EU Angered by Pfizer Delay

Pfizer has said in a statement on Friday that the drop in production is the result of the company upgrading its manufacturing processes, and that there will be an overall increase in supply as a result.

“Although this will temporarily impact shipments in late January to early February, it will provide a significant increase in doses available for patients in late February and March,” Pfizer said.

The German health ministry has said the delays are surprising and regrettable, pointing out that it had secured binding mid-February delivery dates from the company. EU Commission President Ursula von der Leyen said that she had been given assurances by Pfizer’s chief executive that all orders for the first quarter would arrive. She had previously said that Pfizer had promised to double its delivery of doses to the EU to 600 million this year.

However, the EU also has agreements in place with Moderna to supply vaccines, and this is not wholly dependent on Pfizer. However, Johnson & Johnson is also falling behind in its vaccine delivery targets, amidst reports that the US has failed to meet vaccination goals for the end of 2020, and may struggle to meet this year’s goals. Meanwhile, the UK is expected to be slightly impacted by the drop in supply but remains on track to meets its February immunisation goals.

However, the EU has lagged behind the UK in its vaccination programme, for a number of reasons including the fact that the UK ordered and approved its vaccines sooner, while Brussels’ negotiations were slower. Much of the delay is due to the added bureaucracy of the 27 nation political confederation and its decision to acquire vaccines as a single entity instead of individual countries further exacerbated this.

According to Reuters, citing a participant at a meeting last week, a third of the EU’s 27 countries reported difficulties in securing enough vaccines for their vaccination programmes.

Source: BBC News

Itching in Severe Eczema Uses a Different Pathway

A study shows that there are two molecular pathways for conveying sensations of itching, with the itching of severe eczema following an unexpected route.

In normal eczema, cells in the skin convey the itching sensation, releasing histamines. This can be blocked with antihistamines.

“Years ago, we used to think that itch and pain were carried along the same subway lines in the nerves to the brain, but it turned out they weren’t, and these new findings show there’s another pathway entirely that’s causing these episodes of acute itching in eczema patients,” said principal investigator Brian S Kim, MD, Washington University School of Medicine. “The itch can be maddening. Patients may rate their chronic itch at around a 5 on a scale of 10, but that goes up to 10 during acute itch flares. Now that we know those acute flares are being transmitted in an entirely different way, we can target that pathway, and maybe we can help those patients.”

With severe itching in eczema, different cells in the blood are activated, transmitting great quantities of non-histamine molecules which also convey the itching sensation. This renders antihistamines usesles in trying to control the itch. The discovery of this new pathway offers new possibilities for treating other conditions as well. Recent studies have tried to block Immunoglobulin E (IgE) in response to allergies.

“We’ve connected acute itching in eczema to allergic reactions transmitted by an entirely different population of cells,” explained Kim. “In patients who experience episodes of acute itching, their bodies react in the same way as in people with acute allergy. If we can block this pathway with drugs, it might represent a strategy for treating not only itch but other problems, including perhaps hay fever and asthma.”

The team found that when mice with eczema made IgE in response to environmental allergens, they began to itch. However, instead of activating mast cells which produced histamine, the IgE activated basophils (a kind of white blood cell), activating a different nerve pathway to normal itching.

The discovery that eczema is exacerbated by allergens may help people avoid severe itching episodes, as well has helping the development of new targets for treatment.

Source: News-Medical.Net

Journal information: Wang, F., et al, A basophil-neuronal axis promotes itch. Cell, 2021 doi.org/10.1016/j.cell.2020.12.033.

Stellenbosch Doctors Urge Patience on Ivermectin

The South African public should be patient and wait for data on Ivermectin’s effectiveness against COVID, according to Stellenbosch doctors, who urge patience. The doctors wrote an article published in the South African Medical Journal explaining that further studies need to be completed before ivermectin can be authorised for use.

A veterinarian parasiticide that may have relevant antiviral and anti-inflammatory properties, ivermectin has gathered considerable attention for possible use in COVID prophylaxis and treatment since a number of small trials appeared to show effectiveness. However, close examination shows that they are very weak. Doubts have been raised over whether the necessary concentrations used in vitro can be achieved in vivo.

In their article, the doctors noted that several large randomised controlled trials are underway, and the results of these will allow the possible effectiveness of ivermectin to be gauged. “Data for Ivermectin from larger RCTs are expected in early 2021,” the doctors wrote. “These data are very promising, showing large treatment effects and acceptable adverse effect profiles for ivermectin against Covid-19, especially when combined in meta-analyses.”

They pointed out that the hoped-for effectiveness of other medications had not been borne out. “As a recent example, the widely proclaimed benefits of hydroxychloroquine and chloroquine from observational studies proved to be unfounded in larger RCTs,” they wrote.

Ivermectin use has been banned by the government, to considerable resistance. A number of organisations have already demanded that ivermectin be administered as a COVID treatment, including Black First Land First, the New Economic Rights Alliance and AfriForum. Afriforum is contemplating legal action to have ivermectin authorised. These calls have come despite the South African Health Products Regulatory Authority (SAHPRA) repeatedly counselled against the use of ivermectin.

The doctors cautioned that although the data trends indicated a possible efficacy for ivermectin, the optimal dosage if effective still needed to be determined: “Higher than standard Ivermectin doses appear to be safe in humans, but at the time of writing there is still much uncertainty regarding the human dose required to achieve antiviral activity and a favourable benefit-to-risk balance.”

Source: IOL

Johnson & Johnson is Behind on Vaccine Production

Despite releasing promising data on its COVID vaccine, Johnson & Johnson may fall up to two months behind on its vaccine production schedule, Politico reported. The company is still committed to releasing the trial data on its 45 000 participants by the end of January to pave the way for approval.

If approved, as seems likely, the vaccine would be extremely beneficial for vaccination efforts as it would only require a single dose to confer protection and also would not require sub zero refrigeration, greatly simplifying vaccination efforts.

The company’s effort is part of the Operation Warp Speed initiative to vaccinate the US population as fast as possible, with a goal of vaccinating 80% of the country’s 330.7 million population by the end of June. The previous goal to distribute 20 million doses by the end of 2020 had already fallen short owing to insufficient production.

The co-director of Operation Warp Speed, Moncef Slaoui, hinted at a production slowdown, telling the media that the company was expecting to produce “single-digit million” doses by the second half of February. “We’re trying to make that number get as close to a double-digit number as possible, and then a larger number in March and a much larger number in April,” he added.

Johnson & Johnson had previously made a pledge to deliver 12 million doses by the end of February and as many as 100 million by June.

Despite the delay, there is good news in that initial data from 400 participants shows that the vaccine is safe and has a 90% efficacy in establishing antibodies, with immunity for most subjects established 29 days after the shot and lasting at least 57 days. Adverse reactions were reported to be be mild, and younger subjects were more likely to report them, with one subject experiencing a brief, mild fever.

Source: Politico

Telemedicine Promising for Visits After Low-Risk Surgery

A pair of reports suggests that modern communication methods may be appropriate for post-surgery recovery, albeit at the risk of exacerbating the downsides of any language barriers and digital literacy.

In the midst of the COVID pandemic, telemedicine uptake and use has been greatly expanded by health care providers. In one small trial, cut short by COVID, researchers investigated whether telemedicine was an adequate form of patient follow-up after low-risk surgery.

The video-based post-discharge visits were as effective in terms of getting patients to return to the hospital within 30 days for a hospital encounter. The video visits were half an hour shorter but provided patients with the same amount of time with their surgeons.

However, out of 1645 individuals screened, many participants were excluded due to language difficulties, and 50 were excluded due to a “technology barrier”.

Caroline Reinke, MD, MSHP, of Carolinas Medical Center in Charlotte, North Carolina, and her team wrote, “Patients and clinicians should be reassured that the critical visit portion, time together discussing medical needs, is preserved. This information will help surgeons and patients feel more confident in using video-based virtual visits.”

Reinke and her team noted that COVID cut the study short: “Although we did not reach target enrollment, noninferiority was demonstrated for postdischarge virtual visits in our study sample and was further supported via a simulation model.”

In another study, Marie-Laure Cittanova, MD, PhD, of Clinique Saint Jean de Dieu in Paris, and her team compared using SMS to contact patients as opposed to calling them. When contacted after being told to expect a contact throughout the following day, 46.2% of patients were reachable by phone, compared to 85.3% by SMS.

Patients expressed similar levels of satisfaction with the SMS service, which was significantly cheaper than using phone calls. However, the single-centre study lacked generalisability.

Source: MedPage Today

Journal information (primary source): Harkey K, et al “Postdischarge virtual visits for low-risk surgeries: a randomized noninferiority clinical trial” JAMA Surg 2021; DOI: 10.1001/jamasurg.2020.6265.

Journal information (secondary source): Cittanova M, et al “Association of automated text messaging with patient response rate after same-day surgery” JAMA Surg 2021; DOI: 10.1001/jamanetworkopen.2020.33312.

WHO Team Arrives in China for COVID Origin Investigations

Following months of negotiations, and then a list minute hiccough when two team members were denied entry last week, a team of 10 specialists from the WHO arrives in China to carry out their investigations into the origins of COVID.

China, through rapid action and total lockdowns, managed to clamp down on the coronavirus outbreak inside its borders, preventing it from spreading significantly outside of Wuhan, while in Wuhan itself, life has largely returned to normal. In recent weeks, however, new cases have been appearing in Hebei province around Beijing and in Heilongjiang province in the northeast.

Just before travelling, team leader Peter Ben Embarek told AFP news agency that it “could be a very long journey before we get a full understanding of what happened”.

He cautioned against expecting instant results, saying, “I don’t think we will have clear answers after this initial mission, but we will be on the way,” he said.

For a number of months, China has been saying that the virus may not have originated in Wuhan. There has been a lot of unsubstantiated speculation that the SARS-CoV-2 might have been accidentally released from a lab.

Prof Dale Fisher, chair of the global outbreak and response unit at the WHO, told the BBC that he hoped the rest of the world would regard this as a scientific visit. “It’s not about politics or blame but getting to the bottom of a scientific question,” he said.

When the WHO team arrives in China, they will still have to wait through a two week quarantine. Fabian Leendertz, a professor in the epidemiology of highly pathogenic microorganisms at Germany’s public health institute and working remotely with the team, says that their plan of action will be developed over the next two weeks while they are still in quarantine. The team is expected to look at the infamous wet market in Wuhan where it was originally believed the virus made the jump from animals to humans, as well as working with Chinese colleagues and local clinics to establish a picture of the virus’ origins.

Source: BBC News

Light Drinking Still Raises Atrial Fibrillation Risk

Even light drinking is associated with an increased risk of atrial fibrillation (Afib) for both sexes, according to a large cohort study by Renate Schnabel, MD, of University Heart & Vascular Center Hamburg, and colleagues.

Drawing on five European cohorts totalling 100 092 participants, the researchers found that 12g of alcohol (one beer can) was associated with increased risk of Afib (Hazard Ratio 1.16, 95% Confidence Interval 1.11-1.22).  A small amount of alcohol (2g) per day was still marginally associated with an increase in Afib risk after 14 years (HR 1.02, 95% CI 1.0-1.04). The association remained after accounting for heart failure history and the cardiac biomarkers NT-proBNP and hs-troponin I, and there was no difference in results between males and females.

There was a J-shaped relationship observed, where drinking more than 20g per day was associated with increased risk.To date, there had been little information on the cardiac effects of chronic light drinking, and the results showed that lowering alcohol intake was an important part of managing Afib, it was noted in an accompanying editorial. It was also noted that these results needed further randomised trials.

The team acknowledged the study’s limitation on relying on self-reported alcohol consumption, and also cases of Afib not being detected. The editorial noted that the study did not state the absolute risk of Afib, which needed to be taken in consideration along with the benefits of low levels of alcohol consumption

Source: MedPage Today

Journal information (primary source): Csengeri D, et al “Alcohol consumption, cardiac biomarkers, and risk of atrial fibrillation and adverse outcomes” Eur Heart J 2021; DOI: 10.1093/eurheartj/ehaa953.

Journal information (secondary source): Wong JA and Conen D “Alcohol consumption, atrial fibrillation, and cardiovascular disease: finding the right balance” Eur Heart J 2021; DOI: 10.1093/eurheartj/ehaa955.

Mediterranean-type Diets Protect Against Parkinson’s Disease

Researchers at the University of British Columbia have shown that the Mediterranean diet and another diet based on it, have a strong link in protecting against Parkinson’s disease (PD). 

These two diets had previously been shown that they could protect against other neurodegenerative diseases. The Mediterranean‐DASH Intervention for Neurodegenerative Delay (MIND) diet combines aspects of the Mediterranean diet and the DASH diet which protects against hypertension. The MIND diet emphasises consumption of berries, as research shows that they protect against mental decline, eating leafy greens and poultry. The MIND diet also mostly does away with potato, milk and fruit (excluding berries).

Senior author Dr Silke Appel-Cresswell said, “There is a lack of medications to prevent or delay Parkinson’s disease yet we are optimistic that this new evidence suggests nutrition could potentially delay onset of the disease.”
Following the diets delayed the average onset of PD by 17.4 years in women, and 8.4 years in men.

Since PD already has a notable sex difference, with 60% of sufferers being men, despite their shorter average lifespan, the sex difference in response to the diets opens new avenues of research
“It drives home the connection between the gut and the brain for this disease,” Dr Brett Finlay said. “It also shows it’s not just one disease that healthy eating can affect, but several of these cognitive diseases.”

Source: Medical Xpress

Journal information: Avril Metcalfe‐Roach et al, MIND and Mediterranean Diets Associated with Later Onset of Parkinson’s Disease, Movement Disorders (2021). DOI: 10.1002/mds.28464

Stomach Bugs Induce Irritable Bowel Syndrome

Researchers have pinpointed a localised biological mechanism behind irritable bowel syndrome (IBS), a chronic gastrointestinal condition where eating certain foods causes subsequent abdominal pain or discomfort.

Around 20% of people experience IBS, and diets such as gluten-free ones provide some relief. However, the exact cause was unknown, as the patients did not have allergic responses nor did they have coeliac disease, causing many physicians to dismiss it as psychological.A healthy immune system tolerates foods, and the first link is understanding how the tolerance is removed. Previous work showed that there was a link between mast cells and food, and that blocking histamine in people with IBS relieved the symptoms.

People with IBS often report their symptoms begin following a gastrointestinal infection, so the researchers reasoned that an infection associated with a particular type of food in the guy might sensitise the immune system to that food.The team fed mice with ovalbumin (an egg protein) and then infected them with a stomach bug. The mice were then fed ovalbumin again, and the researchers recorded elevated mast cell activation, histamine levels and digestive intolerance. In control mice who were fed with ovalbumin but who were not infected with the stomach bug, there was no response.

Breaking down the chain of events leading to the sensitisation, the researchers discovered that there was a localised immune response in the part of the guy infected by the bacteria, but did not produce the more generalised symptoms of a food allergy.  

Lead author Prof Guy Boeckxstaens, a gastroenterologist at KU Leuven thinks this may point to a spectrum of food-related immune disorders. He said, “At one end of the spectrum, the immune response to a food antigen is very local, as in IBS. At the other end of the spectrum is food allergy, comprising a generalised condition of severe mast cell activation, with an impact on breathing, blood pressure, and so on.”

When researchers injected IBS-associated food antigens into the intestinal walls of IBS patients, they observed localised reactions similar to what they saw in the mice, and there were no reactions in healthy patients. Larger clinical trials will be needed to confirm these observations.

“This is further proof that the mechanism we have unraveled has clinical relevance,”  Prof Guy Boeckxstaens said. “But knowing the mechanism that leads to mast cell activation is crucial, and will lead to novel therapies for these patients,” he goes on. “Mast cells release many more compounds and mediators than just histamine, so if you can block the activation of these cells, I believe you will have a much more efficient therapy.”

Source: Medical Xpress

Journal information: Local immune response to food antigens drives meal-induced abdominal pain, Nature (2021). DOI: 10.1038/s41586-020-03118-2 , www.nature.com/articles/s41586-020-03118-2

Depression May be Influenced by Metabolism

A study by researchers from University of California San Diego School of Medicine and from the Netherlands, has shown that major depressive disorder (MDD) may be predicted by metabolism, in the form of certain metabolites.

MDD is one of the most common disorders, with a lifetime prevalence of 20.6% in the United States. For those with recurrent major depressive disorder (rMDD), the risk is 80% over five years.

MDD is characterised by any combination of feelings of sadness or hopelessness, anger or frustration, loss of interest, sleep disturbances, anxiety, slowed or difficulty thinking, suicidal thoughts and unexplained pain such as backaches.

“This is evidence for a mitochondrial nexus at the heart of depression,” said senior author Prof Robert K Naviaux, at UC San Diego School of Medicine. “It’s a small study, but it is the first to show the potential of using metabolic markers as predictive clinical indicators of patients at greatest risk—and lower risk—for recurring bouts of major depressive symptoms.”

Recruiting 68 participants who were in remission for rMDD and not on antidepressants, the researchers found a range of molecules in participants’ blood that were up to 90% predictive of relapse in 30 months. The most predictive molecules consisted of certain lipids and purines.

Purines are produced from molecules such as ATP and ADP (major cellular energy storage molecules), and also have a role in signalling in stressed cells.The researchers found that in subjects with rMDD, certain metabolites in six metabolic pathways resulted in the alteration of key cellular activities.

“The findings revealed an underlying biochemical signature in remitted rMDD that set diagnosed patients apart from healthy controls,” Naviaux said. “These differences are not visible through ordinary clinical assessment, but suggest that the use of metabolomics—the biological study of metabolites—could be a new tool for predicting which patients are most vulnerable to a recurrence of depressive symptoms.”

Source: Medical Xpress

Journal information: Roel J. T. Mocking et al. Metabolic features of recurrent major depressive disorder in remission, and the risk of future recurrence, Translational Psychiatry (2021). DOI: 10.1038/s41398-020-01182-w