Year: 2021

US Hits Pause on J&J Vaccine

Reacting to reports of potentially dangerous blood clots, the US is recommending a “pause” in immunisations with the single-dose Johnson & Johnson COVID vaccine in order to perform investigations.

The Centers for Disease Control and Prevention and the Food and Drug Administration said in a joint statement that they were investigating blood clots in six women that occurred 6 to 13 days after vaccination. The clots, seen in the sinuses of the brain, also had lowered platelet counts. This renders the use of heparin, the standard treatment for blood clots, potentially dangerous.

Out of 183.5 million vaccine doses administered in the US, over 6.8 million doses are the J&J vaccine — the overwhelming majority without serious side effects. The rest is made up by the two other authorised vaccines, from Moderna and Pfizer.

Use of the J&J shot will be paused in US federal distribution channels, including mass vaccination sites, with states and other providers being expected to follow.

CDC’s Advisory Committee on Immunization Practices will meet Wednesday to discuss the cases and the FDA has also launched an investigation into the cause of the clots and low platelet counts.

“Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” Dr Anne Schuchat, principal deputy director of the CDC, and Dr Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in a joint statement.

They recommend that people who received the J&J vaccine and are experiencing severe headache, abdominal pain, leg pain, or shortness of breath within three weeks after receiving the jab contact their health care provider.

Officials say that they want to bring healthcare providers up to speed on the blood clot’s “unique treatment” .

Meanwhile, Johnson & Johnson had said it was aware of the blood clot reports, but no association with its vaccine had been established.

“We are aware that thromboembolic events including those with thrombocytopenia have been reported with Covid-19 vaccines,” the company said in a statement. “At present, no clear causal relationship has been established between these rare events and the Janssen Covid-19 vaccine.”

In late February, the FDA  granted emergency use authorisation to the J&J vaccine, with hopes that its single-dose and relatively simple storage requirements would speed vaccinations across the country. However, only a fraction of the vaccines administered in the US are the J&J shot. The company has been beset by production delays and manufacturing errors at a contractor’s plant. 

The pharmaceutical company took over the facility to ramp up production to make good on its promise to the US government of 100 million doses by the end of May. Only about 9 million of the company’s doses have been delivered to states and are awaiting administration, according to CDC data.
Previously, concern over the blood clots was confined to AstraZeneca’s vaccine, with European regulators saying last week they found a possible link between the shots and an exceedingly rare type of blood clot presenting with low platelets, a situation found more commonly in young people.

Nevertheless, the European Medicines Agency emphasised that the benefits for the vaccine outweigh the risks. Despite this, several countries imposed restrictions on vaccine eligibility and some such as Britain and Greece recommending that people under a certain age be offered alternatives.

Unlike the Pfizer/BioNTech and Moderna vaccines which use mRNA to train the immune system to recognise the SARS-CoV-2 spike protein, the J&J and AstraZeneca vaccines use an adapted adenovirus to introduce the spike protein antigen into the body. Adenoviruses were first identified in the 1950s as a family of similar disease-causing viruses. AstraZeneca’s vaccine uses a chimpanzee adenovirus while the J&J uses a human one.

Source: Medical Xpress

Mental Health and Physical Activity Impacted by Pandemic

A study from McMaster University suggests that mental health has become both a barrier to and a motivator for physical activity.

Surveying over 1600 subjects, the researchers sought to understand the ways mental health, physical activity and sedentary behaviour have changed throughout the course of the pandemic and why. Their findings show that people want to be active to improve their mental health but find exercise difficult because of stress and anxiety. Previous research indicates that physical activity can contribute to the treatment of depression, while sedentary behaviour has a strong negative impact.
“Maintaining a regular exercise program is difficult at the best of times and the conditions surrounding the COVID-19 pandemic may be making it even more difficult,” said lead author Jennifer Heisz, associate professor at the Department of Kinesiology, McMaster University.

“Even though exercise comes with the promise of reducing anxiety, many respondents felt too anxious to exercise. Likewise, although exercise reduces depression, respondents who were more depressed were less motivated to get active, and lack of motivation is a symptom of depression,” she said.

The survey respondents reported higher psychological stress and moderate levels of anxiety and depression due to the pandemic. Their weekly aerobic activity reduced about 20 minutes, strength training down roughly 30 minutes, and sedentary time per day was up about 30 minutes per day compared to six months prior to the pandemic. Physical activity may have exerted a protective effect, as those with the greatest drops in physical activity had the worst mental health outcomes, while those who kept their physical activity levels the same level fared better in terms of mental health. 
Notably, economic disparities played a role, the researchers found, especially among younger adults.

“Just like other aspects of the pandemic, some demographics are hit harder than others and here it is people with lower income who are struggling to meet their physical activity goals,” said co-lead author Maryam Marashi, a graduate student in the Department of Kinesiology. “It is plausible that younger adults who typically work longer hours and earn less are lacking both time and space which is taking a toll.”

After the researchers analysed the data, the researchers produced a guideline to help people become more physically active:

  • Adopt a mindset: Some exercise is better than none.
  • Lower exercise intensity if feeling anxious.
  • Move a little every day.
  • Break up sedentary time with standing or movement breaks.
  • Plan your workouts like appointments by blocking off the time in your calendar.

“Our results point to the need for additional psychological supports to help people maintain their physical activity levels during stressful times in order to minimize the burden of the pandemic and prevent the development of a mental health crisis,” concluded Heisz.

Source: News-Medical.Net

Journal information: Marashi, M. Y., et al. (2021) A mental health paradox: Mental health was both a motivator and barrier to physical activity during the COVID-19 pandemic. PLOS ONE. doi.org/10.1371/journal.pone.0239244.

Sleep Doctors are Concerned Over CPAP Negative Evaluation

Sleep doctors are concerned about a draft report casting doubt on the clinical benefits of continuous positive airway pressure (CPAP), the clinical gold standard for sleep apnoea.

Reviewers from the Agency for Healthcare Research and Quality (AHRQ) found that studies of continuous positive airway pressure (CPAP) have consistently failed to show improvements in non-sleep-related outcomes linked to obstructive sleep apnea (OSA), such as stroke, heart attack, diabetes, and depression.

The report concluded that the published evidence “mostly does not support that CPAP prescription affects long-term, clinically important outcomes,” and it highlighted research gaps and methodological weaknesses in the available studies, along with significant CPAP compliance issues, which have all contributed to the failure to show long-term benefits for the treatment.

OSA specialists who spoke to MedPage Today about AHRQ’s research review agreed that CPAP remains by far the most effective treatment for sleep-related symptoms of OSA. They worried that the report could be misinterpreted as meaning that the treatment has no value. 
The US offers coverage for CPAP therapy under Medicare for patients with OSA, amounting to hundreds of millions of dollars per annum.. One recent study of Medicare recipients 56% were at high risk for OSA and possible candidates for treatment.

“The big fear that I have, and many of my colleagues have, is that the way this report is worded could easily be misinterpreted as saying that prescribing CPAP doesn’t improve these (long-term) outcomes, so we shouldn’t be paying for it,” said David Rapoport, MD, who directs the sleep medicine research program at the Icahn School of Medicine at Mount Sinai in New York City.

He said that it is widely recognised that CPAP is the most effective treatment for improving OSA symptoms, such as snoring and daytime sleepiness.

“Nothing else even comes close,” he said. “CPAP is really a remarkable treatment for addressing the breathing disorder associated with obstructive sleep apnea. But it has to be used, and compliance remains a big issue.”

The AHRQ review included data from 47 long term (≥6 or 12 months) randomised clinical trials for OSA.

Investigators noted that the studies used “highly inconsistent” definitions of measures such as respiratory events, as well as the Apnoea-Hypopnoea Index (AHI) metric.

“No standard definition of this measure exists and whether AHI (and associated measures) are valid surrogate measures of clinical outcomes is unknown,” the report states.

Elise Berliner, PhD, of AHRQ, told MedPage Today that addressing the inconsistencies and limitations of the existing studies should be a top priority of the sleep research community. She added that definitions should be standardised.

“I do think the community needs to get together and figure out how to do better studies,” she said. “We need larger and longer studies, and there is also the issue of compliance. In most of the studies, people were not using these devices all night long.”

The report found that the existing randomized controlled trials provide low strength of evidence that CPAP affects all-cause mortality, stroke and myocardial infarction risk, or other cardiovascular outcomes. Researchers also concluded that insufficient evidence exists showing an impact for CPAP on the risk for automobile accidents, depression, and anxiety and hypertension.

Sanjay Patel, MD, of the University of Pittsburgh, agreed inconsistency and poor CPAP compliance in sleep studies have made it difficult to assess its  impact on mortality and most other long-term outcomes.

But he, like Dr Rapoport, expressed concern that some will interpret the findings to mean that CPAP is ineffective.

“The thinking in the field has been that treatment may help prevent diseases like diabetes and heart disease that are related to sleep apnea,” he told MedPage Today. “This report says we don’t have good evidence on this, but it doesn’t really distinguish between outcomes where we do and do not have enough research to say definitively that treatment with CPAP isn’t beneficial.”

Dr Patel served on the writing committee for the American Academy of Sleep Medicine’s (AASM) latest clinical practice guidelines for OSA treatment with CPAP. He observed that the guidelines differ from the AHRQ findings, in that CPAP has been shown to lower blood pressure in hypertensive OSA patients.

The AHRQ analysis was also restricted to 6 month follow-ups or longer, while the AASM’s writing committee considered studies with shorter follow-up times.

“The effect [of CPAP] on blood pressure can be seen at 1 month,” he said. “Multiple studies with 3 months of follow-up show improvements in blood pressure, but AHRQ did not look at those studies.”

While CPAP is still considered the most effective treatment for OSA, Dr Rapoport said there is a growing recognition within the sleep medicine field that it’s not for everyone, given the ongoing issues with compliance.

“In the past, other treatments such as mandibular advancement devices have been marginalized,” he said. “These treatments don’t work nearly as well as CPAP in terms of lowering AHI, but they do work well for many patients, and people who are prescribed them actually use them. Until recently, there wasn’t much acceptance that this was good enough. But there is now greater recognition that we should maybe be prescribing treatments that aren’t perfect if people are more likely to use them.”

Source: MedPage Today

Donated Afro Hair Wigs Now Possible Thanks to UK Girl

A silhouetted woman with afro hair reading a book by a window. Photo by Thought Catalog from Pexels

A British girl who was told her afro hair was too delicate to donate for wig-making prompted a new wig-making approach to use it, BBC News reports.

When eleven year old Carly Gorton wanted to donate her afro hair to the Little Princess Trust charity, which makes natural hair wigs for children who have lost theirs from cancer treatment and other causes, she was initially frustrated as the charity said the hair was too delicate. Undeterred, Carly had urged the charity to rethink, which it did.

Following research and a trial to make them possible, the charity described the new wigs as a “historic breakthrough”.

“It’s really beautiful,” said Carly, of one of the new wigs.

A BMJ study showed that wigs positively impact psychological wellbeing for people with alopecia, attributed to increasing their confidence of going out in public and the perception of fewer comments about hair loss.

At a special school assembly, Carly’s mother Anna Mudeka then cut her daughter’s hair and it was donated for use in the first new wigs to be worn by other children.

Phil Brace, The Little Princess Trust’s chief executive, said Carly’s “determination” to donate her hair had pushed them to find a solution.

The charity worked with the 120-year-old London company Raoul to develop a wefting method to weave and tie the donated locks.

Carly’s mother, Anna Mudeka, said: “History has been made and we are so proud of Carly.

“Through her sheer determination and everyone pulling together to hear her voice, children of black and mixed heritage can now donate their hair to the Little Princess Trust.”

Ms Mudeka, of Southburgh, added that children needing wigs through illness could now receive a wig “true to their heritage”.

Carly and her mother’s campaign had created a “fundamental change in wig manufacturing”, said Mr Brace. “The commitment and work that has gone on has shown just what is possible when groups of people get together and bring different skills to find a solution.”

Source: BBC News

CD40 Agonists Before Therapy Kick Off T Cell Response

Giving a CD40 immune-stimulating drug to early-stage pancreatic cancer patients helped kick off a T cell attack on the tumour’s stubborn microenvironment before surgery and other treatments, according to a new study.

Altering the tumour microenvironment to host more T cells using a CD40 agonist earlier could help slow cancer progression and prevent metastasis.

The data was presented by Katelyn T Byrne, PhD, an instructor of Medicine in the division of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania, during a plenary session at the American Association for Cancer Research annual meeting.

“Many patients with early-stage disease undergo surgery and adjuvant chemotherapy. But it’s often not enough to slow or stop the cancer,” Dr Byrne said. “Our data supports the idea that you can do interventions up front to activate a targeted immune response at the tumor site–which was unheard of five years ago for pancreatic cancer–even before you take it out.”

CD40 is a tumour necrosis factor receptor superfamily member expressed broadly on antigen-presenting cells (APC) such as dendritic cells, B cells, and monocytes as well as many non-immune cells and a range of tumours.

CD40 agonists serve to accelerate the immune system by activating antigen-presenting cells, such as dendritic cells, to “prime” T cells and also through enhancement of destruction of the tumour site through non-immune system means. This has been investigated mostly in combination with other therapies for pancreatic cancer patients. This is the first study showing the drug drove immune response in early-stage patients both at the tumour site and systemically, mirroring mouse study findings.

Prior to surgery, 16 patients were treated with selicrelumab. Of those, 15 underwent surgery and received adjuvant chemotherapy and a CD40 agonist. Data collected from those patients’ tumours and responses were compared to data from controls (CD40 not received before surgery) treated at Oregon Health and Science University and Dana Farber Cancer Institute.

Multiplex imaging of immune responses revealed that in patients who received the CD40 agonist before surgery, 82% of tumours were T cell enriched, compared to 37% of untreated tumors and 23% chemotherapy or chemoradiation-treated tumours.

Selicrelumab tumours also had less tumour-associated fibrosis, which are tissue bundles inhibiting T cell and drug entry, and antigen-presenting cells known as dendritic cells were more mature.

Disease-free survival was 13.8 months in the treatment group, and median overall survival was 23.4 months, with eight patients alive at a median of 20 months after surgery.

“This is a first step in building a backbone for immunotherapy interventions in pancreatic cancer,” Dr Byrne said.

On the strength of these findings, researchers are pursuing combining CD40 with other therapies to help further boost immune response in pre-surgery pancreatic cancer patients.

“We’re starting to turn the tide. This latest study adds to growing evidence that therapies such as CD40 before surgery can trigger an immune response in patients, which is the biggest hurdle we’ve faced,” said senior author Robert H Vonderheide, MD, DPhil, and Director, Abramson Cancer Center (ACC), University of Pennsylvania. “We’re excited to see how the next-generation of CD40 trials will take us even closer to better treatments.”

Source: News-Medical.Net

Blood Clotting Concerns Resulting in Vaccination Delays

Vaccination programmes are facing increasing delays because of concerns over AstraZeneca’s very rare blood clotting incidents.

Australia and Greece are the latest governments deciding to offer young people alternatives to AstraZeneca’s vaccine. This will delay inoculation campaigns by around a month in Australia, France and Britain. Meanwhile, the World Health Organization said most countries lacked vaccines to cover health workers and others at high risk from exposure to the virus.

WHO Director-General Tedros Adhanom Ghebreyesus said high income countries had on average vaccinated one in four people whilst low income countries the figure was one in over 500.

“There remains a shocking imbalance in the distribution of vaccines,” he told a press briefing on Friday.

The WHO and GAVI vaccine alliance’s COVAX mechanism seeks to secure vaccines for poorer nations. GAVI alliance head Seth Berkley said AstraZeneca’s supply chain had in fact “picked up” when asked whether the vaccine was being shunned.

“As countries decide they are going to prioritise one vaccine or another, that may free up doses, and in so doing we will try to make sure those doses are made available without delay, if countries are willing to make that happen,” he said.

Australia doubled its orders for Pfizer after its health body recommended that people under 50 receive an alternative vaccine. Greece followed Britain’s example in recommending that people under 30 seek an alternative jab.

AstraZeneca said it was working with regulators “to understand the individual cases, epidemiology and possible mechanisms that could explain these extremely rare events”.

Sabine Straus, chair of the EMA’s safety committee, said that the European Medicines Agency (EMA) received reports of 169 cases of the rare brain blood clot by early April, after 34 million doses had been administered.

Most of the cases reported had occurred in women under 60.

On Friday, the EMA said that if a causal relationship is confirmed or considered likely, regulatory action will be needed to minimise risk. It is also investigating Johnson & Johnson’s (J&J) vaccine over reports of blood clots. US infectious disease expert Anthony Fauci however said there were no red flags reported for the J&J vaccine.

The AstraZeneca vaccine is the cheapest and most high-volume vaccine to date to curb the pandemic and avert damaging lockdowns, but supplies have been beset by delays.

However, new data in the EU, beset by delays, showed that the pace of vaccine deliveries was picking up. Germany said it was accelerating inoculations but needed a new lockdown as well.

“Every day in which we don’t act, we lose lives,” Lothar Wieler, president of the Robert Koch Institute, said.

Hong Kong Health Secretary Sophia Chan said the city would defer its order of the AstraZeneca vaccine this year “so as not to cause a waste when the vaccine is still in short supply globally”, adding that the government was considering buying a new, more effective type of vaccine.

All the countries recommending age limits for the AstraZeneca shot have emphasised that its benefits far outweigh the risks of catching COVID for older people. Even so, some people have been put off; in Madrid half of over 60s meant to receive the AstraZeneca vaccine turned up, a day after Spain’s recommendation that younger people get a different shot.

In France, where vaccine hesitancy is high, the top health body recommended that those over 55 who had received a first dose of the AstraZeneca shot get a new-style messenger-RNA vaccine for the second one: either the Pfizer/BioNTech one or Moderna’s.

Source: Reuters

South African Variant Escapes Pfizer Vaccine More Easily

The South African variant escapes protection of the Pfizer/BioNTech vaccine better than other forms of the virus, Israeli experts said Sunday.

The study by Tel Aviv University and Clalit Health Services, Israel’s largest healthcare provider, compared patients with COVID, 400 unvaccinated patients to 400 partially or fully vaccinated ones.

Less than one percent of COVID cases in Israel were due to the South African variant. However, among the 150 people who were fully vaccinated yet had developed COVID, “the prevalence rate [of the B.1.351 variant] was eight times higher than the rate in the unvaccinated [individuals],” the authors wrote.

“This means that the Pfizer-BioNtech vaccine, though highly protective, probably does not provide the same level of protection against the South African (B.1.351) variant of the coronavirus,” the authors added.

“The South African variant is able, to some extent, to break through the vaccine’s protection,” said professor Adi Stern of Tel Aviv University’s Shmunis School of Biomedicine and Cancer Research, one of the study’s authors.

Prof Stern said that the study did not assess whether the eight people infected with the South African developed severe COVID.
“Since we found a very small number of vaccinees infected with B.1.351, it is statistically meaningless to report disease outcomes,” he said.

The possibility of reduced protection was already hinted at in two studies conducted by principal vaccine manufacturers Pfizer/BioNTech and Moderna, showing that the presence of antibodies after vaccination was less pronounced in people exposed to the B.1.351 variant. This marked the first real-world assessment of B.1.351’s ability to bypass a vaccine.

Israel’s vaccination campaign has seen 5.3 million people receive a first dose, while 4.9 million, or 53 percent of the population, have had two shots. 

Clalit’s earlier study on 1.2 million Israelis found that the Pfizer/BioNTech jab gave 94 percent protection against COVID.

Israel has eased many of its restrictions since its vaccine rollout, but various measures remain in place including mask-wearing and a “green passport” system that allows vaccinated people access to certain locations. With cases down 97% since January, Israel may have achieved “herd immunity”, according to Eran Segal, a computational biologist at the Weizmann Institute of Science.

Ran Balicer of Clalit said inoculations, plus mask-wearing and other safety measures had likely helped contain the B.1.351 variant, despite its apparent ability to break through the Pfizer/BioNTech vaccine.

A combination of all these factors “are most likely… preventing the virus strains, including the South African one, from spreading” significantly in Israel, he said.

“As we taper down the non-pharmaceutical interventions, we must do so gradually to ensure we do not cross a threshold that would enable these variants to spread.”

Source: Medical Xpress

Sleep Apnoea Treatment May Reduce Risk of Dementia

Older adults receiving positive airway pressure therapy for obstructive sleep apnoea (OSA) may have a lower risk of developing Alzheimer’s disease and other kinds of dementia, according to a new study.

In a nationally representative study, Researchers from Michigan Medicine’s Sleep Disorders Centers analysed Medicare claims of over 50 000 Medicare beneficiaries 65 and older with OSA. They sought to find out whether people using positive airway pressure therapy had less risk of receiving a new diagnosis of dementia or mild cognitive impairment over the next 3 years, compared to those not using positive airway pressure therapy.

“We found a significant association between positive airway pressure use and lower risk of Alzheimer’s and other types of dementia over three years, suggesting that positive airway pressure may be protective against dementia risk in people with OSA,” said lead author Galit Levi Dunietz, PhD, MPH, an assistant professor of neurology and sleep epidemiologist.

The findings stress the impact of sleep on cognitive function. “If a causal pathway exists between OSA treatment and dementia risk, as our findings suggest, diagnosis and effective treatment of OSA could play a key role in the cognitive health of older adults,” said principal investigator Tiffany J. Braley, MD, MS, associate professor of neurology.

Obstructive sleep apnoea is a condition where there are episodes of complete or partial collapse of the airway with an associated decrease in oxygen saturation or arousal from sleep. This disturbance results in fragmented, nonrestorative sleep, and is associated with a variety of other neurological and cardiovascular conditions. Many older adults are at high risk for OSA. Dementia is prevalent as well, with roughly 5.8 million Americans currently living with it, said Prof Braley.

Source: Medical Xpress

Journal information: G L Dunietz et al, Obstructive Sleep Apnea Treatment and Dementia Risk in Older Adults, Sleep (2021). DOI: 10.1093/sleep/zsab076

Chronic Sinusitis Linked to Neural Functions

A small proof-of-concept study found that sinonasal inflammation was associated with neural changes that could precede cognitive symptoms in young people.

In comparison to healthy controls, people with chronic rhinosinusitis showed decreased functional connectivity within the frontoparietal network, a major cognition modulating hub, in resting-state functional MRI imaging. The frontoparietal network allows individuals to coordinate behaviour in a rapid, accurate, and flexible goal-driven manner.

These individuals also had greater connectivity of this region to the default mode network (areas that are activated during introspective and self-referential processing) and decreased connectivity to the salience network (areas involved in detection and response to stimuli) on brain imaging, reported Aria Jafari, MD, of University of Washington in Seattle, and colleagues.

Compared to controls, individuals with more severe rhinosinusitis inflammation tended to have greater differences in functional connectivity, Dr Jafari and colleagues stated. 

“Although definitive conclusions are not possible given the limitations inherent in the data set, including lack of rhinosinusitis-specific clinical information, our results present initial evidence for functional connectivity alterations as a potential basis for cognitive impairments seen in patients affected by chronic rhinosinusitis and may help direct future research,” Dr Jafari and colleagues said.

However, in this study, no cognitive deficits accompanied the functional connectivity changes. People with chronic rhinosinusitis and their matched controls shared similar cognitive status and similar sleep quality, with no between-group differences in olfaction, taste, and pain, either.

It was suggested by the researchers that, “given the brain’s ability to adapt and compensate, particularly in young and cognitively healthy individuals, our findings may represent early and subclinical functional brain alterations that may precede or be more sensitive than anticipated behavioral responses.”

“It is possible that a clinical chronic rhinosinusitis cohort with broader age distribution and more significant symptoms may have even greater changes in functional brain connectivity in the regions identified in this study,” they added.

“Overall, I do think that this study gives credence to the large body of evidence that patients with chronic rhinosinusitis, or in this case sinonasal inflammation, do have issues with cognition,” commented Nicholas Rowan, MD, of Johns Hopkins University School of Medicine in Baltimore, who was not part of the study.

Sinonasal inflammation and chronic rhinosinusitis have well established negative impacts on quality of life, according to Rowan. Previous research has found that medical or surgical intervention for chronic rhinosinusitis can alleviate cognitive dysfunction.

“Though unfortunately, the findings here are not actionable from a clinical standpoint, they do provide novel information for further prospective study of patients with chronic rhinosinusitis, as well as laboratory studies that are aimed to better understand the mechanism of why patients with CRS have such substantial quality of life implications,” according to Dr Rowan.

Although comorbid psychiatric disorders and sleep dysfunction are among the proposed mechanisms for cognitive dysfunction, the researchers said their data was supportive of a direct association of immune molecules with brain function.

Using data from The Human Connectome Project, the case-control study included 22 people with radiologic sinonasal inflammation who were matched 1:1 by age and sex to healthy controls. Sinonasal inflammation was classified as moderate in 13 people and severe in nine.

All were young adults age 22 to 35, and 68% were male.

Limitations included the retrospective nature of the study and the small sample size. Since cognitively normal participants identified radiographically from a large database, this limited the generalisability of the results, the authors added.

“Future prospective studies are warranted to determine the applicability of these findings to a clinical chronic rhinosinusitis population,” they said.

Source: MedPage Today

Journal information: Jafari A, et al “Association of sinonasal inflammation with functional brain connectivity” JAMA Otolaryngal Head Neck Surg 2021; DOI: 10.1001/jamaoto.2021.0204.

Unique Genetic Basis for Chronic Pain in Women Discovered

A meta-analysis of UK genetic data has found a different genetic basis for chronic pain in women compared to men.

While the results are still preliminary, this is one of the largest genetic studies on chronic pain analysing by sexes.

“Our study highlights the importance of considering sex as a biological variable and showed subtle but interesting sex differences in the genetics of chronic pain,” said population geneticist Keira Johnston of the University of Glasgow in Scotland.

Chronic pain conditions are among the most prevalent, disabling, and expensive conditions in public health, and are frequently overlooked for research funding. With 100 million people in chronic pain in the US in 2016, overprescription of opioids for chronic pain has resulted in an epidemic of opioid misuse, with 66% of overdose cases being for opioids. Even very moderate opioid use carries the risk of addiction and abuse.

Even when studies are done, they often overlook underlying sex differences, and that’s a huge and detrimental oversight. Compared to men, women are far more likely to develop multiple chronic pain disorders, and yet historically, 80 percent of all pain studies have been conducted on male mice or male humans. This means we know very little about how and why females are suffering more and what treatments can help them best.

While there are probably multiple biological and psychosocial processes in this sex discrepancy, the current genome-wide study suggests there’s a genetic factor in the mix, too.

The researchers compared gene variants associated with chronic pain in 209 093 women and 178 556 men from the UK Biobank, and found 31 genes associated with chronic pain in women and 37 genes associated with chronic pain in men with barely any overlap. This might be due to the slightly smaller sample size of men but the results are nonetheless intriguing, the researchers maintained.

The vast majority of these genes were active in a cluster of nerves within the spinal cord, known as the dorsal root ganglion, which transmits messages from the body to the brain.
While several genes in the male-only or female-only list were linked with psychiatric disorders or immune function, only one, called DCC, was found in both lists.
DCC encodes for a receptor that binds with a protein crucial for the development of the nervous system, especially the dopaminergic system. The dopaminergic system is the ‘reward centre’ but also has been linked to pain.

DCC is also linked to depression, and DCC mutations appear in those with congenital mirror movement disorder, which results in movements on one side of the body being replicated on the other side.

It’s not how DCC is linked to chronic pain, but the researchers believe their results support several theories “of strong nervous system and immune involvement in chronic pain in both sexes”, which will, they hope, result in the development of better treatments.

Should chronic pain be more closely linked to immune function in women, immune-targeting drugs may have very different side-effects than in men. Opioids negatively impact immune function, indicating that they could in fact worsen the situation for women suffering chronic pain. However, more research is needed to strengthen these findings and understand their impacts.

“All of these lines of evidence, together, suggest putative central and peripheral neuronal roles for some of these genes, many of which have not been historically well studied in the field of chronic pain,” the authors concluded.

Source: Science Alert

Journal information: Johnston KJA, Ward J, Ray PR, Adams MJ, McIntosh AM, Smith BH, et al. (2021) Sex-stratified genome-wide association study of multisite chronic pain in UK Biobank. PLoS Genet 17(3): e1009428. doi.org/10.1371/journal.pgen.1009428