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The novel oral drug venetoclax can be safely added to standard therapies for some high-risk myeloid blood cancers and in early studies the combination shows promise of improved outcomes, say scientists from Dana-Farber Cancer Institute.

Venetoclax targets cancer's survival proteins, making them more vulnerable to treatments that cause cancer cells to self-destruct. It is the first in a new class of drugs called BCL-2 inhibitors and was first approved in 2016 for certain patients with chronic lymphocytic leukemia.

At the virtual 62nd American Society of Hematology (ASH) Annual Meeting, Dana-Farber's Jacqueline Garcia, MD, reported on two studies examining the safety and efficacy of combining venetoclax with standard treatments for high-risk patients with myeloid blood cancers such as acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

In one study, venetoclax was added to the standard chemotherapy administered to patients with AML or MDS prior to receiving reduced intensity conditioning stem cell transplantation. Older patients or those with co-morbidities are commonly recommended for reduced intensity conditioning transplants because they are less toxic to patients. Reduced intensity conditioning chemotherapy is given to deplete the immune system of the patient (recipient) to prevent rejection of the donor stem cells (transplant). However, reduced intensity conditioning chemotherapy approaches are associated with high risk of disease recurrence. Because outcomes are poor in patients with myeloid blood cancers who relapse following transplantation, the investigators proposed adding venetoclax to the chemotherapy that is designed to kill the AML or MDS cells before the patient receives a transplant to restore the blood-forming and immune systems. The hope was that venetoclax would make the pre-transplant chemotherapy, consisting of the drugs fludarabine and busulfan, more effective - lessening the risk of relapse.

To test this strategy for efficacy and safety, the combination was given to 22 patients ranging in age from 25 to 71, who had AML, MDS, or MDS/MPN. Of these patients, 35% had intermediate-risk disease and 65% had adverse risk disease.

Garcia and collaborators reported that all 22 patients engrafted donor cells (had restoration of count recovery after transplant) and no serious additional toxicities were observed with the addition of venetoclax. Further, graft-versus-host disease (GVHD) rates were not increased with the addition of venetoclax. At the time of this analysis, seven of the 22 patients relapsed and five of them died. Median survival of the living patients has not been reached, but the 6-month overall survival for the cohort is 84% and progression-free survival is 76%. Overall, results have been encouraging for a very high risk patient population.

Garcia noted that the addition of venetoclax did not result in any increased toxicity. The combination of venetoclax, fludarabine, and busulfan "demonstrates promising clinical activity supporting further evaluation for high risk disease features," she said.

In a second study reported by Garcia, venetoclax was combined with the drug azacitidine in treating patients with higher-risk MDS requiring treatment and not immediately undergoing transplantation at time of study start. Azacitidine is known as a hypomethylating agent - a drug that increases the expression of tumor-suppressor genes to slow the growth of cancer cells. However, azacitidine alone has a low overall response rate in MDS and median overall survival is around 15 months.

The researchers noted that venetoclax has shown synergistic activity with hypomethylating agents in laboratory studies. This combination was recently FDA approved for the treatment of untreated AML in patients ineligible for intensive chemotherapy. To test the safety and efficacy of this combination in humans, investigators administered it to 57 patients with high-risk MDS who had not previously been treated. The patients ranged in age from 26-85 years of age, with a median of 71.

Results showed an impressive overall response rate of 77%, including complete remission in 42% and marrow complete response rate of 42%. Median overall survival was not reached; median duration of response was 14.8 months. Median progression-free survival was 17.5 months.

MDS patients commonly report fatigue and poor quality of life due to underlying disease. The study also evaluated patient-reported outcome of the population while on treatment. The researchers said physical functioning was maintained through 48 weeks of treatment confirming tolerability of therapy. In addition, clinically meaningful improvement in fatigue and shortness of breath was achieved by the beginning of cycle 5 and was maintained through week 48.

The most common adverse events were constipation, neutropenia, and nausea. The most common serious adverse event was neutropenia with fever, at 42%. Prophylactic antibiotics were required to help reduce complications.

Garcia and colleagues concluded that the combination of venetoclax and azacitidine "demonstrates promising efficacy, including response durability, and an acceptable safety profile for patients with high-risk MDS." A phase 3 clinical trial (VERONA) was launched comparing azacitidine plus venetoclax to azacitidine plus placebo for the treatment of frontline higher risk MDS based on these encouraging data.

These presentations are scheduled for Session 721, Abstract 190 on Saturday, Dec. 5 at 3:15 p.m., and Session 637, Abstract 656 on Monday, Dec.7 at 3:15 p.m. EST.

Researchers from Case Western Reserve University presented research today in which Hemex Health's Gazelle platform diagnostic technology successfully tested 46 patients with 100% sensitivity and over 92.3% specificity for anemia and with 100% accuracy for hemoglobin variants. The preliminary study included blood samples collected from Cleveland-area patients studied for anemia and sickle cell disease.

The combined, single test for anemia and sickle cell disease is thought to be a first and should provide a vital new tool for disease detection and management in low resource settings where incidents of sickle cell disease are high and often go undiagnosed. This test is expected to be available in mid-2021 after regulatory permission in identified countries.

"Health practitioners with whom we spoke in Africa and Asia told us that one of the greatest obstacles to better diagnosis and management for anemia and sickle cell disease is the lack of an affordable, easy to use test that can provide regular data to help optimize treatment," said Patti White, co-founder and CEO, Hemex Health. "The study from Case Western Reserve demonstrates that a software enhancement to our Gazelle platform holds the potential to allow our current sickle cell disease test to also check for anemia, which could help clinicians and patients to optimize disease management through a single, low cost test."

The research team compared the study samples to the current clinical standard detection of anemia (complete blood count [CBC]) and sickle cell disease (High-Performance Liquid Chromatography [HPLC]).

"With an integrated total hemoglobin and hemoglobin variant test, clinicians can help patients better understand their condition, because iron deficiencies and nutrition issues can cause anemia without a patient having sickle cell disease," said Umut Gurkan, PhD, Associate Professor, Case Western Reserve University, lead researcher of the team that presented the findings at the 62nd American Society of Hematology Annual Meeting. "Gazelle reminds me of Tesla because the technology transforms with a software upgrade, and that's all it takes to add the hemoglobin test to the existing platform."

Dec. 4, 2020-- A new study published online in the Annals of the American Thoracic Society discusses a steep drop off from prior years in asthma-related emergency department (ED) visits at Boston Children's Hospital during the spring 2020 COVID-19 surge and lockdown.

In "Impact of the COVID-19 Pandemic on Pediatric Emergency Department Utilization for Asthma," Tregony Simoneau, MD, assistant professor of pediatrics, Boston Children's Hospital, and co-authors looked at the medical records of children ages 2-22 who visited the hospital's ED for asthma treatment between Jan. 5 and May 23 in 2018, 2019 and 2020.

Pediatric asthma flareups frequently result in emergency department visits. Dr. Simoneau and colleagues noticed in their clinic visits with patients with asthma that their symptom control seemed to have improved with the onset of the pandemic. Given this observation, they hypothesized there would also be a decrease in asthma-related ED visits.

Massachusetts Gov. Charlie Baker issued a pandemic-related stay-at-home order--including closure of schools, day care centers and after-school programs--effective March 24, 2020. Due to this shutdown order, the researchers determined they would compare two time periods for each of the three years: Jan. 5-March 21 ("pre-shutdown") and March 22-May 23 ("post-shutdown") to determine whether the number of pediatric asthma ED visits changed year-to-year.

"Our most significant finding was the drastic, sudden drop in ED visits shortly after schools closed and the stay-at-home order went into effect," said Dr. Simoneau. "How this drop was sustained over several months is quite notable."

For the week of March 15-March 21 (pre-shutdown), the rate of ED visits was similar across the three years included in the study. However, the following week (post-shutdown) the rate of ED visits decreased 80 percent and 82 percent in 2020 relative to 2018 and 2019, respectively. This decrease in visits continued through May 23, with an 82 percent reduction from the 2018 rate and 87 percent reduction from the 2019 rate.

The percent of total ED visits due to asthma was lower in 2020 compared with 2018 and 2019. The authors noted that, "This suggests that the effect was not just due to an overall avoidance of the emergency department" during the shutdown.

The researchers also looked at whether hospital admission rates for asthma declined during the shutdown. They found that the number of admissions for asthma declined, while the proportion of asthma-related ED visits that required hospital admission remained similar to previous years.

Dr. Simoneau noted, "We felt this was important to evaluate in order to see whether patients presenting to the ED during the pandemic were sicker and therefore would have a higher rate of admission. While there are many unmeasured factors that contribute to the decision to admit someone to the hospital, we think that our findings suggest a similar severity when comparing the 2020 ED visits with previous years. We believe this is more reflective of an overall decrease in exacerbations rather than just patients with milder exacerbations being managed at home."

"This study adds to the body of literature that provides reassurance from a pediatric perspective that COVID is not necessarily resulting in an increase in asthma exacerbations," she said. "In fact, the social distancing measures in place seem to have resulted in a significant decrease in exacerbations."

A new clinical trial offers the most compelling evidence to date that a donor stem cell transplant can improve survival rates for older patients with higher-risk myelodysplastic syndrome (MDS), Dana-Farber Cancer Institute investigators report at the virtual 62nd American Society of Hematology (ASH) Annual Meeting.

Despite being the only current cure for MDS and widely used for younger patients, transplant generally hasn't been offered to older patients because it has not been proven beneficial in that population. The new trial, conducted by the Blood and Marrow Transplant Clinical Trials Network, is likely to change that, according to study leaders. Involving 384 patients at 34 medical centers across the U.S., the trial found that transplantation of hematopoietic stem cells from compatible donors nearly doubled the survival rate of patients age 50-75.

"Transplantation has been underutilized, historically, in this patient group," said study senior author Corey Cutler, MD, MPH, FRCPC, of Dana-Farber. "Based on our findings all patients should at least be referred to a transplant center so that those who are eligible and have a suitable donor can undergo transplant and have better survival. It is important to refer these patients early so the transplant center can work on finding an optimal donor right from the get-go."

MDS encompasses a group of disorders in which blood-forming cells in the bone marrow become abnormal, resulting in the production of defective blood cells. In about one in three patients, MDS can progress to acute myeloid leukemia, a rapidly growing cancer of bone marrow cells.

Allogeneic hematopoietic stem cell transplantation replaces a patient's abnormal blood-forming stem cells with healthy ones from a compatible donor. Because the procedure hadn't been proven to be helpful for older patients, it hasn't been covered by Medicare for people over age 65 unless done as part of an approved study. Medicare approved the design of the trial and is expected to consider the findings when determining future payment policies.

Participants in the new trial were referred to transplant centers, which searched for suitable stem cell donors. The 260 patients who were matched with a donor within 90 days were assigned to receive a stem cell transplant; the other 124 patients received standard supportive care.

Roughly three years after enrolling in the trial, 47.9% of those slated for transplant were alive, compared to 26.6% of those for whom no donor had been found at the 90-day mark. Survival without a recurrence of leukemia was also higher in those assigned to receive a transplant (35.8%) than in those who were not (20.6%). The researchers observed no significant differences among subgroups and no differences in quality of life between the two study arms.

Cutler will present findings on this study at the "What's on the Horizon: Practice-Changing Clinical Trials" press briefing on Friday, Dec. 4 at 12:30 p.m. EST. Further details will be presented during Session 732, Abstract 75, on Saturday, Dec. 5 at 10:30 a.m. EST.

When swarms of bubbles are driven upwards through a fluid by their buoyancy, they can generate complex flow patterns in their wake. Named 'pseudo-turbulence,' these patterns are characterised by a universal mathematical relationship between the energy of flows of different sizes, and the frequency of their occurrence. This relationship has now been widely observed through 3D simulations, but it is less clear whether it would still hold for 2D swarms of bubbles. Through research published in EPJ E, Rashmi Ramadugu and colleagues at the TIFR Centre for Interdisciplinary Sciences in Hyderabad, India, show that in 2D simulated fluids, this pattern changes within larger-scale flows in less viscous fluids.

The team's discoveries address a key oversight in fluid dynamics simulations, and could enable researchers in areas from oceanography to acoustics to improve their predictions. In the past, many studies of pseudo-turbulence have found the statistical properties of 3D bubble swarms remain universal over a wide range of bubble surface tensions, fluid viscosities, and density ratios between bubbles and fluids. In 2D fluids, however, an effect named an 'inverse energy cascade' enables energy to be transferred from small- to large-scale flows. In their study, Ramadugu's team aimed to investigate the implications of this mechanism for the first time.

The researchers achieved their results through a simulation approach which fully accounts for turbulent flows on all scales in space and time, removing the need for them to approximate any unpredictable behaviours. They found that while the usual pseudo-turbulence relationship holds on larger scales within more viscous fluids; and on smaller scales in less viscous fluids, different behaviours can be found in larger-scale flows within more viscous fluids. Here, Ramadugu and colleagues discovered that an inverse energy cascade occurs in the wake of the bubble swarm; as well as a different mathematical relationship between flow energy and frequency than any observed previously.

Pyroptosis is a highly inflammatory form of programmed necrotic cell death that acts as a defense mechanism against the infection of bacterial and viral pathogens. Pyroptosis is executed by gasdermin, a family of pore-forming proteins.

Gasdermin-mediated pyroptosis is characterized by rapid cell swelling, membrane disruption, and massive cytoplasmic content release. To date, pyroptosis-inducing gasdermins have only been reported in vertebrates. It remains enigmatic whether functional gasdermins exist in invertebrates.

Recently, a research team led by Prof. SUN Li from the Institute of Oceanology of the Chinese Academy of Sciences (IOCAS), in collaboration with Prof. ZHOU Zhi from Hainan University, has identified gasdermin E (GSDME) from the reef-building coral Orbicella faveolata and demonstrated that coral GSDME triggers pyroptosis and is involved in pathogen-induced coral death.

Their study was published in Science Immunology on Dec. 4, 2020.

Via biochemical and cellular studies, the researchers revealed that O. faveolata GSDME was activated by caspase 3, which cleaved GSDME at two different sites. This resulted in two forms of the N-terminal domain of GSDME, and both of them were able to induce pyroptosis.

"When co-present with caspase 3, GSDME switched cell fate from caspase 3-induced apoptosis to pyroptosis," said Dr. JIANG Shuai, the first author of the study.

Vibrio coralliilyticus is a coral pathogen worldwide. In this study, the researchers demonstrated in a coral death model that V. coralliilyticus infection caused rapid tissue necrosis with activation of caspase 3 and GSDME, as well as subcellular structural damage including disorganization of mitochondria and Golgi apparatus.

Furthermore, inhibition of caspase 3 was found to block GSDME cleavage and protect corals from necrotic death.

The researchers revealed the activation mechanism and pyroptosis-executing capacity of coral GSDME as well as its involvement in pathogen-induced coral necrotic death.

Their findings shed light on the evolution, function, and activation mechanism of gasdermins, and promote our understanding of coral death caused by environmental stress.

This work was supported by the National Natural Science Foundation of China and the National Key Research and Development Project of China.

It sounds too good to be true - and it is. But Jose Bianco Moreira and the CERG research group at the Norwegian University of Science and Technology (NTNU) are convinced that some of the positive health effects of physical exercise can be achieved using gene therapy and medication.

"We're not talking about healthy people and everyone who can exercise. They still have to train, of course," says Moreira. He and his colleagues at NTNU's Department of Circulation and Medical Imaging are studying the effect of exercise on our cells.

"But some people can't train, or only in a limited way. This could include individuals who've been in accidents, who are in wheelchairs, or who have diseases that prevent the possibility of physical expression. We want to create hope for these folks."

"A small group of healthy people out there also obtain very little effect from physical exercise - so-called low responders - and would benefit from a method that worked at the cellular level," says Moreira.

A lot of research confirms the health benefits of physical exercise, but we know far less about what happens in the cells that provides the positive effects.

"International research in this field is brand new. We've barely scratched the surface," says the researcher.

"We think increasing our knowledge about what happens at the cellular level will be important for discovering medications and treatments for heart disease. My group studies genes, proteins and mitochondria that produce energy and are key for chemical processes in the cells."

Moreira believes that gene therapy is the most effective method for reproducing the health benefits we normally get through physical exercise.

A medicine that uses gene therapy is already in use for spinal muscle atrophy, a serious disease that leads to muscle wasting. The drug uses a harmless virus to deliver a copy that replaces the damaged motor neuron network in patients.

This form of therapy can inhibit or enhance the expression of a gene. This is a very expensive medicine and has not been tried for heart disease, for example.

Moreira believes CRISPR will be the future go-to gene therapy method. He believes this method of editing the genes will revolutionize a lot of disease treatments.

"CRISPR is easier to use, faster and cheaper than today's gene therapy, which only attenuates or enhances the expression of a gene. CRISPR's potential is almost limitless. It can alter the gene itself. The parts of the gene that don't work properly are replaced with well-functioning parts."

Experiments on rats and mice have shown that the method works. Experiments have also been performed on human cells in the laboratory to confirm CRISPR's effectiveness, but it has not yet been tested on humans.

"CRISPR still has to be tested in large clinical studies. I'd be optimistic if I say gene editing will come into regular use in 10-15 years," says Moreira.

Moreira's research group has used CRISPR in its research, but the results are not yet ready for publication.

"We believe gene therapy is the most powerful method because patients don't have to take a pill every day. Usually, gene therapy changes the gene forever, perhaps with an injection or two. The challenge is to find the right gene that needs change, and an effective method to repair it," he says.

NTNU researchers are focusing on the heart. They have identified a protein that heart-diseased rats are deficit in, but which increases when the rats go through training.

"By increasing the amount of this protein through gene therapy, we've managed to strengthen the muscle cells and have replicated some of the positive effects of physical exercise," says Moreira.

Medications are another possible method of mimicking the effects of exercise. Some existing medicines might even be able to recreate some of the positive effect on the heart.

"The research now has powerful technology platforms to find possible other uses for medicines we already have. One problem, of course, is that medicine is chemistry that affects the whole body, not just the organ you want to help. Something that's good for the heart could be detrimental for the liver, for example. Compared to gene therapy, though, the potential for medications is much more limited," Moreira says.

When the research group at NTNU started their study, they had no idea which genes were affected by exercise. They performed experiments where rats with heart defects underwent training. Afterwards, the hearts were removed and examined. Then these hearts were compared with those from untrained rats with heart disease. Afterwards, the hearts of the trained and untrained rats with heart disease were compared to healthy rat hearts.

"We observed that genes were altered in the diseased hearts, but discovered that some of them were repaired in the rats that had trained. This way, we find genes that we can target. Through our measurements, we can find out exactly what training changes at the cellular level," says Moreira.

WASHINGTON--A study published in the Journal of the Academy of Nutrition and Dietetics by researchers with the Physicians Committee for Responsible Medicine--a nonprofit of 12,000 doctors--debunks the "blood type diet" by finding that blood type was not associated with the effects of a plant-based diet on body weight, body fat, plasma lipid concentrations, or glycemic control.

This new study is based on a randomized control trial whose main findings were published in JAMA Network Open on Nov. 30. That trial randomly assigned overweight participants with no history of diabetes to an intervention or control group on a 1:1 ratio for 16 weeks. Participants in the intervention group followed a low-fat, plant-based diet. The control group made no diet changes. The key finding is that a plant-based diet ramps up metabolism as measured by an increase in after-meal calorie burn of 18.7%, on average, for the intervention group over the control.

To consider a potential connection between blood type and diet, researchers took the additional step of conducting a secondary analysis among intervention-group participants of the 16-week randomized clinical trial. They considered whether the effects of a plant-based dietary intervention on body weight, blood lipids, and glycemic control are associated with ABO blood type. The "blood type diet" recommends a mainly plant-based diet for those with blood type A, while it recommends a diet heavy in meat for people with blood type O.

"We found that blood type made no difference," says study author Neal Barnard, MD, president of the Physicians Committee. "While the blood type diet says that a plant-based diet should be better for blood type A and less so for blood type O, it turned out to be beneficial for people of all blood types, and there was no evidence that meaty diets are good for anyone.

"Our research shows that all blood types benefit equally from a vegan diet based on the consumption of fruits and vegetables, legumes and whole grains, looking specifically at weight loss and cardiometabolic health in overweight adults," he says.

Main outcomes that were measured were body weight, fat mass, visceral fat volume, blood lipids, fasting plasma glucose, and HbA1c. T-tests compared participants with blood type A to all other participants (non-A), and individuals with blood type O to all other participants (non-O).

There were no significant differences in any outcome between individuals of blood type A and non-A, or between individuals of blood type O and non-O. Mean body weight change was -5.7 kg for blood type A participants and -7.0 kg for non-A participants, and was -7.1 kg for type O participants and -6.2 kg for non-O participants. Mean total cholesterol decreased 17.2 mg/dl in the type A group and 18.3 mg/dl for non-A participants, and decreased 17.4 mg/dl among type O participants and 18.4 mg/dl for non-O participants.

Immunity passports are a means of registering whether an individual has developed immunity to COVID-19 and is therefore unlikely to either catch or spread the disease. They may take the form of certificates, bracelets, mobile phone apps or other types of document. However, their use has generated many doubts from both a scientific and an ethical standpoint. Science mistrusts them because it is as yet unclear whether having had and recovered from the disease automatically confers immunity, and even if it does, no one really knows how long said immunity lasts. Indeed, there have been some cases of reinfection, although this phenomenon seems to be fairly rare. These science-related doubts will gradually be clarified as more data is gathered.

The ethical problems linked to immunity passports, however, will not be so easy to resolve. 'If we accept that, as their detractors argue, immunity passports are unacceptable because they could prompt people to catch the disease on purpose, or because they would increase state surveillance, particularly of vulnerable groups, or because they would create a new black market, then we should obviously reject them,' says Iñigo de Miguel Beriain, Dr of Law and Philosophy and an Ikerbasque Research Professor working at the UPV/EHU who has recently published an article on the issue. 'However, it is not as simple as that,' he explains. 'To understand why, it is important to put yourself in the shoes of someone who is immune.'

The rights of immune people

'If you cannot spread the virus, then it is extremely hard to justify the curtailment of some of your rights, particularly the fundamental right to freedom of movement. Both the Spanish Constitution and the European Convention on Human Rights clearly limit any curtailment of this right,' he adds. 'It is difficult to defend the limitation of our freedom of movement on the basis of avoiding reckless behaviour by third parties.'

In the opinion of the researcher from the Department of Public Law, the issue will become even more pressing when vaccines become available and governments start vaccinating large segments of the population. Vaccination certificates will de facto generate a sort of immunity passport. According to de Miguel Beriain, in the next phases of the pandemic, different immunity statuses will be at stake, 'because the need to identify who can spread COVID-19 is unavoidable. If a person does not pose a threat to public health because they cannot spread the infection, then their right to freedom of movement should be respected, regardless of how they acquired that immunity. However, if there are not enough vaccines for everyone at that time, what we will be doing is recognising the validity and moral admissibility of immunity passports, at least in terms of fundamental rights.'

Complementary information

The research group working with the Chair in Law and the Human Genome, at the UPV/EHU Department of Public Law, focuses on studying and developing 'Biolaw', understood as the combination of all legal issues linked to living beings in general, their ecosystems and evolution, and in particular to humans in terms of health, genetics and biotechnologies. On their website they have set up a research and dissemination space on the COVID-19 pandemic.

The monoclonal antibody secukinumab is approved for the treatment of moderate to severe plaque psoriasis in children and adolescents from the age of six years who are candidates for systemic therapy. The German Institute for Quality and Efficiency in Health Care (IQWiG) now examined in an early benefit assessment whether the drug offers an added benefit for these patients in comparison with the appropriate comparator therapy (ACT). Since the drug manufacturer did not provide appropriate treatment to the participants in the control arm of the study on which its dossier was based, no fair comparison is possible. IQWiG therefore concluded that an added benefit is not proven.

Approval is broader than that of the comparator therapy

The approval of the new drug is broader than the approval of the ACT option chosen by the manufacturer, regarding both disease severity and line of treatment: Etanercept may only be used for the treatment of chronic severe plaque psoriasis in children and adolescents from the age of six years who are inadequately controlled by, or are intolerant to, other systemic therapies or phototherapies - but not in moderate disease severity or as the first systemic therapy after topical treatment.

Children in the etanercept arm continued treatment despite non-response

The manufacturer presented data from the CAIN457A2310 study, which includes two secukinumab arms with different dosages and, for comparison, one etanercept and one placebo arm. It used analyses after 52 weeks (end of the maintenance phase) in its dossier. There was another data cut-off after 24 weeks, for which no analyses were presented.

In case of non-response, children and adolescents in the placebo arm were switched to secukinumab after 12 weeks. For the other control arm - and thus for the ACT - there was no possibility of switching treatment, however: According to the Summary of Product Characteristics, etanercept treatment should be discontinued in patients who show no response after 12 weeks. In this study, treatment was continued in the entire arm until the end of the maintenance phase, although, according to the European Public Assessment Report, about one third of the patients did not respond to this therapy at the end of the 12-week induction phase (as measured by the Psoriasis Area and Severity Index [PASI 75]). These children and adolescents were thus deprived of switching to a possibly more effective therapy.

Regardless of response, etanercept was given for too long

According to the approval, the treatment of children and adolescents with etanercept should be ended after a total of 24 weeks. Continuing the therapy for another 28 weeks not only means that patients who do not respond to the treatment continue to receive ineffective therapy: Patients with good response are also put at risk of adverse events if they continue treatment. Continuous etanercept treatment beyond 24 weeks exceeds the maximum approved duration for all patients.

Katrin Nink from IQWiG's Drug Assessment Department sums up the situation: "Hence, there are two reasons why the study is not suitable for assessing the added benefit of secukinumab in comparison with the appropriate comparator therapy. Treatment with etanercept after a non-response at week 12 no longer complies with the Summary of Product Characteristics - and if continued beyond 24 weeks, also does not comply with the approval for all patients. Apparently, not all children and adolescents in this control arm received appropriate medical care. This is not a fair comparison between secukinumab and etanercept."

A new study, led by experts from the University of Nottingham, has shown that people with rare autoimmune rheumatic diseases are at a greater risk of dying at a younger age during the Covid-19 pandemic.

The findings of the study, published in the British Society for Rheumatology's journal, Rheumatology, was the work of a team of doctors and researchers from RECORDER (Registration of Complex Rare Diseases Exemplars in Rheumatology), which is a joint project between the University of Nottingham and the National Disease Registration Service at Public Health England.

Experts looked at the electronic health records of 170,000 people in England with rare autoimmune rheumatic diseases. During March and April 202 (the first two months of the Covid-19 pandemic), the team found that 1,815 (1.1%) of people with these diseases died.

Study co-author, Dr Fiona Pearce from the School of Medicine at the University of Nottingham, said: "People with rare diseases often have poorer health outcomes generally, so we wanted to find out what impact the Covid-19 pandemic has had. From our study we know that during the early months of the pandemic, people with these diseases were more likely to die than the general population.

"The next steps in our research are to look at death certificate data and find out why people have died. We'll be examining whether it's due to Covid-19 infection or how much is due to the disruption to healthcare services."

The results also showed that:

The risk of dying during Covid-19 for people with these conditions increased from age 35

Women with rare autoimmune rheumatic diseases had a similar risk of death to men during Covid-19 - whereas usually their risk of death is lower

For people of working age with rare autoimmune rheumatic diseases, the risk of dying during Covid-19 was similar to that of someone 20 years older in the general population

Paul Howard, Chief Executive of Lupus UK, said: "This study is an important step in helping us to understand the impact of the Covid-19 pandemic on people with rare autoimmune rheumatic conditions in the UK. The findings demonstrate that, as a group, people with conditions such as lupus have been disproportionately impacted and therefore the provision of additional support is necessary.

"We hope that the next steps of this research will lead to a clearer understanding about whether Covid-19 or other factors caused the increased mortality, and also whether other health and quality of life measures have been disproportionately affected in these patient groups." Paul Howard, Chief Executive of LUPUS UK."

Dr Peter Lanyon, Consultant Rheumatologist at Nottingham University Hospitals NHS Trust, said: "Our study illustrates the unique ability of collaboration with the National Disease Registration Service to generate findings that can improve health in rare diseases. Further work to understand them in greater depth and more support for people with rare autoimmune rheumatic diseases is now needed."

Dr Sanjeev Patel, President of the British Society for Rheumatology, said: "These results are incredibly important to the rheumatology community. These conditions might be rare, but when we look at them together it's a significant number of people.

"This is a large study which shows for the first time that a subgroup of patients in our care are at an increased risk of dying during the pandemic and at a much younger age. We don't yet know the reasons why, but this study brings into sharp focus the need to be more vigilant with these patients and it should help inform future shielding advice."

This release has been removed upon request of the submitter.

According to the World Health Organization, the global prevalence estimates of sexually transmitted infections for men in 2016 were 2.7% for chlamydia, 0.7% for gonorrhoea and 0.6% for trichomoniasis. In men, these and other sexually transmitted infections may lead to urethritis, inflammation of the urethra.

There are several methods for detecting these infections. In recent years, new technologies have emerged in the field of urinalysis methodology, offering quick and standardised opportunities in everyday clinical practice. One of the authors of the study, teaching physician at the Men's Clinic of Tartu University Hospital and doctoral student at the University of Tartu Faculty of Medicine Stanislav Tjagur said that one of such innovative diagnosing methods is flow cytometry: "Compared with other methods, this technique is simple to perform, automated, provides results rapidly, and is not invasive."

However, there is only limited information about how to use flow cytometry in diagnosing male urethritis. Therefore, medical researchers of the University of Tartu and andrologists of Tartu University Hospital conducted a study to evaluate the performance of flow cytometry on first-voided urine in males with infectious urethritis. "We aimed to find the optimal cut-off levels for a faster and more precise diagnosing of sexually transmitted infections associated with urethritis to improve the cost-effectiveness of the management of infectious urethritis in men in a busy outpatient clinic," described Tjagur.

Patients who had come to the Men's Clinic of Tartu University Hospital either after a case of high-risk sexual behaviour, for fertility check, or for prophylactic health control were involved in the study. Cases included 306 patients aged 18 to 50 years with chlamydia, gonorrhoea, Mycoplasma genitalium infection and/or trichomoniasis. The control group consisted of 192 patients of the same age group without urogenital complaints and negative for the listed infections.

The study indicated that among men who consulted with an andrologist, the most prevalent sexually transmitted infection was chlamydia (64.1%), followed by Mycoplasma genitalium infection (20.9%), gonorrhoea (7.8%) and trichomoniasis (1.6%). The total proportion of different combined infections was 5.6%. "The results measured by flow cytometry showed that gonorrhoea caused the highest inflammatory reaction and the highest bacterial count in first-voided urine," described Tjagur, who considers this finding one of the greatest values of the study, in addition to providing a good overview of the prevalence of sexually transmitted infections and the efficiency of diagnostics.

Tjagur concluded that flow cytometry can be considered a rapid and objective screening method in case of suspected male infectious urethritis, although further studies are needed to confirm the initial findings.

Scientists from Cardiff University have helped produce a brand-new, three-dimensional survey of our galaxy, allowing them to peer into the inner structure and observe its star-forming processes in unprecedented detail.

The large-scale survey, called SEDIGISM (Structure, Excitation and Dynamics of the Inner Galactic Interstellar Medium), has revealed a wide range of structures within the Milky Way, from individual star-forming clumps to giant molecular clouds and complexes, that will allow astronomers to start pushing the boundaries of what we know about the structure of our galaxy.

SEDIGISM has been unveiled today through the publication of three separate papers in the Monthly Notices of the Royal Astronomical Society, authored by an international team of over 50 astronomers.

"With the publication of this unprecedentedly detailed map of cold clouds in our Milky Way, a huge observational effort comes to fruition", says Frederic Schuller from the Max Planck Institute for Radio Astronomy (MPIfR), lead author of one of the three publications, presenting the data release.

Dr Ana Duarte Cabral, a Royal Society University Research Fellow from Cardiff University's School of Physics and Astronomy, was lead author on one of the papers and has provided a catalogue of over 10,000 clouds of molecular gas in our Milky Way.

The Milky Way, named after its hazy appearance from Earth, is a spiral galaxy with an estimated diameter between 170,000 and 200,000 light-years which contains between 100-400 billion stars.

The Milky Way consists of a core region that is surrounded by a warped disk of gas and dust that provides the raw materials from which new stars are formed.

For Dr Duarte Cabral, the new catalogue of gas clouds will allow scientists to probe exactly how the spiral structure of our own Milky Way affects the life cycle of clouds, their properties, and ultimately the star formation that goes on within them.

"What is most exciting about this survey is that it can really help pin down the global galactic structure of the Milky Way, providing an astounding 3D view of the inner galaxy," she said.

"With this survey we really have the ability to start pushing the boundaries of what we know about the global effects of the galactic structures and dynamics, in the distribution of molecular gas and star formation, because of the improved sensitivity, resolution, and the 3D view."

The catalogue of molecular gas clouds was created by measuring the rare isotope of the carbon monoxide molecule, 13CO, using the extremely sensitive 12-metre Atacama Pathfinder Experiment telescope on the Chajnantor plateau in Chile.

This allowed the team to produce more precise estimates of the mass of the gas clouds and discern information about their velocity, therefore providing a truly three-dimensional picture of the galaxy.

Dr Duarte Cabral and colleagues are already beginning to tease out information from the vast amount of data at their disposal.

"The survey revealed that only a small proportion, roughly 10%, of these clouds have dense gas with ongoing star formation," said James Urquhart from the University of Kent, the lead author of the third publication.

Similarly, the results from the work led by Dr Duarte Cabral suggest that the structure of the Milky Way is not that well defined and that the spiral arms are not that clear.

They have also shown that the properties of clouds do not seem to be dependent on whether a cloud is located in a spiral arm or an inter-arm region, where they expected very different physics to be playing a role.

"Our results are already showing us that the Milky Way may not be a strong grand design type of spiral galaxy as we thought, but perhaps more flocculent in nature," Dr Duarte Cabral continued.

"This survey can be used by anyone that wants to study the kinematics or physical properties of individual molecular clouds or even make statistical studies of larger samples of clouds, and so in itself has a huge legacy value for the star formation community."

The evidence for the harmful effects of alcohol on brain health is compelling, but now experts have pin-pointed three key time periods in life when the effects of alcohol are likely to be at their greatest.

Writing in The BMJ today, researchers in Australia and the UK say evidence suggests three periods of dynamic brain changes that may be particularly sensitive to the harmful effects of alcohol: gestation (from conception to birth), later adolescence (15-19 years), and older adulthood (over 65 years).

They warn that these key periods "could increase sensitivity to the effects of environmental exposures such as alcohol" and say harm prevention policies "must take the long view."

Globally, around 10% of pregnant women consume alcohol, with the rates considerably higher in European countries than the global average, they write.

Heavy alcohol use during pregnancy can cause fetal alcohol spectrum disorder, associated with widespread reductions in brain volume and cognitive impairment. But data suggest that even low or moderate alcohol consumption during pregnancy is significantly associated with poorer psychological and behavioural outcomes in offspring.

In terms of adolescence, more than 20% of 15-19 year olds in European and other high income countries report at least occasional binge drinking (defined as 60 g of ethanol on a single occasion), they add.

Studies indicate that the transition to binge drinking in adolescence is associated with reduced brain volume, poorer white matter development (critical for efficient brain functioning), and small to moderate deficits in a range of cognitive functions.

And in older people, alcohol use disorders were recently shown to be one of the strongest modifiable risk factors for all types of dementia (particularly early onset) compared with other established risk factors such as high blood pressure and smoking.

Although alcohol use disorders are relatively rare in older adults, the authors point out that even moderate drinking has been shown to be linked to a small but significant loss of brain volume in midlife, although further studies are needed to test whether these structural changes translate into functional impairment.

Furthermore, demographic trends may compound the effect of alcohol use on brain health, they write. For example, women are now just as likely as men to drink alcohol and experience alcohol related harms, and global consumption is forecast to rise further in the next decade.

The effects of the covid-19 pandemic on alcohol use and related harms are unclear, but alcohol use increased in the long term after other major public health crises, they add.

As such, they call for an integrated approach to harm reduction at all ages.

"Population based interventions such as guidelines on low risk drinking, alcohol pricing policies, and lower drink driving limits need to be accompanied by the development of training and care pathways that consider the human brain at risk throughout life," they conclude.