Olfactory dysfunction in COVID patients is common. Researchers recently searched the medical literature for studies reporting changes in olfactory structures detected through imaging tests of patients with COVID, and found that swelling in nasal passages is responsible for some temporary olfactory dysfunction. Their results in were published in The Laryngoscope.
A recent meta-analysis based on 83 studies provided high-quality evidence of a combined prevalence of olfactory dysfunction in 47.9% of COVID patients. Olfactory dysfunction is diagnosed more commonly among female patients and outpatients.
The researchers observed abnormality in olfactory clefts, which provide a crucial channel for airborne molecules to reach sensory olfactory neurons. The rate of abnormalities was nearly 16-fold higher in patients with COVID and olfactory dysfunction (63%) compared with controls (4%).
“Before this study, most scientists thought that the loss of smell in COVID was mainly due to inflammation and damage to the olfactory nerves. Now, we have compiled evidence from medical imaging that COVID loss of smell is also due to swelling and blockage of the passages in the nose that conduct smells,” said senior author Neville Wei Yang Teo, MRCS, MMed, of Singapore General Hospital.
“We think this is good news for patients who want to recover their sense of smell, since these blockages are expected to resolve with time, while nerve damage in comparison would likely be more difficult to recover from,” added lead author Claire Jing-Wen Tan, of the National University of Singapore. “These findings may not fully account for those who suffer from prolonged olfactory dysfunction, however, and further studies that evaluate patients in this group may provide more information.”
The data underpinning a controversial study of the use as vitamin C as a sepsis treatment may in fact be fraudulent, according to an analysis by an Australian physician and statistician, reports MedPage Today.
PhD student Kyle Sheldrick, MBBS, alleges that the pre- and post- comparison groups involved in the 94-patient study were too similar to be realistic.
In an interview with MedPage Today, Sheldrick said the case is “extreme”, stating that “This is probably the most obviously fake data I have seen. … These groups are more similar than would be probable.”
The paper, led by Paul Marik, MD – who led another COVID protocol study that has since been retracted – has been the subject of much debate in the intensive care community since it was published in 2017. The so-called HAT protocol was a simple regimen of hydrocortisone, ascorbic acid (vitamin C), and thiamine which could have saved many lives easily if it indeed worked. Obviously, there was much excitement worldwide about the significance of the findings – but not all were convinced.
“The effect size seemed just impossible,” said Nick Mark, MD, an ICU physician at Swedish Medical Center. “It seemed too good to be true.”
The trial was followed by larger studies, and so far none have shown shown a similar reduction in mortality, raising suspicions even further, Dr Mark said. With Sheldrick’s analysis, the penny dropped: “This was under our noses for 5 years,” Mark said. “This isn’t just a mistake. We know things can be done unethically, but to actually fake it? That it’s not just flawed, but perhaps actually fraudulent?”
Sheldrick told MedPage Today the key problem with the Marik paper is “probably the most common sign of fraud that we see, which is overly similar groups at baseline.” That is, people tend to fake data which do not vary enough from the average.
Sheldrick said he first looked at the study methods, which noted a pre- and post- comparison design, rather than a randomised or matched case-control design. With such a design, one would expect a more random distribution of baseline characteristics, but that wasn’t the case for the Marik paper, he said.
A further analysis with Fisher’s test showed that most P-values were 1, meaning they were distributed perfectly evenly across two time periods – and only one fell below 0.5. Instead, an even spread should be expected with an overall value of 0.5.
Sheldrick sent his findings to the journal CHEST and to Marik’s former employer Sentara Norfolk General Hospital, but had not heard back from either.
While Sentara Norfolk General Hospital did not respond to comment, and the journal CHEST could not confirm whether an investigation was underway but that it did take ethical concerns very seriously.
A spokesperson for Dr Marik emailed a statement to MedPage Today, claiming that the conclusions had been validated in several meta-analyses, and recommended the source examine “this and other research on the data before making false allegations on social media. Such claims are harmful and do not add to the public discourse.”
This wouldn’t be the first time concerns have been raised about data in a paper that Dr Marik co-authored. In November 2021, the Journal of Intensive Care Medicine (JICM) retracted an article by Marik and others on their MATH+ protocol for COVID. The retraction followed a communication that raised concerns about the accuracy of COVID mortality data from the hospital used in the article.
“It seems a bit improbable for someone to discover two miracle cures in three years,” Dr Mark commented to MedPage Today.
Dr Mark noted that the 2017 paper is widely cited, and even if the intervention was not directly harmful, the resources invested in subsequent large, high-quality trials of vitamin C and sepsis could have been better spent.
“While I’m really glad we did high-quality studies and had brilliant people working on this, it’s kind of a shame,” he said. “Instead of studying vitamin C based on a faulty premise, we could have spent our efforts elsewhere.”
An observational study with over 100 000 participants suggests that some artificial sweeteners are associated with increased cancer risk. The findings, published in PLOS Medicine, reflect other results from experimental studies.
The safety of artificial sweeteners has long been a subject of debate. To evaluate the potential carcinogenicity of artificial sweeteners, researchers analysed data from 102 865 French adults participating in the NutriNet-Santé study. The NutriNet-Santé study is an ongoing web-based cohort initiated in 2009 by the Nutritional Epidemiology Research Team (EREN). Participants enrolled voluntarily, and self-reported their medical history, sociodemographic, diet, lifestyle, and health data.
Researchers gathered data concerning artificial sweetener intake from 24-hour dietary records. After collecting cancer diagnosis information during follow-up, the researchers conducted statistical analyses to investigate the associations between artificial sweetener intakes and cancer risk. They also adjusted for a range of variables including age, sex, education, physical activity, medical history and dietary intake.
The researchers found that participants who consumed larger quantities of artificial sweeteners, particularly aspartame and acesulfame-K, had higher risk of overall cancer compared to non-consumers (hazard ratio 1.13). Higher risks were observed for breast cancer and obesity-related cancers.
In addition to being an observational study, there were a number of limitations; dietary intakes are self-reported. Selection bias may also have been a factor, as participants were more likely to be women, to have higher educational levels, and be more health-conscious. Additional research will be required to confirm the findings and clarify the underlying mechanisms.
According to the authors, “Our findings do not support the use of artificial sweeteners as safe alternatives for sugar in foods or beverages and provide important and novel information to address the controversies about their potential adverse health effects. While these results need to be replicated in other large-scale cohorts and underlying mechanisms clarified by experimental studies, they provide important and novel insights for the ongoing re-evaluation of food additive sweeteners by the European Food Safety Authority and other health agencies globally”.
First author Charlotte Debras added: “Results from the NutriNet-Santé cohort (n = 102 865) suggest that artificial sweeteners found in many food and beverage brands worldwide may be associated with increased cancer risk, in line with several experimental in vivo / in vitro studies. These findings provide novel information for the re-evaluation of these food additives by health agencies.”
Though light alcohol consumption may provide heart-related health benefits has been suggested observational research, a large study published in JAMA Network Open showed a link between all levels of alcohol intake and higher risks of cardiovascular disease. The researchers found that the supposed benefits of alcohol consumption may in fact be attributable to other healthy lifestyle factors common among light to moderate drinkers.
The study included 371 463 adult participants from the UK Biobank, average age 57 and consuming an average of 9.2 drinks per week. In line with previous findings, researchers found that the lowest heart disease risk was in light to moderate drinkers, followed by people who abstained from drinking. People who drank heavily had the highest risk. However, light to moderate drinkers also tended to have healthier lifestyles than abstainers, such as more physical activity and vegetable intake, and less smoking. One a few lifestyle factors were taken into account, any benefit associated with alcohol consumption was significantly reduced.
The study also used new techniques in Mendelian randomisation, which uses genetic variants to determine whether an observed link between an exposure and an outcome is consistent with a causal effect. “Newer and more advanced techniques in ‘non-linear Mendelian randomisation’ now permit the use of human genetic data to evaluate the direction and magnitude of disease risk associated with different levels of an exposure,” said senior author Krishna G. Aragam, MD, MS, a cardiologist at MGH and an associate scientist at the Broad Institute. “We therefore leveraged these new techniques and expansive genetic and phenotypic data from biobank populations to better understand the association between habitual alcohol intake and cardiovascular disease.”
When such genetic analyses were performed on samples taken from participants, they found that individuals with genetic variants that predicted higher alcohol consumption were indeed more likely to consume greater amounts of alcohol, and more likely to have hypertension and coronary artery disease. The analyses also revealed significant differences in cardiovascular risk across the spectrum of alcohol consumption for both males and females, with minimal risk increase when going from zero to seven drinks per week, much higher risk increases when progressing from seven to 14 drinks per week, and greatly increased risk for 21 or more drinks per week. Notably, the findings suggest a rise in cardiovascular risk even at “low risk” levels (ie below two drinks per day for men and one per day for women).
This discovery of an exponential rather than liner relationship between alcohol intake and cardiovascular risk is was supported by an additional analysis of data on 30 716 participants in the Mass General Brigham Biobank. Therefore, cutting back on large consumption of alcohol may have even more clinical benefits than cutting back on moderate amounts.
“The findings affirm that alcohol intake should not be recommended to improve cardiovascular health; rather, that reducing alcohol intake will likely reduce cardiovascular risk in all individuals, albeit to different extents based on one’s current level of consumption,” said Dr Aragam.
The amygdala, which is enlarged in two-year-old children with autism spectrum disorder (ASD), begins its accelerated growth between 6 and 12 months of age, suggests a study appearing in the American Journal of Psychiatry. The findings indicate that therapies to reduce the symptoms of ASD might have the greatest chance of success if they begin in the first year of life, before the amygdala begins its accelerated growth.
The amygdala, which is involved in processing emotions, such as interpreting facial expression in typically developing children increases substantially in volume from 7.5 to 18.5 years of age. The amygdala in children with autism is initially larger, but does not undergo the age-related increase observed in typically developing children.
The study included 408 infants, 270 of whom with an increased ASD risk from having an older sibling with ASD, 109 typically developing infants, and 29 infants with Fragile X syndrome. The researchers conducted MRI scans of the children at 6, 12 and 24 months of age. They found that the 58 infants who went on to develop ASD had a normal-sized amygdala at 6 months, but an enlarged amygdala at 12 months and 24 months. Moreover, the faster the rate of amygdala overgrowth, the greater the severity of ASD symptoms at 24 months. The infants with Fragile X syndrome had no differences in amygdala growth but enlargement of the caudate, which was linked to increased repetitive behaviours.
The researchers suggested that difficulty in processing sensory information during infancy may stress the amygdala, leading to its overgrowth.
