Tag Archives: drug

Drug prices in the US rose three times faster than inflation over the last decade

Credit: Flickr.

For the first time, researchers have analyzed trends in net drug costs for all brand-name products in the United States. According to the analysis published today in the journal JAMA, the net cost of prescription drugs — that’s sticker price minus manufacturer discounts — rose three times faster than the rate of inflation over the course of the previous decade.

We’ve known for a long time that drug prices have only gone up since their list price is plainly visible and easy to research. However, researchers at the Center for Pharmaceutical Policy and Prescribing (CP3) at the University of Pittsburgh’s Health Policy Institute have been among the first to account for manufacturer discounts in order to understand net prices for the most important brand name drugs in the country.

“In prior work, we observed that prices of drugs more than doubled in the last decade. However, because this prior research was based on list prices, it did not account for manufacturer discounts, which have also increased in the past few years. We leveraged net pricing data from the investment firm SSR Health to estimate increases in drug prices after accounting for discounts,” Inmaculada Hernandez, Assistant Professor of Pharmacy and Therapeutics at the University of Pittsburgh School of Pharmacy, told ZME Science.

Medicaid discounts remain higher than for all other insurance types from 2007 to 2018. Credit: UPMC.

The new analysis covers 602 brand-name drugs, whose revenue and usage data were employed to track their list and net prices from 2007 and 2018. The net prices take into account increasingly rising manufacturer discounts, such as rebates, coupon cards, and 340B discounts.

“We found that, after adjusting for inflation, list prices increased by 159% in 2007-2018, and net prices by 60%. Discounts offset 62% of increases in list prices. In other words, there is a widening gap between list and net prices due to increasing discounts. After accounting for discounts, net prices increased every year by an average of 4.5 percentage points or over 3 times faster than inflation,” Hernandez said.

According to the results, net prices have leveled off since 2015. However, this doesn’t necessarily mean that prescription drugs are becoming more affordable since sometimes patients don’t actually pay the net price. “A lot of the discount is not going to the patient,” said Walid Gellad, associate professor of medicine and health policy at the University of Pittsburgh and senior author of the new study.

“We’re seeing a lot of discussion that net prices have stabilized over the last few years, and that does appear to be the case,” said Gellad. “But the stabilization of net price comes on top of large increases over the last decade, many times faster than inflation, for products that have not changed over this time period. In addition, this net price is an average, with substantial variability across payers and drugs.”

Instead, the majority of the discount is paid directly to public and private insurers. That being said, rebates shouldn’t normally affect the amount of money patients have to pay through copays or coinsurance, which are based on the list price, not net.

“Although discounts partially offset increases in list prices,  net prices still increased 3 times faster than inflation.  This evidence is important in advancing the current policy debate around drug prices, because it shows that drug prices still increase substantially after accounting for discounts. Moreover, the widening gap between list and net prices may be increasing disparities in health care access, because underinsured and uninsured patients are exposed to list prices. Thus, policymakers should not only focus on how much drug prices are increasing after discounts, but also in list prices. This is important because uninsured and underinsured patients are arguably the ones with the most access barriers, and they are exposed to list prices,” Hernandez said.

The net price increases were not uniform but rather varied significantly across different drug classes. For instance, for insulins or TNF inhibitors, the gap between list and net prices widened. For some cancer drugs, list and net prices increased in parallel.

The study also found that discounts were much larger for Medicaid than for other programs. This is likely due to the mandatory Medicaid rebate based on price increases over inflation.

Americans spend about $1,200 on prescription drugs a year, according to the latest figures from the Organization for Economic Cooperation and Development. Previously, a 2019 study published in Health Affairs by Hernandez and colleagues found that drug prices have gone up because companies are raising the price of drugs that are already available. This undermines the common narrative among pharmaceutical companies claiming that drug price hikes are due to them bearing the cost of innovation.

“In future research, we would like to quantify to what extent discounts are passed on to patients, and how competition affects trends in discounts. Our study is important because those opposed to regulating drug prices often argue that prices have barely increased at the rate of inflation after discounts. However, our study demonstrates that this has not been the case, lending support to the implementation of new policies to control increases in drug prices,” Hernandez concluded.

First antiviral drug approved to fight novel coronavirus

The first anti-viral drug for Coronavirus disease 2019 (COVID19), also known as 2019-nCoV acute respiratory disease, has been approved for marketing by the National Medical Products Administration since the outbreak. Developed by Zhejiang Hisun Pharmaceutical Company, the drug is expected to play an important role in preventing and treating the outbreak which has now infected 70,553 in China (1,772 deaths), the government said on its official WeChat account.

COVID-19, is an infectious disease caused by SARS-CoV-2 (2019 novel coronavirus), a virus closely related to the SARS virus. The disease was discovered during, and is the cause of, the 2019–20 coronavirus outbreak.

Three potential anti-COVID19 medicines have been officially announced by the Ministry of Science and Technology: Favilavir, Chloroquine Phosphate, and Remdesivir. They all initially showed more obvious curative effects and lower adverse reactions in clinical trials.

Favilavir, formerly known as Fapilavir, an antiviral that has shown efficacy in treating the novel coronavirus, was approved for marketing, the Taizhou government in Zhejiang province announced Sunday.

It is the first anti-novel coronavirus drug that has been approved for marketing by the National Medical Products Administration since the outbreak. Developed by Zhejiang Hisun Pharmaceutical Company, the drug is expected to play an important role in preventing and treating the epidemic, the government said on its official WeChat account.

Chloroquine Phosphate is in a class of drugs called antimalarials and amebicides. It is used to prevent and treat malaria. It is also used to treat amebiasis.

The other one with the most potential – so far – has been Remdesivir, which Gilead had already been developing as a treatment for Ebola disease and Marbug virus infections. It has subsequently also been found to show antiviral activity against other single-stranded RNA viruses such as respiratory syncytial virusJunin virusLassa fever virusNipah virus, Hendra virus, and coronaviruses (including MERS and SARS viruses).

Based on success against other coronavirus infections, Gilead provided Remdesivir to physicians that treated an American patient in Snohomish County, Washington infected with 2019-nCoV, and is providing the compound to China, to conduct a pair of trials in infected individuals with and without severe symptoms.

Chinese pharma BrightGene has successfully developed and manufactured copies of the drug, it has also maintained that it will not launch the drug until it has received licensing from Gilead, conducted clinical trials and obtained approval. A study of Remdesivir in COVID-19 has already begun enrolling patients in China, with a Gilead spokesman confirming that two clinical trials will be conducted in Wuhan, the city where the first cases of the novel coronavirus were observed.

Dolphins are seeing a rise of antibiotic-resistant bacteria and it’s our fault

Antibiotic resistance is reaching dramatic levels in some wild ecosystems, reports a study on bottlenose dolphins living in Florida’s Indian River Lagoon.

Image credits Claudia Beer.

One of the scariest public health issues we’re contending with today is the rise of antibiotic resistance. Many common bacterial strains are evolving to resist the drugs we rely on to treat them, making even mundane infections potentially deadly — and antibiotic development isn’t keeping up.

Once primarily confined to health care settings, these resistant strains of bacteria are now commonly found in other places, especially marine environments, a new study reports.

No cure for the porpoise

“In 2009, we reported a high prevalence of antibiotic resistance in wild dolphins, which was unexpected,” said Adam M. Schaefer, MPH, lead author and an epidemiologist at Florida Atlantic University’s (FAU) Harbor Branch. “Since then, we have been tracking changes over time and have found a significant increase in antibiotic resistance in isolates from these animals.”

“This trend mirrors reports from human health care settings.”

The team from Florida Atlantic University’s Harbor Branch Oceanographic Institute, in collaboration with the Georgia Aquarium and the Medical University of South Carolina and Colorado State University, conducted a long-term study from 2003 to 2015 of antibiotic resistance among bacteria retrieved from dolphins (Tursiops truncatus) in Florida’s Indian River Lagoon. The site was picked because this lagoon has a large coastal human population with a pronounced environmental impact.

Using the Multiple Antibiotic Resistance (MAR) index, the researchers obtained a total of 733 pathogen isolates from 171 individual bottlenose dolphins. Several of these strains are important human pathogens, the team explains.

“Based on our findings, it is likely that these isolates from dolphins originated from a source where antibiotics are regularly used, potentially entering the marine environment through human activities or discharges from terrestrial sources,” Schaefer explains.

The overall prevalence of resistance to at least one antibiotic for the 733 isolates was 88.2%. The highest prevalence of resistance found by the team were to erythromycin (91.6% of isolates), ampicillin (77.3%) and cephalothin (61.7%), and resistance to cefotaxime, ceftazidime, and gentamicin increased significantly between sampling periods for all the isolates.

Resistance to ciprofloxacin among E. coli isolates more than doubled between sampling periods, the team reports, reflecting recent trends in human clinical infections. The MAR index increased significantly from 2003-2007 and 2010-2015 for Pseudomonas aeruginosa and Vibrio alginolyticus. P. aeruginosa causes respiratory system and urinary tract infections among others, while the latter is a common pathogenic strain of Vibrio found to cause serious seafood-poisoning.

“The nationwide human health impact of the pathogen Acinetobacter baumannii is of substantial concern as it is a significant nosocomial pathogen with increasing infection rates over the past 10 years,” said Peter McCarthy, Ph.D., co-author, a research professor and an associate director for education at FAU’s Harbor Branch.

“The high MAR index for this bacteria isolated from dolphins in the Indian River Lagoon represents a significant public health concern.”

The paper “Temporal Changes in Antibiotic Resistance Among Bacteria Isolated from Common Bottlenose Dolphins (Tursiops truncatus) in the Indian River Lagoon, Florida, 2003-2015” has been published in the journal Aquatic Mammals.

US FDA approves new treatment for drug-resistant TB

TB Medicine Pretomanid approved by the US FDA

The US Food and Drug Administration approved Pretomanid tablets as part of a three-drug combination regimen together with linezolid (Zyvox) and Johnson & Johnson’s bedaquiline (Sirturo) for the treatment of a specific type of highly treatment-resistant tuberculosis (TB) of the lungs.

TB is a bacterial infection that caused about 1.6 million deaths globally in 2017. It spreads through droplets when someone sick with TB sneezes or coughs. TB primarily attacks the lungs but can sometimes affect other organs.

Multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) are forms of tuberculosis that do not respond to first-line anti-TB drugs. XDR-TB, a more serious form of MDR-TB, is unresponsive even to the two most powerful anti-TB drugs – isoniazid and rifampicin – in addition to being resistant to certain second-line treatments.

Only a small fraction of the 10 million people infected by TB each year get drug-resistant TB, but very few of those who do survive it. According to the World Health Organization, in 2016, there were an estimated 490,000 new cases of multidrug-resistant TB worldwide, with a smaller portion of cases of extensively drug-resistant TB.

Pretomanid is the generic name for the anti-bacterial drug formerly called PA-824.

The safety and efficacy of Pretomanid, taken orally in combination with bedaquiline and linezolid, was primarily demonstrated in a study of 109 patients with extensively drug-resistant, treatment intolerant or non-responsive multidrug-resistant pulmonary TB (of the lungs).

Of the 107 patients who were evaluated six months after the end of therapy, 95 (89%) were successes, which significantly exceeded the historical success rates for treatment of XDR- TB. Many TB patients are also infected with HIV. In the trial, the treatment worked as well for them as it did for other study participants. The drug regimen also appears to stop patients spreading the deadly bacterial infection after a few days’ treatment.

The most common adverse reactions observed in patients treated with Pretomanid in combination with bedaquiline and linezolid included damage to the nerves (peripheral neuropathy), acne, anemia, nausea, vomiting, headache, increased liver enzymes, indigestion (dyspepsia), rash, increased pancreatic enzymes (hyperamylasemia), visual impairment, low blood sugar (hypoglycemia), and diarrhea.

TB Alliance developed Pretomanid, the first-ever US FDA-approved drug for XDR-TB

Pretomanid, was developed by the nonprofit group TB Alliance. “We can have a huge impact on the lives of people who are afflicted and also take a major step ultimately toward, really, the eradication of a disease like TB,” said Mel Spigelman, president and chief executive of TB Alliance.

Pretomanid is the first tuberculosis medication to be developed by a nonprofit organization. In addition to the United States, TB Alliance filed for approval of pretomanid in the European Union. TB Alliance hopes FDA’s approval will enable other countries, such as China, India and South Africa, to okay the drug and to make it available to their residents.

 “The threat of antimicrobial-resistant infections is a key challenge we face as a public health agency,” said FDA Principal Deputy Commissioner Amy Abernethy, M.D., Ph.D.

“The bacterium that causes tuberculosis can develop resistance to the antibiotics used to treat it. Multidrug-resistant TB and extensively drug-resistant TB are public health threats due to limited treatment options. New treatments are important to meet patient national and global health needs. That’s why, among our other efforts to address antimicrobial resistance, we’re focused on facilitating the development of safe and effective new treatments to give patients more options to fight life-threatening infections.”

Medicinal plants used in the Civil War can stomp our modern antibiotic-resistant germs

New research into old germ-fighting methods suggests they could prove effective in combating antibiotic-resistant bacteria today.

abraham-lincoln-statue

Bronze statue of Abraham Lincoln in Virginia, USA.
Image credits Dennis Larsen

At the height of the Civil War, the paper reports, the Confederate Surgeon General released a guide of traditional plant remedies from the South that battlefield physicians could draw upon when faced with shortages of conventional medicine. Three of the plants in this guide — white oak (Quercus alba), tulip poplar (Liriodendron tulipifera), and devil’s walking stick (Aralia spinosa) — have antiseptic properties that could be useful today, the authors explain.

The seeds of salvation

“Our findings suggest that the use of these topical therapies may have saved some limbs, and maybe even lives, during the Civil War,” says Cassandra Quave, senior author of the paper and assistant professor at Emory’s Center for the Study of Human Health and the School of Medicine’s Department of Dermatology.

The team found that extracts from these three plants have significant antimicrobial properties in the face of three dangerous species of multi-drug-resistant bacteria: Acinetobacter baumannii, Staphylococcus aureus, and Klebsiella pneumoniae. These bacteria are often seen in wound-associated infections.

Quave’s research focuses on understanding the role of plants in traditional healing and other practices, a field known as ethnobotany.

“Ethnobotany is essentially the science of survival—how people get by when limited to what’s available in their immediate environment,” she says. “The Civil War guide to plant remedies is a great example of that.”

“Our research might one day benefit modern wound care, if we can identify which compounds are responsible for the antimicrobial activity,” adds Micah Dettweiler, the first author of the paper.

If the active ingredients in these plants are identified, explains co-author Daniel Zurawski from the Wound Infections Department at the Walter Reed Army Institute of Research, they can be tested through modern “models of bacterial infection.” In a way, he says, this is mixing the “wisdom of our ancestors” with modern techniques to create new solutions for the problems we’re facing today.

Around 1 in 13 soldiers that lived through the Civil War went back home with missing limbs, the authors report. “Far more Civil War soldiers died from disease than in battle,” Zurawski explains, adding that he was surprised to see how “common amputation was as a medical treatment for an infected wound.” At the time, germ theory was still crude, and very much a work-in-progress. The training medical personnel at the time received was also shoddy at best.

An antiseptic was simply defined as a tonic used to prevent “mortification of the flesh.” Iodine and bromine were sometimes used to treat infections, according to the National Museum of Civil War Medicine, although the reason for their effectiveness was unknown. Other conventional medicines available at the time included quinine for treating malaria, and morphine and chloroform to block pain.

Union blockade

The Confederacy, however, didn’t have reliable access to these compounds. In the 1863 copy of “Resources of the Southern Fields and Forests,” Francis Peyre Porcher (who was commissioned by the Confederacy for this task) set about detailing alternatives to the essential but lacking medicine. Porcher was a botanist and surgeon from South Carolina, and his book represents a compilation of medicinal plants of the Southern states, including plant remedies used by Native Americans and enslaved Africans. Among others, the book contains a description of 37 species for treating gangrene and other infections. His work formed the foundation upon which Samuel Moore, the Confederate Surgeon General, produced the “Standard supply table of the indigenous remedies for field service and the sick in general hospitals.”

The team collected samples of the three plants from around their university’s campus, abiding to the specifications Porcher set out in his book. Extracts were produced from white oak bark and galls; tulip poplar leaves, root inner bark and branch bark; and the devil’s walking stick leaves, and were then tested on multi-drug-resistant bacteria commonly found in wound infections.

White oak and tulip poplar extracts inhibited the growth of S. aureus, while the white oak extracts also inhibited the growth of A. baumannii and K. pneumoniae, the team writes. Extracts from both of these plants also inhibited S. aureus from forming biofilms, which can insulate it against antibiotics.

Staphylococcus aureus is considered the most dangerous of the staph bacteria, and can spread from skin infections or medical devices to infect internal organs. Klebsiella pneumoniae is a leading cause of hospital infection and can result in life-threatening cases of pneumonia and septic shock. Aceinetobacter baumannii is particularly worrisome as it exhibits extensive resistance to most first-line antibiotics, and is closely associated with combat wounds. Extracts from the devil’s walking stick inhibited both biofilm formation and quorum sensing — a signaling system that staph bacteria use to manufacture toxins — in S. aureus.

“There are many more ways to help cure infections, and we need to focus on them in the era of drug-resistant bacteria,” says Quave.

“Plants have a great wealth of chemical diversity, which is one more reason to protect natural environments,” Dettweiler adds.

The paper “American Civil War plant medicines inhibit growth, biofilm formation, and quorum sensing by multidrug-resistant bacteria” has been published in the journal Nature Scientific Reports.

Credit: Pixabay.

Hallucinations may be the side effect of over-processing in brain’s visual center

Credit: Pixabay.

Credit: Pixabay.

Hallucinations are the apparent perception of something not present, be them a tiny dragon in your cupboard, the smell of burned tires in your coffee, or menacing voices in your head. Hallucinations are reported by millions of people around the world affected by mental conditions such as schizophrenia and depression, but they can also be caused by psychedelics like LSD or ‘magic mushrooms’. In a new study, researchers at the University of Oregon found that mice

given a psychedelic drug had dampened activity in the brain’s visual center. Their results suggest that hallucinations may occur when the brain over-interprets the information in front of it.

What’s going on inside the hallucinating brain

The research team at the University of Oregon in Eugene injected mice with a hallucinogenic drug called 4-iodo-2,5-dimethoxyphenylisopropylamine (DOI). Like other hallucinogenic substances, DOI produces its effects by binding with serotonin 2A receptors. Serotonin is often called ‘the happy chemical’ because it contributes to wellbeing and happiness. However, it is involved in a wide range of functions in the body, including vision. Previous research showed that drugs which block these receptors in the brain prevent hallucinations in people with schizophrenia.

The hallucinating mice were placed in front of a digital screen which flashed various pictures. All the while, researchers examined the brain activity of the mice and compared it to normal conditions. They found that while the mice were hallucinating on the images, brain activity in the visual cortex — the region of the brain responsible for interpreting visual information — was dampened.

This was a very counter-intuitive finding. One would expect that neurons in the visual cortex would fire in over-drive when a person is hallucinating, not the other way around. However, this makes sense if you look at it from the context of visual processing. The most important clue was that the visual signals sent to the visual cortex were almost the same as those sent in the absence of the drug, which shows that the brain still received the same information. What differed was the way that information was processed.

Writing in the journal Cell Reportsthe researchers conclude that hallucinations may be the product of over-interpretation. Essentially, the brain is filling the blanks in what it perceives as missing information.

“Understanding what’s happening in the world is a balance of taking in information and your interpretation of that information,” Cristopher Niell, a neuroscientist at the University of Oregon in Eugene, said in a statement. “If you’re putting less weight on what’s going on around you but then over-interpreting it, that could lead to hallucinations.”

The study’s main limitation is that it worked only with mice, but the findings could reasonably translate to humans as well. Hallucinating mice shared many characteristics seen in humans, such as visible movement and behavioral changes.

The authors are also careful to mention that over-interpretation isn’t the only cause for hallucinatory experiences. Instead, there are likely many causes and uncovering each of them may be important in a medical setting for the treatment of schizophrenia and other mental disorders that cause hallucinations.

Yalenusresea

Drug cocktails can almost double lifespan — in worms and fruit flies, so far

A cocktail of drugs has been shown to effectively double lifespan — but so far, it only works for flies and worms.

Yalenusresea

Microscope image of Caenorhabditis elegans worms used in the study.
Image credits Jan Gruber.

One research team from Singapore wants to extend human lifespan through pharmacological means. It’s a lofty goal, but the results are already coming in. In a new study, the team reports they’ve successfully increased the healthy lifespan and delayed the rate of aging in a tiny little worm known as Caenorhabditis elegans. The study is the product of a collaboration between the Yale-NUS College, and the National University of Singapore (NUS).

Longer life for simple life

“Many countries in the world, including Singapore, are facing problems related to ageing populations,” said Dr. Gruber, an Assistant Professor of Biochemistry at Yale-NUS College, who lead the research effort.

“If we can find a way to extend healthy lifespan and delay ageing in people, we can counteract the detrimental effects of an ageing population, providing countries not only medical and economic benefits, but also a better quality of life for their people.”

Some widely-employed drugs have quite interesting effects beyond their primary indented use. For example, rapamycin/sirolimus, a drug administered following organ transplants to prevent organ rejection, has been shown to increase the lifespan of several simple (non-human) species. Gruber’s team wanted to see whether cocktails of such life-prolonging drugs could be more efficient at staving off old age than the sum of their individual components. They tested combinations of two or three compounds at a time. Drugs in each mix were selected to target a different metabolic pathway related to aging in C. elegans, a free-living roundworm that grows to around 1 mm (0.03 in) in length.

The first good sign is that the drugs didn’t have any negative impact on the worms’ health. The second good sign was that the cocktails were much more efficient than the individual compounds. For example, three-drug cocktails almost doubled the average lifespan of the worms. Needless to say, this is quite the achievement — no other drug intervention has ever had such an effect on lifespan in adult animals, the team reports.

The third and arguably most exciting finding is that treated worms were healthier and spent a larger part of their life in good health across all ages. So not only did they live more, but they lived better for a greater part of their lives compared to untreated worms. In collaboration with Associate Professor Nicholas Tolwinski (also at the Yale-NUS), the researchers found that the common fruit flies (Drosophila melanogaster) treated with the drug cocktails also had significantly increased lifespans.

The fact that the drugs worked in two organisms with distinct evolutionary backgrounds suggests that they work on ancient aging-related pathways. It’s likely, then, that they would work similarly in humans.

“We would benefit not only from having longer lives, but also spend more of those years free from age-related diseases like arthritis, cardiovascular disease, cancer, or Alzheimer’s disease,” Dr. Gruber said. “These diseases currently require very expensive treatments, so the economic benefits of being healthier for longer would be enormous.”

Dr. Gruber says that the research is just a proof-of-principle. It’s meant to show that the approach is viable, that a multiple-drug approach could be used to extend the healthy lifespan of adult animals — perhaps even humans.

In the future, the team plans to extend their research to cover three key areas. First, they want to develop drugs and drug mixes that are even more effective than the ones used in this study. They also want to determine exactly how each compound works to delay aging, in a bid to create computer models that can test quickly test many more potential drug combinations. Ultimately, they want to try and apply the findings in slowing down aging for humans.

The paper “Drug Synergy Slows Aging and Improves Healthspan through IGF and SREBP Lipid Signaling” has been published in the journal Developmental Cell.

Combining antibiotics may be more effective, new study suggests

The traditional belief is that combining two or more antibiotics yields diminishing returns. But a new study suggests that this might not always be the case. Instead, scientists argue, there are thousands of viable combinations.

In a world where germs are becoming more and more drug-resistant, doctors and physicians need all the help they can get. While designing new drugs and limiting existing resistance are essential, scientists are also trying to get as much as possible out of existing resources. With this in mind, a team of researchers tried to see whether the conventional approach of using just one antibiotic is always the correct way to go, or if there are more efficient alternatives.

“There is a tradition of using just one drug, maybe two,” said Pamela Yeh, one of the study’s senior authors and a UCLA assistant professor of ecology and evolutionary biology. “We’re offering an alternative that looks very promising. We shouldn’t limit ourselves to just single drugs or two-drug combinations in our medical toolbox. We expect several of these combinations, or more, will work much better than existing antibiotics.”

Working with 8 different antibiotics, they analyzed every possible four and five-drug combination, varying the dosage in different ratios, ending up with a total of 18,278 combinations in all. They tested out all these combinations on E. coli, a common type of bacteria that can live in our intestines.

They were expecting a few fringe combinations to be very effective at killing the bacteria, but they were surprised to see just how many effective combinations they discovered. Among the 4-drug combinations, there were 1,676 groupings that performed better than expected, while in the 5-drug combinations, 6443 groupings did better than expected.

“I was blown away by how many effective combinations there are as we increased the number of drugs,” said Van Savage, the study’s other senior author and a UCLA professor of ecology and evolutionary biology and of biomathematics. “People may think they know how drug combinations will interact, but they really don’t.”

The key to this success might lie in the way different antibiotics target pathogens.

“Some drugs attack the cell walls, others attack the DNA inside,” Savage said. “It’s like attacking a castle or fortress. Combining different methods of attacking may be more effective than just a single approach.”

Of course, this doesn’t necessarily mean that antibiotic combinations should become the new norm. There are still many things that need to be accounted for, both in terms of different pathogens and how different treatments would work on different people. But the study suggests that at least in some cases, combinations could be useful — and efficient.

Researchers are currently creating open-access software based on their results, in order to help other researchers and clinicians further develop this approach. It’s certainly a thing worth looking into more, and it’s something that one day could very well change the way antibiotics are administered

Antibiotic resistance infograph.

The CDC thwarted 220 cases of pathogens with ‘unusual’ antibiotic resistance last year alone

Over 220 instances of germs with ‘unusual’ antibiotic resistance genes were reported to the CDC across the U.S., the CDC’s Vital Signs report states.

Bacteria.

Image via Pixabay.

The increasing prevalence of drug-resistant bacteria is, for good reason, one of the most worrying trends in modern medicine. Simply put, we’re developing new treatment options much more slowly than bacteria and their ilk can adapt (read: become immune) to the ones currently at our disposal.

In light of this fact, I’m sure you’ll be comforted to hear that health departments working with CDC’s Antibiotic Resistance (AR) Lab Network throughout the U.S. found more than 220 instances of germs with ‘unusual’ antibiotic resistance genes last year, according to the Vital Signs report. This category includes germs that are impervious to most or all antibiotics we currently possess, are uncommon in one particular geographic area or the U.S. as a whole, or have genetic mechanisms that allow them to spread their resistance to other germs.

To kill a mockinggerm

Antibiotic resistance infograph.

Image credits CDC.

Needless to say, because of the danger they pose to public health, the CDC considers the early detection of these pathogens a top priority. After a threat is identified, the next step in the Centers’ strategy is containment: facilities working with the CDC’s AR Lab try to isolate infected patients as quickly as humanly possible, then initiate special procedures intended to root out any unknown infectees, as well as reduce or stop the pathogen’s spread to new patients.

Luckily, this strategy proved effective in all the reported cases.

“CDC’s study found several dangerous pathogens, hiding in plain sight, that can cause infections that are difficult or impossible to treat,” said CDC Principal Deputy Director Anne Schuchat, M.D. “It’s reassuring to see that state and local experts, using our containment strategy, identified and stopped these resistant bacteria before they had the opportunity to spread.”

The Vital Signs report explains that the CDC’s approach, when faced with such pathogens, calls for rapid identification of resistance, infection control assessments, testing patients who may carry and spread the germ (even those that don’t exhibit symptoms), coupled with continued infection control assessments until spread is stopped. Initial screening is performed within 48 hours of the initial report, and maintain follow-up procedures over several weeks to ensure the threat is neutralized.

CDC prevention strategy.

Image credits CDC.

The CDC estimates that such efforts prevented over one and a half thousand new cases of difficult-to-treat or potentially untreatable infections, including high-priority threats such as Candida auris and carbapenem-resistant Enterobacteriaceae (CRE). The AR Lab Network is crucial for this effort, as it allows for a coordinated response from several healthcare facilities, labs, health departments, and members of the CDC itself.

Other highlights published in the report include:

  • One in four germ samples sent to the AR Lab Network for testing had genetic mechanisms that allow them to spread resistance to other populations.
  • Investigations in facilities that work with unusual resistance pathogens show that about 10% of screening tests on patients without symptoms identified a hard-to-treat strain that spreads easily. This would suggest that germs can spread relatively undetected in such facilities.
  • For CRE alone, estimates show that the containment strategies would prevent as many as 1,600 new infections in three years’ time, in a single state — representing a 76% slash in the total number of cases.

CDme

So what can you do to help the CDC contain such dangerous pathogens in the future? Well, it’s not that much — as you can imagine, tackling populations of drug-resistant bacteria isn’t something you do for fun on a Wednesday evening if you want to be effective. But you can help by being the Center’s scout; its eyes on the ground, if you will. If you want to pitch in, the CDC recommends you:

  • Inform your health care provider if you recently received health care in another country or facility. This lets them tie the dots together and trace down a pathogen’s potential movements in case a threat is determined.
  • Talk to your healthcare provider about preventing infections, taking good care of chronic conditions and getting recommended vaccines. An ounce of prevention beats a pound of cure, as the old saying goes — especially if that pound of cure can’t even kill off the infection.
  • Lastly, practice good hygiene — such as keeping hands clean with handwashing or alcohol-based hand rubs — and make sure you keep cuts and other open wounds clean until healed.

The entire Vital Signs report, as well as more information on the CDC’s containment strategy,  can be accessed on the CDC’s website, here.

Petri dish.

New method developed to stop bacteria from sharing antibiotic resistance genes

The molecular mechanisms underpinning the spread of drug resistance in bacteria populations have been identified — and a new class of molecules has been designed to fight it.

Petri dish.

Image credits via Pixnio.

The rise of multi-drug resistant bacteria is often — and to my mind, as well as the WHO’s — rightly held to be one of the biggest current threats to global health. A large part of what constitutes this threat is that bacteria can share resistance among themselves — like IT guys swapping USB sticks with new firewall software, bacteria can share genes encoding antibiotic resistance.

In a bid to nip this growing threat in the bud, researchers at the European Molecular Biology Laboratory (EMBL) have uncovered and then unraveled one of the major resistance-transfer mechanisms. They’ve also developed proof-of-concept molecules to carry out this bacterial sabotage.

Resisting the resistance

Over time, bacteria have developed a certain resistance level to most drugs we use today. The worst are arguably those that have developed resistance to multiple classes of antibiotics; examples range from MRSA (methicillin-resistant Staphylococcus aureus), VRE (vancomycin-resistant enterococcus), and ESBL (extended spectrum beta-lactamase) producing Enterobacteriaceae.

One of the major drivers of resistance spread throughout bacterial populations are transposons. Also called ‘jumping DNA’, they are bits of genetic code that can autonomously move throughout the genome. When this movement occurs between bacteria, it spreads antibiotic resistance genes among individuals. Very bad for us.

Under the leadership of Orsolya Barabas, one research team at the EMBL became the first to determine the structure of a crystal-like, protein-DNA structure which inserts these transposons in recipient bacteria. Dubbed the transposase protein, this molecule could hold the key to throwing the whole process into disarray.

Protein structure.

The unusual shape of the transposase protein (blue) forces the transposon DNA (grey) to unwind and open up.
Image credits Cell.

The protein has an unusual shape, which allows it to bind to DNA in an inactive state, keeping the transposon safe from potential chemical or physical damage until it’s delivered to its new host. Its shape also forces the transposon DNA to unwind, the team notes, allowing the protein to insert these genes into a wide array of locations within the genomes of many different bacteria.

“If you think of ropes or wires, they are usually bundled and wound-up to make them stronger. If you want to tear or cut one, it’s much easier if you unwind and loosen it first,” says EMBL group leader Orsolya Barabas, who led the work.

“It’s the same for DNA, and the transposon transfer mechanism takes advantage of this.”

Because the transposase protein first unwinds and separates the transposon’s strands, they can more readily be cut and pasted to a new site in the recipient genome. Again, very bad for us.

Luckily, Barabas’ team used the protein’s crystal structure to develop molecules that should block the transposons’ movement through two mechanisms. The first prevents the transposase protein from activating by blocking its architecture with a newly designed peptide, a short chain of amino acids — in other words, it wedges itself in the transposase so that it can’t unfurl and deliver the DNA cargo.

The second method ‘corrupts’ the genetic data. This molecule, a DNA-mimic, binds to the transposon and blocks the DNA strand replacement in the host; no replacement, no resistance transfer.

“As we believe these features are broadly present in these jumping DNA elements, but not in related cellular systems, they may be quite specific to transposons. This way, we can target only the bacteria we want, and not the many good bacteria in our bodies and the environment,” Barabas explains.

The molecules are still far from trials with living hosts. For now, Barabas and her colleagues will focus on better understanding the transfer mechanisms, as well as on developing and testing new strategies to block it.

The paper “Transposase-DNA Complex Structures Reveal Mechanisms for Conjugative Transposition of Antibiotic Resistance” has been published in the journal Cell.

Marijuana farm in Colorado. Credit: Pixabay.

Marijuana Scientists Are Getting High Wages

Marijuana farm in Colorado. Credit: Pixabay.

Marijuana farm in Colorado. Credit: Pixabay.

Marijuana has almost always been a controversial topic in public and in the scientific community as well. It makes headlines, and is, of course, the craving of many addicts. Many renowned authors have sampled the cannabis drug in the hopes of improving or embellishing their creative writings. Such writers include Alexander Dumas, Victor Hugo, Jack Kerouac, Carolyn Cassady, and William S. Burroughs.

The recreational use of the drug also assisted in feeding the Hippie Movement of the 1960’s and ’70’s. It has been the subject of much discussion, resulting in several publications dedicated solely to this purpose such as The High Times and Dope Magazine. However, marijuana does seem to have some healthful pros going for it when applied properly in certain circumstances. Among a number of benefits, it has been known to protect the brain following a stroke, to control some kinds of muscle attacks, and even to reduce the spread of cancerous cells.

The historical record places the date of one of the earliest medicinal uses of cannabis in the 2700’s BC in China. Emperor Shen Nung who reigned during that time wrote that it was employed to help with ailments such as rheumatism and malaria. In the 16th century AD, it was introduced in the Americas. Since then, practically anything having to do with weed makes headlines. In particular, current information relating to the legalities of the drug makes for hot news.

California, the Golden State, is the eighth state to make the recreational use of marijuana legal as of January 1, 2018. Now Hollywood stars (and all the others who want to) are free to openly smoke weed whenever they please. But medical marijuana is a different animal in the legal game because, as it has already been stated, it can improve or safeguard human health in some cases. Medical marijuana is currently legal to use in 29 of the 50 states.

A lot of “dough” can be made off of dope. Those in the business of growing and providing pot can definitely make a decent income from it. But many of the people doing this have found their banks will not allow their cannabis cash to be deposited. This is because marijuana is illegal under federal law. (The banks are operated by the federal government.) So I would not advise anyone to go down that type of career path. If pot fascinates you, there are other job opportunities which are growing more popular as they are in demand.

One such open career choice is for cannabis researchers, sometimes referred to as “weed scientists.” By the year 2020, it is predicted the marijuana science industry will be employing about 300,000 individuals. Simple tasks such as bud trimming can pay anywhere from $8 to $12 per hour. More experienced positions for marijuana scientists are comprised of tasks like teaching, conducting research, and even formulating regiments for biological control agents. In order to go into this profession, one has to have a valid interest in topics like weed science (duh), soil science, and agriculture. An aspiring weed scientist will require a BS degree in an area such as agronomy, horticulture, or soil science. The specific type of education required will depend on the kind of work one wants to go into.

pharmaceuticals

Retails drug price varied by more than 600% among 10 high-income countries

Researchers looked at the volume and daily cost of primary care prescriptions in 10 high-income countries with universal health care. Everyone expected to see some pretty wild variation but not quite like this. For drugs in the six largest categories of primary care, pricing varied by more than 600%, and that’s not including the famous highly priced American pharmaceuticals. The United States was not included in the study because it does not offer universal health care.

pharmaceuticals

Credit: Pixabay.

The countries analyzed by the researchers include Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland and the United Kingdom. The focus was on pharmaceuticals from 6 widely used categories purchased at retail pharmacies rather than in a hospital setting like:

  • hypertension treatments;
  • pain medications (nonsteroidal anti-inflammatory drugs as well as opioids);
  • cholesterol-lowering drugs;
  • noninsulin diabetes treatments;
  • gastrointestinal medications and
  • antidepressants.

The Canadian researchers measured the frequency of use and calculated how much the therapy costs in each country.

Across countries, the average annual per capita expenditure on the primary care medicines studied varied by more than 600%: from $23 in New Zealand to $171 in Switzerland.

In the 5 countries with universal, single-payer coverage of prescription medications, the average per-person cost was $77. Average costs were $99 in the 4 countries with universal social insurance for prescription drugs. In Canada, whose system is a mix of private and public financing, the annual cost was $158.

“The volume of therapy purchased in Canada was about the same as that in the comparator countries; however, Canadians spent an estimated $2.3 billion more than they would have in 2015 if these primary care treatments had had the same average cost per day in Canada as in the 9 comparator countries combined,” writes Dr. Steven Morgan, School of Population and Public Health, University of British Columbia, with coauthors.

The findings suggest that citizens living in countries with single-payer financial systems get the best deals as the system seems to promote lower prices. Universal pharmacare could thus help reduce prices for consumers in both Canada and the United States.

“Average expenditures are lower among single-payer financing systems, which appear to promote lower prices and selection of lower-cost treatment options within therapeutic categories,” the study authors conclude in the journal CMAJ.

 

For $20, high school students create medicine which sells for between $35,000 and $110,000

We all know some drugs are overpriced, but do you have any idea just how overpriced they are?

Pyrimethamine is the active substance in the medicine Daraprim. It’s used to treat parasitic infections in people with vulnerable immune systems, such as HIV sufferers or pregnant women. In August 2015, the price of Daraprim in the US rose from $US13.50 per tablet to $US750, a move made by controversial then-chief executive Martin Shkreli. In most countries, Daraprim is sold for between $1 to $2 per pill.

Daraprim sells for absurdly high prices in the US.

Well, two high school students in Australia have shown just how cheaply the drug can be produced.

Milan Leonard and his high-school colleagues created 3.7 grams of the active ingredient for $20 – something which in the US would sell for up to $110,000. They worked for a year, but in the end, they achieved what they wanted.

“It was ecstatic, it was bliss, it was euphoric,” he said. “After all of this time spent working and chemistry being such a high and low, after all the lows, after all the downs, being able to make this drug, it was pure bliss.”

Fellow student Brandon Lee said he almost couldn’t believe they managed to do it in just their high school lab.

“At first there was definitely disbelief,” he said. “We spent so long and there were so many obstacles that we, not lost hope, but it surprised us like ‘oh, we actually made this material’ and ‘this can actually help people out there’. “So it was definitely disbelief but then it turned in to happiness as we realised we finally got to our main goal.”

The students didn’t do it all by themselves, they were guided by University of Sydney research chemist Alice Williamson, who guided them through an online research-sharing platform called Open Source Malaria. In case you’re wondering how they knew the ingredients to make this drug… well, they got it off Wikipedia.

“The original route that we got, so the original recipe if you like to make this molecule, was from a patent that was referenced on Wikipedia,” Dr Williamson said. “Now of course we checked to see if it looked reasonable … but the route that was up actually had one step that involved a really dangerous chemical. The boys had to navigate a difficult step and do this in a different way, and they’ve managed to do that, and they’ve managed to do that in their high school laboratory.”

At the moment, Turing Pharmaceuticals is the only company to sell the FDA-approved drug, and they refuse to lower the price. Following backlash and legal threats, all the company did is reduce the price by 50% for hospitals – but it’s still absurdly high.

bacteria spreading agar

Scientists film bacteria becoming virtually drug-immune — and it took them only 10 days

Researchers mixed Hollywoodian magic with science to create a striking — and worrying — demonstration of how bacteria encounter, adapt, and finally thrive even in the presence of antibiotics.

bacteria spreading agar

Credit: Harvard Medical School

Acquired drug resistance is rapidly becoming a problem for medicine — germs adapt to our medicine much faster than we can develop and distribute new ones. But exactly how fast this adaptive process takes place isn’t really something people realize. A new Harvard Medical School and Technion-Israel Institute of Technology experiment, inspired by Hollywood’s tv-magic, offers the first large-scale example of how fast bacteria evolve to deal even with immense concentrations of antibiotics.

“It’s a powerful illustration of how easy it is for bacteria to become resistant to antibiotics”

The experiment consisted of placing the bacterium Escherichia coli in a huge 2-by-4-foot petri dish filled with agar (the jelly-like material used to nurture bacterial colonies in the lab). The team then divided this area into seven sections and treated them with various doses of medicine. The outermost slices were drug-free, followed by slices with just enough antibiotics to kill the bacteria. Each section that followed would receive a ten-fold increase in dose, so the middle area contained 1,000 times the minimum required concentration. Dubbed the MEGA (Microbial Evolution and Growth Area) plate, the design represents a more realistic environment to study how species overcome the spatial and evolutionary challenges that drive evolution, the researchers said.

“We know quite a bit about the internal defense mechanisms bacteria use to evade antibiotics but we don’t really know much about their physical movements across space as they adapt to survive in different environments,” said study first author Michael Baym, a research fellow in systems biology at HMS.

The team pointed a camera at the MEGA plate and took snaps of the colonies over the next two weeks. The time-lapse they made with these snaps is a powerful display of evolution at work — and a bone-chilling reminder of just how flimsy our drugs are against pathogens.

This plate isn’t a perfect illustration of how bacteria behave in the real world — in hospitals for example — but it does mimic them more closely than a traditional petri dish. This is because in bacterial evolution, space, size, and geography play a hugely important role, the team explains. Just like walking on a paved street is different from hiking in rough terrain for us, expanding in environments with varying antibiotic properties in the wild or in homogeneous settings in the lab are two very different things if you’re a bacteria.

The experiment proposes to teach HMS students about evolution in an engaging and visually captivating way. Senior study investigator Roy Kishony of HMS and Technion say the inspiration came from a digital billboard for the 2011 film Contagion. It showed a giant lab dish where glowing microbes crept slowly over a darker background to spell out the movie’s title.

“This project was fun and joyful throughout,” Kishony said. “Seeing the bacteria spread for the first time was a thrill. Our MEGA-plate takes complex, often obscure, concepts in evolution, such as mutation selection, lineages, parallel evolution and clonal interference, and provides a visual seeing-is-believing demonstration of these otherwise vague ideas. It’s also a powerful illustration of how easy it is for bacteria to become resistant to antibiotics.”

Postdoctoral research fellow at MIT and co-investigator Tami Lieberman, who was a graduate student in the Kishony lab at the time of the experiment, says the images captivate laymen and trained professionals alike.

“This is a stunning demonstration of how quickly microbes evolve,” she said.

“When shown the video, evolutionary biologists immediately recognize concepts they’ve thought about in the abstract, while nonspecialists immediately begin to ask really good questions.”

Spreading the news

Image credits NIAID / Flickr.

The experiment also allows us insight into how bacteria adapted to environmental constraints — in this case, increasingly deadly concentrations of drugs:

Bacteria first spread until they reached a concentration (antibiotic dose) in which they could no longer survive. A small number of individuals would eventually acquire resistance to the higher concentration through successive genetic changes. These mutants’ descendants migrated in the new area, competing with other resistant strains. The winning strains progressed to the area with the higher drug dose, until they again reached a drug concentration at which they could not survive.

Through small increments, non-resistant bacteria gave rise to moderately then highly resistant mutants. In just 10 days, the culture spawned mutants capable of surviving 1,000 times the dose of antibiotic trimethoprim that was deadly to the initial bacteria. When researchers used another antibiotic — ciprofloxacin — bacteria adapted to 100,000 times the initial deadly dose.

These mutations initially stiffen the bacteria’s growth rate — suggesting that while adapting to the dose, bacterias still found it hard to develop. Once fully resistant to the drug, they regained their normal growth rates.

The most resistant strains weren’t always the first to expand. Sometimes, they lagged behind weaker strains as they were developing into areas with higher doses of antibiotics. This goes against the commonly held belief that only the most resistant mutants survive high concentrations of a drug.

“What we saw suggests that evolution is not always led by the most resistant mutants,” Baym said. “Sometimes it favors the first to get there. The strongest mutants are, in fact, often moving behind more vulnerable strains. Who gets there first may be predicated on proximity rather than mutation strength.”

The full paper “Spatiotemporal microbial evolution on antibiotic landscapes,” has been published in the journal Science.

Untreatable bacteria identified in the US

A strain of E. coli resistant to last-resort antibiotics has been identified on United States soil for the first time. Health officials say this could be “the end of the road for antibiotics,” leaving us virtually helpless in fighting future infections.

Last month, researchers identified a 49-year-old Pennsylvania woman as the carrier for a strain of E. coli resistant to the antibiotic Colistin. The woman visited a clinic in Pennsylvania, which forwarded a sample to Walter Reed National Military Medical Center. Walter Reed found the bacteria in her urine.

Think of this drug as our nuclear option — it’s employed for particularly dangerous pathogens, when every other drug fails. This includes the CRE family, a group of germs so resilient and deadly that health officials have dubbed it “nightmare bacteria”. Infection with these superbugs ends up killing up to 50 percent of patients in some instances, and the CDC lists them among the country’s most urgent public health threats.

Finding a bug that can shrug off even Colistin on home soil “heralds the emergence of a truly pan-drug resistant bacteria,” say the authors of the paper detailing the discovery.

“It basically shows us that the end of the road isn’t very far away for antibiotics — that we may be in a situation where we have patients in our intensive-care units, or patients getting urinary tract infections for which we do not have antibiotics,” CDC Director Tom Frieden said in an interview Thursday.

This is the first known carrier of a Colistin-resistant strain in the United States. Last November, a report by Chinese and British researchers who found the Colistin-proof strain in pigs, raw pork meat and several people in China was met with shock by public health officials worldwide. The deadly strain was later discovered in Europe and elsewhere.

Escherichia coli (E. coli) naturally occurs in your gut and most strains are harmless. Some, however, can cause food-borne diseases with fever, nausea and vomiting to bloody diarrhea. The infections are transmitted by eating or drinking contaminated food and water. E. coli resistance for a spectrum of drugs has been increasingly reported in cases of urinary tract infections, and the WHO warns that the most widely used oral treatment — fluoroquinolones — are rapidly becoming ineffective. Seeing strains develop virtual immunity to any of our antibiotics is very bad news, Frieden says.

“I’ve been there for TB patients. I’ve cared for patients for whom there are no drugs left. It is a feeling of such horror and helplessness,” he added. “This is not where we need to be.”

The CDC and the Pennsylvania State Health Department mobilized immediately to investigate the case and to trace the patient’s contacts to see if the bacteria had spread. The CDC also said it is looking for other potential cases in the healthcare facility the patient visited.

The full paper, titled “Colistin resistance in the USA” has been published online in the journal Antimicrobial Agents and Chemotherapy and can be read here.

Acetaminophen affects the ability to detect errors

Acetaminophen, commonly sold as Tylenol or Paracetamol may affect our ability to solve errors, a new study has found. The impairment is minor, but noticeable.

Acetaminophen is one of the most common drugs, usually taken for mild pains and fever. But recently, more and more studies are starting to point out the negative effects of the drug. The latest in the string of side effects was pointed out by Canadian researchers, who report that people taking the drug are less likely to observe errors.

“It looks like acetaminophen makes it harder to recognize an error, which may have implications for cognitive control in daily life,” said Dan Randles, a researcher at the University of Toronto. “This is the first study to address this question, so we need more work and ideally with tasks more closely related to normal daily behavior.”

For the study, published in the journal Social Cognitive and Affective Neuroscience, they recuited 62 people for a double-blind, randomized study with half the participants receiving 1,000 milligrams of acetaminophen, the normal maximum dose, and the rest given a placebo. They were then hooked up to an electroencephalogram and given a target-detection task called Go or No Go, hitting a button when an “F” appeared on a screen but not hitting the button if an “E” appeared on the screen. Not only did the acetaminophen group hit the button more often when an “E” appeared, but they also missed more “F” screens, suggesting that the drugs has an effec that goes beyond just numbing the pain.

“An obvious question is if people aren’t detecting these errors, are they also making errors more often when taking acetaminophen,” Randles asks.

Acute overdoses of acetaminophen can cause liver damage and might even be fatal. The toxicity associated with Paracetamol and Tlenol is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia and New Zealand.According to the FDA, in the United States there were “56,000 emergency room visits, 26,000 hospitalizations, and 458 deaths per year related to acetaminophen-associated overdoses during the 1990.

ibuprofen patch

This is an ibuprofen patch that relieves pain 12 hours straight

Researchers at the University of Warwick in the UK, in collaboration with drug delivery research firm Medherant, devised the first ever ibuprofen patch.

ibuprofen patch

Its made out of a polymer matrix which allows the painkiller to be steadily diffused in the body of the patient over the course of 12 hours. During whole time the seemingly flimsy patch can prevent pain since its made out of 30% ibuprofen by weight.

“Many commercial patches surprisingly don’t contain any pain relief agents at all, they simply soothe the body by a warming effect. Our technology now means that we can for the first time produce patches that contain effective doses of active ingredients such as ibuprofen for which no patches currently exist. Also, we can improve the drug loading and stickiness of patches containing other active ingredients to improve patient comfort and outcome,” said University of Warwick research chemist Professor David Haddleton.

“Our success in developing this breakthrough patch design isn’t limited to ibuprofen; we have also had great results testing the patch with methyl salicylate (used in liniments, gels and some leading commercial patches). We believe that many other over the counter and prescription drugs can exploit our technology and we are seeking opportunities to test a much wider range of drugs and treatments within our patch.”

A drug used for decades for liver diseases could effectively slow down Parkinson’s

It seems like re-purposing drugs can be a gold mine for future drug development. Now, scientists have discovered that a drug used for decades in liver treatments might effectively slow down Parkinson’s disease.

Parkinson’s disease is a degenerative disorder of the central nervous system mainly affecting the motor system. It’s a nasty condition, and there is no effective treatment for it – we don’t even fully understand why it occurs in some people. But now, medics might be getting an unexpected ally: ursodeoxycholic acid (UDCA).

I say unexpected because UDCA has already been in clinical use for decades, but for a completely different problem. Also, since it’s been used in treatments, we already know that it’s safe, so this new treatment could hit the markets much sooner. Dr Heather Mortiboys, Parkinson’s UK Senior Research Fellow from the University of Sheffield, explained:

“We demonstrated the beneficial effects of UDCA in the tissue of LRRK2 carriers with Parkinson’s disease as well as currently asymptomatic LRRK2 carriers. In both cases, UDCA improved mitochondrial function as demonstrated by the increase in oxygen consumption and cellular energy levels.”

The rest of the team echoed his optimism. Oliver Bandmann, Professor of Movement Disorders Neurology at the University of Sheffield added:

“Whilst we have been looking at Parkinson’s patients who carry the LRRK2 mutation, mitochondrial defects are also present in other inherited and sporadic forms of Parkinson’s, where we do not know the causes yet. Our hope is therefore, that UDCA might be beneficial for other types of Parkinson’s disease and might also show benefits in other neurodegenerative diseases.”

There is a tremendous need for Parkinson treatments, especially as it affects approximately seven million people globally and one million people in the United States. We need something to happen in years, not decades. Dr Arthur Roach, Director of Research and Development at Parkinson’s UK, which part-funded the study, said:

“There is a tremendous need for new treatments that can slow or stop Parkinson’s. Because of this urgency, the testing of drugs like UCDA, which are already approved for other uses, is extremely valuable. It can save years, and hundreds of millions of pounds. It’s particularly encouraging in this study that even at relatively low concentrations the liver drug still had an effect on Parkinson’s cells grown in the lab.”

Journal Reference:

  1. H. Mortiboys, R. Furmston, G. Bronstad, J. Aasly, C. Elliott, O. Bandmann. UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2G2019S carriers and in vivo. Neurology, 2015; DOI: 10.1212/WNL.0000000000001905

 

Use of Psychedelics Could Reduce Suicide Rates

Suicide rates have generally remained the same for decades, with slight increases in some areas of the world. Basically, scientists and medics don’t really know how to effectively tackle this issue, so they’re considering more unorthodox approaches. A new study has found that classic psychedelic use may reduce suicidal thinking, ultimately dropping suicide rates.

Image via Wine and Bowties.

“Despite advances in mental health treatments, suicide rates generally have not declined in the past 60 years. Novel and potentially more effective interventions need to be explored,” researcher Peter S. Hendricks, PhD, assistant professor in the department of health behavior at the University of Alabama at Birmingham, said in a press release. “This study sets the stage for future research to test the efficacy of classic psychedelics in addressing suicidality as well as pathologies associated with increased suicide risk (eg, affective disturbance, addiction and impulsive-aggressive personality traits).”

The thing is, several studies concluded that psychedelic drugs could have medical potential, and are not as damaging to the brain as previously thought. Now, Hendricks and his colleagues sed 2008 to 2012 data from the National Survey on Drug Use and Health survey of the Substance Abuse and Mental Health Services Administration of the U.S. Dept. of Health and Human Services, detailing the relationship between psychedelic (and other) drugs and suicide rates.

“Mental health problems are endemic across the globe, and suicide, a strong corollary of poor mental health, is a leading cause of death. Classic psychedelic use may occasion lasting improvements in mental health, but the effects of classic psychedelic use on suicidality are unknown”, the study reads. “Lifetime classic psychedelic use was associated with a significantly reduced odds of past month psychological distress, past year suicidal thinking, past year suicidal planning, and past year suicide attempt”.

The type of psychedelics is also important – classic psychedelics (like “magic mushrooms” or LSD) are the ones which caused the improvement.

Today, 500 million people globally suffer from mental diseases, according to the World Health Organization. A growing number of medical researchers seems to support the potential use of psychedelic drugs to treat and deal with these diseases.

“As a scientist, I am persuaded that classic psychedelics could be potent therapeutic agents,” he said. “Second, personally, I am intrigued by the notion of providing a profoundly meaningful personal or spiritual experience to occasion ‘quantum change’ — sudden, dramatic, lasting change.”

Still, despite this potential, such substances are grossly understudied, which is very strange to me. If you want to keep them completely banned and consider them as illicit, then you want to see what the negative effects are in detail, in order to justify the ban. If you want to use them for medical purposes, then you have all the more reasons to study them, right?

“Classic psychedelics carry a contentious recent history and barriers to their clinical evaluation remain. Growing evidence including the present research suggests that classic psychedelics may have the potential to alleviate human suffering associated with mental illness,” the researchers conclude.

Journal Reference: Hendricks PS, Thorne CB, Clark CB, Coombs DW, Johnson MW. Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. J Psychopharmacol. 2015 Jan 13. pii: 0269881114565653

drug coma patient

Common Anti-Anxiety drug wakes man up from coma

A patient who has been in a near-vegetative state for two years has been awaken after receiving a common anti-anxiety drug.The patient was in this state following a motorcycling accident he had, and after receiving the drug, he immediately became active, talking to his doctor, calling his aunt and congratulating his brother on graduating. Then, as quickly as he emerged from his near vegetative state, he reverted to it.

drug coma patient

Image: Maria Chiara Carboncinia et al.

The patient was a man from Pisa, Italy; he had no recollection of his accident or current status – he acted as if his normal life just resumed from yesterday. Doctors gave him the drug as a mild sedative for a CT scan, but they were shocked to see the patient waking up. To make things even stranger, as the drug wore off, the patient reverted to his previous state.

The drug in case is called midazolam. Midazolam has a wide range of effects, and it has potent anxiolytic, amnestic, hypnotic, anticonvulsant, skeletal muscle relaxant, and sedative properties; the drug is also used for the nduction and maintenance of anesthesia.

After the patient woke up and fell asleep again, the doctors gave him the drug once more, and this woke him up again.

Image: Maria Chiara Carboncinia et al

With help from EEG recordings, the neuroscientists have so far focused on activity in two regions of the brain: the task-positive network and the linguistic network.

“Our attention has focused on these two particular networks because we believe that their functional improvement has substantially contributed to determine the awakening reaction presented by our patient,” they write in the current paper. The task-positive network, in fact, has to deal with the ability to cope with and solve cognitive tasks that require explicit behavioral responses, while the linguistic one deals with language comprehension and production,” the neuroscientists explain.

This is the first time that Midazolam has been used this way. You can read the full article here.