Day: November 4, 2021

Cannabis Use during Pregnancy is on the Rise

Source: Anna Hecker on Unsplash

As cannabis becomes increasingly legalised, for medical or recreational purposes, its use during pregnancy is increasing, along with the potential for abuse or dependence.

A new study, published in JAMA Psychiatry, explored the magnitude and nature of cannabis use disorders during pregnancy by examining hospital discharge codes. Most of those hospitalisations were for childbirth.

The study found that the proportion of hospitalised pregnant patients identified with cannabis use disorder (defined as cannabis use with clinically significant impairment or distress) rose 150% from 2010 to 2018.

Largest such study so far
“This is the largest study to document the scale of cannabis use disorder in prenatal hospitalisations,” said study co-author Claudia Lugo-Candelas, PhD, assistant professor of clinical medical psychology in Columbia University’s Department of Psychiatry. She notes the study found that pregnant patients with the condition had sharply higher levels of depression, anxiety, and nausea – results of clinical concern.  

“It’s a red flag that patients may not be getting the treatment they need,” Dr Lugo-Candelas said.

Some pregnant patients use cannabis instead of prescribed medications, thinking it’s a safer choice as cannabis legalisation has eased safety fears. However, both the American Academy of Pediatrics (AAP) and the American College of Obstetricians and Gynecologists (ACOG) have recommended against using cannabis while pregnant, chiefly because of known and unknown fetal effects. Concerns for maternal effects focus on smoking or vaping risks, not mental health.

The study identified 249 084 hospitalised pregnant patients with cannabis use disorder, who were classified into three sub-groups: those with cannabis use disorder only; those with use disorders for cannabis and other controlled substances; and those with cannabis use disorder and other non-controlled substances (alcohol, tobacco). Data was matched against equivalent patients without any substance use disorders.

Mood disorders more common
Researchers found that those with the cannabis condition were more likely to be younger (ages 15 to 24), Black non-Hispanic, and to not have private insurance.

Researchers analysed patients records for depression, anxiety, trauma, and ADHD, and a broader category of mood-related disorders. Medical conditions measured included chronic pain, epilepsy, multiple sclerosis, nausea, and vomiting.

All disorder sub-groups had elevated rates of nearly every factor studied. Patients with cannabis use disorder alone had triple the levels of depression and anxiety than patients with no use conditions. Mood-related disorders affected 58% of those with cannabis use disorder compared to 5% without.

“The least other substance use you have, the more that cannabis use makes a difference,” Dr Lugo-Candelas said. “That’s really striking.”

High levels of were also seen in the cannabis use disorder hospitalisations, but whether that was due to patients using cannabis to mitigate nausea, or due to cannabis use, which can cause a vomiting syndrome, or a symptom of pregnancy is unknown. Study co-author Angélica Meinhofer, PhD, assistant professor of population health sciences at Weill Cornell Medicine, noted that many states allow medical use of cannabis for nausea and vomiting.

While screening for cannabis during pregnancy could help, doctors could be reluctant to ask about use due to mandatory reporting rules. Patient education could help get them treatment earlier, especially with co-occurring psychiatric problems.

“Hopefully these findings will motivate better conversations between pregnant patients and their health care providers,” said Meinhofer.

The authors stress they aren’t arguing for or against cannabis use in pregnancy. Research on prenatal effects of the disorder is still largely lacking, though frequent use has been linked to low birth weight and other adverse outcomes. Their study, the researchers say, instead underscores the need to further explore the disorder and its links to psychiatric and medical conditions.

The increase of cannabis use by pregnant patients demands immediate investigation. “This is a population that’s showing a level of distress that is very, very high,” said Dr Lugo-Candelas. “Care and attention need to be rolled out.”

Source: Columbia University Irving Medical Center

Enzymes Speed up Production of Molnupiravir for COVID

Photo by Louis Reed on Unsplash

Molnupiravir is being developed for the treatment of COVID, which has been submitted for review by the US Food and Drug Administration, but large-scale production to treat COVID is still a challenge. Now, researchers have engineered enzymes to help manufacture the pill, resulting in a much shorter synthesis with a higher yield than current methods. The details of their work are reported in ACS Central Science.

The oral antiviral molnupiravir was originally developed to treat influenza, and works by causing viruses to make errors when copying their own RNA, introducing mutations that inhibit replication. Recently, interim phase 3 clinical trial findings indicated that molnupiravir reduced the risk of hospitalisation and death from COVID for newly diagnosed, at-risk patients, and that it had equal effectiveness against different SARS-CoV-2 variants. Researchers set out to develop a shorter, higher-yielding and sustainable way to synthesise the molecule.

The team came up with a three-step synthesis of molnupiravir from ribose, a sugar molecule. They identified enzymes or chemical treatments to sequentially add the appropriate chemical groups to ribose to generate the molecule. For the second step of the synthesis, the team identified bacterial enzymes that weakly catalysed the desired reactions. Using in vitro evolution, they greatly enhanced these enzymes’ activities. The new synthetic route, which also included a phosphate recycling strategy, was 70% shorter and had a seven-fold higher overall yield than the original route.

Source: American Chemical Society

Why Does Arthritis Flare Up in the Same Place?

Source: Miika Luotio on Unsplash

A new study has revealed why arthritis has a tendency to flare up in the same location instead of around the body.

When joints flare up in people with rheumatoid arthritis and related diseases, the joints involved are often the same as those previously affected. For example, if arthritis started in the right knee, it is much more likely to flare there than in the left knee, even if the arthritis had been in remission for years. Because of this, each patient develops a highly individual disease pattern, though why this is so has remained unclear.

“Overwhelmingly, flares occur in a previously involved joint,” said Peter Nigrovic, MD, chief of the division of immunology at Boston Children’s Hospital. “Something in that joint seems to remember, ‘this is the joint that flared before.’”

A new study, co-led by Dr Nigrovic and published in Cell Reports, shows where that memory is housed: in a type of immune cell called a tissue-resident memory T cell. Specifically, these T cells reside in the synovium, the tissue that lines the inside of the capsule surrounding the joint.
“We showed that these T cells anchor themselves in the joints and stick around indefinitely after the flare is over, waiting for another trigger,” said Dr Nigrovic. “If you delete these cells, arthritis flares stop.”

The team demonstrated this phenomenon in three separate mouse models of inflammatory arthritis. Two models used chemical triggers to cause joint inflammation, and the third had a protein knocked out that blocks the pro-inflammatory cytokine IL-1. Once activated, resident memory T cells in the joints rallied other immune cells, leading to an arthritis flares limited to specific joints. Elimination of these T cells prevented further flares from occurring.

“Right now, treatment of rheumatoid arthritis has to continue lifelong; although we can successfully suppress disease activity in many patients, there is no cure,” said Dr Nigrovic. “We think our findings may open up new therapeutic avenues.”

Dr Nigrovic also believes the findings apply to other types of autoimmune arthritis, including juvenile idiopathic arthritis.

Dermatology provided a cue for the researchers: tissue-resident memory T cells were originally found in skin, where a ‘memory’ pattern is well known to dermatologists. In psoriasis, for example, patients get recurrent plaques in the same places. The same often holds true in cutaneous hypersensitivity reactions, such as reactions to nickel in jewelry or wristwatches. “A person reacting to nickel through a belt buckle may also develop a rash on their wrist, where they wore a nickel-containing watch as a child,” observed Dr Nigrovic.

Source: EurekAlert!

Over 28 Million More Years of Life Lost in 2020

Source: Pixabay CC0

Over 28 million more years of life were lost than expected in 2020 in 31 upper-middle and high-income countries, according to a University of Oxford-led study published in the BMJ.

Save for a handful of exceptions, 37 countries examined including the US had more premature deaths than expected in 2020, with a higher rate in men than women.

Understanding the full impact of the COVID pandemic requires counting excess deaths, and analysing how premature those deaths are. Years of life lost (YLL) is a more detailed assessment of COVID’s impact on populations as it measures both the number of deaths and the age at which death occurs.

Researchers used this measure to estimate the changes in life expectancy and excess years of life lost from all causes in 2020. They compared the observed life expectancy and years of life lost in 2020 with historical trends in 2005-19 in 37 upper-middle and high-income countries.

Between 2005 and 2019, life expectancy at birth rose for both men and women in all the countries studied. In 2020, a drop in life expectancy was seen in both men and women in all countries save New Zealand, Taiwan, and Norway, where there was a life expectancy gain and Denmark, Iceland, and South Korea saw no change.

The biggest life expectancy drop was in Russia (−2.33 years in men and −2.14 in women), the US (−2.27 and 1.61), Bulgaria (−1.96 and −1.37), Lithuania (−1.83 and −1.21), Chile (−1.64 in men), and Spain (−1.11 in women). Years of life lost declined in most countries in both men and women between 2005 and 2019, except Canada, Greece, Scotland, Taiwan, and the US.  

In 2020, years of life lost were higher than expected in all countries except Taiwan and New Zealand, where there was a reduction in years of life lost, and Iceland, South Korea, Denmark, and Norway, where there was no evidence of a change in years of life lost. In the remaining 31 countries, more than 222 million years of life were lost in 2020, which is 28.1 million more than expected (17.3 million in men and 10.8 million in women).  

The highest excess years of life lost (per 100 000) were in Russia (7020 in men and 4760 in women), Bulgaria (7260 and 3730), Lithuania (5,430 in men and 2,640 in women), and the US (4,350 in men and 2,430 in women).

Overall, excess years of life lost in 2020 were over five times greater (2510 per 100 000) than those associated with the seasonal influenza epidemic in 2015 (458 per 100 000).

The excess years of life lost were relatively low in people under 65 years, except in Russia, Bulgaria, Lithuania, and the US where the excess years of life lost was more than 2 000 per 100 000.

Most countries in Asia, Africa, and Latin America were excluded due to insufficient data, and researchers could not account for other factors, such as socioeconomic status, regional disparities, and race or ethnicity. However, the findings are largely in line with previous studies, and the use of authoritative national mortality data, together with a validated analytical approach, suggests that the results are robust.

“Our findings of a comparable or lower than expected YLL in Taiwan, New Zealand, Denmark, Iceland, Norway, and South Korea underscore the importance of successful viral suppression and elimination policies, including targeted and population based public health policy interventions,” the researchers wrote. “As many of the effects of the pandemic might take a longer time frame to have a measurable effect on human lives, continuous and timely monitoring of excess YLL would help identify the sources of excess mortality and excess YLL in population subgroups.”

Source: University of Oxford

Unmet Lung Cancer Patient Needs Have a Significant Impact

Source: Mart Production on Pexels

Research studies suggest that unmet physical and psychological needs of patients with lung cancer have a significant impact on patients’ quality of life and affect their ability to continue with everyday activities. 

Lung cancer is the leading cause of cancer death in the United States. No specific signs and symptoms exist for lung cancer, and most patients already have advanced disease at the time of presentation. In a study published in the European Journal of Cancer Care, researchers examined the impact of unmet needs on patients’ lives.

Analysing results from six studies involving 562 patients, researchers found that almost two thirds of the patients had been diagnosed with advanced cancer (stage III or IV), and most had been diagnosed for less than two years. There was a negative association between quality of life and unmet needs using two different measures. In two of the studies, the relationship was limited to physical and/or psychological needs.

In the physical domain, lack of energy and tiredness were common unmet needs, and uncertainty about the future, fears, and worry were among the most common in the psychological domain.

“This research underscores the high burden of unmet needs for individuals with lung cancer, often resulting from late diagnosis and associated lack of curative treatment,” said corresponding author Simon Dunne, PhD, of Dublin City University, in Ireland. “There is a need for early intervention and tailoring of pre-existing services to address unmet supportive care needs in this cancer group.”

Source: Wiley

Ultrasound Treatment can Target Neural Circuits of Epilepsy

Image credit: Dr Yu

A pioneering new study from Taiwan showed that focused ultrasound, which can be used to non-invasively target circuits in the brain, may benefit some patients with epilepsy who experience seizures which remain unresponsive to standard anti-seizure medications.

The results showed that of six patients with drug-resistant seizures, two patients had fewer seizures within three days of receiving focused ultrasound; however, one patient showed signs of more frequent subclinical seizures (which are not felt by the individual). The findings from the study were published in the journal Epilepsia.

Imaging tests performed after the treatment show that there were no negative effects on the brain. One patient reported a sensation of heat on the scalp during the treatment, and another patient experienced temporary memory impairment that resolved within three weeks.

“Neuromodulation is an alternative treatment for drug-resistant epilepsy. Compared with the present modalities used in neuromodulation for epilepsy, focused ultrasound can access deeper brain regions and focus on the main target of the epileptic network in a relatively less invasive approach,” explained senior author Hsiang-Yu Yu, MD, of Taipei Veterans General Hospital, in Taiwan. “It gives new hope and sheds new light for patients with drug-resistant epilepsy.”

Source: Wiley

Treating Cancer with the Toxoplasma Gondii Parasite

Source: National Cancer Institute on Unsplash

Scientists have discovered that Toxoplasma gondii, a parasite known to cause illness in pregnant women and immunocompromised patients, could potentially enhance the treatment of various types of tumours.

The parasite Toxoplasma gondii is a single-celled opportunistic protozoan capable of infecting a broad range of warm-blooded animals and has been reported in nearly one-third of the world’s human population. It has a number of health effects, including a strong link to schizophrenia and has even been associated with increased suicide attempts in mothers.

While many treatments have been able to treat tumours and prolong the lives of patients, there is a need to further enhance these. In the study, published in the Journal for ImmunoTherapy Cancer, scientists found that the commonly found parasite  is able to sensitise ‘cold’  tumours, that is, tumours unlikely to trigger a strong immune response, to immune checkpoint blockade therapy.

The researchers believe that this finding could have broader therapeutic implications for many types of cancers.

T. gondii has to live inside the cells of its host and secretes numerous proteins to counter the host’s immune defences and to facilitate their own invasion and colonisation of the host cells. The researchers first built a T. gondii mutant strain with limited growth and disease-causing ability, but which is also able to manipulate the host immune system.

By directly injecting this mutant parasite into solid tumours, it induces inflammatory responses in those tumours and even in tumours located in a distant location in the mouse body. The researchers further demonstrated that this treatment approach has made tumours more responsive to treatment with immune checkpoint inhibitors.

This dual treatment significantly extended the survival of mice and reduced tumour growth in mouse models of melanoma, Lewis lung carcinoma, and colon adenocarcinoma.

Dr Hany Elsheikha, Associate Professor in the School of Veterinary Medicine and Science at the University of Nottingham, and one of the lead authors of the study, said: “The use of a mutant version of Toxoplasma gondii in the treatment of certain tumours in mice models has been previously reported. What makes this study different is the confirmation that intratumoural injection with mutant Toxoplasma gondii strain boosts antitumour immunity and the effectiveness of checkpoint inhibition therapy.

“These are significant findings and are relevant to future tumour therapy. The marked reduction in tumour size and the significant improvement in the survival of mice that received this novel combinational therapy is promising but should be interpreted with caution as further research is needed.”

Source: University of Nottingham