A new study found the use of e-cigarettes containing nicotine has a number of immediate effects, which include increased blood clot formation, blood vessel dysfunction, as well as raised heart rate and blood pressure.
These effects are similar to smoking traditional cigarettes with heart attack or stroke risk with long-term use, according to researchers. The study was presented at the ERS International Congress by Gustaf Lyytinen, a clinician at Helsingborg Hospital and researcher at the Karolinska Institute in Stockholm, Sweden.
Each of the 22 occasional smoker volunteers was tested before and after taking 30 puffs from an e-cigarette with nicotine, and before and after 30 puffs from an e-cigarette without nicotine. These two sets of tests were conducted on separate occasions, at least one week apart.
On each occasion, the researchers measured volunteers’ heart rate and blood pressure and took a blood sample before they used the e-cigarettes, then 15 minutes after use and again 60 minutes after use. A laser was used to measure dilation of skin blood vessels before volunteers used e-cigarettes and 30 minutes afterwards. E-cigarettes with nicotine caused an immediate short-term change: a 23% average increase in blood clots after 15 minutes, that returned to normal levels after 60 minutes. Average heart rates also increased from 66bpm to 73bpm. as did blood pressure from 108mmHg to 117mmHg. Researchers observed temporary narrowing of blood vessels after nicotine-containing e-cigarettes use.
These effects were not observed after volunteers used e-cigarettes without nicotine. Nicotine is known to raise levels of hormones including adrenaline, which can increase blood clot formation.
Dr Lyytinen said: “Our results suggest that using e-cigarettes that contain nicotine have similar impacts on the body as smoking traditional cigarettes. This effect on blood clots is important because we know that in the long-term this can lead to clogged up and narrower blood vessels, and that of course puts people at risk of heart attacks and strokes.”
Credit: National Institute of Allergy and Infectious Diseases, National Institutes of Health
Following treatment with the investigational oral Janus kinase (JAK) inhibitor abrocitinib plus topical therapy, teenagers with moderate or severe atopic dermatitis (AD) showed significant improvement to placebo, according to a new study published in JAMA Dermatology.
Up to 20% of children and adolescents are affected by AD, which has an adverse impact on QoL, academic performance, and social relationships, as well as the QoL of caregivers. Subcutaneous dupilumab is safe and effective in moderate-to-severe AD in adolescents, but there is a lack of an oral option, they said.
Nearly half of the patients had clear or almost clear skin by clinician assessment (IGA), and about 70% of patients treated with either of two doses of the JAK inhibitor had at least 75% improvement in the Eczema Area and Severity Index (EASI-75). In contrast, a fourth of patients who received placebo in addition to topical therapy met the clinician assessment outcome and about 40% met EASI-75 criteria.
Abrocitinib, a JAK-1-selective inhibitor, had already shown to be tolerable and effective in adults. The present trial included 285 patients aged 12 to 17, with coprimary endpoints being an IGA score of 0/1 with at least a two-grade improvement from baseline, plus an EASI-75 response, with both outcomes assessed at 12 weeks. Secondary endpoints included improvement in pruritis.
An IGA 0/1 response was seen in 46.2% of patients treated with abrocitinib 200 mg and 41.6% of those assigned to abrocitinib 100 mg, compared to 24.5% in the placebo group. The proportion of patients who met EASI-75 response criteria was 72% with abrocitinib 200 mg, 68.5% with abrocitinib 100 mg, and 41.5% with placebo. Significant improvement was seen in pruritis compared to placebo, showing an improvement in pruritis. The researchers noted that improved indicators could lead to better sleep and QoL indicators.
AE rates were 62.8% with the higher dose of abrocitinib, 56.8% with the lower dose, and 52.1% in the placebo group, with nausea occurring more often with abrocitinib 200 mg than with abrocitinib 100 mg (18.1% vs 7.4%).
These results suggest abrocitinib has great potential for treating teenage AD, said John C. Browning, MD, of Texas Dermatology and Laser Specialists in Dallas. Current there are no JAK inhibitors indicated for AD, and an oral option is very exciting he to MedPage Today via email. “Not everyone responds to current systemic therapies, so there is a definite need for new treatments.”
“I think more teens will be open to trying an oral option, but they will need to be committed to taking it every day,” he said, adding that compliance is an issue. “Both abrocitinib and dupilumab are effective, so there is not a tradeoff in going from injections to oral therapy.”
A new study based on 400 years of historical records asserts that extreme pandemic events such as COVID are more common than believed.
The Duke University study, published in Proceedings of the National Academy of Sciences, used records of past outbreaks to estimate the intensity of those events and the yearly probability of them recurring.
It found the probability of a pandemic with similar impact to COVID is about 2% in any year, meaning that someone born in the year 2000 by now would have about a 38% chance of experiencing one. That probability is only increasing, highlighting the need to adjust perceptions of pandemic risks and expectations for preparedness, the researchers said.
“The most important takeaway is that large pandemics like COVID and the Spanish flu are relatively likely,” said study co-author William Pan, PhD, associate professor of global environmental health at Duke. The understanding that pandemics are not so rare should raise the priority of future prevention and control efforts, he said.
The study employed new statistical methods to measure the scale and frequency of disease outbreaks for which there was no immediate medical intervention over the past four centuries. Their analysis, including deadly pathogens including plague, smallpox, cholera, typhus and novel influenza viruses, found pandemics occurred with great variability in the past. But they also identified patterns that allowed them to describe the probabilities of similar-scale events happening again.
In the case of a pandemic like the Spanish flu, which killed more than 30 million people between 1918 and 1920, the probability of a pandemic of similar magnitude occurring ranged from 0.3% to 1.9% per year over the time period studied. Taken together, it is statistically likely that such a massive pandemic would occur within the next 400 years.
However, the data also show that the risk of intense outbreaks is increasing rapidly. Based on the increasing rate at which novel pathogens such as SARS-CoV-2 have broken loose in human populations in the past 50 years, the study estimates that the probability of novel disease outbreaks will likely triple in the next few decades.
With this increased risk factor, the researchers estimate that a COVID-scale pandemic is likely within a span of 59 years (by the year 2090), a result they write is “much lower than intuitively expected.” Although not included in the paper, they also calculated the probability of a pandemic capable of eliminating all human life, finding it statistically likely within the next 12 000 years.
That does not mean it will be 59 years before the next COVID-like pandemic, nor that the Spanish flu for another 300 years. Such events are equally probable in any year during the span, said Duke University Professor Gabriel Katul, another of the paper’s authors.
“When a 100-year flood occurs today, one may erroneously presume that one can afford to wait another 100 years before experiencing another such event. This impression is false. One can get another 100-year flood the next year,” explained Prof Katul.
Dr Pan noted that population growth, changes in food systems, environmental degradation and more frequent contact between humans and disease-harboring animals all may be significant factors for increasing frequency of pandemics. However, he stresses that the statistical techniques are not to explain the pandemics.
However, he hopes the study will spark deeper exploration of the factors that may be making devastating pandemics more likely – and how to counteract them.
“This points to the importance of early response to disease outbreaks and building capacity for pandemic surveillance at the local and global scales, as well as for setting a research agenda for understanding why large outbreaks are becoming more common,” Dr Pan said.
The Targeted Therapies Alliance has made a range of evidence-based resources available to help dermatologists and their patients in shared decision making in the treatment of plaque psoriasis.
Psoriasis, of which plaque psoriasis is the most common type, is the most prevalent immune-mediated inflammatory disease. It involves skin and in some cases, joints, and can be associated with abnormalities of other systems.
NPS MedicineWise spokesperson Jonathan Dartnell said: “While the condition currently does not have a cure, it can be well controlled, hence there is a need to support people with plaque psoriasis to understand and follow the treatment to get the best results.”
“The members of the Targeted Therapies Alliance have worked closely with the Australasian College of Dermatologists and Psoriasis Australia to create these resources which were developed with input from consumers with plaque psoriasis,” he said.
Australasian College of Dermatologists Fellow A/Prof Stephen Shumack said the resources were developed through a collaborative effort.
Jonathan Dartnell, Spokesperson, NPS MedicineWise said: “These resources were designed to support optimal patient outcomes by helping improve understanding of, and adherence to, the treatments for plaque psoriasis. The resources cover topical treatments such as creams and ointments, to phototherapy and systemic treatments.”
The new resources available include:
A consumers’ fact sheet with an overview of the topical treatment options (such as creams and ointments) and questions to ask their doctor to make sure they understand why, how and when to use their topical treatments.
A decision aid to help consumers speak to their doctor about treatment options should topical treatments not be enough.
An action plan and information to address some myths and help adherence to low-dose methotrexate.
The new dermatology resources complement existing Targeted Therapies Alliance resources focused on gastroenterological and rheumatological conditions. They also are part of a wider three-year programme to ensure the best possible health and economic outcomes from the use of biological and other specialised medicines.
Scanning electron micrograph of Yersinia pestis, which causes bubonic plague, on proventricular spines of a Xenopsylla cheopis flea.
Credit: National Institute of Allergy and Infectious Diseases/NIH
Analysing a recent outbreak of plague in Madagascar, a team of researchers uncovered evidence of human transmission of antimicrobial-resistant plague.
While COVID dominates the global awareness of infectious diseases, others are still out there, such as Yersinia pestis, which causes plague. Even though plague has been largely eradicated in the developed world, hundreds of people globally contract it each year.
When a human is infected with bubonic plague from a flea bite and it goes untreated, the infection can progress, spread to the lungs and resulting in pneumonic plague. Pneumonic plague is usually lethal if not treated quickly, and infected patients can transmit the disease to others via respiratory droplets. A team of scientists from Northern Arizona University’s Pathogen and Microbiome Institute, led by professor Dave Wagner, recently published their findings from a remarkable study involving antimicrobial resistant (AMR) plague.
Plague is considered to be a reemerging and neglected disease, particularly in the East African island country of Madagascar, which reports the majority of annual global cases. There is no vaccine for it, so preventing mortality from plague requires rapid diagnosis followed by antibiotic treatment. In Madagascar, the antibiotic streptomycin is usually the first-line treatment for plague. The researchers isolated a streptomycin-resistant AMR strain of Y. pestis from a pneumonic plague outbreak that occurred there in 2013, involving 22 cases, including three fatalities. The study was recently published in Clinical Infectious Diseases.
“By characterising the outbreak using epidemiology, clinical diagnostics and DNA-fingerprinting approaches,” Prof Wagner said, “we determined—for the first time—that AMR strains of Y. pestis can be transmitted person-to-person. The AMR strain from this outbreak is resistant to streptomycin due to a spontaneous point mutation, but is still susceptible to many other antibiotics, including co-trimoxazole. Luckily, the 19 cases that were treated all received co-trimoxazole in addition to streptomycin, and all of them survived.
“The point mutation, which also is the source of streptomycin resistance in other bacterial species, has occurred independently in Y. pestis at least three times and appears to have no negative effect on the AMR strain, suggesting that it could potentially persist in nature via the natural rodent-flea transmission cycle. However, AMR Y. pestis strains are exceedingly rare and the mutation has not been observed again in Madagascar since this outbreak.”
A new study revealed that lupus may be triggered by a defective process in the development of red blood cells (RBCs) which leaves mitochondria remnants. The study was published in Cell.
The researchers found that in a number of lupus patients, maturing red blood cells fail to get rid of their mitochondria, which are normally excluded from red blood cells. This abnormal retention of mitochondria can trigger the cascade of immune hyperactivity characteristic of this disease.
“Our findings support that red blood cells can play a really important role in driving inflammation in a subgroup of lupus patients. So this adds a new piece to the lupus puzzle, and could now open the door to new possibilities for therapeutic interventions,” said the study’s senior author, Dr Virginia Pascual, the Drukier Director of the Gale and Ira Drukier Institute for Children’s Health and the Ronay Menschel Professor of Pediatrics at Weill Cornell Medicine
Lupus is a chronic disorder with no cure that features intermittent and sometimes debilitating attacks by the immune system on the body’s own healthy tissues, including skin, joints, hair follicles, heart and kidneys. A common underlying factor in lupus is the abnormally elevated production of immune-activating proteins called type I interferons. Treatments aim to suppress immune activity, including interferon-driven inflammation.
Previous research found defective mitochondria in the immune cells of lupus patients. In the current study, the researchers focussed on red blood cells, which should lack mitochondria. Many lupus patients had red blood cells with detectable levels of mitochondria, and more common in patients with worse symptoms. By contrast, healthy controls had no mitochondria-containing red blood cells.
Lead author of the study, Dr. Simone Caielli, assistant professor of immunology research at the Drukier Institute and the Department of Pediatrics at Weill Cornell Medicine, then studied how human red blood cells normally get rid of mitochondria as they mature, as prior studies had mainly examined this in mice, and why this process could be defective in lupus patients.
Subsequent experiments showed these abnormal red blood cells cause inflammation. Normally, when red blood cells age or display signs of damage they are removed by macrophages, with binding antibodies helping removal. When the macrophages ingest them, the mitochondrial DNA in the red blood cells triggers a powerful inflammatory pathway called the cGAS/STING pathway, in turn driving type I interferon production. These findings show that “those lupus patients with mitochondria-containing red blood cells and evidence of circulating anti-RBC antibodies had higher interferon signatures compared to those who didn’t,” Dr Caielli said.
The researchers are now investigating how the mitochondria is retained in these cells. Identifying lupus patients with these cells could help predict when they are likely to undergo lupus flares and to develop therapies.
Colourised scanning electron micrograph of Marburg virus particles (blue) both budding and attached to the surface of infected VERO E6 cells (orange). Credit: NIAID
Guinea’s health authority announced the first detection of the Marburg virus in the country, which is also the first case in West Africa.
Marburg, a haemorrhagic fever-causing virus related to Ebola, killed more than 200 people in Angola in 2005, the deadliest recorded outbreak. Laboratory tests of samples taken from a now-deceased patient turned out positive for the Marburg virus.
The patient had sought treatment at a local clinic in the southern prefecture of Gueckedou, and a medical team had been sent to investigate the case. Cases of the 2021 Ebola outbreak in Guinea occurred in Gueckedou, as well as the 2014–2016 West Africa outbreak were initially detected.
“We applaud the alertness and the quick investigative action by Guinea’s health workers. The potential for the Marburg virus to spread far and wide means we need to stop it in its tracks,” said Dr Matshidiso Moeti, World Health Organization (WHO) Regional Director for Africa. “We are working with the health authorities to implement a swift response that builds on Guinea’s past experience and expertise in managing Ebola, which is transmitted in a similar way.”
Contact tracing efforts are underway, and health authorities are launching education and awareness programmes on the disease.
Four high-risk contacts, including a healthcare worker, have been identified, as well as 146 others who could be at risk, according to expert Dr Krutika Kuppalli, who spoke to the BBC. A team of WHO experts is on the ground helping to investigate the case and aiding the national health authority’s emergency response.
Cross-border surveillance is also being enhanced to quickly detect any cases, with neighbouring countries on alert. The Ebola control systems in place in Guinea and in neighbouring countries are proving crucial to the emergency response to the Marburg virus.
Marburg is transmitted to people from fruit bats and spreads among humans through direct contact of body fluids.
Illness begins abruptly, with high fever, severe headache and malaise. Within seven days, severe haemorrhagic signs appear in many patients. Case fatality rates are high, ranging from 24% to 88% in past outbreaks depending on virus strain and case management.
With no direct treatments for the virus, supportive care, including rehydration with oral or intravenous fluids, and treatment of specific symptoms, improves survival. There are evaluations underway for potential treatments, including blood products, immune therapies and drug therapies.
A US study showed that adults with atopic dermatitis (AD) had a higher burden of disease than those with other chronic diseases. Even mild dermatitis can negatively affect quality of life (QoL), increasing risk of anxiety, depression, and suicide.
Persistent itching and skin pain can disrupt sleep, leading to poor work or study performance. In moderate to severe disease, oozing, crusting lesions can lead to stigmatisation social isolation. More adults are affected than previously thought, with some 16.5 million adults in the US estimated to have AD.
In a study of 1278 patients using the US web-based Growth from Knowledge (GfK) panel, 60.1% had mild disease, 28.9% had moderate AD, and 11% had severe AD. Patients with more severe disease had higher scores on the dermatology life quality index and on the hospital anxiety and depression scale (HADS) when compared with controls.
This indicates “a worse impact on quality of life and an increased likelihood of anxiety or depression,” the researchers wrote in the Journal of Investigative Dermatology. “Our study confirms the high prevalence and disease burden of atopic dermatitis in this population.”
Quality of life threatened A pair of studies in patients from the GfK panel reinforce these findings. The first, with 602 patients, showed that AD carried a “profound” disease burden, based on a comparison of patient-oriented AD measures between patients with and without AD. Those with moderate and severe AD had lower mean mental health scores compared with those who had mild disease, and lower QoL compared with patients with other chronic disorders.
“We recommend that clinicians incorporate QoL assessments in clinical practice to determine disease burden, identify patients requiring step-up treatment of their skin disease, and potentially screen for patients with mental health disturbance,” wrote Jonathan I Silverberg, MD, PhD, MPH, of George Washington University, and colleagues in the Annals of Allergy, Asthma and Immunology.
A subsequent study in 2137 patients from the GfK Knowledge Panel found that 40% of patients with AD had a higher prevalence of anxiety or depression in the previous 12 months compared with 17.5% of adults without AD. The researchers concluded that anxiety and depression were driven primarily by disease severity, and were heavily underdiagnosed.
Breaking the ‘vicious cycle’ AD can be life-threatening in some patients, warned the authors of a systematic review and meta-analysis of AD studies. The combination of pruritus, visible skin lesions, social isolation, depression, and anxiety likely sets up a “vicious cycle,” according to the authors.
The investigators found a positive and significant association between AD in adulthood and depression, anxiety, and suicidal ideation, regardless of where the patients lived. And while only a few studies examined the risk of completed suicide, the majority showed a positive association, the authors said. A positive association between AD and depression in children was also identified.
They advised that “depression, anxiety, and suicidal ideation should be considered by doctors when treating patients with AD,” adding: “Because AD disease improvement appears to reduce these risks, this should be a priority.”
Better systemic and topical AD therapies are improving the QoL of patients. “It is important to recognise that improvement of AD often results in improvements in symptoms of depression and anxiety, as these mental health symptoms are caused or worsened by the AD,” Dr Silverberg told MedPage Today. “We already have data for dupilumab and the JAK inhibitors that show improvements of HADS scores and other patient-reported outcome measures of mental health.”
Robert Sidbury, MD, MPH, of the University of Washington School of Medicine in Seattle said, “relatively recent literature suggests screening for depression is particularly important for kids with AD, especially those with severe disease.”
AD affects children of all ages, including the very young, and more than 50% of children with AD are diagnosed by age 1 year, he noted.”Dupilumab has been the most effective new available therapy to date by far,” Dr Sidbury told MedPage Today. “Pipeline drugs, particularly the JAK inhibitors like upadacitinib show tremendous promise.”
Helicobacter pyloriis a strong risk factor for gastric cancer and other gastrointestinal disorders, and efforts to eradicate it using a combination of antibiotics and proton pump inhibitors (PPIs) often fail.
A new study has linked this eradication failure with genetic variations that increase the activity of the CYP2C19 enzyme, which metabolises first-generation PPIs.
These so-called ‘fast metabolisers’ may prevent PPIs from suppressing gastric acid production, which is necessary for successful H. pylori eradication.
Analysing 57 studies from 11 countries, the researchers found that the failure rate of H. pylori eradication more than doubled in people with a version of the CYP2C19 gene that increased its metabolic activity. Their results were published in Gastroenterology.
However, CYP2C19 variants were not linked to eradication failure if the fast metabolisers were treated with newer PPIs such as esomeprazole and rabeprazole, which are less metabolised by the enzyme or which bypass CYP2C19 metabolism.
Further well-designed studies are needed to determine whether eradication rates could be improved with higher or more frequent dosages of first-generation PPIs to people with the fast metaboliser gene variant, noted the paper’s corresponding author, Shailja Shah, MD, MPH. “Even small improvements in H. pylori eradication rates would likely translate to substantial collateral health, economic and societal benefits,” the researchers concluded.
Using an innovative 3D imaging technology, researchers at Karolinska Institutet have discovered that a part of the liver’s autonomic nervous system undergoes severe degeneration in non-alcoholic fatty liver disease.
The study showed that the degeneration of nerves is correlated with the severity of liver pathology. The findings are being published in the journal Science Advances.
With a global prevalence of about 25 percent, non-alcoholic fatty liver disease is the most common hepatic disorder. Approximately one third of all fatty liver cases progress to steatohepatitis, a severe disease seriously affecting the entire metabolism.
In the current paper, researchers explore the nervous system in fatty liver using volume immuno-imaging and light sheet microscopy ― a novel imaging technique, which together offers large-scale 3D visualisation with cellular resolution. According to the study, this technology can reveal even early, minor or hidden structural impairments of the liver.
“Now we know that nerves in the liver have multiple subtle regulatory roles” says Csaba Adori, researcher at the Department of Neuroscience, who led the study. “Their role, however, may be more essential during the fight-or-flight response or when subjected to metabolic challenges. Degeneration of liver sympathetic nerves and abnormal operation of the remaining nerve fibres in the fatty liver could compromise all these functions, which may contribute to further aggravation of the disease, as part of a vicious cycle.”
According to the study, changes in liver innervation are already underway in the early stages of fatty liver disease. As it progresses to more severe steatohepatitis, these impairments become a significant degradation of the nerves. The nerve pathology is also similar in mouse models of fatty liver and in human fatty liver samples. The team hopes this will open new avenues for the treatment of steatohepatitis and portal hypertension, through targeting the liver sympathetic nervous system.
