poorly tolerated or contraindicated.

Researchers from Florida Atlantic University’s Schmidt College of Medicine have proposed aspirin as a possible option for consideration by primary care providers who treat the majority of patients with migraine. Their review includes evidence from 13 randomized trials of the treatment of migraine in 4,222 patients and tens of thousands of patients in prevention of recurrent attacks.

Their findings, published in the American Journal of Medicine, suggest that high-dose aspirin, in doses from 900 to 1,300 milligrams given at the onset of symptoms, is an effective and safe treatment option for acute migraine headaches. In addition, some but not all randomized trials suggest the possibility that daily aspirin in doses from 81 to 325 milligrams may be an effective and safe treatment option for the prevention of recurrent migraine headaches.

“Our review supports the use of high dose aspirin to treat acute migraine as well as low dose daily aspirin to prevent recurrent attacks,” said Charles H. Hennekens, M.D., Dr.PH, corresponding author, first Sir Richard Doll Professor and senior academic advisor in FAU’s Schmidt College of Medicine. “Moreover, the relatively favorable side effect profile of aspirin and extremely low costs compared with other prescription drug therapies may provide additional clinical options for primary health care providers treating acute as well as recurrent migraine headaches.”

Common symptoms of migraine include a headache that often begins as a dull pain and then grows into a throbbing pain, which can be incapacitating and often occurs with nausea and vomiting, and sensitivity to sound, light and smell. Migraines can last anywhere from four to 72 hours and may occur as many times as several times a week to only once a year.

“Migraine headaches are among the most common and potentially debilitating disorders encountered by primary health care providers,” said Bianca Biglione, first author and a second-year medical student in FAU’s Schmidt College of Medicine. “In fact, about 1 in 10 primary care patients present with headache and three out of four are migraines. Aspirin is readily available without a prescription, is inexpensive, and based on our review, was shown to be effective in many migraine patients when compared with alternative more expensive therapies.”

Approximately 36 million Americans suffer from migraine headaches and the cause of this disabling disorder is not well understood. There is a higher prevalence in women (18 percent) than men (9 percent). In women, the prevalence is highest during childbearing age.

Approximately 90 percent of migraine sufferers report moderate to severe pain, with more than 50 percent reporting severe impairment or the need for bed rest as well as reduced work or school productivity.

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Story Source:

Materials provided by Florida Atlantic University. Original written by Gisele Galoustian. Note: Content may be edited for style and length.

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Journal Reference:

1. Bianca Biglione, Alexander Gitin, Philip B. Gorelick, Charles Hennekens. Aspirin in the Treatment and Prevention of Migraine Headaches: Possible Additional Clinical Options for Primary Healthcare Providers. The American Journal of Medicine, 2019; DOI: 10.1016/j.amjmed.2019.10.023

https://www.sciencedaily.com/releases/2019/12/191203091010.htm

Successful instrument guidance through deep, convoluted blood vessel networks

A team led by Professor Sylvain Martel at the Polytechnique Montréal Nanorobotics Laboratory has developed a novel approach to tackling one of the biggest challenges of endovascular surgery: how to reach the most difficult-to-access physiological locations. Their solution is a robotic platform that uses the fringe field generated by the superconducting magnet of a clinical magnetic resonance imaging (MRI) scanner to guide medical instruments through deeper and more complex vascular structures. The approach has been successfully demonstrated in-vivo, and is the subject of an article just published in Science Robotics.

When a researcher “thinks outside the box” — literally

Imagine having to push a wire as thin as a human hair deeper and deeper inside a very long, very narrow tube full of twists and turns. The wire’s lack of rigidity, along with the friction forces exerted on the walls of the tube, will eventually render the manoeuvre impossible, with the wire ending up folded on itself and stuck in a turn of the tube. This is exactly the challenge facing surgeons who seek to perform minimally invasive procedures in ever-deeper parts of the human body by steering a guidewire or other instrumentation (such as a catheter) through narrow, tortuous networks of blood vessels.

It is possible, however, to harness a directional pulling force to complement the pushing force, countering the friction forces inside the blood vessel and moving the instrument much farther. The tip of the device is magnetized, and pulled along inside the vessels by the attraction force of another magnet. Only a powerful superconducting magnet outside the patient’s body can provide the extra attraction needed to steer the magnetized device as far as possible. There is one piece of modern hospital equipment that can play that role: an MRI scanner, which has a superconducting magnet that generates a field tens of thousands of times stronger than that of the Earth.

The magnetic field inside the tunnel of an MRI scanner, however, is uniform; this is key to how patient imaging is performed. That uniformity poses a problem: to pull the tip of the instrument through the labyrinthine vascular structures, the guiding magnetic field must be modulated to the greatest possible amplitude and then be decreased as quickly as possible.

Pondering that problem, Professor Martel had the idea of using not the main magnetic field present inside the MRI machine tunnel, but the so-called fringe field outside the machine. “Manufacturers of MRI scanners will normally reduce the fringe field to the minimum,” he explains. “The result is a very-high-amplitude field that decays very rapidly. For us, that fringe field represents an excellent solution that is far superior to the best existing magnetic guidance approaches, and it is in a peripheral space conducive to human-scale interventions. To the best of our knowledge, this is the first time that an MRI fringe field has been used for a medical application,” he adds.

Move the patient rather than the field

To steer an instrument deep within blood vessels, not only is a strong attraction force required, but that force must be oriented to pull the magnetic tip of the instrument in various directions inside the vessels. Because of the MRI scanner’s size and weight, it’s impossible to move it to change the direction of the magnetic field. To get around that issue, the patient is moved in the vicinity of the MRI machine instead. The platform developed by Professor Martel’s team uses a robotic table positioned within the fringe field next to the scanner.

The table, designed by Arash Azizi — the lead author of the article and a biomedical engineering PhD candidate whose thesis advisor is Professor Martel — can move on all axes to position and orient the patient according to the direction in which the instrument must be guided through their body. The table automatically changes direction and orientation to position the patient optimally for the successive stages of the instrument’s journey thanks to a system that maps the directional forces of the MRI scanner’s magnetic field — a technique that Professor Martel has dubbed Fringe Field Navigation (FFN).

An in-vivo study of FFN with X-ray mapping demonstrated the capacity of the system for efficient and minimally invasive steering of extremely small-diameter instruments deep within complex vascular structures that were hitherto inaccessible using known methods.

Robots to the rescue of surgeons

This robotic solution, which greatly outperforms manual procedures as well as existing magnetic field-based platforms, enables endovascular interventional procedures in very deep, and therefore currently inaccessible, regions of the human body.

The method promises to broaden possibilities for application of various medical procedures including diagnosis, imaging and local treatments. Among other things, it could serve to assist surgeons in procedures requiring the least invasive methods possible, including treatment of brain damage such as an aneurysm or a stroke.

This research work received support from the Canada Research Chairs Program.

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Story Source:

Materials provided by Polytechnique Montréal. Note: Content may be edited for style and length.

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Journal Reference:

1. Arash Azizi, Charles C. Tremblay, Kévin Gagné, Sylvain Martel. Using the fringe field of a clinical MRI scanner enables robotic navigation of tethered instruments in deeper vascular regions. Science Robotics, 2019; 4 (36): eaax7342 DOI: 10.1126/scirobotics.aax7342

https://www.sciencedaily.com/releases/2019/12/191203143311.htm