Body

Combining medications that suppress the immune system has been successful in treating young patients with Crohn's disease, but some physicians have been reluctant to use this strategy in older patients because of concerns about safety. Now an Alimentary Pharmacology & Therapeutics study indicates that older patients can be safely and effectively treated with such combined immunosuppression as well.

Among the 1,981 patients in the study, 311 were aged 60 years or older (173 randomised to early combined immunosuppression and 138 to conventional management). Over 24 months, 10 percent of older patients developed Crohn's disease?related complications (6.4 percent of those in the combined immunosuppression group versus 14.5 percent of those in the conventional management group) and 14 patients died (3.5 percent versus 5.8 percent).

Among the patients who received combined immunosuppression in the study, older patients experienced remission of their disease to a similar extent as those aged under 60 years. There was also no increase in side effects from these medicines in older patients.

"It is important to treat aggressive Crohn's disease appropriately regardless of age," said lead author Dr. Siddharth Singh, of the University of California San Diego. "This may include early step-up combination therapy of tumour necrosis factor-alpha antagonists with thiopurines, which is effective and safe even in older patients, rather than treating these patients with chronic or repeated courses of corticosteroids."

Individuals with a history of infection had a two-fold increased risk of developing Sjögren's syndrome in a Journal of Internal Medicine study. Respiratory, skin, and urogenital infections were most prominently associated with this increased risk.

The study included 9,048 individuals from the general population in Sweden and 945 patients with Sjögren's syndrome--an autoimmune disease characterized by dysfunction and destruction of the salivary and lacrimal glands, leading to dry eyes and mouth.

The findings support the hypothesis that environmental triggers of the immune system play an important role in the development of Sjögren's syndrome.

"To design strategies to prevent rheumatic diseases, we need to learn how and why they develop. This is a step in that direction," said senior author Dr. Marie Wahren-Herlenius, of the Karolinska Institutet.

Several previous studies have demonstrated that moderate alcohol consumption is linked with less severe disease and better quality of life in patients with rheumatoid arthritis, but a new Arthritis Care & Research study suggests that this might not be because drinking alcohol is beneficial.

In the 16,762-patient study, patients with a higher severity of disease were more likely to discontinue the use of alcohol and less likely to initiate use, and patients with greater disability and poor physical and mental quality of life were less likely to use alcohol over time. Also, alcohol use or recent changes in use were not associated with disease activity or death when considering the underlying factors influencing the behavior.

"Our data shows that when people aren't feeling well, they tend not to drink alcohol. While this makes it appear that people who drink are better off, it's probably not because the alcohol itself is helping," said lead author Dr. Joshua Baker, of the University of Pennsylvania.

FINDINGS

Researchers from UCLA's Jonsson Comprehensive Cancer Center have identified a possible new therapeutic strategy using two types of drug inhibitors at once to treat one of the world's deadliest cancers. The combination approach uses one drug that inhibits the process -- known as lysosome -- that allows cancer cells to recycle essential nutrients to survive, and another drug that blocks the pathway used to repair DNA. Researchers found the approach to be promising after testing it on pancreatic cancer cells and mice in the laboratory.

BACKGROUND

Pancreatic cancer, which is the third leading cause of cancer-related deaths in the United States, is known to be highly resistant to treatments. The lack of effective treatments also suggests there is an inadequate understanding of the biologic complexity of the disease and the mechanisms to explain why this type of cancer often becomes resistant to therapies that work in treating other types of cancers.

Because of these limitations, researchers have sought to better understand how the cancer cell pathways work to help identify potential new targets for therapies. Pancreatic cancer cells rely on lysosome-dependent pathways, which are an essential component of autophagy, where cancer cells break down and recycle some of their own components for fuel. Understanding the underlying mechanism and impact of inhibiting this pathway can lead to new treatment strategies for the disease.

METHOD

Researchers studied two sets of data to try to understand the mechanism of lysosome-dependent pathways. The team first took chloroquine, a readily available drug used to treat malaria, and combined it with more than 500 different inhibitors to screen for any unexplored interactions that could yield a "synergistic" effect. This occurs when the effects of two drugs combined together produce a more powerful response than if they were used alone. With this information, the team found a complementary inhibitor called replication stress response inhibitor. In the second set of data, the researchers measured metabolites -- small molecules -- in pancreatic tumor cells that were treated with chloroquine alone. They found the drug causes a reduction in aspartate, an important amino acid to synthesize nucleotides, the building blocks for DNA replication and repair.

IMPACT

The study provides evidence that using chloroquine in combination with an inhibitor of the replication stress response pathway could be a new treatment to reduce tumor growth in pancreatic cancer patients and help improve the prognosis for people with the disease. The findings also stress the importance of learning how existing drugs work to repurpose them for potential use in treating other diseases.

OAK BROOK, Ill. - Fewer women are assigned to a dense breast category when evaluated with advanced mammographic screening technologies compared to standard digital mammography, according to a new study published in the journal Radiology.

A woman's breast density, or the relative amount of glandular and connective tissue compared to fatty tissue, is assessed during a breast cancer screening with mammography. Women with the highest level of breast density have an increased risk for breast cancer and are advised to discuss supplemental screening with their physician. Most states in the U.S. have passed legislation mandating that women be notified of their breast density, and a federal law was just recently passed requiring the Food and Drug Administration (FDA) to oversee such notification.

Although digital mammography (DM) has long been the foundation of breast cancer screening, new imaging methods, or modalities, are increasingly being used, including digital breast tomosynthesis (DBT), also known as 3-D mammography, and synthetic mammography (SM).

In DM, two X-ray images are taken of the breast from top-to-bottom and from side-to-side while the breast is compressed against an imaging detector. In DBT, an X-ray tube moves in an arc over the compressed breast capturing multiple images from different angles. The DBT data can then be reconstructed into a quasi-3-D image stack that allows better lesion characterization and localization.

In 2011, the FDA approved the use of DBT in combination with DM imaging. In 2015, the FDA approved the use of synthesized 2-D images, which are reconstructed from the DBT data set to replace DM imaging, lowering the dose of DBT imaging.

In this retrospective study, researchers analyzed data from 24,736 women who underwent mammography screening at the Hospital of the University of Pennsylvania (HUP) between 2010 and 2017. Data collected included the breast density category assigned at the time of the screening using the standardized BI-RADS system, race, age and body mass index (BMI). The study population was 46 percent white and 54 percent African-American (mean age 56.3 years).

"Major strengths of our study were the size of our sample and the diverse patient population, which was approximately half white and half African-American," said Aimilia Gastounioti, Ph.D., lead author and research associate in the Radiology Department at HUP's Perelman School of Medicine.

Of the 60,766 imaging exams included in the study, 8,935 were conducted with DM (14.7 percent), 30,799 (50.7 percent) were performed with DM/DBT, and 21,052 (34.6 percent) used SM/DBT.

A statistical analysis of the study data showed breast density assignments varied greatly by the screening method used.

"We observed an overall trend of downgraded breast density when imaging was performed with either DM/DBT or SM/DBT compared with DM alone," Dr. Gastounioti said. "These effects were more prominent among African-American women and women with higher BMI."

Compared to standard DM imaging, the odds of a high-density assessment were reduced by 31 percent and 57 percent respectively when mammographic imaging was performed with DM/DBT or SM/DBT. The odds of receiving a high breast density assignment after SM replaced DM were reduced by 38 percent.

The density downgrade may be due to the perception of less fibroglandular tissue in the 3-D display of DBT imaging compared to DM's flat, 2-D display, as well as differences in the appearance of the denser glandular tissue and the fatty tissue in the reconstructed SM imaging.

"Our findings may have direct implications for personalized screening since breast density assignments, which often drive recommendations for supplemental screening, may vary greatly by modality, race and BMI," Dr. Gastounioti said.

She added that further research is needed to determine whether BI-RADS guidelines need to be adjusted for new imaging modalities.

OAK BROOK, Ill. - The use of digital breast tomosynthesis (DBT), also known as 3-D mammography, may significantly reduce the number of women who undergo breast biopsy for a non-cancerous lesion following an abnormal mammogram, according to a new study published in the journal Radiology.

Unlike standard or full-field digital mammography (FFDM), which captures two x-ray images of the breast from top-to-bottom and from side-to-side, DBT captures multiple images from different angles that are synthesized into 3-D images by a computer.

"The thin slice images of the breast taken with DBT reduce the effect of tissue overlap, which often leads to cancers being missed or to women who don't have breast cancer being recalled for diagnostic imaging," said lead researcher Nisha Sharma, M.B.Ch.B., director of breast screening and clinical lead for breast imaging at Leeds Teaching Hospital NHS Trust, Seacroft Hospital, in Leeds, England. "In our study, we wanted to determine the impact of DBT on the biopsy rate among women recalled for an abnormal screening mammogram."

The single-institution prospective study included 30,933 women who had a screening FFDM or screening breast MRI through the U.K.'s National Health Service Breast Screening Programme (NHSBSP) at Seacroft Hospital between 2015 and 2016. Within six weeks of their breast screening, the women also underwent DBT.

Of the study group, 1,470 women were recalled for further imaging (4.8 percent recall rate) to assess an abnormality. A final recall group of 827 women after exclusions (mean age 56.7 years) required 571 biopsies, yielding a biopsy rate of 69 percent. Biopsy detected 142 cancers. In 429 of the biopsies performed, the suspicious lesion detected on screening mammography was not cancerous, for a benign biopsy rate of 75 percent.

The researchers read the DBT images blinded to the original FFDM screening results to determine whether 3-D images would have influenced the biopsy recommendation. The inclusion of DBT imaging would have reduced the number of biopsies performed on recalled women from 571 to 298--while still detecting the 142 cancers--for a biopsy rate of 36 percent, and a benign biopsy rate of 52 percent.

"DBT allows for improved reader accuracy and confidence in determining if a mammographic abnormality is concerning or not, leading to a reduction in the number of biopsies performed," Dr. Sharma said. "Our study validates that DBT can help in the diagnostic workup of mammographic abnormalities and reduce harm to women through fewer false positive biopsies without any reduction in the cancer detection rate."

A new tool designed for patients with heart disease is better at predicting death after hospital admission than current tools, according to a study published in CMAJ (Canadian Medical Association Journal) http://www.cmaj.ca/lookup/doi/10.1503/cmaj.181186.

"This cardiac-specific tool, or index, to predict death outperforms current general indexes used to predict death," says Dr. Marc Jolicoeur, Montreal Heart Institute, Université de Montréal, Montréal, Quebec.

"The other available tools are good for all patients, but we developed one that is better specifically for cardiac patients."

Current indexes already exist to help predict likelihood of death and are widely used in clinical settings, although these are not disease-specific, and accuracy for patients with cardiac issues has not been widely investigated.

Researchers analyzed administrative data on cardiac patients admitted to the Montreal Heart Institute to create and test an index, the Cardiac-Specific Comorbidity Index, to help predict death both in-hospital and within one year in a group. They then tested the index in a group of almost 19 000 cardiac patients in Alberta. Their cardiac-specific comorbidity index outperformed both the Charlson-Deyo comorbidity index and the Elixhauser comorbidity index.

"Estimating risk is important for patients and their families, as well as policy-makers, to help them monitor outcomes at various hospitals and guide decisions," says Dr. Jolicoeur.

"With this tool, patients at high risk can be flagged, and appropriate care can be taken to manage their condition," he says.

Most importantly, this tool was derived and validated in Canada and will therefore be suitable for use by Canadian researches, administrators and decision-makers.

In a new case study, researchers at North Carolina State University describe an adolescent human patient diagnosed with rapid onset schizophrenia who was found instead to have a Bartonella henselae infection. This study adds to the growing body of evidence that Bartonella infection can mimic a host of chronic illnesses, including mental illness, and could open up new avenues of research into bacterial or microbial causes of mental disorders.

Bartonella is a bacteria most commonly associated with cat scratch disease, which until recently was thought to be a short-lived (or self-limiting) infection. There are at least 30 different known species of Bartonella, and 13 of those have been found to infect human beings. The ability to find and diagnose Bartonella infection in animals and humans - it is notorious for "hiding" in the linings of blood vessels - has led to its identification in patients with a host of chronic illnesses ranging from migraines to seizures to rheumatoid illnesses that the medical community previously hadn't been able to attribute to a specific cause.

In a case study published in the Journal of Central Nervous System Disease, an adolescent with sudden onset psychotic behavior - diagnosed as schizophrenia - was seen and treated by numerous specialists and therapists over an 18-month period. All conventional treatments for both psychosis and autoimmune disorders failed. Finally a physician recognized lesions on the patient's skin that are often associated with Bartonella, and the patient tested positive for the infection. Combination antimicrobial chemotherapy led to full recovery.

"This case is interesting for a number of reasons," says Dr. Ed Breitschwerdt, Melanie S. Steele Distinguished Professor of Internal Medicine at NC State and lead author of the case report. "Beyond suggesting that Bartonella infection itself could contribute to progressive neuropsychiatric disorders like schizophrenia, it raises the question of how often infection may be involved with psychiatric disorders generally.

"Researchers are starting to look at things like infection's role in Alzheimer's disease, for example. Beyond this one case, there's a lot of movement in trying to understand the potential role of viral and bacterial infections in these medically complex diseases. This case gives us proof that there can be a connection, and offers an opportunity for future investigations."

A study of almost 500,000 women indicates that taking paracetamol or other painkillers during pregnancy is not responsible for increasing the risk of asthma in children.

The research, which uses prescription data on painkillers, does support earlier findings that women taking paracetamol during pregnancy are more likely to have children who develop asthma. However, it also suggests that the painkillers are not the cause of this increase.

Researchers say their results, published in the European Respiratory Journal [1], should give women reassurance to take painkillers during pregnancy when they are prescribed by a doctor.

The research was led by Seif Shaheen, Professor of Respiratory Epidemiology, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK, in collaboration with Professor Catarina Almqvist and colleagues at the Karolinska Institute in Stockholm, Sweden.

Professor Shaheen was the first scientist to discover a link between paracetamol use during pregnancy and an increase in the risk of asthma in children. He said: "This link has now been seen in a number of studies in different countries, but until now there has been very little research on use of other painkillers during pregnancy and the subsequent risk of asthma in children.

"We also do not know whether the link between paracetamol and asthma is causal, in other words we don't know whether paracetamol use in pregnancy per se is leading to more asthma, or whether some other factor is at play. The only way to be sure would be to carry out a trial where pregnant women are randomly assigned to either take paracetamol or not, but there are obvious ethical problems with this approach."

To get around this problem, Professor Shaheen and his colleagues studied 492,999 Swedish mothers and their children. They looked at data on prescriptions for different types of painkillers during pregnancy and compared this with rates of asthma diagnosis in the children. They also looked at other data on the mothers, fathers, and any sisters and brothers.

They found that children born to mothers who had been prescribed paracetamol during pregnancy did have an increased risk of asthma, but the risk was similar when women had been prescribed opioids (such as codeine and tramadol) or migraine medication. For example, the increase in risk for asthma at five years of age was 50% for paracetamol, 42% for codeine and 48% for migraine medication.

Professor Shaheen explained: "These different types of painkillers work in different ways, but our results suggest that when women are prescribed them during pregnancy, the associated increases in children's asthma rates are fairly similar for all types.

"Our interpretation of this is that it's less likely that the drugs are responsible for the asthma. Instead, it seems more likely that another factor that we haven't measured is linked to use of these drugs and to asthma risk. For example, women who are taking prescribed painkillers are likely to be suffering from chronic pain.

"Severe pain, and the stress that it causes, have profound effects on the body, including on levels of some hormones, and there is evidence for a link between high levels of mothers' stress in pregnancy and increased risk of asthma in the offspring.

"If that's the case then it's important to manage chronic pain during pregnancy and we should not avoid prescribing painkillers to pregnant women when they are needed. Similarly, women should feel reassured that infrequent use of paracetamol in pregnancy, which is commonly obtained over the counter and is the recommended painkiller to take in pregnancy, is unlikely to cause asthma in their offspring.

"Our study also suggests that a clinical trial of paracetamol during pregnancy, which poses many challenges, is probably not worthwhile."

Professor Tobias Welte, from Hannover University, Germany, is President of the European Respiratory Society and was not involved in the study. He said: "Paracetamol is the most commonly used painkiller in pregnancy, so it is important to know whether it might be a cause of childhood asthma. Previous research suggested these two were linked in some way, but this large study suggests that this may not be a simple cause and effect relationship, and this means that paracetamol should be prescribed to pregnant women who need it. However, we also need to continue studying the complex reasons why so many children develop asthma."

Boston, MA -- The final results are in for MOMENTUM 3, the largest left-ventricular assist device (LVAD) trial ever conducted. The study of more than 1,000 patients with severe heart failure not only confirms that the HeartMate 3™, a next-generation LVAD device, markedly reduced the need for re-operations due to pump malfunctions, but also found that it lowered risk of bleeding events and strokes, compared to the HeartMate II™. Results were presented in a Late Breaking Clinical Trial at the American College of Cardiology's 68th Annual Scientific Session by Mandeep R. Mehra, MD, executive director of the Center for Advanced Heart Disease and medical director of the Heart & Vascular Center at Brigham and Women's Hospital, and published simultaneously online in the New England Journal of Medicine.

"We are thrilled to have completed the largest LVAD trial in the world, to see that all of the early benefits we observed in interim analyses were sustained, and to report reductions in pump-related thrombosis, strokes and mucosal bleeding -- three measures of hemocompatibility -- compared to the previous generation of cardiac pump," said Mehra. "Our results should spur confidence that we now have a much more forgiving pump and should provide reassurance to clinicians that we do not need to wait until a patient is 'near death' to consider this option for our patients."

MOMENTUM 3, sponsored by Abbott Inc., compared Abbott's HeartMate 3™ left ventricular assist system, a magnetically-levitated, continuous centrifugal-flow circulatory pump, to the HeartMate II™, a commercial axial flow pump. The trial evaluated how many participants, two years after receiving their device, had not suffered a disabling stroke or had an operation to replace or remove a malfunctioning device.

A total of 1,028 patients were randomized to receive either the centrifugal flow pump or the axial flow pump. The team found that 397 patients (76.9 percent) in the centrifugal-flow pump group did not experience a disabling stroke or need a re-operation compared to 332 (64.8 percent) in the axial-flow pump group. Only 12 people who received the centrifugal-flow pump needed a re-operation compared to 57 patients who received the axial pump. The centrifugal-flow pump reduced risk of stroke by 58 percent, major bleeding by 36 percent and gastrointestinal hemorrhage by 36 percent. Infection rates and rates of right heart failure were no different between the two groups.

MOMENTUM 3 launched in 2014 and was designed to dramatically reduce the overall timeline for clinical trials. All patients with refractory heart failure who needed a cardiac pump were eligible for the trial, regardless of whether the pump was intended as a bridge to transplantation or destination therapy. Based on the study's first interim analysis at six months, the HeartMate 3™ was approved in 2017 by the FDA for use as a short-term device, such as for a bridge to transplantation. Last fall, supported by the second interim results of MOMENTUM 3, the pump was approved by the FDA as a long-term use device, such as for patients with advanced heart failure who are not eligible for a heart transplant.

The HeartMate 3™ includes several technological adaptations intended to reduce risk of complications. The fully magnetically levitated device runs like a bullet train -- its rotor has no mechanical bearings in it and pushes the blood using only magnetism. It is designed to reduce shear stress and destruction of blood elements as they pass through the pump, which is thought to cause blood clots to form in pumps.

Reductions in bleeding events, re-operations and strokes could translate to important cost savings. The team calculated that in every 10 patients implanted with the centrifugal-flow pump, compared with the axial-flow pump, 2.2 pump thrombosis events, two strokes and 6.8 bleeding events would be averted over a two-year period.

"Until now, these devices have been considered less cost-effective, which has been a big issue outside of the U.S.," said Mehra. "Our evidence shows a decreased need for hospitalization and re-operations, indicating that the centrifugal-flow pump may be much more cost-friendly in the longer term."

Mehra notes that residual risks remain, including infections, which occur in nearly 50 percent of patients. Many, but not all, of these infections occur at the entry point of the drive line that powers the device. In addition, low-frequency, right-ventricular heart failure events can occur. Mehra is now chairing a follow-up trial that will specifically examine these challenges and what modifications can be made to address them.

Men who receive anti-hormonal treatment after having their prostate removed are 80% more likely to suffer from depression than men who don't receive this treatment. This leads researchers to suggest that patients receiving androgen deprivation therapy should be monitored for post-surgical depression. This is presented at the European Association of Urology congress in Barcelona.

Increasingly doctors are becoming aware that for many men, a cancer diagnosis and treatment leads to depression, with suicide rates seen rising disproportionately for those with urological cancers. Now a group of Danish researchers has shown that men who receive anti-hormonal treatment after a radical prostatectomy have an increased tendency to depression.

"The anti- hormonal treatment is given to control the growth of tumour cells" said lead researcher Dr Anne Sofie Friberg from the Rigshospitalet in Copenhagen. "Unfortunately, we have found that it is also associated with depression."

The researchers examined medical records of 5,570 men from the Danish Prostate Cancer Registry. They found that 773 of these men were treated for depression after surgery. They found that men treated with anti-hormonal medicines were 1.8 times more likely to suffer from depression than men who did not receive the additional treatment. The researchers also checked whether radiotherapy after radical prostatectomy was associated with depression, but these results were inconclusive.

Anne Sofie Friberg said:

"The treatment prevents the production of androgen hormones, like testosterone. We know from other studies that low testosterone can affect a man's well-being, so it may be that limiting testosterone production might have the same effect, perhaps especially after a major stress such as cancer treatment.

It is important to note that compared to men without prostate cancer the patients treated with prostatectomy as a whole has an increased risk of depression. After surgery, erectile dysfunction and urinary incontinence are frequent symptoms. In case of recurrence and hormonal treatment, these symptoms may worsen and in addition, altered body image and loss of libido are common. These treatment effects are likely to increase the risk of depression. Also, low testosterone levels may directly affect mood centres of the brain"

As many as 25% of men undergoing radical prostatectomy will relapse and may be offered hormonal treatment. These men appear to be at a higher risk of developing depression once hormonal treatment is introduced. The reason could be either a consequence of failing surgery, directly caused by the hormonal manipulation, or both."

They note that the definition of depression - antidepressant prescriptions or referral to a psychiatric department for depression - is a possible limitation of the study (not all would have sought treatment, and sometimes anti-depressants are prescribed for other conditions). But the large numbers in the study means that the results are likely to be robust.

Commenting, EAU Adjunct Secretary General for Education, Prof Hendrik Van Poppel (University Hospitals of the KULeuven, Belgium) said:

"This is a large study which shows that prostate cancer treatment can spill over to cause other issues. We need to be aware of this potential. As urologists we have a responsibility to treat the whole patient, so this argues for a multi-disciplinary approach to treating prostate cancer, and underlines the value of following evidence-based guidelines to try to ensure that the patient receives comprehensive care".

Mr Erik Briers MS PhD (patient member of the EAU guidelines committee on prostate cancer) said:

"This study is very relevant from the patient's point of view; it again shows the importance of the holistic treatment of prostate cancer patients and in this treatment the importance of including psycho-oncology and socio psychology professionals. The care for prostate cancer patients does never stop, consequences can show up very late".

EMBARGOED UNTIL 11: 45 a.m. ET, March 17, 2019, NEW ORLEANS -- A Cleveland Clinic-led research team has found that using an absorbable, antibiotic-eluting envelope when implanting cardiac devices like pacemakers and defibrillators can cut the rate of major infections by 40 percent.

The research was presented today at the American College of Cardiology's 68th Annual Scientific Session and simultaneously published in the New England Journal of Medicine. It will also be presented tomorrow at the European Heart Rhythm Association 2019 Congress.

Approximately 1.7 million patients worldwide receive cardiac implantable electronic devices every year. These devices are used to correct abnormal heart rhythms and include pacemakers and implantable cardioverter defibrillators. While the devices are safe, there is a risk of infection, particularly following device replacements, or other secondary procedures such as pocket revisions, lead changes and upgrades.

"While the risk of major infections is low, when they do occur, they can be devastating for patients, resulting in invasive procedures, device removal, prolonged hospital stays and potentially death," said Khaldoun Tarakji, M.D., MPH, associate section head of cardiac electrophysiology at Cleveland Clinic and the lead author of the study. "Other than the use of antibiotics right before the device procedures, this is the first intervention proven to reduce the risk of infection in a randomized clinical trial of this magnitude."

The envelope is made of absorbable mesh that encases the defibrillator or pacemaker and is designed to stabilize the device when it is implanted in the body. It is coated with two antibiotics - minocycline and rifampin - which are continuously released into the device pocket over a minimum of seven days. The envelope is fully absorbed in approximately nine weeks.

The global trial enrolled 6,983 patients at 181 centers in 25 countries, receiving new defibrillators for cardiac resynchronization therapy or undergoing specific procedures on their cardiac implantable electronic devices including pocket revisions, generator replacements or upgrades. They were randomized to receive the envelope or not and were followed for at least 12 months. All patients received the standard preventive antibiotics prior to the operation to minimize infection risks. In the control group, 1.2 percent (42 patients) developed a major infection compared with 0.7 percent (25 patients) in the envelope group - a reduction of 40 percent. Of the major infections, 17 were endocarditis, an infection of the heart's inner lining, and 50 were pocket infections. There were less pocket infections in the envelope group.

"The infection rates in our study were overall very low compared with other trials, and yet, we found the envelope was still able to provide a significant infection reduction benefit to patients. Given the seriousness of cardiac device infections, we strive to bring infection rates to as close to zero as possible," said Bruce Wilkoff, M.D., director of cardiac pacing and tachyarrhythmia devices at Cleveland Clinic and senior author on the study.

The trial also examined the safety of the envelope. Researchers found no increase in complication rates when the envelope was used. The envelope, manufactured by Medtronic, was approved by the FDA in 2013 for use in cardiac implantable electronic devices.

A new study has found that patients with atherosclerotic cardiovascular disease cut their risk of a second major adverse cardiovascular event by almost 50 percent, if they adhere to taking a statin medication as prescribed by their doctors.

While that's good news for patients, the bad news, however, is that researchers from the Intermountain Healthcare Heart Institute in Salt Lake City found that only about six percent of patients are in fact following the statin regimen given to them to lower their cholesterol, negating any potential cardiovascular benefits.

"A lot of clinical trials have shown that statins reduce the risk of secondary outcomes, so it's really important that they take these medications," said the study's principal investigator, Heidi May, PhD, principal investigator of the study, and cardiovascular epidemiologist at the Intermountain Healthcare Heart Institute. "The surprising thing that we found is that so few patients, even within an insured population, just didn't take their statin medication as prescribed."

Results of the study were presented on March 16 at the American College of Cardiology Scientific Sessions in New Orleans.

In the study, researchers identified 5,468 patients first diagnosed with atherosclerotic cardiovascular disease between 1999 and 2013. These patients received a statin prescription to reduce their cholesterol within the first 12 months of diagnosis. Researchers then looked at two things: whether or not the patients took their medication, and how many major adverse clinical events (stroke, heart attack, or death) they had over the next five years.

They found that patients with optimal adherence -- who took their statins as prescribed at least 80 percent of the time -- reduced their risk of dying or having a heart attack or stroke by nearly 50 percent. Unfortunately, though, only 351 out of those 5,468 patients fell into the optimal adherence category -- which is about six percent.

Researchers also found that 25 percent of patients never filled their statin prescription in the first place, and 25 percent didn't fill their second one.

Researchers think there are several reasons for non-adherence, including a bias against statins, concern that they're already taking too many medications, worry about side-effects, the incorrect belief that after a few years on statins, they're cured and don't need to take them anymore, or they are just not that important.

The cost of the drugs is most likely not a factor, researchers say, since all of the patients in the study were enrolled in SelectHealth insurance, and the statins cost them only about $10 for a 90-day supply.

Dr. May believes the importance of taking statins could be lost in the abundance of information patients are given at discharge.

"During this time, patients most likely don't feel their best, they're probably scared about what just happened to them, and nervous about their future. They may not be able to process everything that's happening and how to best follow up," she said.

Dr. May added that the findings of the study should help caregivers see how crucial it is to ensure their patients who are being discharged understand the importance of the medication, and that continual education needs to be provided about the importance of taking their medications as prescribed.

"The patients should be asked about whether or not they're taking their statin at their follow-up appointments, especially soon after discharge," Dr. May said.

For the study, researchers from Intermountain Healthcare collaborated with The Medicines Company.

"This is important research to better understand the real-world treatment of atherosclerotic cardiovascular disease, and to validate the benefits of statins as proven first-line therapy and the challenges associated with poor adherence," said Dr. May. "We appreciate our collaboration with The Medicines Company. They share our commitment to improving cardiovascular care for patients."

A multicenter clinical trial has found that transcatheter aortic valve replacement (TAVR) performed better than open-heart surgery in low-risk patients with severe aortic stenosis. The study found that one year after the procedure, the rate of death, stroke, or rehospitalization was significantly lower with TAVR than with surgery.

The results were presented during the late-breaking clinical trials session at the American College of Cardiology Conference in New Orleans and were simultaneously published online in the New England Journal of Medicine.

"When TAVR was introduced, it was regarded as an alternative for patients who were too sick to undergo open-heart surgery. Today's findings suggest that TAVR may be superior to surgery, even for patients with low operative risk," said Martin B. Leon, MD, a professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, director of the Center for Interventional Vascular Therapy at NewYork-Presbyterian/Columbia University Irving Medical Center, and principal investigator of the trial.

An estimated 5 million adults in the U.S. have aortic stenosis -- a buildup of calcium in the aortic valve that can lead to heart failure. Patients previously had to undergo open-heart surgery to have the valve replaced. But many who most needed valve replacement were too sick or frail to undergo surgery.

For nearly a decade, TAVR has provided a less invasive option for these patients. In TAVR, doctors thread a catheter through an artery in the groin and into the heart so that a new aortic valve can be fitted inside the diseased valve without surgically opening the chest.

As many as 400,000 patients around the world have had TAVR since it was first introduced in the mid-2000s.

The first PARTNER (Placement of AoRtic TraNscathetER) trial, published in 2010 and led by Leon, found that the procedure dramatically reduced the risk of death among inoperable patients -- less than 10 percent of those with severe aortic stenosis -- compared to those managed medically; in subsequent PARTNER trials, published in 2011 and 2016, TAVR was also found to be effective for patients with high- and intermediate-risk of death or serious complications from surgery.

But researchers did not know how TAVR would compare to surgery in the vast majority of patients who are considered good candidates for open surgery. In the new study, PARTNER 3, the researchers enrolled 1,000 patients from 71 centers with severe aortic stenosis and an operative risk of less than 2 percent (surgical risk of less than 4 percent is considered low). The patients were randomized to have TAVR with the SAPIEN 3 balloon-expandable valve or surgical aortic valve replacement.

At one year after the procedure, 42 patients (8.5 percent) in the TAVR group had died, had a stroke, or were hospitalized for a heart-related problem or surgical complication compared with 68 patients (15.1 percent) in the surgery group, a 46 percent reduction.

At 30 days, TAVR patients had fewer strokes and occurrences of new-onset atrial fibrillation than surgical patients. The average hospital stay was shorter for TAVR patients (3 days vs. 7 days for surgical patients).

"The main limitation of the study is that the current results reflect outcomes after one year, which isn't long enough to assess the long-term durability of the replacement valve," said Leon. "Patients in the study will be followed for at least 10 years so that we can measure their long-term outcomes and inform the medical community."

In the largest such study so far undertaken, US researchers have shown that testosterone replacement slows the recurrence of prostate cancer in low-risk patients. This may call into question the general applicability of Nobel-Prize winning hormonal prostate treatment. The work is presented at the European Association of Urology congress in Barcelona.

Background

Doctors have long regarded testosterone as a hormone which promotes prostate cancer. The 1941 work of Huggins and Hodges won Huggins the 1966 Nobel Prize for Medicine*, for reporting the dramatic impact of testosterone reduction on prostate cancer. Since then, medicines which reduce levels of the hormone testosterone have become a standard option for many patients**.

However, in the late 1990s to 2000s, doctors discovered that although men on long term anti-testosterone treatments were not dying from prostate cancer, they were dying prematurely of cardiovascular disease. It seemed that although anti-testosterone therapies were treating the prostate cancer, the extremely low testosterone levels were significantly worsening metabolic complications such as elevated blood sugar, diabetes, elevated cholesterol, mid-abdomen visceral fat, etc. Low testosterone also caused a loss of sexual function in many men on anti-androgen treatment. This led some doctors*** to suggest testosterone treatment of some low risk men after radiation or surgical treatment.

What have they done?

Starting in 2008 a team of doctors from the University of California, Irvine, led by Professor Thomas Ahlering, began to carefully select patients for testosterone replacement after primary treatment of prostate cancer with robotic radical prostatectomy, in hopes of improving recovery of sexual function.

The team worked with 834 patients undergoing radical prostatectomy. They treated 152 low-risk patients with no evidence of disease with testosterone replacement therapy. After a median of 3.1 years following surgery, they tested the patients for biochemical recurrence of the cancer, as indicated by measurement of the Prostate Specific Antigen (PSA) levels. They found that the cancer had recurred in only approximately 5% of treated patients, whereas the cancer had recurred in 15% of the patients who did not receive testosterone. Overall, after accounting for differences between the groups, they found nearly a three-fold reduction by three years.

Importance

Thomas Ahlering commented "This is not what we set out to prove, so it was a big surprise: not only did testosterone replacement not increase recurrence, but it actually lowered recurrence rates. While the testosterone is not curing the cancer per se, it is slowing the growth of the cancer, giving an average of an extra 1.5 years before traces of cancer can be found. We already know that testosterone can help with physiological markers such as muscle mass, better cholesterol and triglyceride levels and increased sexual activity, so this seems to be a win-win".

He continued, "There have been smaller studies which have hinted that testosterone may not be risky for certain patient groups, but this is the largest such study ever conducted. We're not suggesting that treatment methods be changed just yet, but this puts us at the stage where we need to question the taboo against testosterone use in prostate cancer therapy - especially for low-risk patients after radical prostatectomy. We need the oncology/urology community to begin to review testosterone use".

Commenting, Professor Francesco Montorsi (Milano), European Association of Urology's Adjunct Secretary General for Science said:

"The paper is indeed important, as it stresses the importance of checking testosterone levels as a part of the management of patients with sexual disorders following radical prostatectomy. Obviously selection of the right patients is vital, but if confirmed, this may have immediate benefits on quality of life; the possibility of reducing mortality would be an unexpected bonus. We now need bigger studies to support this work".

This is an independent comment; Professor Montorsi was not involved in this work.