Body

A major UK survey has shown that patients with urological cancer such as prostate, bladder or kidney cancer are five times more likely to commit suicide than people without cancer. The analysis also shows that cancer patients generally are around three times more likely to commit suicide than the general population, and that the proportion of attempted suicides which result in a completed or successful suicide was higher in cancer patients, with a higher proportion still in patients with urological cancers.

Severe psychological stress is one of the main side-effects of both a diagnosis of cancer and cancer treatment, with depression affecting between 5 and 25% of cancer patients1, 2: many are also affected by Post-Traumatic Stress Disorder (PTSD)3. Previous research has shown that the vast majority of cancer patients who have symptoms of depression often go untreated2. This study shows a substantial increase in suicide attempts and successful suicides in cancer patients. The work is presented at the European Association of Urology conference in Copenhagen.

This is the largest UK study looking at suicide in cancer patients (see below). The research team led by Mr Prashant Patel at the University of Birmingham retrospectively examined the records from the England and Wales Hospital Episode Statistics database, from the period 2001 to 2011. They linked this with cause of death statistics from the Office of National Statistics.

This is also the first time that a major study has examined suicidal intent in cancer patients - which they defined as the ratio of successful suicides to the rate of attempted suicides. They found that this rate was far higher (1 to 7) in patients with prostate cancer than in the general population (1 to 25), which may show a greater determination to commit suicide in cancer patients. "This is important" said first author Dr Mehran Afshar (St George's Hospital, London), "as we know that people who attempt suicide are at higher risk of subsequently being successful in completing a suicide, and we have shown this 'intent' to commit to be far higher in our cancer population, thus confirming a real need to address psychological issues early on in the management of these patients".

Dr Afshar continued:
"Our data confirms research from other countries that suicide rates are higher in cancer patients, and we show this to be higher particularly in patients with urological cancers. There are particular issues which are specific to this cancer group - for example, men with prostate cancer undergo treatment which can affect their bladder function, their bowel function, erectile function and libido, can result in symptoms similar to the female menopause, and entirely alter the personality, leading to relationship problems, anxiety, depression and post-traumatic stress disorder.

We know from a 2014 study2 by Cancer Research UK that the vast majority of cancer patients who have symptoms of depression go untreated. We can see from the results of our study that although all cancers have a higher suicide rate, inferring a higher level of psychological distress, there are disparities between cancers. This needs to be addressed within our healthcare systems, and more focus is needed on integrating the robust and specialist assessment and treatment of mental health needs in cancer care".

The study also showed significant differences between the time to a successful suicide, which means that some cancer patients are more vulnerable in certain periods.

The numbers

The researchers identified a total of 980,761 (493,234 males and 487,094 female) cancer patients which meant that 13.4 million-person years were included in the final data analysis. The team identified 162 suicides and 1222 suicide attempts.

In the general population, the suicide rate is 10 per 100,000 people. The team found that the all-cancer suicide rate was 30 per 100,000 people. In the urological cancers the figures are 36 per 100,000 people in kidney cancer, 48 suicides per 100,000 in bladder cancer, and 52 per 100,000 people in prostate cancer.

In the general population, there is an average of 25 suicide attempts for each successful suicide. In kidney cancer this ratio is 1 suicide for every 10 attempts. In bladder and prostate cancer, this ratio drops to one suicide for every 7 attempts.

The time taken to commit suicide also varies substantially: median time to suicide is 175 days from diagnosis for kidney cancer, 846 days for prostate cancer, and 1037 days for bladder cancer.

Commenting, EAU Adjunct Secretary General, Prof Hein van Poppel (Leuven) said:
"This important work shows just how distressing cancer can be, but it also shows that there may be special factors associated with urological cancers which make them even more stressful than other cancers. It looks like urological cancers can affect patients' sense of self in a way that many cancers don't.

The work implies that some urological cancers, such as kidney cancer, can lead to fairly immediate distress, whereas the distress associated with prostate and bladder cancer may take a while to hit home - perhaps when patients begin to take up some of the problems associated with returning to normal life.

We also need to put things in context: many patients recover well, and don't reach the stage of despair or distress which brings them to think of suicide. Nevertheless, this is a real problem. We need to recognise that the figures presented here are for suicides, which means that they are at the 'sharp end of emotional distress'. For every suicide or attempted suicide, there will be many more patients who find difficulty in coping.

This distress does not stop when the cancer is removed or contained, and we owe it to patients to ensure that ongoing emotional support and mental health care is fully integrated in cancer care".

(Professor van Poppel was not involved in this work. He is a specialist in urological cancers).

The team noted a limitation of the study: they looked at the general suicide rate, not at the rate of suicides according to age (age-standardised suicide rate), however a comparison to baseline population suicide rates could only be made using crude suicide rates per 100,000 as this is population level data available.

March 15, 2018 -- A study by researchers at Columbia University's Mailman School of Public Health finds that cigars commonly used to roll blunts--hollowed out cigars that are filled with marijuana and smoked--dominate the cigar marketplace in states where recreational marijuana is legal compared to nationally. The findings, which could help direct tobacco prevention efforts, are published online in the journal Drug and Alcohol Dependence.

"Cigars with fruit flavors, the brand Swisher Sweets, and inexpensive, small pack sizes are valued among blunt users," said Daniel Giovenco, PhD, assistant professor of Sociomedical Sciences at Columbia's Mailman School of Public Health, and first author. "Our study demonstrates that these tobacco products hold a larger percent of the market share in states with recreational marijuana laws."

Using 2016 tobacco sales data obtained from the Nielsen Research Company, the authors compared cigarillo sales in regions with legalized recreational marijuana (i.e., Denver, CO; Seattle, WA; Portland, OR) to the overall U.S. marketplace. Nielsen collects electronic point-of-sale data for tobacco products in U.S. convenience stores, gas stations, drug stores, grocery stores, mass merchandisers, dollar stores, and other tobacco retailers.

Although Black & Mild, not traditionally used as blunts, was the top brand nationally, Swisher, more commonly used for blunt making, was the most popular brand in all three market regions where recreational marijuana has been legalized. In Colorado, the first state that legalized marijuana and which has experienced a boom in "weed tourism," cigarillo wraps constituted a sizable portion of overall sales (12 percent vs. 3 percent nationally). The wraps eliminate the need to remove the tobacco filler, facilitating easy blunt-making. Notably, however, per capita sales of cigarillos were lower in markets where marijuana is legal, possibly a reflection of the states' stronger tobacco control laws, cultural attitudes toward tobacco use, or consumer preferences for alternative forms of marijuana consumption.

"Irrespective of the legal status of marijuana, local policymakers should employ strategies that reduce the appeal of cigarillos," he says. "Many of the features that are popular for blunt use, such as flavors and small pack sizes, have been banned for cigarettes. Cigarillos should face similar restrictions to improve public health. Knowing where these products are most popular can help direct prevention efforts."

Shifting physicians' roles from transactional tasks to personalized care would best serve patients, physicians and society. According to a newly-articulated vision of shared care, physicians should reduce their roles in transactional aspects of care, such as gathering and entering data, providing disease-specific patient education, and providing most preventive care. Instead, such duties should be filled by other members of the health care team with complementary skills, leaving physicians to diagnose and help patients meet personal goals and objectives. Physicians' would provide personalized care by synthesizing data from diverse, often discordant sources; adjudicating the competing needs of multiple conditions; adjusting patients' treatment plans to align with their goals and preferences; and advocating for patients in a complicated, fragmented health care environment. To make this approach a reality, changes would need to occur on multiple levels including health care organization and delivery, technology, reimbursement, medical education, and practice and physician "buy-in." The authors state that their vision would meet the needs of patients and society while closing the gap between physicians' intended patient care mission and their current transactional roles. In the process, they explain, physicians could discover joy, purpose, and meaning in their work.

"What patients bring to their clinicians is their stories," writes behavioral scientist Thomas Egnew. It is through these stories that clinicians try to understand and treat patients' health. When patients experience chronic or life-threatening illness and their suffering increases, clinicians can take on the role of holistic healer by addressing the inevitable existential conflicts in patients' narratives and helping them edit their stories to promote acceptance and meaning. In this guiding role, Egnew explains, clinicians can help patients transcend suffering, "assume the mantle of their heritage as healers," and find meaning in their work.

Just as strep throat can run rampant in elementary schools, strangles, the "strep throat" of horses, caused by a different Streptococcus bacterium, Streptococcus equi sp equi, is highly contagious. Lymph nodes in the head and neck region become swollen and develop abscesses, resulting in nasal discharge and drainage from the throat. Though rarely fatal, strangles cases can range from mild to severe, and complications that impair eating and breathing can arise in some instances. Altogether, it's a disease that horse owners want to keep far from their stables.

Veterinarians have an important role to play not only in treating the disease, but also in ensuring that infected horses are kept away from other animals until they have fully recovered from the illness. This recovery is not always so clear cut, as many animals remain carriers of the bacteria even after they appear healthy.

To assist veterinarians, and owners, in understanding the most up-to-date clinical recommendations when it comes to treating strangles, Ashley Boyle, an associate professor of medicine at the University of Pennsylvania's School of Veterinary Medicine, took the lead in writing a new consensus statement, issued by the American College of Veterinary Internal Medicine, on treating, controlling, and preventing strangles in horses.

"From a practical standpoint, the consensus statement serves to advise all veterinarians on what we recommend as a way to treat and deal with the disease," Boyle says. "I'm an internist who sees this disease as a primary care doctor at the horse farms as well as a field researcher. The authors of the consensus statement are a collection of experts in the field of Streptococcal diseases in horses including veterinary microbiologists, epidemiologists, and veterinarians who research this disease, as well as internists who encounter the disease frequently."

Boyle coauthored the report with John Timoney of the Gluck Equine Research Center at the University of Kentucky, Richard Newton and Andrew Waller of Animal Health Trust in the United Kingdom, Melissa T. Hines of the University of Tennessee, and Ben Buchanan of Brazo Valley Equine Hospital in Texas.

The last consensus statement was issued in 2005; the lead author of that report was Corinne Sweeney, professor of medicine and associate dean at Penn Vet's New Bolton Center. Starting around 2012, Boyle began hearing from colleagues that it was time for an update. Sweeney suggested that Boyle take on the project.

Along with an international team of coauthors, some of whom had contributed to the earlier statement, Boyle set about reviewing information on prevention, treatment and control and finding where updates were necessary.

One of the key areas where the guidance has shifted in the new statement is how to determine when an animal is free of disease. This is a critical component of strangles control, as 10 to 40 percent of animals who have had the disease can remain carriers, able to pass on disease to other animals even when they appear healthy.

The previous consensus statement indicated a throat wash should be tested three times to be sure the horse was free of disease.

"But it was hard to get owners and clients to do that three times," Boyle says. "And multiple studies have shown that those three may not even be good enough."

In the new statement, Boyle and colleagues instead recommend "guttural pouch sampling," a technique that tests the fluid that sits in an area between a horse's ear and throat, akin to the human Eustachian tube, in combination with using an endoscope to visually assess the area for unruptured absesses.

"We're trying to encourage more primary care veterinarians to do this, even though it's time consuming, because this is how the disease perpetuates itself," says Boyle. "In the end it is easier, faster, and more effective than doing the three throat washes. That's one of our big take-home messages."

Another change is a shift away from considering bacterial culture to be the gold standard of diagnosis.

"We no longer consider this the gold standard," Boyle says, as horses with low levels of bacteria may still be carriers but not give a positive result on this test. The authors see DNA amplification technologies such as polymerase chain reaction (PCR) along with visualization of the guttural pouch as replacing culture as this standard.

"There is also a lot of work being done by my colleagues in Europe looking at genomic sequencing," she says. "At some point in the future we may be able to use this technology to trace from where an outbreak came."

The publication lays out best practices for quarantine and examination in order to prevent the spread of disease, and biosecurity protocols to reduce transmission in facilities where infected horses have been housed. It spells out treatment protocols, urging judicious use of antibiotics, and explains how to recognize, evaluate the risk for, and treat one of the more serious complications of strangles, an autoimmune reaction known as purpura hemorrhagica, which can be fatal. It also explores the pros and cons of strangles vaccines,the use of different blood tests that can measure previous exposure to disease and determine when it is safe to give vaccines..

While the consensus statement is aimed at veterinarians, Boyle says owners often read them directly, and can implement some of the recommendations. For example, horses are not thought to be contagious until 24 to 48 hours after the onset of fever.

"An owner can start thinking about monitoring their horses' temperatures if they suspect an outbreak, and isolate horses when they first spike a fever," Boyle says. "That way they can catch it right at the beginning and spare any other horses from getting sick."

Even though strangles is not typically deadly, it is a global problem and quite costly, as management protocols can be extensive.

"There are huge financial repercussions not only from dealing with the disease but from quarantining barns and screening potential carriers," Boyle says. "It's also a big problem in the population of rescued horses, as they often come from different locations and are housed in close quarters resulting in the spread of disease."

Boyle and her colleagues hope that the new guidelines will help veterinarians and owners navigate strangles cases more effectively, ideally mitigating the disease's health and financial costs.

New cutting edge technology can be used to grade cancer tumours, eradicating human subjectivity and ensuring patients get the right treatment.

A new imaging technology to grade tumour biopsies has been developed by a team of scientists led by the Department of Physics and the Department of Surgery and Cancer at Imperial College London.

Publishing their results today in the journal Convergent Science Physical Oncology, they describe how their new method promises to significantly reduce the subjectivity and variability in grading the severity of cancers.

Nearly all cancers are still diagnosed by doctors taking a sample of the tumour, a so-called biopsy, then slicing it thinly and staining it with two vegetable dyes used for more than 100 years. They look at this 'H+E stained' sample under a microscope and then judge the severity of the disease by eye alone.

Life-changing treatment decisions have to be based on this 'grading' process, yet it is well known that different practitioners given the same slice will only agree on its grade about 70% of the time, resulting in an overtreatment problem.

The team's new 'Digistain 'technology addresses this problem by using invisible mid-infrared light to photograph the tissue slices in a way that maps out the chemical changes that signal the onset of cancer. In particular, they measure the 'nuclear-to-cytoplasmic-ratio' (NCR): a recognized biological marker for a wide range of cancers.

Lead author Professor Chris Phillips, from the Department of Physics at Imperial, said: "Our machine gives a quantitative 'Digistain index' (DI) score, corresponding to the NCR, and this study shows that it is an extremely reliable indicator of the degree of progression of the disease. Because it is based on a physical measurement, rather than a human judgement, it promises to remove the element of chance in cancer diagnosis. "

In the experiment reported today, the team carried out a double-blind clinical pilot trial using two adjacent slices taken from 75 breast cancer biopsies. The first slice was graded by clinicians as usual, using the standard H+E protocol. It was also used to identify the so-called 'region of interest' (RoI), i.e. the part of the slice containing the tumour.

The team then used the Digistain imager to get a DI value averaged over the corresponding RoI on the other, unstained slice, and ran a statistical analysis on the results.

Professor Phillips said: "Even with this modest number of samples, the correlation we saw between the DI score and the H+E grade would only happen by chance 1 time in 1400 trials. The strength of this correlation makes us extremely optimistic that Digistain will be able to eliminate subjectivity and variability in biopsy grading."

The NCR factor that Digistain measures is known to be common to a wide range of cancers, as it occurs when the reproductive cell cycle gets disrupted in the tumour and cell nuclei get distorted with rogue DNA. It is likely that in the long run, Digistain could help with the diagnosis of all different types of cancer.

At a practical level, the researchers say that the Digistain imaging technology can easily and cheaply be incorporated into existing hospital labs, and be used by their staff. Professor Philips added: "It's easy to prove its worth by checking it with the thousands of existing biopsy specimens that are already held in hospital archives. Together these facts will smooth the path into the clinic, and it could be saving lives in only a couple of years."

In a study of patients with anal cancer, living in low median household income areas was linked with an increased risk of early death. Published early online in CANCER, a peer-reviewed journal of the American Cancer Society, the findings suggest that socioeconomic inequalities may affect cancer outcomes, especially for highly treatable and curable tumors such as anal cancer.

Squamous cell carcinoma of the anus (SCCA) accounts for 8,200 new cancer cases and more than 1,000 cancer-related deaths in the United States annually. Its incidence has been notably rising in recent decades, possibly related to changing trends in sexual behavior combined with known risk factors, such as human papilloma virus and tobacco smoking. Although advances in the treatment of SCCA have improved survival and cure rates, the benefits may not be shared uniformly among patients of disparate socioeconomic status.

To investigate, a team led by Daniel Becker, MD, of Perlmutter Cancer Center at NYU Langone Health examined whether area-based median household income predicts survival of patients with SCCA. Their analysis included 9,550 patients with SCCA from 2004-2013 listed in the US Surveillance, Epidemiology, and End Results registry. Socioeconomic status was defined by census-tract median household income level, and divided into quintiles.

The researchers found that patients living in areas with lower median household income had worse overall survival and cancer-specific survival compared with those in highest income areas. From the lowest to the higher income levels, the risk of dying was 32%, 31%, 19%, and 16% higher for patients when compared with patients in the very highest quintile of median household income. When considering only deaths due to cancer, increased risks ranged from 34% down to 22% for the lowest to higher incomes. Other factors such as older age, black race, male gender, unmarried status, earlier year of diagnosis, higher grade, and later stage were also associated with worse cancer-specific survival. Income was not associated with a patient's likelihood of initiating radiation therapy.

"Our findings reveal that US residents who have anal cancer and live in areas of poverty have worse survival than those who live in more affluent areas, even after accounting for differences in age, stage, and race," said Dr. Becker. "Anal cancer is often a curable disease, and, in light of the tremendous resources available in US healthcare, we do not believe that poverty should determine cancer outcomes. The ultimate goal is to make sure that all patients receive high quality care, regardless of their wealth or zip code."

Dr. Becker noted that to provide high quality healthcare for all, it will be important to get a better understanding of the factors limiting the successful treatment of anal cancer. "Additional resources are urgently needed to study and address disparities in anal cancer care and outcomes."

Scientists reported the development of a robust and streamlined procedure for whole-genome copy number profiling of circulating tumor cells (CTCs) from a simple blood test. In contrast to existing methods that are complex and costly, the single-tube, single-step protocol is able to detect absolute Copy Number Alterations (CNA) in single cells and maintain accuracy at a lower cost than conventional genomic analysis procedure, opening up to the possibility for genome-driven targeted therapy selection and monitoring of disease progression in liquid biopsy.

The genome of tumor cells goes through multiple aberration events which are intimately connected to the underlying tumor biology and are reflected in the CNA profile of the entire genome. Multiple recent findings across several cancer types have pointed to the fact that these pattern of aberrations are linked to increased response or resistance to different classes of drugs, ranging from classical chemotherapy to PARP-inhibitors and Immune checkpoint inhibitors. "A variety of analytical techniques have been developed to analyze copy-number alterations in the research lab," explained Nicolò Manaresi, Ph.D., lead author of the study. "However, they are not well suited for clinical application on CTCs where reproducibility, robustness and scalability are required. Our approach offers a streamlined, less expensive method for genome-wide CNA profiling of single cancer cells." Dr. Manaresi also serves as Chief Scientific Officer at Menarini-Silicon Biosystems, based in Bologna and Huntingdon Valley, PA. (U.S.)

The study, published in the online scientific journal PLOS ONE, presents the characterization of an innovative workflow -- developed and commercialized by Menarini Silicon Biosystems as Ampli1™ LowPass kit. The method exploits the characteristics of Ampli1 WGA, which is based on ligation mediated-PCR WGA of fragments obtained by digestion on specific restriction sites, to produce, in a single amplification step, sequencing-ready, barcoded DNA libraries suitable for genome-wide CNA profiling by low-pass whole-genome sequencing. This allowed decreasing workflow time and efforts, allowing higher throughput while reducing the cost. The approach is also demonstrated on patient CTCs, isolated by DEPArray™ technology following enrichment from blood using the CELLSEARCH® system*.

"In comparison to aCGH, a widely used and accepted method for screening CNAs in clinical diagnostic, our approach allowed us to decrease the cost of analysis while providing comparable or superior performances," said Dr. Manaresi. "Moreover Ampli1 LowPass has the advantage to determine absolute copy numbers changes and this has important implications for the biological inter¬pretation of cancer samples. As sequencing cost per base is decreasing with advances in NGS technologies, our streamlined workflow will further decrease the cost of copy number analysis in the future and pave the way to a simpler blood test to study cancer heterogeneity in liquid biopsy."

Researchers from the University Hospital of the Heinrich-Heine-University of Dusseldorf, the Medical Oncology Unit of the University Hospital of Bologna, The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust (London) also participated in the study.

ORLANDO (March 11, 2018) -- Treatment with the blood-thinning drug dabigatran significantly reduced the risk of death, heart attack, stroke and other heart or blood-vessel complications among patients who were at elevated risk for these events because of heart damage that occurred after major noncardiac surgery, according to research being presented at the American College of Cardiology's 67th Annual Scientific Session.

In the first randomized controlled trial to evaluate a treatment for a condition dubbed myocardial injury after noncardiac surgery (MINS), researchers found that patients treated with dabigatran twice daily were 28 percent less likely to die, have a heart attack or stroke, develop blood clots or need an amputation due to cardiovascular disease, compared with patients who received a placebo.

"We have shown for the first time that dabigatran reduces the risk of major cardiovascular complications and offers an option for improving outcomes in a large at-risk population who have MINS," said P.J. Devereaux, MD, PhD, director of cardiology at McMaster University in Hamilton, Canada, and lead author of the study.

Approximately 8 million people every year develop MINS after undergoing surgery such as a hip or knee replacement, bowel resection or abdominal aortic aneurysm repair.

This study builds on research that Devereaux and his colleagues presented at the American College of Cardiology's 66th Annual Scientific Session in 2017 showing that MINS may account for about 1 in 4 deaths during the first 30 days after surgery. That research also showed a blood test for a protein called high-sensitivity troponin T, which is released into the bloodstream when injury to the heart occurs, can identify patients with MINS whose lives could potentially be saved with timely treatment.

Most cases of MINS currently go undetected, Devereaux said, because at present it is not standard practice in most centers to monitor blood levels of troponin in patients who had major noncardiac surgery. Devereaux said he is hopeful this will change now that this study has shown treatment with dabigatran can improve outcomes for patients with MINS.

"Our findings reaffirm that patients who develop MINS are at high risk for bad outcomes," he said. "We owe it to our patients to identify this risk and do what we can to reduce it."

The study enrolled 1,754 patients in 19 countries, 51 percent of whom were men, with an average age of 70 years. The primary efficacy outcome was the combined rate of death from a cardiovascular cause, heart attack, stroke due to inadequate blood supply, blood clots or amputation due to cardiovascular disease. The primary safety outcome was the combined rate of life-threatening, major and critical organ bleeding. During the study, patients, health care providers and research staff were blinded to which group received dabigatran and which received a placebo.

After an average follow-up of 16 months, 11.1 percent of patients treated with dabigatran experienced one or more of the primary efficacy outcome events, compared with 15.2 percent of patients who received a placebo. This translates to a 28 percent reduction in risk for patients receiving dabigatran.

When researchers analyzed occurrence rates for the events comprising the primary efficacy outcome, they found trends of benefit for each component. For example, patients treated with dabigatran were 20 percent less likely to die of a cardiovascular cause, 20 percent less likely to have a heart attack, 30 percent less likely to have an amputation and 53 percent less likely to have a venous blood clot than patients who received a placebo. The result for nonhemorrhagic stroke also demonstrated a benefit with an 80 percent reduction in risk, a difference that was statistically significant compared with patients who were randomized to placebo.

There were no statistically significant differences between the two groups in life-threatening, major or critical organ bleeding. Compared with the placebo group, however, more patients in the dabigatran group experienced bleeding in the lower gastrointestinal tract and minor bleeding.

An increased risk of bleeding is an expected complication of treatment with a blood-thinning medication.

"It's encouraging that we did not see an increase in major or life-threatening bleeding in patients on dabigatran," Devereaux said.

Researchers noted that while nearly all patients (98.9 percent) completed follow-up, 45.3 percent of those on dabigatran had discontinued the study drug. The most common reason for drug discontinuation was patient request; however, 14 percent of these patients had a major complication (e.g., heart attack, stroke, bleeding). According to Devereaux, analyses that counted patients up to seven days after they discontinued the study drug showed even larger treatment effects, with 46 percent reductions in major cardiovascular complications with dabigatran and no excess of life-threatening, major or critical organ bleeding.

Devereaux said that future research is needed to evaluate other treatment options for this high-risk group of patients.

A new study published today suggests that how empathic we are is not just a result of our upbringing and experience but also partly a result of our genes.

Empathy has two parts: the ability to recognize another person's thoughts and feelings, and the ability to respond with an appropriate emotion to someone else's thoughts and feelings. The first part is called 'cognitive empathy' and the second part 'affective empathy'.

Fifteen years ago, a team of scientists at the University of Cambridge developed the Empathy Quotient (EQ), a brief self-report measure of empathy. The EQ measures both parts of empathy.

Previous research showed that some of us are more empathetic than others, and that on average, women are slightly more empathetic than men. It also showed that, on average, autistic people score lower on the EQ, and that this was because they struggle with cognitive empathy, even though their affective empathy may be intact.

In a new study published in the journal Translational Psychiatry, the Cambridge team, working with the genetics company 23andMe and a team of international scientists, report the results of the largest genetic study of empathy using information from more than 46,000 23andMe customers. The customers all completed the EQ online and provided a saliva sample for genetic analysis.

The study was led by Varun Warrier, a Cambridge PhD student, and Professors Simon Baron-Cohen, Director of the Autism Research Centre at Cambridge University, Thomas Bourgeron, of the University Paris Diderot and the Institut Pasteur, and David Hinds, Principal Scientist at 23andMe.

The new study has three important results. First, it found that how empathetic we are is partly due to genetics. Indeed, a tenth of this variation is due to genetic factors. This confirms previous research examining empathy in identical versus non-identical twins.

Second, the new study confirmed that women are on average more empathetic than men. However, this difference is not due to our DNA as there were no differences in the genes that contribute to empathy in men and women.

This implies that the sex difference in empathy is the result of other non-genetic biological factors, such as prenatal hormone influences, or non-biological factors such as socialisation, both of which also differ between the sexes.

Finally, the new study found that genetic variants associated with lower empathy are also associated with higher risk for autism.

Varun Warrier said: "This is an important step towards understanding the small but important role that genetics plays in empathy. But keep in mind that only a tenth of individual differences in empathy in the population are due to genetics. It will be equally important to understand the non-genetic factors that explain the other 90%."

Professor Thomas Bourgeron added: "This new study demonstrates a role for genes in empathy, but we have not yet identified the specific genes that are involved. Our next step is to gather larger samples to replicate these findings, and to pin-point the precise biological pathways associated with individual differences in empathy."

Dr David Hinds said: "These are the latest findings from a series of studies that 23andMe have collaborated on with researchers at Cambridge. Together these are providing exciting new insights into the genetics influences underlying human behaviour."

Professor Simon Baron-Cohen added: "Finding that even a fraction of why we differ in empathy is due to genetic factors helps us understand people such as those with autism who struggle to imagine another person's thoughts and feelings. This can give rise to disability no less challenging than other kinds of disability, such as dyslexia or visual impairment. We as a society need to support those with disabilities, with novel teaching methods, work-arounds, or reasonable adjustments, to promote inclusion."

Researcher profile: Varun Warrier

Varun Warrier is a PhD student at the Autism Research Centre, where he studies the genetics of autism and related traits. He moved to Cambridge in 2013 from India because of the Centre's world-leading reputation.

There are several key challenges in the field, he says. "First, we have identified only a fraction of the genes associated with autism. Second, no two autistic people are alike. Third, within the spectrum autistic people have different strengths and difficulties. Finally, those with a clinical diagnosis blend seamlessly into those in the population who don't have a diagnosis but simply have a lot of autistic traits. We all have some autistic traits - this spectrum runs right through the population on a bell curve."

Although much of his work is computational, developing statistical tools to interrogate complex datasets that will enable him to answer biological questions, he also gets to meet many people with autism. "When I meet autistic people, I truly understand what's often said - no two autistic people are alike."

Warrier hopes his research will lead to a better understanding of the biology of autism, and that this will enable quicker and more accurate diagnosis. "But that's only one part of the challenge," he says. "Understanding the biology has its limits, and I hope that, in parallel, there will be better social policies to support autistic people."

Cambridge is an exciting place to be a researcher, he says. "In Cambridge, there's always a local expert, so if you have a particular problem there usually is someone who can help you out. People here are not just thinking about what can be done to address the problems of today; they are anticipating problems that we will face in 20 years' time, and are working to solve those."

ORLANDO, Fl. (Mar. 11, 2018) - Data released today from a large multi-center study provides a view into the effectiveness of two drugs used to prevent heart problems resulting from breast cancer treatment.

The data was presented at the American College of Cardiology's 67th Annual Scientific Session, one of the most influential medical symposia on heart-related topics.

"This data is the crucial first step towards establishing a new standard of care to reduce the risk of cardiotoxicity for patients undergoing treatment for HER2-positive breast cancer," said study chair Dr. Maya Guglin of the University of Kentucky's Gill Heart & Vascular Institute.

Chemotherapy drug Herceptin was first approved by the FDA in 1998 to treat an aggressive form of breast cancer called HER2-positive. Its stunning success at reducing cancer recurrence and improving survival came at a cost, however: one in four women develop potentially dangerous heart problems. Physicians began suspending Herceptin treatment or reducing the frequency of treatment if a patient's ejection fraction (a measure of the heart's ability to pump blood) dropped below 50 percent.

The issue was concerning enough to The American Heart Association that they recently released a statement warning doctors and patients to consider carefully the risks when developing a treatment plan for HER2-positive patients.

The multi-arm, placebo-controlled study chaired by Dr. Guglin explored whether two classes of drugs -- ACE inhibitors and beta blockers-- preserved a patient's cardiac function during chemotherapy. The study looked at patients who were treated with Herceptin alone as well as patients who were treated with Herceptin after first receiving another chemotherapy drug known as doxorubicin.

"Herceptin is arguably the most effective treatment for HER2-positive breast cancer," Guglin said. "These patients are already anxious about their future. We don't want to avoid this exceptionally effective treatment just because it might cause damage to the heart."

The data showed that ACE inhibitors and beta blockers did not help preserve ejection fraction in patients receiving Herceptin alone. However, there was a significant reduction in cardiotoxicity for patients on beta blockers or ACE inhibitors who received doxorubicin before Herceptin: cardiac event rates in the placebo group were 47 percent, compared to ACE inhibitors (37 percent) and beta blockers (31 percent).

"The data clearly demonstrated that, for patients with HER2-positive breast cancer taking both doxorubicin and Herceptin, adding either an ACE inhibitor or a beta blocker to the treatment regimen can significantly offset the chance of heart problems," Guglin said.

Funded by the National Cancer Institute, this study is the largest trial on this topic to date, with 167 sites enrolling 468 patients. While many patients with breast cancer fear death from the disease itself, research shows that heart disease is more likely to kill them. Studying how to prevent such negative side effects is an important contributor to optimal patient care.

"In the past few decades, we've made huge strides in successfully treating cancers that used to be very deadly for patients," said Dr. Mark Evers, director of the NCI-designated UK Markey Cancer Center. "But it's important to also think about the patient's future and to help them maintain the best possible quality of life. This study provides valuable information for oncologists who are treating patients with HER2-positive breast cancer, and may help shape the new standard of treatment for this cancer in years to come."

According to Guglin, this study offers some clarity about treatment options, but more questions need to be asked and answered before scientists consider a new standard of care.

"For example, should we always treat with both doxorubicin and Herceptin? Should we re-evaluate our minimum standards for heart function? What if the patient's EF is less than 50 percent but is asymptomatic? And should the patient's wishes carry more weight in the equation?" Guglin said.

"All of these questions require careful consideration, but this part is clear: giving an ACE inhibitor or beta blocker to patients taking doxyrubicin and Herceptin for HER2-positive breast cancer will significantly reduce the risk of cardiotoxic side effects."

New research published today helps explain why people experience muscle loss in old age, increasing the prospects of reversing the condition in the future.

As people grow older, their leg muscles become progressively smaller and weaker, leading to frailty and disability. While this process inevitably affects everyone living long enough, until now the process has not been understood. This new research, published in the Journal of Physiology, suggests that muscle wasting follows on from changes in the nervous system. By the age of 75, individuals typically have around 30 - 50% fewer nerves controlling their legs. This leaves parts of their muscles disconnected from the nervous system, making them functionally useless and so they waste away.

However, healthy muscles have a form of protection, in that surviving nerves can send out new branches to rescue some, but not all, of the detached muscle fibres. This protective mechanism is most successful in older adults with large, healthy muscles. When the internal protective mechanism is not successful and nerves are unable to send out new branches, it can result in extensive muscle loss. This can result in a condition called Sarcopenia, which affects an estimated 10-20% of people aged over 65 years.

The researchers do not yet understand why the connections between muscles and nerves remain healthy in some people and not in others. The race is now on to use this new knowledge to delay old-age weakness by either slowing the decline or by increasing the success of nerve branching to rescue detached muscle fibres.

The research carried out by Manchester Metropolitan University in conjunction with University of Waterloo, Ontario, and The University of Manchester, involved using MRI to gain a detailed look at the muscle tissue, followed by enhanced electromyography to record the electrical activity passing through the muscle to estimate the numbers and the size of surviving nerves available to rescue muscle fibres.

The researchers are currently looking at whether regular exercise in middle- and older-age slows the process of muscles becoming disconnected from the nervous system, or improves the success of nerve branching to rescue detached muscle fibres. The goal is to identify the best type of exercise - strength training or endurance - and to understand the physiology of why the nerve-muscle changes occur as we get older.

Professor Jamie McPhee, the senior author on the research, commented on the significance of the findings:
"Our challenge now is to find ways to increase the success of nerve branching to rescue detached muscle fibres and thereby reduce the numbers of older people in our neighbourhoods with low muscle mass and muscle weakness. Right now in Europe there are at least 10 million older people with low muscle mass, which is a medical condition known as sarcopenia. They are at higher risk of social isolation, falling, bone fracture, disability and hospital admission. Weakness makes them particularly vulnerable to falls in bad weather, as we've had in recent weeks. Our research helps to explain why muscles decline with advancing age and this new knowledge will help in the search for effective countermeasures."

Dr Mathew Piasecki, the study lead author who has since taken up a position at the University of Nottingham, said:
"One of the earliest attempts at research similar to ours showed results from a small group of older people who apparently had just a couple of surviving nerves feeding into a foot muscle. When we started out with our research we were very sceptical of the old data and thought it was an anomaly of out-dated testing procedures. However, now that we have tested a couple of hundred men we think the early observation was probably correct. We have also observed some very old muscles with just a few dozen nerves left, where young and healthy adults have hundreds."

ORLANDO (March 11, 2018) -- Among people younger than 75 years who were given clot busters to treat a heart attack, taking the more potent blood thinner ticagrelor did not increase the risk of major bleeding (the primary endpoint) compared with the standard blood thinner clopidogrel, in a trial being presented at the American College of Cardiology's 67th Annual Scientific Session.

The results align with those of previous studies assessing ticagrelor's safety. However, a key difference between the new study and earlier ones is that participants were taking fibrinolytic therapy or "clot busters," a class of drugs that break up the blood clots that cause heart attacks. These new findings suggest ticagrelor, which reduces clotting by preventing platelets from aggregating, is safe to use in combination with clot busters, at least in patients younger than 75, researchers said.

Clot busters are used to treat heart attacks when it is not feasible to perform percutaneous coronary intervention (PCI), a procedure to open blocked arteries that is the gold standard for treating ST-elevation myocardial infarction (STEMI), the most severe form of heart attack. Use of these drugs is particularly common in countries and health care systems where PCI is not generally available 24 hours a day, which includes most lower- and middle-income countries as well as some higher-income countries such as Canada and Australia. The trial was conducted in 10 countries on five continents: Australia, New Zealand, Argentina, Russia, China, Canada, Peru, Brazil, Colombia and Ukraine.

"This is the first large, international trial of ticagrelor in STEMI patients taking fibrinolytic therapy," said Otavio Berwanger, MD, PhD, cardiologist and clinical epidemiologist at Brazilian Clinical Research Institute, Sao Paulo, and the study's lead author. "I think doctors, some of whom are already using ticagrelor off-label, will find the results reassuring because they suggest that you can use ticagrelor in this population without causing more major bleeding or fatal bleeding than clopidogrel."

The trial enrolled 3,800 patients treated for STEMI at more than 180 centers. All patients had received fibrinolytic therapy within 24 hours of their heart attack. Half of the participants were randomly assigned to take ticagrelor and half took clopidogrel. Patients were given an initial loading dose of their assigned drug and then continued taking the drug for 12 months.

After 30 days, the researchers assessed rates of major bleeding events in both study groups using the criteria defined by the Thrombolysis in Myocardial Infarction (TIMI) score, the standard tool used to score bleeding severity. Bleeding is the most common complication from blood thinners, which are used to help prevent heart attacks and strokes by reducing the body's ability to clot blood.

TIMI-scored major bleeding occurred in roughly 0.7 percent of patients in each group, with no statistically significant difference between the two groups. Thus, the trial met its primary endpoint indicating that ticagrelor is not inferior to clopidogrel in terms of major bleeding at 30 days.

The researchers also found no difference between the study groups in terms of rates of major bleeding according to two other sets of criteria, BARC (Bleeding Academic Research Consortium) and PLATO (Study of Platelet Inhibition and Platelet Outcomes), as well as rates of fatal bleeding and bleeding in the brain. They did observe a significantly higher rate of minor bleeding among patients receiving ticagrelor, which was expected because ticagrelor is a more potent blood thinner.

Researchers will track cardiovascular outcomes for 12 months and plan to report in 2019 on how well each drug performs in preventing major adverse cardiovascular outcomes.

"For patients who may be resistant to clopidogrel, or for those in whom it may be desirable to use the more potent drug, at least from our results doctors can know it is safe to do so," Berwanger said. "However, we will have to wait until next year to assess efficacy."

The risk of bleeding increases with age. Because the new trial was restricted to patients younger than 75 years, Berwanger noted that the findings may not apply to older adults.

PHILADELPHIA - Today, in a late-breaking featured clinical research session at the American College of Cardiology Scientific Sessions 2018, researchers from Penn Medicine present first-of-its-kind data on the impact of real-time CYP2C19 genotype results when prescribing antiplatelet drugs in the clinic.

Following percutaneous coronary intervention (PCI)--a minimally invasive procedure for the treatment of narrowing arteries inside the heart--patients are often prescribed aspirin and antiplatelet medications, which keep stents open by preventing blood platelets from sticking together. However, existing research suggests that some patients--specifically those who carry a mutation of the CYP2C19 gene, which impact the liver's ability to process the antiplatelet drug, clopidogrel--may not benefit from this drug, but instead would require different antiplatelet medications, such as prasugrel or ticagrelor, to prevent heart attack and stroke.

"One of the main things we aimed to do in this study was integrate a clinical trial protocol into the physicians' daily practice, in order to provide the most beneficial medication regimens to patients based on their specific genetic needs, while also identifying what drives physician behavior when prescribing," said senior author Jay Giri, MD, associate director of the Penn Cardiovascular Outcomes, Quality, & Evaluative Research Center and an assistant professor of Cardiovascular Medicine. "Clinicians were provided with a real-time, rapid response genetic test and an appropriate level of education for using said test, which would identify patients' genetic mutation, CYP2C19 Loss-of-Function (LOF) alleles. We thought this precision medicine approach would impact the medications being prescribed to patients following PCI."

As Giri and his colleagues suspected, access to the genotype data in an everyday clinical setting did, in fact, influence prescriber behavior.

In the study, 504 participants from two Penn Medicine hospitals--the Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center--were randomized into two groups: one group received a rapid point-of-care genotyping of CYP2C19, and the other did not receive any genotyping, which is the current standard of care. 249 participants were genotyped and 255 received the standard care. The participants in the genotyped group received a cheek swab within one day after PCI to determine CYP2C19 genotype, and results were available to clinicians within 90 minutes of the test being done. Physicians were verbally provided genotype results along with decision support, a one page summary of the treatment recommendations by genotype according to the Clinical Pharmacogenetics Implementation Guidelines (CPIC). Ultimately, the treating physician was the sole decision maker in the prescribing.

Researchers found that in the genotyped group, the use of prasugrel or ticagrelor was significantly higher and the use of clopidogrel was lower as compared to the usual care group. In fact, genotype-guided drug recommendations were followed in 71 percent of cases, whereas in 29 percent of cases, physicians did not follow the recommendations.

"This implies that physicians consider factors beyond the genotype when deciding the most appropriate antiplatelet medication for their patients, which is the premise of precision medicine." said lead author Sony Tuteja, PharmD, MS, a research assistant professor of Translational Medicine and Human Genetics, who presented the results of the study today in a late-breaking featured clinical research session at ACC 2018. "Ultimately we concluded that access to pharmacogenetic test results significantly impacted antiplatelet prescribing behaviors. It remains to be seen whether a reduction in important clinical outcomes like heart attack, stroke, and cardiovascular related death follow what is predicted by the genetics."

Researchers noted that this study raised more questions for the field, specifically, how do physician behave in an era of precision medicine, and will the availability of patient-specific genetic information impact the standard of care?

"Often times we have a situation where the data in large clinical trials will say one thing, but precision medicine data will say another, so we need to figure out what the physician will do in those situations and what drives their decisions," Giri said. "Are clinicians influenced more by a patients' genetic make-up, or by the population-based research they have access to? Ultimately more research is needed to really identify the impact and usefulness of real-time genetic testing for making clinical decisions, which we intend to evaluate for interventional patients. As it turns out, Precision Medicine is a lot more than just precise genetics."

NEW ORLEANS, LA - Cortisone injections are a common nonsurgical approach to treating rotator cuff injuries. However, researchers presenting their work today at the American Orthopaedic Society for Sports Medicine's Specialty Day in New Orleans suggest that individuals who receive injections less than six months before a rotator cuff repair may have an increased risk for revision rotator cuff repair.

"As more patients elect to undergo a rotator cuff repair, surgeons may want to consider either delaying surgery or avoiding shoulder injections within 6 months to lower the risk of requiring a subsequent, revision rotator cuff repair," said lead researcher, Sophia A. Traven, MD from the Medical University of South Carolina in Charleston, South Carolina.

Traven and her team identified 4,959 patients who had an arthroscopic primary rotator cuff repair. Of these subjects, 553 required reoperation within the following three years and 392, or 70.9%, were for a revision rotator cuff repair. The mean age of those patients was 49.2 years and 53.6% were male. Patients who had an injection within 6 months were at a much higher risk of requiring a revision cuff repair within the following three years at 52.8%. Those who had an injection between 6-12 months before surgery had no increased risk compared to those that did not have an injection at all within the year preceding surgery.

"Our study is the first to demonstrate that there is a time-dependent relationship between shoulder injections and the risk of requiring a revision rotator cuff repair. Additional research on how the type of injection and number of injections affect healing will be critical and help influence better recovery rates and treatment protocol," said Traven.