Body

(Vienna, October 12, 2020) Asthma and food hypersensitivity at age 12 is associated with an increased risk of having irritable bowel syndrome at 16, a new study presented today at UEG Week Virtual 2020 has found.

The research, conducted at the University of Gothenburg and the Karolinska Institute in Stockholm, Sweden, analysed the health of 2,770 children from birth to the age of 16. Those with IBS at 16 were almost twice as likely to have had asthma at the age of 12 (11.2% vs 6.7%). Almost half of children with IBS at 16 (40.7%) reported food hypersensitivity at 12 years (compared to 29.2% of children without IBS at 16).

The research also showed that asthma, food hypersensitivity and eczema were all associated with an increased risk of concurrent IBS at 16 years.

The population-based cohort study was led by Dr Jessica Sjölund from the Institute of Medicine at the University of Gothenburg, Sweden. "The associations found in this large study suggest there's a shared pathophysiology between common allergy-related diseases and adolescent irritable bowel syndrome", she explained. "We knew that allergy and immune dysregulation had been suggested to play a role in the development of irritable bowel syndrome, but previous studies on allergy-related diseases and irritable bowel syndrome are contradictory".

"This knowledge could open up for developing new treatment methods for adolescent IBS, targeting processes of low grade inflammation seen in these allergy-related diseases."

During the study, children and parents were asked to complete questionnaires regarding asthma, allergic rhinitis, eczema and food hypersensitivity at ages 1, 2, 4, 8, 12 and 16 years. At 16, children answered questions based on the Rome III Questionnaire on Pediatric Gastrointestinal Symptoms, allowing participants to be categorised into IBS, functional abdominal pain and function dyspepsia groups.

IBS affects more than one in ten people2 and is the most common functional gastrointestinal disorder. It can be extremely disabling for patients, with abdominal cramps, bloating, diarrhoea or constipation. There are often difficulties in diagnosing functional gastrointestinal disorders like IBS, and just one in three people with symptoms of IBS or constipation consult a healthcare professional.

Hans Törnblom, who was involved in the research and is one of Europe's leading IBS experts, comments, "Even though functional gastrointestinal disorders are common, many patients are, unfortunately, negatively stigmatised and labelled. The fact that many IBS sufferers do not seek medical advice should be of great concern. As well as dedicating resources to improve the physical elements of living with disorders like IBS, care and investment must be committed to providing psychological and emotional support for patients so they are comfortable in seeking medical advice."

Patients of Black ethnicity have an increased risk of requiring hospital admission for COVID-19, while patients of Asian ethnicity have an increased risk of dying in hospital from COVID-19, compared to White patients, a study has found.

Data analysis published today (Friday 9th October, 2020) in EClinicalMedicine, led by researchers at King's College London, with support from the NIHR Guy's and St Thomas' Biomedical Research Centre and the British Heart Foundation (BHF), examines the relationship between ethnic background and the virus SARS-CoV-2.

The study confirms that minority ethnic patients bear a higher burden of the disease than White patients and also finds that Black patients and Asian patients are affected at different stages of the disease.

Professor Ajay Shah, BHF Professor of Cardiology at King's College London and Consultant Cardiologist at King's College Hospital, said: "The finding that Black versus Asian patients are affected in quite different ways, and that significant risk persists even after adjustment for deprivation and long-term health conditions, is striking. It strongly suggests that other factors, possibly biological, are important and that we may need different treatment strategies for different ethnic groups. For Black patients, the issue may be how to prevent mild infection progressing to severe whereas for Asian patients it may be how to treat life-threatening complications."

Professor Chris Whitty, Chief Medical Officer for England and Head of the NIHR, said: "The evidence is now clear that people from Black and minority ethnic groups are more severely affected by COVID-19. This NIHR-supported research shows how different groups are affected, providing important information to help healthcare professionals offer the best possible treatment to minority ethnic patients."

The study analysed data from 1,827 adult patients admitted to King's College Hospital, south-east London, with a primary diagnosis of COVID-19 between 1 March and 2 June 2020.

Researchers analysed mortality in this group, and also compared a subset of 872 admitted patients from inner south-east London with 3,488 matched controls residing in the same region to determine how ethnic background is associated with the need for hospitalisation for severe disease. Of these 872 admitted patients, 48.1% were Black, 33.7% White, 12.6% Mixed and 5.6% were Asian ethnicity.

The analysis showed that Black and Mixed ethnicity patients have a three-fold higher risk of requiring hospital admission once infected with COVID-19 compared to White inner-city residents of the same region. This is only partly explained by comorbidities and deprivation as adjusting for these factors Black patients still have a 2.2 to 2.7-fold higher admission risk. However, in-hospital survival for these patients was not significantly different from White patients.

By contrast, Asian patients did not have a higher risk of requiring hospital admission with COVID-19 than White patients but their in-hospital death rate and need for intensive care unit admission was higher than the other groups.

The researchers observed that the minority ethnic patients were 10-15 years younger than White patients and had a higher prevalence of comorbidities, especially diabetes.

The study suggests that while comorbidities and socioeconomic factors contribute to the impact of COVID-19 on minority communities, there may be an important role for other factors such as biological factors which affect different subgroups in different ways.

The results of this study are likely to be applicable across the whole of London and similar UK cities, but more research is needed to translate to multi-ethnic populations in other countries.

Dr Sonya Babu-Narayan, Associate Medical Director at the British Heart Foundation said: "This study provides further evidence that COVID-19 disproportionally affects those whose ethnic background is a minority where they live, as has been seen across the world. Why coronavirus hits people with an ethnic minority background harder, and how to mitigate this, has been complex to address."

She continued: "People from Black, Asian and other Minority Ethnic backgrounds more often have heart and circulatory risk factors including high blood pressure and diabetes, and are more exposed to socioeconomic disadvantage, but this study indicates the worse effects of COVID-19 are present even after these are accounted for. Research is now needed to assess how other structural and behavioural factors may contribute, including occupation, access to health messaging and health care, and differences in the patient journey once people reach hospital. As we see COVID-19 cases rise again in the UK, we must address these disparities with urgency."

The study, published in PLOS ONE, looked at the number of deaths in each of the 7,251 local authority areas of Italy during the first four months of the year and compared these figures with predictions based on data from 2016-2019.

It found that Lombardy had the most excess deaths of any region in Italy. After comparing with official data on confirmed Covid-19 deaths, the researchers estimated that there were still 10,197 more deaths than predicted based on past trends, or 43% of all excess deaths.

Researchers say this may be attributable to delayed or reduced access to healthcare for other health issues, while some of the deaths may have been people with Covid-19 whose deaths were not recorded as such, perhaps because they were not tested for the virus.

Professor Gianluca Baio (UCL Statistical Science) said: "Calculating excess deaths is important because it tells us how many more people died in a given period than we could have predicted. This gives the full scale of the tragedy, going beyond confirmed Covid-19 deaths to include deaths that were an indirect result of the pandemic. These are the deaths that, with better healthcare planning, could potentially have been avoided."

Professor Marta Blangiardo, of Imperial College London, said: "Our study cannot explain why there was such a large spike in apparent non-Covid-19-related deaths in Lombardy. However, the pandemic had an overwhelming effect on the region's healthcare systems, so reduced or delayed access to healthcare may be a factor."

Researchers compared weekly mortality rates in local authority areas with what they had predicted for that area based on four years of data, accounting for the time of year and including air temperature data (milder weather in winter is associated with lower mortality), as well as for the geographical correlation (that is, the fact that mortality trends are more alike in areas that are geographically close to each other). They say the model is more reliable as it uses data from each local authority area, at a high spatial resolution.

The study found stark geographical differences in mortality. Central and southern Italy appeared to be largely unaffected by the pandemic between January and April, broadly recording no more deaths than the model predicted, most likely as a consequence of the national lockdown imposed by the Italian government from early March.

Meanwhile, Verona, a city just outside the worst-hit region of Lombardy, recorded rates barely above those predicted during the peak of the pandemic. This is despite being about 20 miles (30km) from the badly hit Lombardian province of Brescia, which recorded 80% more deaths than expected.

Similarly, the city of Pesaro in Marche, central Italy, recorded 84% more deaths than expected, while the surrounding region did not have a higher than expected number of deaths.

Professor Baio said: "These big differences in mortality raise questions about authorities' handling of the pandemic. The province of Veneto, where Verona is located, had a much lower mortality rate than neighbouring Brescia. A driving factor for this may have been Veneto's timely and comprehensive mass-testing programme."

The researchers say their model could be used for near-real-time mortality surveillance, to continuously monitor local trends and detect a rise in Covid-19 cases quickly, seeing where mortality rates deviate from the expected range.

Women are 2-3 times more likely to suffer from constipation during pregnancy and right after childbirth than at any other time in their life, a new study from the University of Eastern Finland shows.

"However, constipation-related problems subside surprisingly quickly after delivery," says Moona Kuronen, Lic. Med., the lead author of the newly published article.

Constipation is common, and the risk of infrequent bowel movements is increased by diet that is low in fibre. Constipation becomes more common with age, and women tend to have constipation more often than men.

Docent Hannu Kokki's research group at the University of Eastern Finland is exploring the incidence of constipation and other gastrointestinal problems in more than 1,000 fertile age women. Published in International Journal of Obstetrics & Gynaecology (BJOG), the new study focuses on the incidence of constipation in the second and third trimester, as well as immediately after vaginal and caesarean delivery. The control group comprised 200 non-pregnant women.

44% of women suffer from constipation in the second trimester

The study found that 44% of women have constipation in the second trimester, and 36% in the third. The incidence of constipation after vaginal delivery increases to 47%, and as many as 57% of women who had a caesarean delivery reported gastrointestinal problems and constipation.

According to the researchers, the percentages are surprisingly high and, since gastrointestinal problems have an effect on both physical and mental well-being, their prevention should be discussed in pre-natal clinics early on in pregnancy. Severe constipation increases the risk of haemorrhoids, urinary and faecal incontinence, and pelvic organ prolapse.

"Constipation during pregnancy is more common in women who have suffered from it already before pregnancy, or during their possible earlier pregnancy," Kuronen says.

Daily exercise, eating a balanced diet that is rich in fibre, and drinking enough fluids are the most important ways to prevent constipation. In pregnancy, placental hormones cause bowel movements to slow down, and the growing uterus can make it difficult to pass stool normally. In addition, pregnancy changes the way fluids get absorbed from the gut.

"Indeed, other gastrointestinal problems frequently reported by expecting mothers include feelings of thirst and pressure, and flatulence," Kuronen points out.

If lifestyle changes aren't enough to alleviate constipation, laxatives may be needed.

Constipation is most frequently reported right after childbirth. This can be caused by too much sedentary time and insufficient intake of fluids after delivery. Furthermore, damage to the pelvic muscles during vaginal delivery may lead to problems in bowel function, as can pain in the surgical wound after a caesarean section. According to Kuronen, pain in the first few days after delivery should be managed so that the new mother can move about as soon as possible, regardless of whether the child was delivered vaginally or by caesarean section.

"Pain shouldn't prevent normal passing of stool, and the analgesics used should slow bowel movements down as little as possible."

It gets easier in a month

One of the new discoveries of the study is that normal bowel function is restored quickly after childbirth. When women who had given birth vaginally or by caesarean section were asked about their symptoms one month after childbirth, constipation was reported even less frequently than by the control group. However, other gastrointestinal problems were still frequently reported: feeling of thirst, flatulence and abdominal pain were reported by 68-82%, which was slightly more than in the control group.

"There is very little research into the incidence of constipation during pregnancy and immediately after childbirth. Our findings show that constipation and other gastrointestinal problems are very common. This is why it is important to invest in their prevention and treatment, and in the related counselling, both during pregnancy and after childbirth," Docent Kokki says.

People's exposure to environmental noise dropped nearly in half during the early months of the coronavirus pandemic, according to University of Michigan researchers who analyzed data from the Apple Hearing Study.

Researchers at U-M's School of Public Health and Apple Inc. looked at noise exposure data from volunteer Apple Watch users in Florida, New York, California and Texas. The analysis, one of the largest to date, included more than a half million daily noise levels measured before and during the pandemic.

Daily average sound levels dropped approximately 3 decibels during the time that local governments made announcements about social distancing and issued stay-at-home orders in March and April, compared to January and February.

"That is a huge reduction in terms of exposure and it could have a great effect on people's overall health outcomes over time," said Rick Neitzel, associate professor of environmental health sciences at U-M's School of Public Health. "The analysis demonstrates the utility of everyday use of digital devices in evaluating daily behaviors and exposures."

The four states reviewed in this analysis had differing COVID-19 responses in terms of stay-at-home orders, which showed through the data.

"California and New York both had really drastic reductions in sound that happened very quickly, whereas Florida and Texas had somewhat less of a reduction," Neitzel said.

Initially, the largest drop in environmental sound exposure was seen on the weekends, where nearly 100% of participants reduced their time spent above the 75 dBA threshold (a sound level roughly as loud as an alarm clock) between Friday and Sunday.

"But after the lockdowns, when people stopped physically going to work, the pattern became more opaque," Neitzel said. "People's daily routines were disrupted and we no longer saw a large distinction in exposures between the traditional five working days versus the weekend."

These data points allow researchers to begin describing what personal sound exposures are like for Americans who live in a particular state, or are of a particular age, or who have or do not have hearing loss.

"These are questions we've had for years and now we're starting to have data that will allow us to answer them," Neitzel said. "We're thankful to the participants who contributed unprecedented amounts of data. This is data that never existed or was even possible before."

New Rochelle, NY, October 6, 2020—Battling the COVID-19 pandemic and preparing for the inevitable next surge requires a data-driven population health approach. A special issue of the peer-reviewed journal Population Health Management is dedicated to combatting COVID-19. It embraces systems thinking and key insights from other industries. Click here to read the issue now. 

“This series of editorials, papers, and roundtable discussions highlights the need to harness the tools of population health to successfully combat COVID-19. The authors represent some of the most important companies and organizations tackling the pandemic, including Quest Labs, Humana, Microsoft, and many provider groups too. This dedicated issue will serve as a guide as we confront the next possible surge--it should be required reading for all healthcare leaders,” says David Nash, MD, MBA, Editor-in-Chief of Population Health Management and Founding Dean Emeritus and Dr. Raymond C. and Doris N. Grandon Professor, Jefferson College of Population Health, Philadelphia, PA.

Point-of-view, original research, and two roundtable articles comprise the special issue. Included in the issue are the following articles:

If Aviation Were in Control of the COVID-19 Response
A Simple Algorithm for Return to Workplace Employer Antibody Testing
Health Inequalities in the Use of Telehealth in the United States in the Lens of COVID-19
We Know Health Is Not Elective: Impacts of COVID-19
Changes in Health Care Following COVID-19

Volume 11, Issue 28 of Oncotarget features "Rapid onset type 1 diabetes with anti-PD-1 directed therapy", by Yun et al. and reported that Type 1 diabetes is a rare immune-related adverse event caused by checkpoint inhibitors with serious risk for diabetic ketoacidosis.

Of the patients who received immunotherapy, 5 patients were found to have type 1 diabetes, all of whom presented with DKA requiring insulin at 20 to 972 days from their first anti-PD- 1 dose.

Four patients had new-onset diabetes with mean Hb A1c of 9.1% on DKA presentation and persistent elevations over time.

Two patients who tested positive for glutamic acid decarboxylase antibodies presented with DKA at 20 and 106 days from first anti-PD-1 administration whereas patients who were autoantibody negative had DKA more than a year later.

The case series suggests that monitoring glycemia in patients on PD-1 inhibitors is not predictive for diabetes occurrence.

Dr. Sandip Pravin Patel from The Division of Hematology-Oncology in the Department of Medicine at The University of California San Diego said, "Cancer immunotherapy has broadened in clinical use over the last decade with FDA approval for treatment of various malignancies including melanoma, non-small cell lung cancer (NSCLC), renal cell carcinoma, urothelial carcinoma, head, and neck carcinomas, cutaneous squamous cell cancer, microsatellite unstable tumors, and Hodgkin's lymphoma."

Autoimmune type 1 diabetes is generally associated with positive autoantibodies to islet proteins including glutamic acid decarboxylase, insulin, insulinoma-associated antigen-2, zinc transporter 8, and islet cells.

However, only a subset of patients who acquire type 1 diabetes is found to have autoantibodies and specific HLA alleles, making these biomarkers poor predictors of diabetes incidence.

Given the rarity of type 1 diabetes as an ir AE, the authors sought to characterize the real-world diagnosis, management, and sequelae of patients who developed this ir AE in the context of their immune checkpoint blockade.

This Oncotarget paper highlights the rapid kinetics of type 1 diabetes in patients on checkpoint inhibitors.

"This Oncotarget paper highlights the rapid kinetics of type 1 diabetes in patients on checkpoint inhibitors"

Type 1 diabetes presented as DKA for all patients in this series and all but one patient had a new diagnosis of diabetes, without antecedent laboratory or imaging findings.

The Patel Research Team concluded in their Oncotarget Research Paper that their case series illustrates the rare incidence of immunotherapy-induced type 1 diabetes and describes the rapid course of this disease in patients.

Regardless of whether or not patients remain on checkpoint inhibitors, those with immunotherapy-induced diabetes are at risk for hyperglycemia and recurrent DKA. Surveillance of glycemia or Hb A1c does not predict diabetes but does have a role after type 1 diabetes arises as glycemia fluctuates and elevated Hb A1c levels persist.

Furthermore, GAD antibodies are present in about half of patients who develop type 1 diabetes after immunotherapy, warranting additional investigations into whether this is all association and a marker of immune attack.

Given the absence of prescient laboratory or imaging findings in patients who develop type 1 diabetes on anti-PD-1 therapy, patients should be counseled on the symptoms of hyperglycemia which include polyuria, polydipsia, abdominal pain, nausea and emesis and seek medical attention immediately.

CHAMPAIGN, Ill. -- In a collaborative effort between scientists and personnel on military bases in 31 states in the continental U.S. and Puerto Rico, researchers surveyed for an infection caused by an emerging fungal pathogen that afflicts snakes. The effort found infected snakes on military bases in 19 states and Puerto Rico, demonstrating that the fungus is more widely distributed than was previously known. The team reports the findings in the journal PLOS ONE.

"Ophidiomycosis - formerly known as 'snake fungal disease' - is an emerging infectious disease caused by the fungus Ophidiomyces ophidiicola," said Dr. Matt Allender, a professor in the veterinary diagnostic laboratory at the University of Illinois Urbana-Champaign who led the new study. "It has been documented in over 15 genera of wild and captive snakes. Infection with the pathogen causes a wide range of clinical signs in snakes, from difficulty shedding skin, to crusts and ulcers on the head and body, and even death in some cases."

Allender is the director of the Wildlife Epidemiology Lab at the U. of I. and an expert on ophidiomycosis.

"We looked for this pathogen in samples from 657 snakes and found that 17% were infected. Our findings include the first reports of this disease in Oklahoma, Idaho and Puerto Rico," he said.

The team tested swab samples taken from snakes representing 58 species. The researchers used a qPCR assay they developed, which amplifies the DNA in small samples to detect and measure the extent of infection. Biologists who collected the samples also inspected the snakes for scabs or other signs of disease. The scientists detected the pathogen in samples from 113 snakes representing 25 species including copperheads, eastern diamondback rattlesnakes, Puerto Rican boas, sidewinders and whip snakes.

"Adults had greater odds of being diagnosed with ophidiomycosis than younger snakes," the researchers reported. "Snakes from Georgia, Massachusetts, Pennsylvania, and Virginia all had greater odds of ophidiomycosis diagnosis, while snakes from Idaho were less likely to be diagnosed with the disease."

This likely reflects a larger distribution of this disease in snakes in the eastern U.S. than previously thought, and its possible expansion from east to west, Allender said. The disease was first confirmed in 2006 in a population of timber rattlesnakes in New Hampshire.

Snakes worldwide are suffering as a result of habitat loss, climate change and infectious diseases like ophidiomycosis. Their health and abundance are important to human health, as snakes control populations of small mammals that carry and amplify pathogens that also cause disease in humans such as hanatavirus and Lyme disease, Allender said.

Natural lands on military bases provide an unexpected sanctuary for many threatened or endangered species, he said.

Previous studies by project co-investigators with the Department of Defense have found that amphibian and reptile species living on DOD lands represent nearly two-thirds of the total native amphibian and reptile species documented in the continental U.S.

"Ophidiomycosis has potentially serious consequences for the success of snake conservation efforts in North America, threatening biodiversity across several habitats," Allender said.

Malignant tumours of the peripheral nerve are rare but aggressive and very difficult to treat successfully. Now, researchers in the US have shown that a combination of two types of anti-cancer drugs, MEK and SHP2 inhibitors, is effective in targeting the mechanism that drives the cancer's growth.

Although the work has been carried out in cells and mice, this discovery means that there are immediate implications for improving the treatment and outcomes for patients with this cancer, according to Dr Jiawan Wang, who will be presenting her findings at the 32th EORTC-NCI-AACR [1] Symposium on Molecular Targets and Cancer Therapeutics, which is taking place online. One of the drugs tested is already approved by the Food and Drug Administration (FDA) in the US, and the other is currently in clinical trials, either as a single agent or in combination with other drugs, for a number of cancers.

Malignant peripheral nerve sheath tumours (MPNST) are cancers of the connective tissue surrounding the nerves, and are classified as sarcomas. Although they occur in approximately 1.5 people per 100,000 of the general population, they account for between 5 to 10% of all soft tissue sarcomas. They are treated with surgery, chemotherapy and sometimes radiotherapy but prognosis is poor overall and the average length of survival among children is 30 months.

"There is an urgent, unmet need for new treatments for this disease," said Dr Wang. "Our findings have immediate translational implications and may inform future clinical trials for patients with MPNST."

Dr Wang, a postdoctoral research fellow at the Department of Oncology/Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, USA, and her colleagues, led by Dr Christine Pratilas, also at Johns Hopkins, knew that in the majority of these tumours growth is driven by the loss of a protein called neurofibromin 1 (NF1), which regulates a cell signalling pathway called RAS/MEK/ERK [2]. Neurofibromatosis is a genetic condition in which tumours, normally benign, grow in the nervous system. However, these benign tumours can change to malignant tumours, and therefore people with neurofibromatosis type 1 are at high risk of developing MPNST. Anti-cancer drugs designed to inhibit MEK have had limited effect against MPNST when tested in cells and mice in the lab.

Dr Wang discovered how MPNST adapts its response to anti-cancer drugs that disrupt the signals that drive its growth. She found that cell surface receptors called receptor tyrosine kinases (RTKs) interacted with the RAS protein, which is involved in cell signalling, to limit the cancer cells' sensitivity to drugs that inhibit MEK.

"As there are no drugs available that inhibit RAS, we thought that an alternate strategy would be to use a drug against a protein called SHP2, which plays a role in the activation of RAS when RTKs are active, to regulate cell survival and proliferation," she said.

Dr Wang investigated the activity of an existing SHP2 inhibitor, SHP099, on MPNST cells in the lab and found that it produced a modest response. However, the combination of the SHP2 inhibitor with a MEK inhibitor worked even better.

"We found that this combination was effective in MPNST that were resistant to MEK inhibition and it also showed efficacy in plexiform neurofibroma, which is an abnormal yet benign tumour that occurs commonly in patients with neurofibromatosis type 1," she said. "We then confirmed the efficacy of the combination in MPNST in mice.

"The MEK inhibitor that we tested is trametinib, which is an FDA-approved drug for melanoma, lung and thyroid cancers, and the SHP2 inhibitor, SHP099, is a compound related to another drug, TNO155, which is currently in clinical development as single agent or in combination with other drugs for several cancer types. The low dose combination of trametinib and SHP099 was well tolerated in mice we tested."

There may be concerns related to treating patients with combinations of SHP2 and MEK inhibitors because of potential adverse side-effects, so studies in patients are needed to evaluate the safety of the combination. However, Dr Wang believes that side effects expected at high doses of the drugs may be minimised if lower doses of both drugs are used.

"In our work, we used a low-dose treatment schedule of 0.3 mg/kg trametinib and/or 50 mg/kg SHP099 once daily, five days on and two days off, and we did not observe obvious weight loss, despite some hair loss indicating possible skin toxicity in some mice receiving a combination of the two drugs," she said.

The next step is for the researchers to test the drug combination in a wide range of patient-derived MPNST that have been grafted into mice. If the results are successful, the combination could then move into clinical trials in patients. This means it could be two years before the results from this research could be translated into new and better treatments for patients.

Professor Emiliano Calvo is co-chair of the EORTC-NCI-AACR Symposium on behalf of the EORTC; he is Director of START Madrid Group in Madrid, Spain, and Director of Clinical Research at the START Madrid-Centro Integral Oncológico Clara Campal hospital in Madrid and he was not involved in the research. He commented: "This research is an innovative biology-based and mechanistic approach to tackling the problems of tumours that are driven by RAS activation and are resistant to current treatments; this is a definitely important unmet need. As with most combinations, it will be a clinical challenge to be able to give both drugs together in large enough doses so that the right amount reaches the tumour without exposing the patient to severe adverse side effects. We look forward to the early phase trials of this combination in patients with great interest and excitement. New and better ways of treating these patients are urgently needed."

The coronavirus pandemic has widened existing gaps in access to abortion services across Europe, finds a review of country-wide policy changes in response to COVID-19, published in the journal BMJ Sexual & Reproductive Health.

But enforced innovations adopted in some countries, such as telemedicine and the provision of abortion at home, could reverse that trend and prompt long lasting change for this essential health service, suggest the researchers.

Abortion is one of the most common procedures for women of reproductive age in Europe, ranging from 6.4/1000 women aged 15-44 in Switzerland to 19.2/1000 in Sweden. The need for it is likely to have increased in the wake of COVID-19, because of economic uncertainties, increased exposure to sexual violence, and limited access to contraception, say the researchers.

In light of the extensive public health measures restricting freedom of movement at the height of the pandemic, they wanted to find out what impact these might have had on access to abortion services across Europe.

They therefore compiled information on practice in 46 countries/regions. Survey information, filled in by national experts, was collected for 31, while desk research was carried out for the remaining 15.

The data revealed that European countries adopted different approaches in response to the pandemic, ranging from imposing restrictions to relaxing certain requirements.

New restrictions included delay or denial of abortion care to women with COVID-19 symptoms, or living with those who had them, and decreased availability of surgical abortion. A few countries expanded medical abortion availability via telemedicine, and relaxed regulations around the use of drugs to induce medical abortion.

In detail, abortions were banned in six countries (Andorra, Liechtenstein, Malta, Monaco, San Marino and Poland) and suspended in one (Hungary).

Access to surgical abortion was restricted in 12 countries/regions and services weren't available at all, or delayed, for women with COVID-19 symptoms in 11: The Netherlands, Belgium, Germany, Iceland, Latvia, Luxembourg, Montenegro, Slovenia, England, Wales and Scotland. No country expanded its gestational limit for abortion.

Changes to reduce face to face consultations were made in 13 countries/regions (Belgium, Estonia, Ireland, Finland, France, Germany, Norway, Portugal, Switzerland, England, Wales, Scotland and Northern Ireland).

But only seven countries/regions offered abortion by telemedicine. In two this was already provided before the pandemic (Denmark and the Stockholm region of Sweden) and five other countries adopted it (England, Wales, Scotland, France and Ireland).

Eight countries/regions provided home medical abortion with mifepristone and misoprostol beyond 9 weeks (up to 11 weeks+6 days) while 13 countries/regions did so up to 9 weeks.

Pharmacy access to prescribed mifepristone was permitted in two countries/regions: Denmark, where it was permitted before COVID-19, and France, where it wasn't permitted before. And these drugs could be delivered by post in England, Wales, Scotland and Georgia or home delivered in England, Wales, Scotland and Ireland.

"Abortion is an essential component of women's sexual and reproductive care. While extremely safe under recommended procedures, it is responsible for substantial maternal morbidity and mortality when women do not have access to safe abortion care," emphasise the researchers.

Abortion services are particularly vulnerable to any move to restrict provision, because "politics often trumps evidence," they point out. "With each passing week of political inaction, thousands of women are denied treatment that cannot be postponed,and face the prospect of carrying an unwanted pregnancy to term or of undergoing unsafe procedures," they add.

"Altogether, the diversity of pre-COVID-19 rules regulating abortion coupled with inconsistent responses to the COVID-19 crisis has exacerbated a heterogeneous landscape of abortion provision in Europe," write the researchers.

"The lack of political will to lift unnecessary regulations is discouraging, yet we recognise the concerted efforts of some governments and providers who swiftly acted to sustain abortion care during COVID-19 disruptions," they note.

And they conclude: "The lack of a unified policy response to COVID-19 restrictions has widened inequities in abortion access in Europe, but some innovations including telemedicine deployed during the outbreak, could serve as a catalyst to ensure continuity and equity of abortion care.

"We believe that these advances, mostly conceived as temporary responses to a health crisis, could serve as catalyst towards 'liberalising' abortion provision and that they should become the standard of care."

Dr Edward Morris, President of the Royal College of Obstetricians and Gynaecologists (RCOG), which co-owns the journal, comments: "This review has shone a light on some of the shocking inequalities in access to abortion care that women face across Europe during the COVID-19 pandemic."

He continues: "The abortion telemedicine pathway introduced into England, Scotland and Wales has enabled thousands of women to access safe abortion care during the COVID-19 pandemic. This is during a time when access to other essential women's health services were hampered.

"We have seen huge benefits for women arise out of this simple, yet effective, innovation. There has been a reduction in waiting times for women who have requested an abortion, visits to clinics have reduced, which has limited the transmission of the COVID-19 virus among both women and staff, and complications related to abortion have decreased."

He adds: "We welcome the steps taken by those governments that have ensured that abortion care has continued to be provided in a safe, timely and compassionate manner and applaud in particular the new innovative ways to abortion care provision, including the introduction of telemedicine in some countries, including Great Britain. We would urge governments to ensure that these positive changes remain in place beyond the pandemic."

An international research team has discovered a principle that explains the metastasising of prostate cancer. When cancer evolves within the prostate, multiple spatially intermixed cancer cell clones are created that may invade the organs surrounding the prostate. However, only one dominant cell clone spreads systemically in the body and creates metastases. In addition, new subcellular clones are often generated in metastases, which pass on to other metastases.

The researchers also discovered that the routes through which the disease spreads also vary between patients. The genetic drivers occurring in cancer cell clones are likely to distinguish which sub-clones spread to the entire body and which are confined to the prostate within each patient.

The study led by Professor of Cancer Pathology Steven Bova from Tampere University and Professor David Wedge from the University of Oxford was published in the prestigious Nature Communications journal.

The study analysed samples from ten men over the course of their prostate cancer from diagnosis to death from metastatic disease.

It was the first to combine the genomic evolutionary analysis of local and metastatic prostate cancer with which of these evolutionary signals can be detected in blood and cerebrospinal fluid, ie in the so-called liquid biopsy.

Among other things, the study discovered that the analysis of circulating DNA in the blood of men with prostate cancer does not always detect metastatic cancer DNA. When cancer DNA is found, the main cancer cell clones connecting the metastases are always detected and subclones - which are present in only a subset of metastatic sites - are variably detected. According to the researchers, using liquid biopsy to monitor metastatic prostate cancer appears warranted even though it is not always a perfect reflection of what is contained in the patient's body. Thus, further research is needed to improve and extend these findings.

"The study showed remarkably that prostate cancer subclones, which have not yet spread and are present only in the prostate, were not detected in the patients' blood. If this proves true in larger studies, it could mean that the presence of circulating tumour DNA itself is diagnostic of metastatic prostate cancer," says Professor Steven Bova.

"Metastatic prostate cancer can spread to the brain and form subdural metastases. An analysis of the cerebrospinal fluid of men with metastatic prostate cancer should help identify which men have subdural metastases and which subclones are present. This may have therapeutic implications as the subclones may respond differently to therapy," Bova adds.

The study is based on a cohort study entitled "PELICAN integrated clinical-molecular autopsy study of lethal metastatic prostate cancer", which Professor Bova initiated at Johns Hopkins University in 1994.

The study is conducted with the tissue and liquid biopsy samples and patient histories of 33 men with metastatic prostate cancer who agreed to donate their bodies for research autopsy at the time of death. Bova has continued studying this cohort since he transferred to Tampere University in Finland in 2011.

Reston, VA--A new radioimmunotherapy has proven effective in reversing resistance to the most commonly used lymphoma drug, rituximab, according to research published in the October issue of The Journal of Nuclear Medicine. When used in combination with rituximab, 177Lu-lilotomab-satetraxetan was shown to substantially increase rituximab binding and rituximab-mediated antibody-dependent cellular cytotoxicity (ADCC) activity, resulting in significant tumor growth delay in a non-Hodgkin's lymphoma mouse model.

Non-Hodgkin's lymphoma is the most common blood cancer, with the eleventh highest mortality rate of all malignancies worldwide in 2018, according to the American Cancer Society. The monoclonal antibody rituximab was approved for treatment of non-Hodgkin's lymphoma more than 20 years ago and is currently the standard of care. However, many patients eventually develop resistance against rituximab, which is often associated with changes in expression of the CD20 antigen.

177Lu-lilotomab-satetraxetan (177Lu-lilotomab)--a next-generation b-particle-emitting radioimmunoconjugate--has been shown to increase CD20 expression in different rituximab-sensitive non-Hodgkin's lymphoma cell lines and to act synergistically with rituximab in a non-Hodgkin's lymphoma animal model. As such, researchers hypothesized that 177Lu-lilotomab could be used to reverse rituximab resistance in non-Hodgkin's lymphoma.

In the study, two non-Hodgkin's lymphoma cell lines--Raji (parent line) and Raji2R (rituximab-resistant line)--were cultured and incubated with either lilotomab, 177Lu-lilotomab or saline. Xenografted mice were then administered either saline, rituximab monotherapy, 177Lu-lilotomab monotherapy or a combination therapy of 177Lu-lilotomab-satetraxetan and rituximab. Tumor volume and survival time were calculated and analyzed.

Exposure of the cell lines to 177Lu-lilotomab resulted in an increase in rituximab binding, as compared with control cells. With no 177Lu-lilotomab exposure, binding in the rituximab-resistant Raji2R cells was on average 36±5 percent compared to untreated Raji cells. After treatment with 177Lu-lilotomab, the rituximab-binding in Raji2R cells increased to 53±3 percent. In contrast, treatment with unlabeled lilotomab or saline had no effect on rituximab binding. Treatment with 177Lu-lilotomab also increased ADCC induction to 30±3 percent of Raji cells, representing a 50 percent increase.

In the xenografted mice, the combination of rituximab with 177Lu-lilotomab synergistically suppressed RajiR2 tumor growth. The median survival time of mice treated with this combination doubled when compared to survival of mice given 177Lu-lilotomab monotherapy and was five times longer than for mice given rituximab monotherapy.

"This work is potentially very important, as it could be a last way out for patients that have become resistant to rituximab. If those patients receive an injection of 177Lu-lilotomab-satetraxetan, they can be treated again with rituximab and have an improved effect," said Dr. Jostein Dahle, PhD, chief scientific officer at Nordic Nanovector. "In a phase 1b clinical trial, a 100 percent complete response rate was achieved in the first group of patients treated with 177Lu-lilotomab-satetraxetan followed by rituximab. Achieving a complete response is very important, since it usually correlates with an improved duration of response and overall survival."

Dahle continued, "Combination treatments are the future for cancer therapy. By exploring strategies with radioimmunotherapy together with other drugs, nuclear medicine may play an important role in lymphoma therapy."

Gender, age, education level, and political affiliation predict where people turn for information about COVID-19--and what sources they use and trust is linked to differing beliefs about the pandemic, according to a new study by NYU School of Global Public Health researchers.

The findings--drawn from surveys of more than 11,000 U.S. adults during the first few months of the pandemic--are published in JMIR Public Health and Surveillance.

"Our study is one of the first data-driven efforts to not only think about what is being said across different sources of COVID-19 information, but who is using what source, who is trusting what source, and what real impact this is having on knowledge and beliefs about the pandemic," said Shahmir Ali, a doctoral student at NYU School of Global Public Health and the study's lead author.

The COVID-19 pandemic created an urgent need to communicate health information to the public--but how can public health officials best reach people, given the myriad channels available? In March 2020, as it became clear that the coronavirus was spreading in the U.S., NYU researchers created and deployed an online survey to gauge how people were getting their information on COVID-19. The survey was based on a model used to study information sources during previous outbreaks of SARS and Ebola.

Using Facebook to recruit 11,242 U.S. adults from all 50 states, the researchers surveyed one group of participants in March and another in April. The survey asked what sources people use and trust to get information on COVID-19: traditional media (TV, newspapers, and radio), social media, government websites, other websites, personal connections (family, friends, and partners), medical professionals, and religious leaders.

The researchers also measured participants' knowledge (e.g. whether masks, hand sanitizer, and avoiding school and work can protect you against the coronavirus) and beliefs (e.g. the virus was released as an act of bioterrorism) about COVID-19.

When combined, traditional media sources--TV, radio, or newspapers--were the largest sources of COVID-19 information, with 91.2 percent of respondents turning to at least one. Popular outlets included CNN (24 percent of those using traditional media sources), FOX News (19.3 percent), and other local or national networks (35.2 percent).

After traditional media, government websites (87.6 percent) and social media (73.6 percent) were the most common sources of COVID-19 information, although participants reported trusting the government far more than social media: 43.3 percent listed the government as the most trusted source of information, compared with 1.2 percent for social media. Of note, trust in government websites varied by demographic--men and those 40 and older were less likely to trust the government--and faltered over time. The researchers measured a dramatic drop in people citing government websites as the most trusted source, from 53.3 percent in March to 36.8 percent in April.

"Perceptions and use of information sources can vary across different stages of a health crisis," said study author Yesim Tozan, assistant professor of global health at NYU School of Global Public Health. "Public health officials need to continually keep an eye on public perceptions and trust, and should adapt their communication strategies as needed so they remain effective."

The study also found that people use on average six different sources to gather information about COVID-19--although they tended to use more sources in March than in April. Participants with children and more education were likely to use more sources, while those who were male, aged 40 and older, not working or retired, or Republican were likely to use fewer sources.

"Twenty-five years ago, people would get their information by picking up the paper or watching the nightly news, but now, people get information from a variety of sources. While this can have benefits, many online sources are not vetted and may disseminate erroneous information, leaving it up to you as a consumer to sort it out," said Ralph DiClemente, chair of the Department of Social and Behavioral Sciences at NYU School of Global Public Health and the study's senior author. Additional study authors include postdoctoral associate Joshua Foreman and doctoral students Ariadna Capasso and Abbey Jones of NYU School of Global Public Health.

The association between what sources participants used and their knowledge about COVID-19 was mixed. Using some information sources, such as medical professionals and traditional media, was associated with having more knowledge in some areas but less in others.

However, many beliefs about COVID-19 were predicted by which sources of information people used. For example, those relying on CNN or MSNBC were more likely to agree that the coronavirus is deadlier than the flu, the amount of media attention to the coronavirus has been adequate, and the coronavirus is a bigger problem than the government suggests. Conversely, those relying on FOX News were more likely to agree that the coronavirus was released as an act of bioterrorism, warmer weather will reduce the spread of coronavirus, and the coronavirus is not as big of a problem as the media suggest.

"As public health professionals, it's important that we consider targeting information sources that are used and trusted by certain population groups in order to make sure that COVID-19 information is reaching a diverse audience," added Ali. "We have already started to see this, for instance, through initiatives by social media platforms to connect users with COVID-19 information while they are using these apps. Our research provides crucial evidence to push for these types of initiatives to get COVID-19 information out to the public in a manner that matches what sources they already use and trust."

By José Tadeu Arantes | Agência FAPESP – The most widely used model to describe the epidemic evolution of a disease over time is called SIR, short for susceptible (S), infected (I), and removed (R). A susceptible person can be infected, and the infected person will eventually be removed owing to either immunization or death. The number of people in each class varies, whereas the total population, given by the sum of individuals in all three classes, is considered constant in the time scale of epidemic contamination.

The function I(t) resulting from the model describes the increase in the number of infected people over time. The curve rises sharply during the phase in which the pathogen is spreading quickly, peaking at maximum contamination, and sloping down more gently as contagion slowly decreases until there are no longer any infectious people. The SIR model has been applied in several studies of the COVID-19 pandemic.

“Although this model is a very useful tool to investigate the temporal evolution of the pandemic, it provides few insights into how contagion progresses spatially, which is key to the planning of social distancing programs that effectively protect people and at the same time reduce the socio-economic impact of the disease,” Airton Deppman, a professor in the University of São Paulo’s Physics Institute (IF-USP), told Agência FAPESP.

Deppman is one of the authors of a paper published in the journal Chaos, Solitons & Fractals reporting some of the findings.

The study was supported by FAPESP via a Thematic Project for which Arnaldo Gammal is principal investigator and Deppman is one of several co-principal investigators.

The results point to the fractal nature of transmission in the case of COVID-19, as is also the case for many other variables relating to social life. This means contagion occurs discontinuously but in accordance with the same pattern at different scales. An infected person initially transmits the virus to a relatively small group with which he or she is in direct contact. Then there is a gap in transmission, followed by another phase in which the initially infected group transmits the virus to a larger group, and so on.

“When you construct a graph crossing the number of infected people with the population and quantify the variables on a logarithmic scale on the x and y axes, the result is a straight line. This is typical of a fractal phenomenon, in which the same pattern is repeated at various scales,” Deppman explained.

The study investigated this spatial distribution using data for China, the United States, and the state of São Paulo and tested the results by comparing the data for São Paulo and Europe. “The model successfully described in great detail the temporal evolution of contagion,” Deppman said. “As a rule of thumb, the curve rises steeply at first, and this is followed by smaller peaks and troughs as the virus is transmitted from one area to the next.”

The model can be used to find an optimal point at which to begin and end isolation, which should happen region by region and not generically for an entire state or country, he concluded.

The article “Fractal signatures of the COVID-19 spread” can be read at: www.sciencedirect.com/science/article/pii/S0960077920305166?via%3Dihub#!.

DOI

10.1016/j.chaos.2020.110119

A study published in the scientific journal Addiction suggests that, contrary to what some are claiming, people in the US may not be substituting cannabis for opioids.

This study examined the direction and strength of association between cannabis and opioid use over 90 consecutive days. Among adults who used non-medical opioids, the study compared the probability of non-medical opioid use on days when cannabis was used with days when cannabis was not used. The study included 13,271 days of observation among 211 participants from the greater New York area. The participants were predominantly male, urban, unemployed, unmarried, and had a high prevalence of substance misuse and pain. The results showed that opioid use was at least as high on days when cannabis was used as on days when it was not. This was true irrespective of the levels of pain being experienced by participants.

The study was limited by virtue of reliance on self-report of substance use and the fact that it did not determine whether cannabis or opioids were used first on a given day.

Study co-author, Deborah Hasin, states, "Our study is among the first to test opioid substitution directly, suggesting that cannabis seldom serves as a substitute for non-medical opioids among opioid-using adults, even among those who report experiencing moderate or more severe pain. In other words, our study suggests that cannabis is not an effective way to limit non-medical opioid use."

In 2017, there were over 2 million people with opioid use disorder and over 70,000 opioid-related deaths in the US. Illicit opioid use, including non-medical use of prescription opioids, synthetic opioids and heroin, is the primary cause of overdose deaths among US adults. Understanding how cannabis may change non-medical opioid use is critical to informing discussions around cannabis-based interventions for addressing the opioid crisis.