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Some women can stop taking blood thinners for unexplained vein clots

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A Canadian-led research group has developed and validated a rule that could let half of women with unexplained vein blood clots stop taking blood thinners for life.

Over 1.5 million Canadians will experience a vein blood clot their lifetime, known as venous thrombosis. If part of the clot breaks off and travels to the lungs, it can be fatal. Half of these blood clots happen for no apparent reason, and are known as unexplained or unprovoked clots.

Once an unprovoked vein clot is treated, guidelines recommend that patients take blood thinners for the rest of their lives. If they do not, their risk of having a second clot is 30 to 40 percent in the next 10 years. Taking life-long blood thinners virtually eliminates this risk, but comes at a cost of a 1.2 percent chance of major bleeding per year.

‘Patients can get very anxious trying to balance the risks of the treatment with the risks of another blood clot,’ said Dr. Marc Rodger, senior scientist and thrombosis specialist at The Ottawa Hospital and professor at the University of Ottawa. ‘With this rule we can confidently tell half of the women we see that they are at low risk of having another blood clot. This means they can stop taking blood thinners once their initial clot is treated, sparing them the cost, inconvenience and risks of taking life-long medication.’

The HERDOO2 rule, so named to help physicians remember the criteria, was developed by an international team led by Dr. Rodger and published in 2008. According to the rule, if a woman has one or none of the following risk factors she is at low risk for having another blood clot:

Discoloration, redness or swelling in either leg (HER= Hyperpigmentation, (o)edema or redness)

High levels of a clotting marker (D-dimer) in the blood

Body mass index of 30 kg/m2 or more (Obesity)

Older than age 65

The team could not find factors to identify low-risk men.

The Ottawa Hospital Research Institute www.ohri.ca/newsroom/newsstory.asp?ID=903

Common drugs similar to ibuprofen could help treat sepsis, study suggests

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A potentially life-saving treatment for sepsis has been under our noses for decades in the non-steroidal anti-inflammatory drugs (NSAIDs) most people have in their medicine cabinets, a new University of Colorado Boulder study has found.

More than 30 billion doses of non-steroidal anti-inflammatory drugs (NSAIDS) are taken annually in the United States.
Each year more than 1 million people in the United States contract sepsis, an overwhelming immune response to infection. It kills as many as half of those who contract it, sometimes within days, according to the National Institutes of Health. As the number of cases rises, particularly in intensive care units, pharmaceutical companies have been scrambling to develop a drug to combat the condition.

‘NSAIDS like ibuprofen and aspirin are among the most prevalent pharmaceuticals worldwide, with over 30 billion doses taken annually in the United States alone. But their precise mechanisms of action are not entirely understood,’ said Hang Hubert Yin, a biochemistry professor at CU Boulder’s BioFrontiers Institute and lead author of the new paper, published today in Cell Chemical Biology. ‘We provide the first evidence for a novel mechanism of action for NSAIDS, one we believe could have a direct impact on people’s lives.’

Researchers have long known that NSAIDs work in part by inhibiting an enzyme called cyclooxygenase (COX). They’ve also known that these NSAIDs can come with serious side effects. Some NSAIDs have been removed from the market after showing they boosted risk of heart attack and stroke.

But Yin’s research found that a subgroup of NSAIDs also act strongly and independently on another family of enzymes, caspases, which reside deep within the cell and have recently been found to play a key role in aggressive immune responses, like sepsis.

‘For instance, some chemicals derived from bacteria actually penetrate the cell and trigger the caspase response, prompting the cell to commit suicide. This also is known as apoptosis,’ said Yin. ‘Such activation, in turn, potentially causes inflammation.’

After the disappointing failure of late-stage clinical trials of anti-sepsis drugs targeting an immune receptor called toll-like receptor 4 (TLR4), located on the surface of cells, Yin and other scientists began to wonder if the key to halting the disease was to develop an antiseptic therapy that simultaneously targets caspases.

As a first step, his team screened 1,280 existing FDA-approved drugs for caspase-inhibiting activity. Of the 27 that lit up, half were NSAIDs. NSAIDs also comprised eight of the top 10 most potent caspase inhibitors.

‘It was a complete surprise,’ said Yin.

He and study co-author Ding Xue, a professor in the department of Molecular Cellular and Developmental Biology, then used biochemical and biophysical assays in the lab, as well as experiments with roundworms to test the theory further.

‘We showed that NSAIDs were effective in delaying cell death in worms, presumably by blocking caspase activity.’

It remains questionable whether existing NSAIDs, perhaps in higher doses, could be used to treat sepsis. The risk of side effects may be too great, said Yin. But he is already working on follow-up studies looking at whether new sepsis drugs could be developed combining caspase-inhibiting NSAIDS and TLR4 inhibitors.

University of Colorado at Boulders www.colorado.edu/today/2017/02/23/common-drugs-similar-ibuprofen-could-help-treat-sepsis-study-suggests

3-D photography could offer better orthodontic diagnosis using less radiation

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Common orthodontic problems such as crossbite, overbite, underbite, and crowding of the teeth can have a negative impact on a person’s physical appearance, dental function, and overall self esteem. To make a diagnosis and plan treatment, orthodontists currently take multiple x-ray images of the entire skull before, during and after orthodontic treatment. Part of the skull, the cranial base, is used as a stable reference for determining the position and orientation of the jaws and teeth when planning treatment changes. While the amount of radiation is small, x-rays of the whole skull taken multiple times during treatment can be a concern, especially for paediatric patients who are generally more susceptible to the harmful effects of ionizing radiation than adults.
A recent study suggests that another approach using non-radiographic 3-D dental photogrammetry could offer accurate dental and facial measurements based on using the eyes and natural head orientation as references rather than the cranial base.
Mohamed Masoud, director of Orthodontics in the Department of Developmental Biology at the Harvard School of Dental Medicine, along with his research team studied 180 females and 200 males between the ages of 18 and 35 using 3-D facial and dental imaging to produce an adult sample with near ideal occlusion and a pleasing facial appearance. The goal was to provide reference values that can aid practitioners in determining the relative position and orientation of a patient’s dental and facial structures without exposing the cranium to radiation.


Harvard University
news.harvard.edu/gazette/story/newsplus/new-research-suggests-3-d-photography-could-offer-better-orthodontic-diagnosis-using-less-radiation/

MRI scans for suspected prostate cancer could improve diagnosis

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A researcher from Hull York Medical School (HYMS) has helped design and set up a study which has been hailed as the biggest leap in diagnosing prostate cancer in decades.  The study was led by researchers from University College London, with collaboration from a multi-disciplinary team including Dr Rhian Gabe from HYMS. Prostate cancer is the most common cancer in British men. If men have high prostate specific antigen (PSA) levels in the blood, they are referred for a biopsy.
Researchers revealed that an advanced MRI technique can pick up 93 per cent of aggressive cancers, compared with 48 per cent for a standard biopsy. The study on 576 men showed more than a quarter could be spared invasive biopsies.
The current standard technique for prostate biopsy can miss a cancer that is there, fail to spot whether it is aggressive, and biopsies can cause side-effects including bleeding, serious infections and erectile dysfunction.
Around 100,000 to 120,000 men go through this every year in the UK.
The trial, at 11 hospitals in the UK, used multi-parametric MRI on men with high PSA levels.
Dr Gabe said: “The study is ground-breaking because of the implications for future recommendations regarding diagnostic tests for prostate cancer and the potential benefit derived by the vast numbers of men referred for prostate biopsies on the basis of elevated PSA levels.
“The study has highlighted inadequacies with standard biopsies with only half the clinically significant cancers being detected in a cohort of men with elevated PSA.
“The results also suggest that advanced MRI prior to biopsy could identify about a quarter of men who could safely avoid unnecessary biopsies and in future, could be used to guide prostate biopsy to greatly improve detection of clinically significant cancer.”
For this strategy to be implemented across the NHS, a number of important capacity issues such as training of radiologists would be need to be addressed, Dr Gabe added.

Hull York Medical Schoolhttp://tinyurl.com/yd9cmrqz

Low-dose CT scanning improves assessment of ankylosing spondylitis patients

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The results of a study presented at the Annual European Congress of Rheumatology (EULAR) 2017 showed that low dose computed tomography (LD-CT) is more sensitive than conventional radiographs (X-rays) in the monitoring of disease progression in patients with Ankylosing Spondylitis (AS).
LD-CT, using a newly developed scoring method for assessing bone formation in AS patients, had previously been shown to be reliable and sensitive, with good consistency between different individuals interpreting the images.
In this latest study, designed to further validate LD-CT, a comparison of its ability to demonstrate the formation of new bony growths (known as syndesmophytes) and / or an increase in size of these syndesmophytes, showed that LD-CT consistently detected more AS patients with these signs of disease progression than conventional X-rays.1
“Standard dose computed tomography is a sensitive method for assessing structural changes in the spine in patients with AS,” said lead author Dr. Anoek de Koning from the Leiden University Medical Centre, Leiden, Netherlands. “However, its clinical utility has been limited due to its use of relatively high doses of ionising radiation.”
“Our findings support the use of LD-CT as a sensitive method for the assessment of new or growing syndesmophytes in future clinical research without exposing patients to high doses of radiation,” she concluded.
Comparing the percentage of patients with newly formed syndesmophytes, growth of existing syndesmophytes and the combination of both, scored by two separate investigators and as a consensus score, LD-CT detected more patients with progression in all comparisons. This was especially apparent where there was a higher number of new or growing syndesmophytes per patient.
With the strictest comparison of the consensus score for both LD-CT and X-rays, 30% of the patients showed bony proliferation (newly formed and growth) at 3 or more sites on LD-CT, compared with only 6% on conventional X-rays. Patients were recruited from the SIAS (Sensitive Imaging of Axial Spondyloarthritis) cohort from Leiden, the Netherlands and Herne, Germany. 50 AS patients were included based on modified New York criteria , the presence of one or more syndesmophytes on either the cervical and / or lumbar spine seen on X-ray, and one or more inflammatory lesions on an MRI of their whole spine.
Each of these patients had conventional X-rays of the lateral cervical and lumbar spine and LD-CT of the entire spine at baseline and two years. Two investigators independently assessed the images in separate sessions. Images were paired per patient, blinded to time order, patient information, and the result of the other imaging technique. For LD-CT, syndesmophytes were scored in the coronal and sagittal planes for all ‘‘quadrants’ per view, thus scoring 8 ‘‘quadrants’ per vertebral unit. The formation of new syndesmophytes, growth of existing syndesmophytes and the combination of both was calculated per quadrant. Syndesmophytes were scored as absent (score 0), <50% of the intervertebral disc height (IVDH) (score 1), ≥50% of the IVDH but no bridging (score 2) or as bridging the IVDH (score 3).2 Consensus about each of these outcomes was defined by agreement of both readers on the same vertebral level. Data were compared per reader and for the consensus score.

The European League Against Rheumatism
www.eular.org/congresspressreleases/Low-dose_CT_scanning_improves_assessment_of_Ankylosing_Spondylitis_patie.pdf

New material could save time and money in medical imaging

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Chemists at The University of Texas at Austin have developed a material that holds the key to cheap, fast and portable new sensors for a wide range of chemicals that right now cost government and industries large sums to detect. The innovation could lead to major public health gains, as it holds the potential to drastically reduce the costs associated with cleaning-up accidental chemical spills, remediating old industrial sites, detecting radioactive contamination in drinking water, and operating medical and research imaging devices.

‘A company with an abandoned chemical plant that has barrels of unlabelled solvents or a public utility concerned its water supply has been contaminated today face a cumbersome process of identifying the chemicals before they can start clean-up,’ said Simon Humphrey, associate professor of chemistry who led the research. ‘It’s costly and can take two or three days. We can now do that with a rapid, on-site method – and that difference could improve people’s health and reduce pollution a lot more efficiently.’

Humphrey envisions disposable paper dipsticks coated with the new material. A user would dip one into an uncharacterized substance and stick it into an ultraviolet (UV) reader. Based on the colours of light emitted, the device would indicate what components, such as organic solvents, fluoride, mercury and heavy metals, are in the substance.

The material, called PCM-22 is a crystal made of lanthanide ions and triphenylphosphine. When a chemical bonds to the material and a UV light shines on it, the material emits specific colours of visible light. Each chemical produces a unique eight-factor signature of colour and brightness that can be used to identify and quantify it in an uncharacterized sample.

Once scientists calibrate the sensor on known samples to create a catalogue of fingerprints that can be used to identify the components of uncharacterized samples, the dipstick-type sensors would be relatively simple to produce, Humphrey said. He and UT Austin share joint patents on the sensor material and on the process of analysing results, and UT Austin’s Office of Technology Commercialization has already begun work to license the technology to companies.

Another beneficial feature of PCM-22 is that it can distinguish between two types of water -the ordinary water (H2O) that we experience in everyday life and so-called heavy water (D2O), used in the operation of medical and research imaging.

With D2O, hydrogen atoms are replaced by deuterium atoms, but the two types of water are notoriously hard to tell apart because they look and, in most cases, behave the same chemically. It normally requires a costly test with a sophisticated piece of laboratory equipment called a laser spectrometer to tell the two apart.

Because the new material makes distinguishing between the two types of water simpler, it could become much easier for government agencies to detect the presence of radioactive contamination in drinking water or other bodies of water such as lakes and rivers. When ordinary water interacts with radioactive material, such as uranium, some of it is converted to heavy water, so elevated levels of heavy water give an early warning of contamination with radioactive material.

The ability to detect and quantify the two forms of water quickly, cheaply and at the point of need also would pave the way for more affordable and reliable medical and research imaging, such as nuclear magnetic resonance spectroscopy (NMR), which requires heavy water to operate. For NMR to function properly, this heavy water has to be very pure, but it is easily contaminated with ordinary water from moisture in the atmosphere.

‘When you buy heavy water from a manufacturer it starts out ultrapure,’ Humphrey said. ‘But as soon as you unscrew the bottle, hydrogen atoms from the air start swapping with deuterium atoms. A week later, all of the H’s have become scrambled with the D’s and it effectively ruins the heavy water. It’s an exchange that you can’t stop.’

The new material, which is sensitive enough to detect concentrations of ordinary water as low as 10 parts per million in a solution of heavy water, could make it cheaper and faster to verify the purity of this important reagent.

University of Texas at Austin news.utexas.edu/2017/04/13/universal-chemical-sensor-could-help-boost-public-health

Majority of incontinence treatments deliver poor results

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Surgery is the most reliable method of treatment for incontinence – curing the condition in just over eight in ten cases; other types of treatment, meanwhile, do not deliver the same kind of success. These are the findings of a comprehensive systematic overview of cure rates for the treatment of incontinence around the world during the last ten years.

‘Unfortunately we are not actually curing the condition in that many cases. Surgery aside, the results delivered are poor. And the problems are only going to get worse in the future because the population, as we know, is aging,’ says Ian Milsom, Professor of Gynecology and Obstetrics at the Sahlgrenska Academy and Head of the Gothenburg Continence Research Center (GCRC).

He and a group of researcher colleagues have together studied thousands of research articles and other scientific documentation written about different treatments of urinary and faecal incontinence in adults around the world, published between 2005 and 2015.

The sheer scope of the research makes this work unique. The researchers sifted through the mass of material using harmonized criteria and ultimately came up with percentages indicating how well or poorly different methods had worked. For the results to be considered successful, the individual must have been cured of incontinence three months after the treatment.

Surgery ranks well ahead of other methods, delivering success in 82 percent of cases. Pelvic floor exercises rank second, with 53 percent, followed by drug treatment, with 49 percent.

Bottom of the pile was treatment using so-called bulking agents, which was only successful in 37 percent of cases. This method involves injections of fillers into damaged tissue around the urethra in order to keep the area tight.
Drugs are mainly prescribed to treat urinary incontinence and calm down overactive bladders. Ian Milsom finds it remarkable, including from a financial perspective, that these antimuscarinic drugs are not even helping half of all patients.

‘The results don’t look good at all considering the cost in billions that these drugs incur on health care systems. In contrast surgery on the other hand has become simpler and more effective and is delivering strong results even in the long term,’ he says.

Relatively few studies over the ten-year period focused on the elderly, despite their susceptibility to the condition. The same goes for people with neurological conditions. There were also insufficient studies into how individuals can live normal lives with incontinence by modifying their behaviour and using catheters and absorbent protection.

Urinary and faecal incontinence have an impact on well-being and quality of life and sometimes lead to people feeling isolated in life, both professionally and socially. They also have an adverse effect on sexual health and, as far as the elderly as a group are concerned, increase the risk of institutionalization.

‘This is a major issue for humans that we need to devote more research resources to, not just in Sweden but around the world. Five hundred million people on this planet are suffering from the condition; we need to improve treatment methods, not least for the elderly and those with neurological conditions, who it hits particularly hard,’ says Ian Milsom.

University of Gothenburg www.gu.se/english/about_the_university/news-calendar/News_detail//majority-of-incontinence-treatments-deliver-poor-results.cid1433832

Controversial test could be leading to unnecessary open heart operations

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An approved international test to check whether people need open-heart surgery could be sending twice as many people under the knife unnecessarily, at a cost of nearly GBP 75m, research by the University of Leicester has suggested.

Since 2012 doctors have been using exercise testing on people with a condition called aortic stenosis (AS) to determine whether they need an operation to save their life.

However, a study, led by Gerry McCann, Professor of Cardiac Imaging and Honorary Consultant Cardiologist from the University of Leicester Department of Cardiovascular Sciences, who conducted the research as part of a NIHR Fellowship, has shown the current approach is ‘highly inaccurate’ and if followed may send thousands of patients to surgery before it is needed.

The exercise test, which involves cycling on a stationary bike, is used to determine whether surgery is needed for people with the condition – but it only has a 60 per cent accuracy rate, the study found.

AS, which is the narrowing of the aortic heart valve, affects predominantly older people and affects up to three per cent of people over 75 years of age. Symptoms, such as chest pain, breathlessness and feeling faint, can take years to develop. However, when they do it means the person is seriously ill and could die from heart failure or sudden death.

If exercise test participants become breathless, they are recommended to have valve replacement therapy. About 10,000 aortic valve replacements are performed every year at a cost of up to GBP 15,000. Hospital recuperation then takes between seven and 10 days.

Professor McCann, who is also a consultant cardiologist from the NIHR Leicester Cardiovascular Biomedical Research Unit (BRU), said: ‘There is no doubt that valve replacement therapy is highly effective for patients with symptoms, however there are risks involved. It’s a major operation and there’s a one per cent chance of people dying or having a stroke during or after. There’s also the chance they could develop an infection.

‘It can often take six months to recover, but if they survive they tend to do very well afterwards. However, if we know a patient has AS and no symptoms and we do nothing there’s also a one per cent chance they will die so there’s a fine line between whether we should intervene or not.

‘Our findings showed that this exercise test, which has been approved by the American Heart Association/American College of Cardiology and the European Society of Cardiology, was highly inaccurate as almost twice the number of people who became breathless during the test did not develop symptoms within a year.’

Professor McCann now wants to conduct further research to find a more accurate way to determine whether doctors should wait for symptoms to develop or to intervene beforehand. Ultimately a clinical study comparing early surgery versus waiting for symptoms to develop is needed.

University of Leicester www2.le.ac.uk/offices/press/press-releases/2017/february/controversial-test-could-be-leading-to-unnecessary-open-heart-operations

Automated embryo assessment system more accurate than that of embryologists

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Embryo quality has long been considered the main determinant of implantation and pregnancy in IVF. Morphology – a visual assessment of an embryo’s shape and development – has since the very first days of IVF been the key to measuring this embryo quality, and only in recent years has this morphological grading been made somewhat more scientific with the introduction of time-lapse imaging. Yet the fact remains that many morphologically "good quality" embryos in IVF – between 30 and 60% in various studies – fail to implant in the uterus and make a pregnancy. What’s going wrong?
There is a strong case that chromosomal abnormalities in the embryo, which are not detectable by morphological assessment, carry some responsibility. Studies over several years have confirmed that the rate of chromosomal anomalies (aneuploidy) in embryos increases with patient age, which may explain a higher rate of implantation failure and miscarriage in older IVF patients. But even with embryo testing for chromosomal anomalies, embryos destined for transfer are still assessed morphological.
"The issue is that morphological grading by humans leads to wide inter- and intra-operator variation," said investigator Professor José Celso Rocha from São Paulo State University, Brazil. A study presented today at the 33rd Annual Meeting of ESHRE in Geneva will suggest that these long-standing difficulties may now be improved by using advances in artificial intelligence. Thus, mathematical variables derived from time-lapse images of embryo development may now be used such that an algorithm can classify images of an embryo’s development automatically – and so remove the human variable from the crucial task of morphological assessment. "To classify images automatically will increase the predictive value of our embryo assessment," said Professor Rocha. "By increasing objectivity and repeatability in embryo assessment, we can improve the accuracy of diagnosing embryo viability. Clinics can use this information as ‘artificial intelligence’ to customise treatment strategies and better predict a patient’s chance of pregnancy."
Behind the claims lies an analysis of images taken from the development of 482 seven-day-old bovine embryos, which were used to "train" the artificial intelligence system. This analysis identified 36 assessment variables, 24 of which formed the input of the artificial network architecture. It was notable that during this initial set-up phase only “serious errors” occurred in only 6% of the assessments. Overall, the artificial intelligence system had a 76% accuracy.
Moreover, says Professor Rocha, artificial intelligence demonstrated an improved inter-operator variation (embryologist accuracy score lower than the artificial intelligence score) and improved consistency and overall accuracy of results.
Professor Rocha notes that this work has now moved on to its early stages of development in human embryos, which is being carried out at the São Paulo State University (Dr Marcelo Nogueira) in collaboration with the Boston Place Clinic in London (Dr Cristina Hickman).
Professor Rocha described the main sources of error in morphological assessment by embryologists as their degree of professional experience, emotional stress, physical fatigue, and laboratory routine. "Those features will cause subjectivity in classification of the embryo," he said.
However, because the artificial intelligence system is a technique which analyses the embryo through mathematical variables, it offers low subjectivity and high repeatability, making embryo classification more consistent. "Nevertheless," said Professor Rocha, "the artificial intelligence system must be based on learning from a human being – that is, the experienced embryologists who set the standards of assessment to train the system."


The European Society of Human Reproduction and Embryology
www.eshre2017.eu/Media/ESHRE-2017-Press-releases/Hickman.aspx

New MRI method aids long-term concussion prognosis

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For concussion sufferers, even those who never lost consciousness, physicians may now be able to predict early on who is more likely to continue experiencing symptoms months or years after the head-jarring event, using a new non-invasive magnetic resonance imaging (MRI) method devised by a consortium of researchers led by UC San Francisco scientists.
In their new study the researchers used functional MRI (fMRI), coupled with sophisticated statistical analysis, to track activity in the brain networks of 75 patients, aged 18 to 55, within the first two weeks of their having experienced concussions.
The study revealed tell-tale patterns of brain activity that, six months later, were associated with worse performance on behavioural and cognitive tests and were different from patterns seen in healthy control subjects.
The fMRI method and analysis developed for the study highlighted abnormal patterns of brain activity that pointed to a higher risk for long-term, post-concussive symptoms, even among the 44 study participants who had no evidence of bleeding or bruising in the brain in the immediate aftermath of brain trauma on computed tomography (CT) or ordinary MRI scans.
“This is an exploratory, proof-of-concept study showing that we can identify patients soon after mild brain trauma who may have more persistent symptoms, despite no other evidence of injury within the brain,” said Pratik Mukherjee, MD, PhD, professor of radiology and biomedical imaging at UCSF and the senior author of the study. “We may be able to use this information to help guide treatment decisions and counselling of patients early on, when it may be more effective.”
Only subjects who had lost consciousness for less than 30 minutes were eligible for the study, and many study subjects never lost consciousness during their injury.

University of California – San Franciscohttp://tinyurl.com/yc6cfxrn

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