Publisher Health

The anti-parasitic drug ivermectin, which has surged in popularity as an alternative treatment for Covid-19 despite a lack of strong research to back it up, showed no sign of alleviating the disease, according to results of a large clinical trial published on Wednesday.The study, which compared more than 1,300 people infected with the coronavirus in Brazil who received either ivermectin or a placebo, effectively ruled out the drug as a treatment for Covid, the study’s authors said.The researchers shared a summary of these results in August during an online presentation hosted by the National Institutes of Health, but the full data set had not been published until now, in The New England Journal of Medicine.“Now that people can dive into the details and the data, hopefully that will steer the majority of doctors away from ivermectin towards other therapies,” Dr. David Boulware, an infectious-disease expert at the University of Minnesota, said.For decades, ivermectin has been widely used to treat parasitic infections. Early in the pandemic, when researchers were trying thousands of old drugs against Covid-19, laboratory experiments on cells suggested that ivermectin might block the coronavirus — though at much higher concentrations than would be safe for human use.Some small studies suggested possible benefits in humans, but subsequent analysis found the studies to be flawed and the benefits illusory. The clinical trial whose data was published on Wednesday was much larger and more rigorous.Researchers in Brazil provided the drug to 679 patients over the course of three days between March and August 2021 in a double-blinded treatment, meaning that neither the patients nor the medical staff knew whether any particular patient was receiving a Covid treatment drug or a placebo.The results were clear: Taking ivermectin did not reduce a Covid patient’s risk of ending up in the hospital.The researchers zeroed in on different groups of volunteers to see if they experienced benefits that others didn’t. For example, it might have been possible that ivermectin worked only if taken early in an infection. But volunteers who took ivermectin in the first three days after a positive coronavirus test turned out to have worse outcomes than did those in the placebo group.There are other large randomized trials of ivermectin, with thousands of volunteers, that are still in progress and have yet to share their results. The National Center for Advancing Translational Sciences, which is part of the N.I.H., has been running one closely watched trial of ivermectin and several other drugs for Covid patients for more than a year, with no results released yet.

The New England Journal of Medicine (NEJM) today published final results of a nationwide multicenter study led by researchers at Johns Hopkins Medicine and the Johns Hopkins Bloomberg School of Public Health that show plasma from patients who have recovered from COVID-19 and whose blood contains antibodies against SARS-CoV-2, the causative virus, is an effective and safe option as an early outpatient treatment for the disease.
The research showed that high-titer (antibody-rich) COVID convalescent plasma — when administered to COVID-19 outpatients within nine days after testing positive — reduced the need for hospitalization for more than half of the study’s predominantly unvaccinated outpatients. The U.S. Food and Drug Administration (FDA) currently authorizes this plasma as a treatment option for outpatients with immunocompromising diseases or receiving immunocompromising medications, and for all patients hospitalized with early-stage COVID-19.
The findings were first presented in a preprint posted to MedRxiv on Dec. 21, 2021. Details of the study, including authors and funding sources, may be found in the Johns Hopkins news release issued at that time (https://www.hopkinsmedicine.org/news/newsroom/news-releases/early-use-of-convalescent-plasma-may-help-outpatients-with-covid-19-avoid-hospitalization).
“Based on our findings and conclusions — which are now validated through the peer-review process — we encourage health care professionals to keep SARS-CoV-2 antibody-rich blood plasma available in their blood banks as part of the treatment arsenal against early-stage COVID-19,” says study co-lead author David Sullivan, M.D., professor of molecular microbiology and immunology at the Johns Hopkins Bloomberg School of Public Health with a joint appointment in infectious diseases at the Johns Hopkins University School of Medicine.
“We believe that the best role for convalescent plasma is extending its use to early outpatient treatment when other therapies, such as monoclonal antibodies or drugs, are either not readily available — as in low- and middle-income countries — or ineffective, as with SARS-CoV-2 variants that are resistant to certain monoclonal antibodies,” Sullivan adds.
In the outpatient early-treatment study conducted between June 2020 and October 2021, the researchers provided 1,181 randomized patients with one dose each of either polyclonal high-titer convalescent plasma (containing a concentrated mixture of antibodies specific to SARS-CoV-2) or placebo control plasma (with no SARS-CoV-2 antibodies). The patients were 18 and older, and had tested positive for SARS-CoV-2 within eight days prior to transfusion. A successful therapy was defined as a patient not requiring hospitalization within 28 days after plasma transfusion.

Findings describe a novel way to reduce the energy people spend to walk, as much as by half, which could have applications for therapy received by patients with impaired walking abilities.
The research, conducted at the University of Nebraska at Omaha and published in the journal Science Robotics, demonstrates that the optimal way to assist with a wearable device does not always align with intuition.
Based on previous literature, the researchers believed they would see the highest energy savings by pulling with a waist tether when the individual is trying to propel forward against the ground. That hypothesis was based on a bioinspired assistance strategy, meaning it is inspired by how our biological muscles work during walking.
“Although bioinspired actuation can have certain benefits, our study demonstrates that this is not necessarily the best strategy for providing the greatest reduction in metabolic cost or energy expended,” said Prokopios Antonellis, Ph.D., first author of the study and now a postdoctoral fellow at Oregon Health & Science University. “This finding supports a greater emphasis on biomechanical testing rather than trying to predict optimal bioinspired strategies,” said Antonellis, who performed the research during his doctoral program at UNO.
The approach of using biomechanical testing to optimize a robotic waist tether is highlighted as one of different unique approaches for designing personalized assistance in an editorial published March 30 by Amos Matsiko, Ph.D., senior editor of Science Robotics.
The timing
This research shows that a strategically-timed pull from a waist belt connected to a pulley can help an individual use less energy for each step while walking. However, the optimal timing of that forward pull was what came as a surprise.

Global opioid sales increased by an estimated 4% annually from 2015 to 2019, but massive disparities in access to essential pain relief medications persist between countries, finds a study led by UCL researchers.
Opioid use in some countries in Africa and South America was less than one tenth of 1% of the rates in wealthier countries in North America, Europe and Australia, according to the findings published in The Lancet Public Health.
Some countries are starting to catch up, as the overall picture is one of gradual geographic convergence in opioid consumption.
North America has seen a decline in opioid use, likely the result of efforts to reduce inappropriate prescribing to curb deadly opioid misuse, so multiple European countries, led by Switzerland, Germany, and Spain, have surpassed the United States in opioid sales.
Lead author Dr Wallis Lau (UCL School of Pharmacy) said: “We found that while there is some improvement in a lot of countries, there are still concerningly low rates of opioid use in large parts of the world, even in numerous middle-income countries.
“Opioids have been listed by the World Health Organization as an essential class of medicine for acute pain, cancer-related pain, and palliative care since 1977, so it is troubling that in many parts of the world, people are unable to access this medicine. There is an urgent need to tackle the global gap in opioid access.

In recent years, the number of people worldwide who are dissatisfied or anxious about their sleep has been increasing due to the diversification of lifestyles. Simple sleep measurement and quantitative understanding of individual sleep patterns are very important not only in the field of healthcare but also from the medical perspective, such as in the diagnosis of sleep disorders.
A research group of The University of Tokyo led by Professor Hiroki Ueda (also a Riken team leader) and Machiko Katori, and Assistant Professor Shoi Shi (RIKEN) used ACCEL(1), an original machine learning algorithm developed by their research laboratory, to determine sleep and waking states based on arm acceleration and converted the acceleration data of approximately 100,000 people in the UK Biobank(2) into sleep data, which was then analyzed in detail. They found that the sleep patterns of these 100,000 people could be classified into 16 different types.
The research group first focused on the arm acceleration data of approximately 100,000 people in the UK Biobank. This data was obtained from men and women in their 30s to 60s, mainly in the UK, who were measured for up to 7 days using wristband-type accelerometers. Using an algorithm (ACCEL) they had developed in 2022, the research group generated sleep data(3) for approximately 100,000 people from the acceleration data. The obtained sleep data were converted into 21 sleep indicators, and then, using dimension reduction(4) and clustering(5) methods, the sleep patterns were classified into 8 different clusters. These included clusters related to “social jet lag” and clusters characterized by mid-onset awakenings and considered insomnia, enabling the extraction of clusters related to lifestyles and to sleep disorders. Next, in order to examine sleep patterns associated with sleep disorders in more detail, the research group focused on 6 of the 21 sleep indicators, including sleep duration and intermediate waking time, which are known to be closely related to sleep disorders. By applying the same analysis to data where one indicator deviated significantly from general sleep (data in the upper 2.28th percentile or higher or the lower 2.28th percentile or lower (6) in the overall distribution), they were able to classify the data into 8 clusters. These included clusters related to morning-types and evening-types. They also identified several clusters associated with insomnia, and were able, along with the clustering using the entire dataset, to classify 7 types of sleep patterns associated with insomnia.
Thus, by analyzing sleep on a large scale, they have revealed the landscape of human sleep phenotype. This study has made it possible to quantitatively classify clusters related to lifestyle such as “social jet lag” and morning/evening types, which are usually difficult to determine with short-term PSG measurements(7), In addition, detailed analysis of outlier and classification of sleep patterns revealed 7 clusters related to insomnia. These clusters are classified based on new indicators differing from conventional methods, and are expected to be useful in the construction of new methods in terms of diagnosing insomnia and proposing treatment methods.
These results were obtained through the “Ueda Biological Timing Project,” ERATO Program funded by the Japan Science and Technology Agency (JST). In this project, JST develops “systems biology that contributes to understanding human beings,” using sleep-wake rhythms as a model system, and aims to understand in human sleep-wake behavior the “biological time” information that extends from molecules to individual humans living in society.
Notes:
(1) ACCEL : An original sleep determination algorithm developed by the research team. For details, refer to the following paper. “A jerk-based algorithm ACCEL for the accurate classification of sleep-wake states from arm acceleration” DOI: 10.1016/j.isci.2021.103727

People who survive an ischemic stroke are much more likely to develop major heart complications during the first month after their stroke, and, as a result, they also have an increased risk of death, heart attack or another stroke within five years, compared to people who don’t develop heart problems soon after a stroke, according to new research published today in Stroke, the peer-reviewed, flagship journal of the American Stroke Association, a division of the American Heart Association.
Ischemic stroke is the most common type of stroke — accounting for 87% of all strokes — and occurs when blood flow to the brain is blocked. After a stroke, people often have cardiovascular complications, known as stroke-heart syndrome. Heart complications include acute coronary syndrome, angina (chest pain), heart rhythm issues such as atrial fibrillation, arrhythmia and ventricular fibrillation; heart attack; heart failure or Takotsubo syndrome (broken heart syndrome), a type of stress-induced temporary enlargement of a part of the heart that impacts its ability to pump effectively. These conditions increase the risk of disability or death in the short term, yet the long-term consequences for people with stroke-heart syndrome is unknown.
“We know heart disease and stroke share similar risk factors, and there’s a two-way relationship between the risk of stroke and heart disease. For example, heart conditions such as atrial fibrillation increase the risk of stroke, and stroke also increases the risk of heart conditions,” said Benjamin J.R. Buckley, Ph.D., lead author of the study and a postdoctoral research fellow in preventive cardiology at the Liverpool Centre for Cardiovascular Science, University of Liverpool in the United Kingdom. “We wanted to know how common newly diagnosed heart complications are after a stroke and, importantly, whether stroke-heart syndrome is associated with increased risk of long-term major adverse events.”
Researchers analyzed the medical records of more than 365,000 adults treated for ischemic stroke at more than 50 health care sites predominantly in the United States, between 2002 and 2021. People who were diagnosed with stroke-heart complications within four weeks after a stroke were matched to an equal number of stroke survivors who did not have these heart complications within four weeks (the control group).
After adjusting for potential confounding factors, such as age, sex and race/ethnicity, and comparing the stroke survivors who had new heart complications to those who did not, the analysis found: Overall, among all stroke survivors in the study, about 1 in 10 (11.1%) developed acute coronary syndrome, 8.8% were diagnosed with atrial fibrillation, 6.4% developed heart failure, 1.2% exhibited severe ventricular arrythmias and 0.1% developed ‘broken heart’ syndrome within four weeks after the stroke. Risk of death within five years after a stroke significantly increased among the participants with new heart complications: 49% more likely if they had developed acute coronary syndrome; 45% more likely if they had developed atrial fibrillation/flutter; and 83% more likely if they developed heart failure. Severe ventricular arrhythmias doubled the risk of death. Chance of hospitalization and heart attack within five years after a stroke was also significantly higher among those who developed heart complications within the one-month window. Stroke survivors with Takotsubo syndrome were 89% more likely to have a major heart event within the five years after their stroke. People who developed atrial fibrillation after stroke were 10% more likely to have a second stroke within five years after their stroke. People with stroke and newly diagnosed cardiovascular complications were 50% more likely to have a recurrent stroke within five years after the first stroke.”I was particularly surprised by how common stroke-heart syndrome was and the high rate of recurrent stroke in all subgroups of adults with stroke-heart syndrome” Buckley said. “This means that this is a high-risk population where we should focus more secondary prevention efforts.”
The study’s results build on the understanding of the two-way link between the brain and the heart and extend this understanding to long-term health outcomes. “We are working on additional research to determine how stroke-heart syndrome may be better predicted,” Buckley said.
“We also need to develop and implement treatments to improve outcomes for people with stroke-heart syndrome,” Buckley said. “For example, comprehensive exercise-based rehabilitation may be helpful after a stroke, so for people with stroke and newly developed heart complications, it should also be beneficial, maybe even more so. I think this is an interesting area for future research.”
Study limitations include that it is a retrospective analysis and knowing whether the heart complications diagnosed following an ischemic stroke were caused by stroke or rather contributed to the stroke, is unclear.
“This research underscores why it’s so important for neurologists and cardiologists to work hand-in-hand with their patients and each other to understand why the first stroke occurred and perform a comprehensive assessment to identify new risk factors for another stroke and for cardiovascular disease that may require initiation of prevention therapies,” said Lee H. Schwamm, M.D., volunteer chair of the American Stroke Association Advisory Committee and the C. Miller Fisher Chair in Vascular Neurology at Massachusetts General Hospital in Boston. “The American Stroke Association recommends a personalized secondary stroke prevention plan for every stroke survivor.”
Co-authors are Stephanie L. Harrison, Ph.D.; Andrew Hill, M.B.Ch.B.; Paula Underhill; Deirdre A. Lane, Ph.D.; and Gregory Y.H. Lip, M.D.
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Researchers at the Okinawa Institute of Science and Technology Graduate University (OIST) have revealed how poxviruses build their scaffold — a temporary protein coat that forms and disappears as the virus matures.
Reporting today in Nature Communications, the scientists revealed the structure of a protein called D13, in near-atomic resolution, and showed how it assembles with other copies of D13 to form scaffold-like structures.
“D13 is a key target for research, because if you know how the scaffold is assembled, you can design new drugs that prevent it from forming,” said Professor Jaekyung Hyun, a former staff scientist in the OIST Molecular Cryo-Electron Microscopy Unit, and now Assistant Professor at Pusan National University in South Korea. “If the scaffold can’t form, then replication of the virus stops.”
D13 is a trimer protein, as it is formed from three identical protein chains. Once synthesized, it acts as a scaffold building block for the Vaccinia virus — a harmless strain developed in the laboratory as a vaccine against smallpox. Researchers now use the Vaccinia virus as a model for all poxviruses.
“Smallpox is the most famous and lethal disease caused by a poxvirus, with 1 in 3 infected people dying,” said Professor Wolf, who leads the Molecular Cryo-Electron Microscopy Unit. “But while smallpox has been eradicated in the wild, there are fears that it could be used as a bioweapon. Also, numerous other poxviruses still infect humans and livestock, so further research into how these viruses replicate is essential.”
The scaffold seen in immature poxviruses is of particular interest to scientists, as the structure differs from the protein coats typically seen in viruses.

Skin cells and their DNA varies between individuals, but new data from Flinders University shows that some groups of people have higher variability in their cell deposits.
The South Australian forensic science researchers are building a suite of new insights into crime scene investigation — including the difference between high, intermediate and low skin ‘shedders’ that will help understanding of trace or ‘touch DNA’.
The latest research, ‘DNA deposited in whole thumbprints’ (just published in Forensic Science International: Genetics), further studies inter-variation of DNA shedding obtained from experiments on samples gathered from 10 different people and 30 of their thumbprints.
“The first challenge at a scene is finding touch DNA, which is why we have developed an accurate special aerosol fluorescent dye ‘marker’,” says Professor Adrian Linacre, who leads Flinders University’s forensic DNA technology research group.
“A further challenge is evaluating the value of the evidence, and that’s where shedders are a factor.
“Data like this new study allows a growing understanding of differences in DNA ‘shedding’ between people, and why we might find traces of people’s DNA a long time after an event.”
Flinders University PhD candidate Todd Kaesler says: “We have found that some people have higher intra-variability, indicating that these individuals will not always reliably pass on similar amounts of cellular material and DNA. This is individual-dependent.
“Any new data on cell deposition goes to strengthen our understanding of how cells are deposited and why some are found well after a criminal event.”
The study used a nucleic acid binding dye that shows the number of cells deposited when a person touches an object.
“Our work leads to more reliable touch DNA collection methods, which can be key in forensic casework,” says Professor Linacre.
“We look forward to producing more accurate methods and informative research to help forensic scientists to fulfill their roles in a challenging environment.”
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Dogs and cats may be exposed in their homes to a potentially toxic group of chemicals, with their discovery in the pets’ stool being a sign of health issues for humans living with them, a new study shows.
Called aromatic amines, the chemicals — found in tobacco smoke and in dyes used in cosmetics, textiles, and plastics — are known to cause cancer. Notably, the study revealed that tobacco smoke was not a major source of pet exposure, suggesting that the latter products were likely the main culprits.
Led by researchers at NYU Grossman School of Medicine, the study identified eight types of aromatic amines in stool samples collected from dozens of dogs and cats. It also found traces of the chemicals in more than 38% of urine samples taken from a separate group of pets.
“Our findings suggest that pets are coming into contact with aromatic amines that leach from products in their household environment,” says study lead author Sridhar Chinthakindi, PhD, a postdoctoral fellow at NYU Langone Health. “As these substances have been tied to bladder, colorectal, and other forms of cancer, our results may help explain why so many dogs and cats develop such diseases.”
He adds that the results suggest that, aside from such direct exposures, pets are likely indirectly exposed. For example, past research has shown that a common flea control medication called amitraz can be broken down into an aromatic amine called 2,6-dimethylaniline by microbes living in animals’ digestive systems. This was the most common aromatic amine detected in the new study, accounting for almost 70 percent of those found in dogs and nearly 80 percent of those found in cats.
The study authors’ previous investigations have measured other hormone-disrupting chemicals, including phthalates, melamine, and bisphenols in pet urine. However, the new study, published online March 30 in the journal Environment International, is the first designed to explore pet exposure to aromatic amines in the household, according to Chinthakindi.

Law enforcement seizures of pills containing illicit fentanyl increased dramatically between January 2018 and December 2021, according to a new study. The number of individual pills seized by law enforcement increased nearly 50-fold from the first quarter of 2018 to the last quarter of 2021 and the proportion of pills to total seizures more than doubled, with pills representing over a quarter of illicit fentanyl seizures by the end of 2021. The study also found an increase in the number of fentanyl-containing powder seizures during this time.
This study was published today in Drug and Alcohol Dependence and funded by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health. According to the most recent Centers for Disease Control and Prevention data, the United States hit a record high in the number of overdose deaths ever recorded, estimating that nearly 106,000 people died from drug overdoses in the 12-month period ending in October 2021. This rise is largely driven by illicit fentanyl and other synthetic opioids.
Illicit fentanyl is highly potent, cheaply made and easily transported, making it a profitable narcotic. While people may seek out illicit fentanyl intentionally, many people are not aware that the drug they are using — including heroin, cocaine, methamphetamine, or benzodiazepines — may actually be fentanyl, or has been adulterated or contaminated with fentanyl. Because fentanyl is about 50 times more potent than heroin and a lethal dose may be as small as two milligrams, using a drug that has been laced with fentanyl can greatly increase overdose risk.
“An increase in illicit pills containing fentanyl points to a new and increasingly dangerous period in the United States,” said NIDA Director Nora D. Volkow, M.D. “Pills are often taken or snorted by people who are more naïve to drug use, and who have lower tolerances. When a pill is contaminated with fentanyl, as is now often the case, poisoning can easily occur.”
Illicitly manufactured powder fentanyl has been a known adulterant in drugs since 2013, but the extent that fentanyl is found in counterfeit pills has been largely unknown. To address this question, a team led by Joseph J. Palamar, Ph.D., M.P.H., associate professor at the NYU Grossman School of Medicine and co-investigator on the NIDA-funded National Drug Early Warning System (NDEWS), analyzed data on drug seizures by law enforcement. The data were collected between January of 2018 and December of 2021 from the High Intensity Drug Trafficking Areas (HIDTA) program, a grant program aimed at reducing drug trafficking and misuse administered by the Office of National Drug Control Policy in which the Drug Enforcement Administration and the CDC play an active role.
Comparing data from the first quarter of 2018 with the last quarter of 2021, the team found that the number of seizures of pills containing fentanyl increased from 68 to 635, and the total number of individual pills seized by law enforcement increased from 42,202 to 2,089,186. Seizures of powder containing fentanyl also increased from 424 to 1,539, and the total weight of powder seized increased from 298.2 kg to 2,416.0 kg.
Unlike most survey data and surveillance systems which can be lagged for a year or more, HIDTA data are made available quarterly, allowing evaluation in almost real time. HIDTA also distinguish between the presence of fentanyl in pill or powder form. Analyzing these data can therefore help identify trends in availability of illicit substances and act as a type of early warning system to shift public health education or interventional resources more quickly.
HIDTA data does not differentiate between fentanyl and its analogs, nor estimate the amount of fentanyl present in seized substances; however, given the small amount necessary for an overdose, the authors note that the presence of any fentanyl is an important indicator of overdose risk. People who purchase counterfeit drugs, such as illicit oxycodone, hydrocodone, or benzodiazepines may be at risk for unintentional exposure to fentanyl, which is associated with increased risk of overdose death. Further, people who use these types of pills are less likely to have a tolerance built to opioids, and when coupled with the sedative effects of non-fentanyl opioids or benzodiazepines, may further increase risk of overdose and death.
“For the first time we can see this rapid rise in pills adulterated with fentanyl, which raises red flags for increasing risk of harm in a population that is possibly less experienced with opioids,” said Dr. Palamar. “We absolutely need more harm reduction strategies, such as naloxone distribution and fentanyl test strips, as well as widespread education about the risk of pills that are not coming from a pharmacy. The immediate message here is that pills illegally obtained can contain fentanyl.”
The researchers emphasize that drug seizure rates are not direct measures of actual drug availability. However, the increase in fentanyl-related drug seizures coincides with increasing synthetic opioid-related overdose death rates. These data also corroborate data from the DEA National Forensic Laboratory Information System showing a steady increase in fentanyl seizures in recent years, even across the earlier parts of the COVID-19 pandemic. For additional NDEWS research and reports, visit: https://ndews.org/
“To address the overdose crisis, you need real-time, high-quality drug surveillance data to inform the public health response,” said Linda B. Cottler, Ph.D., M.P.H, principal investigator of NDEWS, and last author on the paper. “Through collecting and sharing data on drug use trends as we do through our NIDA-funded NDEWS, we aim to guide strategies to curb the overdose crisis of today, while also keeping our eye on the horizon to prepare for the problems of tomorrow.”