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DALLAS, Nov. 15, 2020 -- Among patients who stopped taking their cholesterol-lowering statin medication due to side effects, researchers found the statin may not have been the culprit because patients taking a placebo reported the same side effects, according to late-breaking research presented today at the American Heart Association's Scientific Sessions 2020. The virtual meeting is Friday, November 13-Tuesday, November 17, 2020, and is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care worldwide.

Statins lower LDL (bad) cholesterol. Some people, however, experience side effects such as muscle pain and stop taking the medication.

"We know that many patients are not able to take statins because of side effects such as muscle pain, called myalgia," said James Philip Howard, M.B., Ph.D., lead study author and a Ph.D. fellow at Imperial College in London. "Prior placebo-controlled randomized trials have not found evidence of what should be an overwhelmingly obvious difference in side effect symptoms while a person is taking statins rather than taking a placebo. This randomized study allowed us to examine participants' symptoms when they were off all tablets and compare them with symptoms occurring when on statin therapy vs. placebo therapy."

The Self-Assessment Method for Statin Side-effects Or Nocebo (SAMSON) Trial measured patients' self-reported symptoms throughout a 12-month period of randomly alternating months of statin use, placebo and no medications. The study, conducted in London, enrolled adults who had previously taken one or more statins but stopped taking them due to side effects.

About 60 people completed the study, which involved four months of a statin, four months of placebo and four months of neither. At the start of the study, the participants were each given 12 medication jars: four contained statins (20 mg daily of atorvastatin), four contained placebos and four were empty. At the beginning of each month, they opened and started a new jar without knowing what the jar contained. Study participants tracked the intensity of their symptoms daily on a smart phone and ranked them on a scale from zero ("no symptoms") to 100 ("worst imaginable"). The participants could stop the tablets for the month if the symptoms became intolerable.

Researchers found:

90% of the symptoms that were reported when participants were taking a statin were also reported when the participants unknowingly took the placebo tablets.

Patients were just as likely to need to temporarily stop placebo tablets due to intolerable side effects as the statin tablets.

This could point to a psychological rather than pharmacological effect of statins, the researchers noted.

"Patients should be taken seriously when they report side effects, because they are genuinely suffering," Howard said. "We were surprised how severe some of the symptoms experienced during the study were. Twenty-four patients, on 71 occasions, had symptoms so severe they had to stop taking their tablets temporarily. However, this occurred just as frequently when patients took a placebo as when they took a statin."

Researchers also noted that six months after the participants completed the trial, half of them had restarted taking a statin medication and were still taking it.

"The design of the trial - alternating statin, placebo and no-treatment periods - can help patients explore the symptoms they suffer when taking a medication like a statin," Howard said.

Study limitations include that researchers could only recruit patients who developed their previous statin symptoms within two weeks of starting the tablets. In addition, they tested only a single statin at a single dose (atorvastatin 20mg daily), and the trial did not require blood samples to avoid discouraging participation, prevent delays to stopping tablets and maximize clinical applicability.

People taking dummy pills and statins experienced similar side effects in a new study.

In a clinical trial of 60 patients, led by researchers at Imperial College London and clinicians at Imperial College Healthcare NHS Trust, 90 per cent of symptoms experienced by patients whilst taking statins were all present when they took placebo pills.

Statins are one of the most commonly prescribed drugs in the UK, with around seven or eight million adults in the UK taking them. They help lower cholesterol in the blood. Having a high cholesterol level is potentially dangerous as it can cause hardening and narrowing of the arteries, leading to cardiovascular disease.

Previous studies have shown that, in certain people, statins reduce the risk of heart attack, stroke, and even death from heart disease by about 25-35 per cent. Most people tolerate statins but it is estimated that around one fifth of patients stop taking or refuse the drug due to reported side effects such as muscle aches, fatigue or joint pain.

The researchers behind the new study suggest that these side effects are mostly caused by the nocebo effect - where people experience side effects from a therapy because of a negative association with it - rather than an actual pharmacological effect of the drug.

The team suggests that doctors should inform patients of the nocebo effect when prescribing statins and manage their expectations of taking them, to help encourage people to stay on or take the medication.

The study, funded by the British Heart Foundation, is published in the New England Journal of Medicine and will be presented at the American Heart Association Conference today.

Dr James Howard, Clinical Research Fellow at Imperial College London and Cardiologist at Imperial College Healthcare NHS Trust, said: "Statins are life-saving treatments that can help prevent the risk of heart attacks, strokes and cardiovascular disease.

Previous studies have shown that statins are safe and effective at preventing serious health conditions but some patients stop taking or refuse the drug due to reported side effects, potentially increasing their risk of heart attack and stroke in the long-term.

"Our study suggests that the reported side effects of statins are not caused by the statin themselves but by the effect of taking a tablet. Some of the side effects could also be from the typical aches and pains of getting older. Our findings are significant because they are further evidence that side effects from statins are minimal. These drugs play a significant role in keeping patients who are at risk of cardiovascular disease healthy. One way to help encourage patients to take or stay on their medication is for doctors to talk to their patients about the nocebo effect. In more severe cases patients could be referred for talking therapies."

Frances Wood, from Imperial's National Heart and Lung Institute and joint first author, added:

"Statins play a vital role in lowering cholesterol levels and decreasing the risk of serious vessel-related diseases. However, some patients are stopping their treatment as a result of perceived side effects. Our study can help doctors manage patients' expectations of statins and to explain more clearly to patients the possibility that some side effects they experience may be caused by the nocebo effect and provide further support if needed."

The research team believe that the symptoms patients experienced may be the psychosomatic effect of taking pills, or sometimes just the typical aches and pains of getting older.

The team recruited 60 patients aged between 37-79 who were on statins, and had stopped their treatment due to side effects, from June 2016 - March 2019. During the trial, which took place at Hammersmith Hospital, patients were given four bottles containing a statin, four bottles of a placebo and four empty bottles to take over a course of a year. Patients took identical tablets, blinded to statin or placebo for eight months, and took nothing for four months. The patients took these bottles in a random order and were required to score from 0 - no symptoms - to 100 - worst imaginable symptoms- of any daily side effects they experienced, on a smartphone. Forty-nine of the 60 patients completed the full 12 months of the trial.

The team found that 90 per cent of symptoms experienced by patients on statins were present when they took placebo tablets. They also found that among the 60 patients, the mean symptom intensity score was eight during no-tablet months, 15.4 during placebo months and 16.3 during statin months.

Twenty-four of the 49 participants who completed the trial stopped tablets early due to intolerable side effects for at least one month of the trial, with 71 stoppages in total. Of the 71 stoppages, 31 occurred during placebo months and 40 were during statin months.

Six months after completion of the trial, 30 of the patients had successfully restarted statins and four planned to do so. Twenty-five of the patients were not receiving statins and were not planning to restart their statins.

A further analysis is required to see whether 10 per cent of the symptoms experienced by patients were a result of the statins or the nocebo effect.

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, said:

"The beauty of this study is that it's personalised. For the first time, patients were able to see for themselves that statins did not cause their side effects but the physical act of taking a pill did. These results undeniably show that statins are not responsible for many of the side effects attributed to them. Decades of evidence have proven that statins save lives and they should be the first port of call for individuals at high risk of heart attack and stroke.

"This study empowered many of the participants to go back onto statins, which will undoubtedly lower their risk of having a life-threatening heart attack or stroke. We now hope that these findings continue to encourage more people to consider statins with an open mind, and help healthcare professionals to have evidence-based conversations with their patients to ensure they receive the treatment that's right for them."

The researchers will now conduct a further study to investigate symptoms caused by beta-blockers, medications that reduce blood pressure, in heart failure.

What The Study Did: This randomized trial examines the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk.

Authors: Steven E. Nissen, M.D.,of the Cleveland Clinic Heart and Vascular Institute in Cleveland, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jama.22258)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

#  #  #

Media advisory: The full study, editorial and editor's note are linked to this news release. The study is being released to coincide with the American Heart Association Scientific Sessions 2020.

Embed this link to provide your readers free access to the full-text article This link will be live at the embargo time https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2020.22258?guestAccessKey=eb2eccec-6038-4a0f-a639-4ff557aaed60&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=111520

DALLAS, Nov. 14, 2020 -- Diagnostic imaging techniques were able to find the underlying cause of heart attack in many women who had no major artery blockage, according to late- breaking research presented today at the American Heart Association's Scientific Sessions 2020. The virtual meeting is Friday, November 13-Tuesday, November 17, 2020, and is a premier global exchange of the latest scientific advancements, research and evidence-based clinical practice updates in cardiovascular science for health care worldwide.

Previous research has found that up to one in 10 heart attacks among adults is classified as MINOCA, or myocardial infarction with non-obstructive coronary arteries, as determined by an angiogram (heart x-ray). Women are three times more likely to have MINOCA than men, and these non-obstructive heart attacks are also twice as common in non-white patients than white patients.

The Women's Heart Attack Research Program (HARP) is an international, multi-center study to assess the mechanisms of MINOCA and to try to find the cause of the heart attack in these patients. The study enrolled 301 women who experienced a heart attack but who did not have prior obstructive coronary artery disease and had no visible blockages on an angiogram. Their median age was 60 years, and 50% were non-Hispanic whites.

"Our findings are important because women (or men) with MINOCA have historically been told that since the angiogram is OK, they never had a heart attack. This is entirely wrong for about two-thirds of the women who had both imaging tests, and misleading for one-quarter of the women because we found they had another problem that was not related to blood flow and could be diagnosed via cardiac MRI," said Harmony R. Reynolds, M.D., director of New York University Langone's Sarah Ross Soter Center for Women's Cardiovascular Research and an associate professor in the department of medicine at NYU Grossman School of Medicine in New York City.

In this study, women diagnosed with MINOCA received two additional imaging tests:

coronary optical coherence tomography (OCT), which is performed as part of an angiogram and uses light waves to take near-photographic quality images of blood vessel walls; and

cardiac magnetic resonance imaging (MRI), which shows the areas of the heart muscle that have been injured and whether that injury is related to decreased blood flow, inflammation or another reason.

The results of images from OCTs and cardiac MRIs explained why women had symptoms and blood tests consistent with heart attack for 84% of the study participants:

Three-quarters of the women with abnormal optical coherence tomography or cardiac MRI had evidence of heart damage from reduced blood flow.

The arteries often had ruptured plaque or recently ruptured plaque as a cause of the heart attack. This is akin to a typical heart attack with blocked arteries but with an important difference: the plaques that ruptured were smaller than in a typical heart attack.

Cardiac MRIs showed evidence of heart damage related to reduced blood flow in more than half of the women overall, and in two-thirds of those with a causal finding on the optical coherence tomography images.

In 21% of the women, the cardiac MRI showed an inflammatory condition known as myocarditis or another reason for heart dysfunction unrelated to artery blockage or blood clotting. These are alternate diagnoses to heart attack and show the women did not have heart attack in the first place at all.

For the remaining 16% of the women, both the OCT and MRI scans were normal, and the cause of the heart attack was not found.

"Our findings demonstrate that even if the angiogram does not show substantial artery blockage, when women have symptoms and blood test findings consistent with a heart attack, it is likely a true heart attack and not heart inflammation," Reynolds said. "Additional imaging tests can get to the root of the problem and help health care professionals make an accurate heart attack diagnosis for women and to ensure they receive timely treatment."

While the study was not a clinical trial assessing treatments, Reynolds noted, "The results set the stage for future research to find out why women are more likely than men to have MINOCA when they have a heart attack and for clinical trials of treatments."

Reynolds noted that this study suggests identification of the underlying etiology of MINOCA is feasible and has the potential to guide medical therapy for secondary prevention.

What The Study Did: This study used a large U.S. registry of out-of-hospital cardiac arrests to asses the association between the COVID-19 pandemic and the outcomes of out-of-hospital cardiac arrests, including in areas with low and moderate COVID-19 disease.

Authors: Paul S. Chan, M.D., M.Sc., of Saint Luke's Mid America Heart Institute in Kansas City, Missouri, is the corresponding author.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

(doi:10.1001/jamacardio.2020.6210)

Editor's Note: The article includes conflicts of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, conflict of interest and financial disclosures, and funding and support.

ARLINGTON HEIGHTS, Ill (November 13, 2020) - During the COVID-19 pandemic, attention has been focused on how those with both allergies and asthma might be affected should they become ill. A new study being presented at this year's virtual American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting examines hospital data to determine if those with allergic conditions had more severe COVID-related disease than those without.

"We examined the charts of 275 patients admitted to the hospital who tested positive for the SARS-CoV-2 virus for any history of allergic disease," said allergist Dylan Timberlake, MD, ACAAI member and lead author of the study. "Over the two-month period when we examined the charts, we found the severity of disease didn't seem to differ between COVID-19 patients with allergies, versus COVID-19 patients without allergies."

Factors considered to determine severity of disease included ICU admission, length of stay, supplemental oxygen requirement and intubation rate.

"In looking at the outcomes for patients based on allergic diseases such as allergic rhinitis, asthma, eczema, and food allergy, we didn't find significant differences in the numbers of interventions needed for those with allergies versus those without when it came to COVID-19," says allergist Mitchell Grayson, MD, ACAAI member and co-author of the study. "For example, with regard to ICU admission, 43% of those with allergic disease were admitted versus 45% without. And 79% of those with allergy needed supplemental oxygen versus 74% of those without."

In the study, more patients with allergies had COPD (39% vs. 17%), which is a known risk factor for severe disease with COVID. After statistically controlling for the presence of COPD and its association with more severe COVID-related illness, the researchers found a statistical trend suggesting possible protection in those with pre-existing allergic disease but not asthma.

Presentation Title: Effects of Atopic Disease on Disease Severity in COVID-19
Presenter: Dylan Timberlake, MD

ARLINGTON HEIGHTS, Ill (November 13, 2020) - COVID-19 has, among other things, pushed patients of all ages into greater use of telemedicine to carry out regular doctor visits. A new study being presented at this year's virtual American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting reveals that "show rates" for children with asthma - how often parents brought their kids to an appointment rather than being a "no show" - increased with the use of telemedicine during four months of the pandemic.

"It would be normal to expect parents to be hesitant to bring kids into an asthma checkup during a pandemic," says allergist Kenny Kwong, MD, study author. "We run the LAC+USC Breathmobile program (an urban school-based mobile asthma program) in Los Angeles and have regular asthma patients we work with. The pandemic in 2020 resulted in closure of most Los Angeles schools and face to face visits were converted to telemedicine visits. We found that not only did kids show up for appointments, but their show rates were also significantly higher than during the same period in 2019."

In addition to show rates increasing, Dr. Kwong found that during the telemedicine period over 90% of patients reported well controlled asthma on their asthma control (ACT) test. This was comparable to pre-Covid visits. Finally, provider and nursing staff from the Breathmobile reported a 32% to 62% increase in time spent with each patient while conducting telemedicine visits compared to in-person visits.

"Kids with asthma need treatment that is consistent and specialized to their individual needs," says allergist Lyne Scott, MD, ACAAI member and co-author of the study. "It's reassuring and encouraging that the quality of care young patients, including those in underserved populations, received via virtual access kept their asthma under control. This study shows it's possible to move towards new models of treatment that increase access and convenience for the patient, and still maintain quality of care."

ARLINGTON HEIGHTS, Ill (November 13, 2020) - While research shows Black and Hispanic children suffer disproportionately with asthma, other allergic diseases have also been found to be more prevalent in those groups. A presentation at this year's virtual American College of Allergy, Asthma and Immunology (ACAAI) Annual Scientific Meeting reveals the disparities that exist for Black and Hispanic children when it comes to Atopic Dermatitis (AD), commonly known as eczema.

"Not only do Black children in the U.S. have significantly higher incidence of AD and more nights of disturbed sleep compared to white children, their AD also tends to last longer into childhood," says dermatologist Jonathan Silverberg, MD, presenter at the meeting. "In addition, Black children and adults with AD are more likely to have an emergency department or urgent care visit for AD and be hospitalized for AD."

Allergists and other health care specialists who treat AD recognize the need to approach the issue of health disparities with increased education, innovation, and evidence-based solutions.

"AD looks different on black and brown skin than it does on white skin," says allergist Luz Fonacier, MD, ACAAI president-elect. "Unfortunately, the textbooks from which medical students learn often don't contain images of AD in Black and Hispanic patients, and that's something we are looking to change. When AD in Black and Hispanic patients goes undiagnosed due to lack of education on the part of the medical community, getting positive treatment outcomes becomes even more difficult."

Dr. Silverberg's presentation outlined potential solutions to helping minorities get the treatment they need for skin allergies. Among the suggestions:

Increased diversity of physicians and staff.

Increased local community engagement to build trust.

Expand office hours to nights and weekend to increase access.

Have flexible appointment slots to allow for urgent visits.

24-hour telephone coverage for patients.

Telehealth visits to reduce travel and lost productivity.

Spend adequate time to educate patients about their disease and treatment course.

Says Dr. Silverberg, "We need to pay special attention to minorities when it comes to treating skin allergies because how these conditions appear on a person's skin varies, and the treatment will also vary. We need to consider all patients' individual needs."

PITTSBURGH, Nov. 13, 2020 - The bodies of people with uncontrolled diabetes appear to be the perfect environment for a common type of superbug to thrive unchecked and do its worst damage, according to new research by University of Pittsburgh School of Medicine scientists.

The researchers report today in Science Advances that Staphylococcus aureus--a bacteria that often is resistant to antibiotics--thrives in glucose-rich diabetic conditions, which trigger it to activate some of its most virulent features. A lack of insulin prevents the immune system from responding to the infection.

"This explains why a wound or cut in a patient with diabetes really must be treated aggressively," said senior author Anthony Richardson, Ph.D., associate professor in Pitt's Department of Microbiology & Molecular Genetics. "The immune system needs help recognizing and clearing the infection before it's able to take hold."

Diabetes is a disease that occurs when the levels of sugar in the blood--measured as blood glucose--are too high. This happens in people who either do not produce enough insulin, a hormone that helps cells convert glucose into energy, or respond poorly to insulin in their blood. In the U.S., 11% of people have diabetes, and more than a third of all adults have pre-diabetes.

Among people with diabetes, up to a third develop diabetic foot ulcers, which are the most common reason for foot infection and leg amputation, according to the American Diabetes Association. S. aureus most often is associated with these types of invasive infections, especially in people with poorly controlled diabetes.

Rates of S. aureus infections and diabetes have grown in lockstep over the past three decades.

Previously, lead author Lance Thurlow, Ph.D., who conducted the research at Pitt and now is at the University of North Carolina at Chapel Hill, had shown that S. aureus had evolved an additional two "glucose transporters" on top of the two already common to most staphylococcal species. This gives S. aureus an advantage over other bacteria in making use of excess blood sugar to proliferate.

In this recent study, Richardson, Thurlow and the rest of the team experimented with diabetic and non-diabetic mice and strains of staphylococcus with and without the extra transporters.

In the diabetic mice, the strain of S. aureus with four glucose transporters quickly formed biofilms and activated pathways to make it more virulent. Meanwhile, the immune system of those diabetic mice was particularly slow to respond, resulting in unchecked infection and severe diabetic ulcers. In the nondiabetic mice, the immune system was able to contain and fight the infection. When the diabetic mice were given a drug that lowers blood sugar, they contained the infection almost as well as the regular mice.

Diabetic mice infected with strains of staphylococcus that didn't have the extra glucose transporters had less invasive infections, though their immune systems were still slower to respond than those of their nondiabetic counterparts.

Knowing the mechanism that S. aureus uses to cause such devastating infections in people with diabetes could lead to treatments that capitalize on the bacteria's hunger for glucose, tricking it into consuming a toxic analogue, said Richardson.

"But we also can't lose sight of the need to prevent and control diabetes," he added. "If we can keep people from developing diabetes and help people who have it to control their blood sugar, then S. aureus will have a much more difficult time causing such terrible infections."

Findings from a national study published today in the Journal of the American Medical Association (JAMA) "do not support" the use of hydroxychloroquine for the treatment of adult patients hospitalized with COVID-19.

The Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease (ORCHID) study found that, when compared to inactive placebo, hydroxychloroquine did not significantly improve clinical outcomes of patients hospitalized for respiratory illness related to COVID-19.

The study, which was funded by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, was conducted at 34 hospitals in the Prevention and Early Treatment of Acute Lung Injury (PETAL) Clinical Trials Network.

"Hydroxychloroquine became a very commonly used medication for COVID-19 in the spring of 2020 without strong evidence that it would be beneficial," said the study's lead investigator, Wesley H. Self, MD, MPH, an emergency medicine physician and vice president for Clinical Research Networks and Strategy at Vanderbilt University Medical Center.

"Therefore, we conducted a clinical trial with the strongest methods possible to provide high quality information on whether hospitalized patients with COVID-19 should be treated with hydroxychloroquine," Self said. "Combined with other studies that showed similar findings, we believe this trial provides compelling data for clinicians to stop using hydroxychloroquine for hospitalized adults with COVID-19."

Some laboratory studies suggested hydroxychloroquine can inhibit replication of SARS-CoV-2, the virus that causes COVID-19. Observational studies early in the COVID-19 pandemic suggested that the drug may have beneficial effects for patients with COVID-19, which sparked great enthusiasm for hydroxychloroquine as a potential treatment.

However, clinical trials, which are considered the highest quality research studies for understanding the effect of a drug in patients, have failed to show beneficial effects of hydroxychloroquine for patients with COVID-19, Self said.

Between April and June 2020, 479 patients hospitalized for respiratory illness from COVID-19 were enrolled in the ORCHID study, a blinded, placebo-controlled randomized clinical trial.

Patients who were acutely ill and hospitalized with COVID-19 were treated with 10 doses of hydroxychloroquine or placebo over five days. The patient's clinical status, including hospital discharge, oxygen use, mechanical ventilator use and death, was followed for a month after the medication was started.

The study showed no evidence that hydroxychloroquine prevented death or helped patients recover from COVID-19 more quickly. One month after starting the study, 10.4% of patients treated with hydroxychloroquine and 10.6% of patients treated with placebo had died.

In June the NHLBI halted the study after determining that hydroxychloroquine was not likely to be of benefit to hospitalized patients with COVID-19.

"Our diverse teams of clinicians and research staff worked nimbly under extremely difficult circumstances to accomplish what the NIH and the PETAL Network do best: 'gold standard' studies of important questions for patients suffering from life-threatening conditions," said Samuel M. Brown, MD, MS, a critical care physician at Intermountain Healthcare and PETAL Network investigator who helped lead the trial.

"While we hoped that hydroxychloroquine would help, even this clearly negative result is critical as we work together to find effective treatments for COVID-19," Brown said.

"Having a rigorously designed clinical trial that captured patient-centered, clinically meaningful outcomes was critical to reaching the unequivocal conclusions about the use of hydroxychloroquine in COVID-19," said James P. Kiley, PhD, director, Division of Lung Diseases at NHLBI.

"ORCHID shows that hydroxychloroquine does not improve clinical outcomes in hospitalized COVID-19 patients," Kiley said. "We hope this clear result will help practitioners make informed treatment decisions and researchers continue their efforts pursuing other possible safe and effective treatments for patients suffering with this disease."

SINGAPORE, 30 October 2020 - Researchers from Duke-NUS Medical School, Erasmus University Medical Center, Yale-NUS College and Duke University have found a potential way to predict who will respond to cancer therapies that block Wnt production, such as the novel made-in-Singapore drug ETC-159. This discovery brings the goal of personalised medicine in cancer therapy a step closer to reality.

Wnt proteins are important signalling molecules that help neighbouring cells to communicate with each other. However, when the protein is produced in excess, it causes cancers. Wnt has been implicated as a key driver of many common cancers, including colorectal and breast cancers as well as leukaemia and pancreatic cancer. Many mutations can trigger an excess activity of Wnt, and finding reliable biomarkers has been challenging.

This research, published in Cancer Research, has identified an actionable biomarker--a protein called RNF43--that is altered in a distinct class of Wnt-addicted cancers.

"RNF43 is one instance that can help us predict whether a cancer cell might be dependent on the Wnt pathway," said Assistant Professor Babita Madan, a research in Duke-NUS' Cancer and Stem Cell Biology programme and the corresponding author of the study. RNF43 is frequently mutated in colorectal, endometrial, mucinous ovarian, pancreatic and gastric cancers.

The drug ETC-159, which was jointly developed by Duke-NUS and the Agency for Science, Technology and Research, is a novel small molecule drug candidate that targets a range of cancers including colorectal, ovarian and pancreatic cancers. It is currently in Phase 1B human trials and was used in this pre-clinical study to determine whether cancers with RNF43 mutations would respond to Wnt inhibitor therapy.

"It has been shown in the past that RNF43 regulates cell surface Wnt receptors and RNF43 mutations could cause sensitivity to Wnt inhibitor in pancreatic cancers," said Research Fellow Yu Jia, the first author of the study.

This study expands the landscape of actionable RNF43 mutations, opening the door for more patients to benefit from these therapies. Moving forward, the team hopes that their study can help clinicians who are involved in clinical trials for Wnt inhibitors to develop a look-up table based on the team's list of actionable RNF43 mutations.

"This is another major step towards bringing personalised medicine to cancer patients in Singapore and across the globe," said Professor Patrick Casey, Senior Vice-Dean of Research at Duke-NUS. "Being able to customise treatments to the unique genetic signature of a patient's cancer will allow healthcare providers to better customise treatment plans and greatly increase the chance of real impact on the disease."

SINGAPORE, 14 November 2020 - Patients with chronic kidney disease are more likely to take an active role in managing their health if they have specific information about what to eat, good communication with their doctor, and strong family support, researchers from Duke-NUS Medical School and SingHealth Polyclinics report in the journal BMJ Open.

Chronic kidney disease, which is the gradual loss of kidney function, is often linked with diabetes, and is one of the most rapidly rising causes of death worldwide. Most patients do not have symptoms until the disease is very advanced. Managing the condition through diet, exercise, taking medications and not smoking can prevent progression to end-stage kidney disease, which requires dialysis or a transplant.

"Self-management is key to managing chronic kidney disease," said Professor Tazeen Jafar, from Duke-NUS' Health Services and Systems Research Programme, the principal investigator and a senior co-author of the study, who is a kidney specialist. "However, the barriers and facilitators to self-management early on in the disease have not been well studied. Identifying ways to empower patients can help improve health outcomes and reduce the need for expensive treatment."

Prof Jafar and colleagues, including Duke-NUS medical student Sun Joon Hwang, interviewed 20 patients with diabetes and chronic kidney disease from three SingHealth polyclinics, who had not yet moved into dialysis, to get a better sense of their perceptions of their condition. In Singapore, one in four adults suffers from chronic kidney disease. Despite this prevalence, the researchers found many patients lacked knowledge about the disease.

"This research indicates that family physicians need to pay attention to patients with chronic kidney disease. We need to raise their awareness on how to effectively manage their risk factors to prevent the deterioration of their kidney function," said Associate Professor (Dr) Tan Ngiap Chuan, Director of Research at SingHealth Polyclinics and a co-author of the study.

"The public needs to recognize that chronic kidney disease is a common medical condition, especially among those with hypertension and diabetes mellitus and is largely preventable if mitigating measures are started early. Patients can take precautions to prevent it from rapidly progressing to more advanced stages. Do not hesitate to ask their family doctors for advice,", added Dr Tan.

Many patients reported feeling overwhelmed and confused by information, either in the form of brochures at the doctor office or online. They felt they were not given specific guidance, especially on what to eat, for managing chronic kidney disease. Many are not sure what are acceptable options for when they frequently eat out. Patients suggested that a health coach providing tailored guidance on lifestyle, especially diet, will be helpful.

Another key finding was that most patients felt their doctors did not explain things clearly and did not listen to them, so patients did not feel comfortable asking questions about their condition. In contrast, patients took a more active role in their care when they had a good, trusting relationship with their doctor.

A third major factor was family support. Some patients did not seek help from family members in managing their disease because they did not want to burden their families. However, those who did have more family support, such as an adult family member reminding them what they should or should not eat, reported feeling more able to manage their disease.

A few patients took a passive attitude about their condition, saying that it was too late to do anything, and essentially delegated responsibility to doctors to manage the disease for them. Prof Jafar noted that the initial findings from this study showed how clearer information about diet and disease management, improved communication with doctors, and optimised family support can help increase the number of patients taking a more active role in their health.

Leesburg, VA, November 13, 2020--According to an article in ARRS' American Journal of Roentgenology (AJR), positive conclusions--but not titles--were associated with a shorter time from study completion to publication, which may contribute to an overrepresentation of positive results in the imaging diagnostic test accuracy (DTA) literature.

"We included primary imaging DTA studies from systematic reviews published in 2015," explained first author Lee M. Treanor of Ottawa Hospital Civic Campus. Extracting both the conclusion and the title of each study, positivity was independently classified in duplicate. The time from study completion to publication was also extracted and calculated. Hazard ratios were estimated using a multivariable Cox regression model to determine the strength of the associations, adjusting for potentially confounding variables.

Based up the researchers' MEDLINE search, 781 studies appeared eligible for inclusion. Excluding seven studies (three for not having an abstract, three for not being a primary DTA study, and one because it was a duplicate) yielded a total of 774 imaging DTA studies; however, time from study completion to publication could only be calculated for 516 studies.

The median time from study completion to publication was 18 months (interquartile range [IQR], 13-26 months) for the 413 studies with positive conclusions, compared with 23 months (IQR, 16-33 months) for the 63 studies with neutral conclusions and 25 months (IQR, 15-38 months) for the 40 studies with negative conclusions.

For studies with positive titles, the median time from study completion to publication was 18 months (IQR, 11-26 months), compared with 19 months (IQR, 13-28 months) for studies with neutral titles and 30 months (IQR, 24-34 months) for studies with negative titles.

"Of all included studies," Treanor et al. tallied, "39 (5%) had positive titles, 731 (94%) had neutral titles, and 4 (

Because an inflated perception of test performance could adversely influence clinical decision making and patient care, the authors of this AJR article suggested bias reduction strategies "should undergo trials by both journal editors and researchers in the imaging DTA community."

Losing a few kilograms in weight almost halves people's risk of developing Type 2 diabetes - according to a large scale research study led by the Norfolk and Norwich University Hospital and the University of East Anglia.

A new study published in the international journal JAMA Internal Medicine shows how providing support to help people with prediabetes make small changes to their lifestyle, diet and physical activity can almost halve the risk of developing Type 2 diabetes.

The findings come from the Norfolk Diabetes Prevention Study (NDPS) - the largest diabetes prevention research study in the world in the last 30 years. The NDPS clinical trial ran over eight years and involved more than 1,000 people with prediabetes at high risk of developing Type 2 diabetes.

The study found that support to make modest lifestyle changes, including losing two to three kilograms of weight and increased physical activity over two years, reduced the risk of Type 2 diabetes by 40 to 47 per cent for those categorised as having prediabetes.

There are about eight million people with prediabetes in the UK and 4.5 million have already developed Type 2 diabetes.

The NDPS, funded by £2.5m from the National Institute for Health Research (NIHR), and NIHR CRN Eastern, was led by the Norfolk and Norwich University Hospital (NNUH) and University of East Anglia (UEA), together with colleagues from Ipswich Hospital, and the Universities of Birmingham and Exeter.

The research trial tested a simple lifestyle intervention, which helped people make small achievable lifestyle changes that led to a modest weight loss, and increases in physical activity.

Importantly these changes were sustained for at least two years and the weight lost was not put back on.

These findings are important as they show that a 'real-world' lifestyle programme really can make a difference in helping people reduce their risk of Type 2 (adult onset) diabetes.

Prof Mike Sampson, NDPS Chief Investigator and Consultant in Diabetes at NNUH, said: "We are delighted with the results of this trial, as until now no one was very sure if a real-world lifestyle programme prevented Type 2 diabetes in the prediabetes population we studied, as there have been no clinical trials that had shown this.

"We have now shown a significant effect in Type 2 diabetes prevention, and we can be very optimistic that even a modest weight loss, and an increase in physical activity, in real world programmes like this have a big effect on the risk of getting Type 2 diabetes.

"This is really great news for the eight million people in the UK with a prediabetes diagnosis. The results of this trial, show that diabetes prevention is possible in the same prediabetes populations being treated in the NHS national diabetes prevention programme.

"This is important to know, as the clinical methods for diagnosing diabetes and prediabetes have changed a lot in recent years."

The Norfolk Diabetes Prevention Study ran between 2011 and 2018 and worked with 135 GP practices in the East of England, and found 144,000 people who were at risk of developing Type 2 diabetes.

In screening sites across the East of England, 13,000 of these people then took a fasting glucose and glycosylated haemoglobin (HbA1c) blood test to detect prediabetes.

More than 1,000 people with prediabetes were then entered into a randomised controlled trial, testing a pragmatic real-world lifestyle intervention, compared to a control group, with average follow-up of just over two years.

Earlier studies have used quite intense and expensive research interventions in different groups of prediabetes participants, but this is the first time a real world group delivered intervention has been shown to reduce the risk of Type 2 diabetes.

NDPS also asked lay members of the public who had Type 2 diabetes themselves, to help support participants with prediabetes in the trial, but for this particular population this did not further reduce the risk of getting Type 2 diabetes.

NDPS co-investigatro Prof Max Bachmann, from UEA's Norwich Medical School, said: "The NDPS intervention was delivered in groups which was far less expensive than individual-focused interventions which have previously shown to be effective under optimal conditions.

"For every 11 people who received the NDPS intervention, one person was prevented from getting Type 2 diabetes, which is a real breakthrough."

Prof Colin Greaves from the University of Birmingham, who jointly led the development of the NDPS intervention, said: "If you have been diagnosed with prediabetes, this approach offers a way to take a different direction in your life - to get off the path to type 2 diabetes and onto the road to a healthier future."

Dr Jane Smith, NDPS collaborator from the University of Exeter, said: "Type 2 diabetes is a huge health challenge globally. NDPS is an incredibly positive story for individuals and healthcare systems, and underlines the importance of providing national diabetes prevention programmes, which can use our research findings."

Prof Jonathan Valabhji, National Clinical Director for Diabetes and Obesity for NHS England, said: "This study with similar referral criteria and a similar intensive lifestyle intervention to the NHS Diabetes Prevention Programme has surpassed expectations in preventing Type 2 diabetes. This is hugely encouraging for the NHS Diabetes Prevention Programme, and what participants might expect to achieve in the longer term."

Dr Elizabeth Robertson, Director of Research at Diabetes UK, said: "We welcome this new research showing that a group-based support programme can help people at high risk of developing type 2 diabetes reduce their risk.

"This trial again highlights how achieving modest weight loss through diet and physical activity changes can lead to huge benefits for people at high risk of developing type 2. Type 2 diabetes is a serious condition, but with the right help many cases can be prevented or delayed.

"Diabetes UK's Know Your Risk' tool helps people to determine their risk and take steps to reduce it, including by self-referring on to NHS England's Diabetes Prevention Programme in their local area."

The question of sleep apnea as the risk factor for COVID-19 arose in a study conducted by the Turku University Hospital and the University of Turku on patients of the first wave of the pandemic. This is the first COVID-19-related study where sleep apnea as suspected risk factor emerges as the main finding.

The study focused on the register information of COVID-19 patients who were admitted to Turku University Hospital during the first wave of the pandemic in the spring 2020. Southwest Finland, with a population of 480,000, managed the first wave of the pandemic with a relatively small number of infected people. Patients with a positive test result amounted to 278 individuals. From the infected patients, 28 were admitted to hospital care at Turku University Hospital by 3 May 2020. The register information of these patients was studied with the aim to unravel the risks for the severe form of COVID-19 and the need for intensive care.

"The idea behind the study was the need for real time information about covid-19. The research permission was extensive, because little was known about the novel coronavirus. We quickly observed that there was quite a few cases of sleep apnea among the patients," states MD Thijs Feuth, a fellow in pulmonary diseases and the first author of the research article.

The comparison of the register information revealed that 29 percent of the patients admitted to hospital care had already been diagnosed with sleep apnea. The number is significant, as only 3.1 percent of the population of Southwest Finland is getting treatment for sleep apnea. Even though the total number of patients in the study was low, the share of sleep apnea patients was high. The extent of sleep apnea among the patients cannot only be explained by the obesity often met in sleep apnea patients, being one of the already known risk factors for severe COVID-19.

"The finding was strong enough to justify the question of sleep apnea as a risk factor for COVID-19. In principle, a patient may need hospital care when they have a COVID-19 infection if they also have sleep apnea. Sleep apnea anticipates a severe form of COVID-19," estimates Feuth in the light of the research findings.

Sleep apnea causes breaks in breathing (apnea) while a person is asleep. The disease is diagnosed by a nocturnal polysomnography.

The connection between sleep apnea and COVID-19 has been confirmed by other studies which are now under review but are already available as pre-publications. The findings of this new study were comparable with other reported findings. Other findings included higher levels of C-reactive protein (CRP) in those patients that were eventually admitted to intensive care. Most viral diseases do not elevate the CRP levels that much.