Credit: CC0 Public DomainTelemedical interventional management reduces hospitalisations and prolongs the life of patients with heart failure. Researchers from Charité - Universitätsmedizin Berlin have shown that these findings apply equally to patients in rural and in metropolitan settings. Results from this research have been published in The Lancet.
31 aug 2018--As part of a research and development project titled 'Health Region of the Future North Brandenburg—Fontane', Prof. Dr. Friedrich Köhler and his team of researchers from Charité's Centre for Cardiovascular Telemedicine conducted a trial involving 1,538 patients with chronic heart failure. Half of the patients enrolled in the trial received a remote patient management intervention in addition to usual care; the other half received usual care only. The study was conducted nationwide in collaboration with 113 cardiology care providers and 87 general practitioners.
Patients in the remote patient management group received four measuring devices: one ECG monitoring unit with finger clip to measure oxygen saturation, a blood pressure monitor, scales to measure body weight, and a tablet computer to record self-reported health status data. Using the tablet computer, all patient data were transferred automatically to Charité's Telemedical Centre, where a team of doctors and nurses was available 24/7 to review the transmitted data. A deterioration in values led to the initiation of specific measures, such as changing the patient's medication, recommending an outpatient visit or inpatient treatment. The primary aims of the study were the avoidance of unplanned hospitalisations for cardiovascular reasons, the continuation of treatment outside the hospital setting for as long as possible, and an increase in life expectancy. Other study aims included an increase in patient quality of life and enabling patients to self-manage their own care. A further study objective was to test whether remote patient management might be able to compensate deficits in health care coverage between rural and urban areas.
According to the results of the study, patients in the telemedical intervention group spent fewer days in hospital due to unplanned hospitalizations for heart failure than patients in the control group—namely, a mean of 3.8 days per year compared with a mean of 5.6 days per year in the control group. Therefore, based on the one-year study period, patients assigned to remote patient management lost significantly fewer days due to unplanned hospitalizations for cardiovascular reasons or death than patients in the control group (17.8 days vs 24.2 days). All-cause mortality for patients assigned to remote patient management was also significantly lower than for patients in the control group. Over the course of a year, the death rate among patients in the usual care group was approximately 11 out of every 100 patients (11.3 per 100 person-years of follow-up), compared with approximately 8 patients (7.8 per 100 person-years of follow-up) in the group assigned to remote patient management.
"The trial was able to show that the use of telemedicine can increase life expectancy," explains Prof. Köhler. This finding applied irrespective of whether patients lived in rural areas with inadequate health care infrastructure or in metropolitan areas. This means that, in addition to improving the overall quality of health care provision, telemedicine is suitable for use as a compensatory strategy to offset regional differences in health care provision between rural and urban areas.
"As a next step, we would like to evaluate our data from a health economics perspective and identify where telemedicine might be able to deliver cost savings for our health care system," says Prof. Köhler. He adds: "One year after the end of our study, we will also be evaluating whether telemedical interventional management has a lasting effect on disease progress even after the intervention has finished."
More information: Friedrich Koehler et al, Efficacy of telemedical interventional management in patients with heart failure (TIM-HF2): a randomised, controlled, parallel-group, unmasked trial, The Lancet (2018). DOI: 10.1016/S0140-6736(18)31880-4
Provided by Charité - Universitätsmedizin Berlin
Tuesday, August 28, 2018
Clock drawing cognitive test should be done routinely in patients with high blood pressure
Credit: European Society of CardiologyA clock drawing test for detecting cognitive dysfunction should be conducted routinely in patients with high blood pressure, according to research presented today at ESC Congress 2018. Patients with high blood pressure who have impaired cognitive function are at increased risk of developing dementia within five years. Despite this known link, cognitive function is not routinely measured in patients with high blood pressure.
28 aug 2018--"The ability to draw the numbers of a clock and a particular time is an easy way to find out if a patient with high blood pressure has cognitive impairment," said study author Dr. Augusto Vicario of the Heart and Brain Unit, Cardiovascular Institute of Buenos Aires, Argentina. "Identifying these patients provides the opportunity to intervene before dementia develops."
The Heart-Brain Study in Argentina evaluated the usefulness of the clock drawing test compared to the Mini-Mental State Examination (MMSE) to detect cognitive impairment in 1,414 adults with high blood pressure recruited from 18 cardiology centres in Argentina. The average blood pressure was 144/84 mmHg, average age was 60 years, and 62% were women.
For the clock drawing test, patients were given a piece of paper with a 10 cm diameter circle on it. They were asked to write the numbers of the clock in the correct position inside the circle and then draw hands on the clock indicating the time "twenty to four". Patients were scored as having normal, moderate, or severe cognitive impairment. The MMSE has 11 questions and produces a score out of 30 indicating no (24-30), mild (18-23), or severe (0-17) cognitive impairment.
The researchers found a higher prevalence of cognitive impairment with the clock drawing test (36%) compared to the MMSE (21%). Three out ten patients who had a normal MMSE score had an abnormal clock drawing result. The disparity in results between the two tests was greatest in middle aged patients.
Dr. Vicario said: "Untreated high blood pressure silently and progressively damages the arteries in the subcortex of the brain and stops communication between the subcortex and frontal lobe. This disconnect leads to impaired 'executive functions' such as planning, visuospatial abilities, remembering details, and decision-making. The clock drawing test is known to evaluate executive functions. The MMSE evaluates several other cognitive abilities but is weakly correlated with executive functions."
He continued: "Our study suggests that the clock drawing test should be preferred over the MMSE for early detection of executive dysfunction in patients with high blood pressure, particularly in middle age. We think the score on the clock drawing test can be considered a surrogate measure of silent vascular damage in the brain and identifies patients at greater risk of developing dementia. In our study more than one-third of patients were at risk."
Dr. Vicario concluded: "The clock drawing test should be adopted as a routine screening tool for cognitive decline in patients with high blood pressure. Further studies are needed to determine whether lowering blood pressure can prevent progression to dementia."
Provided by European Society of Cardiology
Monday, August 27, 2018
Aspirin disappoints for avoiding first heart attack, stroke
This Thursday, Aug. 23, 2018 photo shows an arrangement of aspirin pills in New York. New studies find most people won't benefit from taking daily low-dose aspirin or fish oil supplements to prevent a first heart attack or stroke. Results were discussed Sunday, Aug. 26, 2018, at the European Society of Cardiology meeting in Munich. (AP Photo/Patrick Sison)Taking a low-dose aspirin every day has long been known to cut the chances of another heart attack, stroke or other heart problem in people who already have had one, but the risks don't outweigh the benefits for most other folks, major new research finds.
27 aug 2018--Although it's been used for more than a century, aspirin's value in many situations is still unclear. The latest studies are some of the largest and longest to test this pennies-a-day blood thinner in people who don't yet have heart disease or a blood vessel-related problem.
One found that aspirin did not help prevent first strokes or heart attacks in people at moderate risk for one because they had several health threats such as smoking, high blood pressure or high cholesterol.
Another tested aspirin in people with diabetes, who are more likely to develop or die from heart problems, and found that the modest benefit it gave was offset by a greater risk of serious bleeding.
Aspirin did not help prevent cancer as had been hoped.
And fish oil supplements, also tested in the study of people with diabetes, failed to help.
"There's been a lot of uncertainty among doctors around the world about prescribing aspirin" beyond those for whom it's now recommended, said one study leader, Dr. Jane Armitage of the University of Oxford in England. "If you're healthy, it's probably not worth taking it."
The research was discussed Sunday at the European Society of Cardiology meeting in Munich. The aspirin studies used 100 milligrams a day, more than the 81-milligram pills commonly sold in the United States but still considered low dose. Adult strength is 325 milligrams.
WHO'S REALLY AT RISK?
A Boston-led study gave aspirin or dummy pills to 12,546 people who were thought to have a moderate risk of suffering a heart attack or stroke within a decade because of other health issues.
After five years, 4 percent of each group had suffered a heart problem—far fewer than expected, suggesting these people were actually at low risk, not moderate. Other medicines they were taking to lower blood pressure and cholesterol may have cut their heart risk so much that aspirin had little chance of helping more, said the study leader, Dr. J. Michael Gaziano of Brigham and Women's Hospital.
One percent of aspirin takers had stomach or intestinal bleeding, mostly mild— twice as many as those on dummy pills. Aspirin users also had more nosebleeds, indigestion, reflux or belly pain.
Bayer sponsored the study, and many researchers consult for the aspirin maker. Results were published by the journal Lancet.
ASPIRIN FOR PEOPLE WITH DIABETES?
People with diabetes have a higher risk of heart problems and strokes from a blood clot, but also a higher risk of bleeding. Guidelines vary on which of them should consider aspirin.
Oxford researchers randomly assigned 15,480 adults with Type 1 or 2 diabetes but otherwise in good health and with no history of heart problems to take either aspirin, 1 gram of fish oil, both substances, or dummy pills every day.
After seven and a half years, there were fewer heart problems among aspirin users but more cases of serious bleeding, so they largely traded one risk for another.
FISH OIL RESULTS
The same study also tested omega-3 fatty acids, the good oils found in salmon, tuna and other fish. Supplement takers fared no better than those given dummy capsules—9 percent of each group suffered a heart problem.
"We feel very confident that there doesn't seem to be a role for fish oil supplements for preventing heart disease," said study leader Dr. Louise Bowman of the University of Oxford.
The British Heart Foundation was the study's main sponsor. Bayer and Mylan provided aspirin and fish oil, respectively. Results were published by the New England Journal of Medicine.
Other studies are testing different amounts and prescription versions of fish oil, "but I can't tell people go spend your money on it; we think it's probably better to eat fish," said Dr. Holly Andersen, a heart disease prevention specialist at New York-Presbyterian/Weill Cornell who was not involved in the study.
The new research doesn't alter guidelines on aspirin or fish oil, said Dr. Nieca Goldberg, a cardiologist at NYU Langone Medical Center and an American Heart Association spokeswoman. They recommend fish oil only for certain heart failure patients and say it's reasonable to consider for people who have already suffered a heart attack.
Sunday, August 26, 2018
Sitting for long hours found to reduce blood flow to the brain
A team of researchers with Liverpool John Moores University in the U.K. has found evidence of reduced blood flow to the brain in people who sit for long periods of time. In their paper published in the Journal of Applied Physiology, the group outlines the experiments they carried out with volunteers and what they found.
26 aug 2018--Most people know that sitting for very long periods of time without getting up now and then is unhealthy. In addition to contributing to weight gain, sitting for a long time can cause back pain and leg problems and possibly other ailments. And now, evidence has been reported that it can reduce blood flow to the brain—something shown in the past to contribute to the likelihood of developing neurological disorders such as dementia.
Suspecting that sitting for a long time could cause circulation problems to the brain, the researchers enlisted the assistance of 15 adult volunteers—each of them had a day job that required long hours of sitting. Each of the volunteers participated in three exercises over a period of time—each came to the lab on three separate occasions and sat for four hours. On each visit, they were fitted with a headband that measured blood flow to the brain using ultrasound. Each subject also wore a face mask that captured and measured carbon dioxide levels.
During the first exercise, the volunteers were asked to sit at a desk for four straight hours, leaving their chairs only to use the restroom. For the second exercise, each rose from their chair every 30 minutes and walked on a treadmill for two minutes. In the third exercise, each subject remained in their chair for two hours and then walked on the treadmill for eight minutes, then returned to the chair.
The researchers found evidence of reduced blood flow in all of the volunteers during all of the exercises. However, they also found that normal blood flow was restored by walking breaks. They report that the best outcome was when the volunteers took frequent two-minute walking breaks.
More information: Sophie E. Carter et al. Regular walking breaks prevent the decline in cerebral blood flow associated with prolonged sitting, Journal of Applied Physiology (2018). DOI: 10.1152/japplphysiol.00310.2018
Abstract
Decreased cerebrovascular blood flow and function are associated with lower cognitive functioning and increased risk of neurodegenerative diseases. Prolonged sitting impairs peripheral blood flow and function, but its effects on the cerebrovasculature are unknown. This study explored the effect of uninterrupted sitting and breaking up sitting time on cerebrovascular blood flow and function of healthy desk workers. Fifteen participants (10 male, 35.8±10.2 years, BMI: 25.5±3.2 kg∙m-2) completed, on separate days, three 4-hr conditions in a randomised order: a) uninterrupted sitting (SIT), b) sitting with 2-min light intensity walking breaks every 30-min (2WALK) or c) sitting with 8-min light intensity walking breaks every 2-hrs (8WALK). At baseline and 4-hrs, middle cerebral artery blood flow velocity (MCAv), carbon dioxide reactivity (CVR) of the MCA and carotid artery were measured using transcranial Doppler (TCD) and duplex ultrasound respectively. Cerebral autoregulation (CA) was assessed with TCD using a squat-stand protocol and analysed to generate values of gain and phase in the very low, low, and high frequencies. There was a significant decline in SIT MCAv (-3.2±1.2 cm.s-1) compared to 2WALK (0.6±1.5 cm.s-1, p=0.02), but not between SIT and 8WALK (-1.2±1.0 cm.s-1, p=0.14). For CA, the change in 2WALK very low frequency phase (4.47±4.07 degrees) was significantly greater than SIT (-3.38±2.82 degrees, p=0.02). There was no significant change in MCA or carotid artery CVR (p>0.05). Results indicate that prolonged, uninterrupted sitting in healthy desk workers reduces cerebral blood flow, however this is offset when frequent, short-duration walking breaks are incorporated.
Saturday, August 25, 2018
I have had a heart attack. Do I need open heart surgery or a stent?
New advice on the choice between open heart surgery and inserting a stent via a catheter after a heart attack is launched today. The European Society of Cardiology (ESC) and European Association for Cardio-Thoracic Surgery (EACTS) Guidelines on myocardial revascularization are published online in European Heart Journal.
25 aug 2018--Coronary artery disease, also called ischaemic heart disease, is the top cause of death worldwide. Arteries supplying oxygen-rich blood to the heart become narrowed with fatty material, causing chest pain and increasing the risk of heart attacks and death. Patients should stop smoking, be physically active, and consume a healthy diet. They also need lifelong medication which can include a statin to control blood lipids, blood pressure lowering drugs, and aspirin.
Myocardial revascularization can be performed in patients with stable (chronic) coronary artery disease or an acute event (heart attack) to improve blood flow to the heart, reduce chest pain (angina), and improve survival. There are two types of myocardial revascularization: open heart surgery to bypass clogged arteries (coronary artery bypass grafting; CABG) and percutaneous coronary intervention (PCI) to open clogged arteries with a stent.
Patients should be involved in choosing the procedure, state the guidelines. They need unbiased, evidence-based information with terminology they can understand explaining the risks and benefits in the short- and long-term such as survival, relief of chest pain, quality of life, and requirement for a repeat procedure. In non-emergency situations, patients must have time to reflect on the trade-offs and seek a second opinion. Patients have the right to obtain information on the level of experience of the doctor and hospital in performing these procedures.
Outcomes from the two procedures vary according to the anatomical complexity of coronary artery disease. This is graded using the SYNTAX Score, which predicts whether PCI can provide similar survival as bypass. For patients with more simple disease, surgical bypass and PCI provide similar long-term outcomes. For patients with complex disease, long-term survival is better with surgical bypass. Also, patients with diabetes have better long-term outcomes with surgical bypass even with less complex disease.
A heart team of cardiologists, cardiac surgeons and anaesthetists should be consulted for patients with chronic coronary artery disease and a complex coronary anatomy, while respecting the preferences of the patient.
Professor Miguel Sousa-Uva, EACTS Chairperson of the Guidelines Task Force, Santa Cruz Hospital, Carnaxide, Portugal, said: "Despite the development of new stents, studies show that patients with complex coronary artery disease have better survival with bypass surgery and this should be the preferred method of revascularization."
In patients with stable disease, another aspect to consider when choosing the procedure is whether it is possible to bypass or insert a stent into all blocked arteries, as this improves symptoms and survival. Preference should be given to the procedure most likely to achieve this so-called complete revascularization.
When PCI is chosen, stents that release a drug to prevent clots, heart attacks, and reinterventions should be used in all procedures. Bioresorbable stents, which are absorbed by the body, should only be used in clinical trials.
Professor Franz-Josef Neumann, ESC Chairperson of the Guidelines Task Force, University Heart Centre Freiburg ? Bad Krozingen, Germany, said: "The guidelines aim to help patients and doctors make a logical decision on the type of revascularization based on the scientific evidence. They will also be consulted by governments and health insurers as the standard of care for coronary artery disease."
More information: 2018 ESC/EACTS Guidelines on myocardial revascularization. European Heart Journal. 2018. DOI: 10.1093/eurheartj/ehy394.
Provided by European Society of Cardiology
Single pill with two drugs could transform blood pressure treatment
A single pill with two drugs could transform blood pressure treatment, according to the 2018 European Society of Cardiology (ESC) and European Society of Hypertension (ESH) Guidelines on arterial hypertension published online today in European Heart Journal.
25 aug 2018--The guidelines recommend starting most patients on two blood pressure lowering drugs, not one. The previous recommendation was for step-wise treatment, which meant starting with one drug then adding a second and third if needed. This suffered from "physician inertia", in which doctors were reluctant to change the initial strategy despite its lack of success. At least 80% of patients should have been upgraded to two drugs, yet most remained on one drug.
It is now recognised that a major reason for poor rates of blood pressure control is that patients do not take their pills. Non-adherence increases with the number of pills, so administering the two drugs (or three if needed) in a single tablet "could transform blood pressure control rates", state the guidelines.
Professor Bryan Williams, ESC Chairperson of the Guidelines Task Force, University College London, UK, said: "The vast majority of patients with high blood pressure should start treatment with two drugs as a single pill. These pills are already available and should massively improve the success of treatment, with corresponding reductions in strokes, heart disease, and early deaths."
More than one billion people have hypertension (high blood pressure) worldwide. Around 30-45% of adults are affected, rising to more than 60% of people over 60 years of age. High blood pressure is the leading global cause of premature death, accounting for almost ten million deaths in 2015, of which 4.9 million were due to ischaemic heart disease and 3.5 million were due to stroke. High blood pressure is also a major risk factor for heart failure, atrial fibrillation, chronic kidney disease, peripheral artery disease, and cognitive decline.
High blood pressure does not usually cause symptoms. However, people with very high blood pressure may have headaches, blurred or double vision, regular nosebleeds, difficulty breathing, chest pain, irregular heartbeat, blood in the urine, confusion, or pounding in the chest, neck, or ears. See your doctor if you have any of these symptoms.
Treatment thresholds in the 2018 Guidelines are less conservative, with drugs recommended for patients who would previously have received lifestyle advice only. These are patients with low to moderate risk grade I hypertension (140-159/90-99 mmHg), including 65-80 year-olds, and those with high normal blood pressure (130-139/85-89 mmHg).
Professor Williams said: "Many more millions of people, particularly in the older age groups, should be receiving treatment for high blood pressure. See your doctor if you are 65 to 80 years old and your blood pressure is above 140/90 mmHg. The evidence suggests that treatment would reduce your risk of stroke and heart disease."
The guidelines state that "treatment should never be denied or withdrawn on the basis of age". It is increasingly recognised that frailty, independence and biological, rather than chronological, age determine the tolerability and likely benefit of blood pressure lowering medications. For people over 80 years who have not yet received blood pressure treatment, therapy should be started if systolic blood pressure is 160 mmHg or above. People already taking medication should not have it withdrawn at 80 years of age if it is well tolerated.
Blood pressure targets for patients of all ages are lower than in previous guidelines. Systolic blood pressure targets are now 120-129 mmHg for patients under 65 years of age, and 130-139 mmHg for patients over 65 years of age, taking into account treatment tolerability, independence, frailty, and comorbidities. Blood pressure below 120 mmHg should not be the target for any patient since the risk of harm outweighs the potential benefits.
When blood pressure is not controlled by three drugs given in a single pill, a condition known as resistant hypertension, a second pill containing a diuretic such as spironolactone should be added. Device-based therapy is not recommended for routine treatment of these patients and should only be administered within clinical trials.
A healthy lifestyle is recommended for all patients, regardless of blood pressure level, as it can delay the need for drugs or complement their effects. Advice includes salt restriction, alcohol moderation, healthy eating, regular exercise, weight control, smoking cessation, and a new recommendation to avoid binge drinking.
A new section on hypertension and cancer therapy states that temporary discontinuation of anticancer therapy may be considered when blood pressure values are exceedingly high despite multidrug treatment. A section on blood pressure during exercise and high altitude has been added, with the advice that patients with severe, uncontrolled hypertension should avoid exposure to very high altitude (above 4000 metres).
Professor Giuseppe Mancia, ESH Chairperson of the Guidelines Task Force, University of Milano-Bicocca, Milan, Italy, said: "We have effective treatments and, theoretically, 90-95% of patients should have their blood pressure under control, but in reality only 15-20% achieve target levels. The 2018 Guidelines aim to improve these poor rates of blood pressure control by introducing a treatment strategy that is simple and easier to follow."
More information: 12018 ESC/ESH Guidelines for the management of arterial hypertension. European Heart Journal. 2018. doi:10.1093/eurheartj/ehy339
Provided by European Society of Cardiology
Do doctors really know how to diagnose a heart attack?
Confusion over how to diagnose a heart attack is set to be cleared up with new guidance launched today. The 2018 Fourth Universal Definition of Myocardial Infarction is published online in European Heart Journal.
25 aug 2018--"Unless there is clarity in the emergency room on what defines a heart attack, patients with chest pain may be wrongly labelled with heart attack and not receive the correct treatment," said Professor Kristian Thygesen, Aarhus University Hospital, Denmark.
"Many doctors have not understood that elevated troponin levels in the blood are not sufficient to diagnosis a heart attack and this has created real problems," continued Professor Thygesen, who is joint chair of the Task Force that wrote the document, together with Professor Joseph S. Alpert, University of Arizona, USA and Professor Harvey D. White, Auckland City Hospital, New Zealand.
The international consensus document spells out that a heart attack (myocardial infarction) has occurred when the heart muscle (myocardium) is injured and has insufficient oxygen. Troponin is a protein normally used by the heart muscle for contraction, but is released into the blood when the muscle is injured. Oxygen shortage (ischaemia) is detected by electrocardiogram (ECG) and symptoms such as pain in the chest, arms, or jaw, shortness of breath, and tiredness.
Myocardial injury on its own is now considered a separate condition. There are numerous situations which can cause myocardial injury, and therefore a rise in troponin. These include infection, sepsis, kidney disease, heart surgery, and strenuous exercise. The first step of treatment is to address the underlying disorder.
As for myocardial infarction, there are different types which require specific treatment. Type 1 is the situation which most people associate with a heart attack. Here a fatty deposit in an artery, called a plaque, ruptures and blocks blood flow to the heart which deprives it of oxygen. Treatment can include antiplatelet medication to stop platelets clumping together and forming a clot, inserting a stent via a catheter to open up the artery, or surgery to bypass the artery.
In type 2, oxygen deprivation is not caused by plaque rupture in an artery but is due to other reasons such as respiratory failure or severe hypertension. Professor Alpert said: "Some doctors have incorrectly called this type 1 and given the wrong treatment, which can be harmful. Treatment should be directed at the underlying condition, for example blood pressure lowering medications for patients with hypertension."
Efforts by doctors to correctly diagnosis myocardial infarction and its subtypes have not been helped by the lack of diagnosis codes in the International Classification of Diseases (ICD). The subtypes of myocardial infarction were first introduced by the joint Task Force in 2007, but were not incorporated into the ICD until October 2017.3,4
Professor White said: "In the consensus document we have expanded the section on type 2 myocardial infarction and included three figures to help doctors make the correct diagnosis. The incorporation of type 2 into the ICD codes is another step towards accurate recognition followed by appropriate treatment. A code for myocardial injury will be added to the ICD next year."
The international consensus document was produced by the European Society of Cardiology (ESC), American College of Cardiology (ACC), American Heart Association (AHA), and World Heart Federation (WHF).
More information: 2018 ESC/ACCF/AHA/WHF Fourth Universal Definition of Myocardial Infarction. European Heart Journal. 2018. doi: 10.1093/eurheartj/ehy462
Provided by European Society of Cardiology
Monday, August 20, 2018
VAT score improves predictive value of MMSE for dementia
Administering the Visual Association Test (VAT) improves the predictive value of the Mini-Mental State Examination (MMSE) score for dementia, according to a study published in a recent issue of the Annals of Family Medicine.
20 aaug 2018--Susan Jongstra, M.D., Ph.D., from the University of Amsterdam, and colleagues analyzed data from 2,690 primary care patients aged 70 to 78 years. Change in the 30-point MMSE score was assessed over two years, and the VAT score was dichotomized as perfect (6 points) or imperfect (≤5 points) at two years. The predictive value of these tests was assessed in the next four to six years.
The researchers found that patients with a decline of 2 or more points in total MMSE score had an odds ratio of 3.55 for developing dementia over two years. For patients with the same decline in MMSE score plus an imperfect VAT score, the odds ratio for developing dementia was 9.55. The odds of dementia were increased with a 1-point decrease in MMSE score only when the VAT score was imperfect. Patients with a 2- or 3-point decrease in MMSE and a perfect VAT score did not have a significantly different average risk for dementia than the cohort as a whole.
"Administering the VAT in patients with a small decline on the MMSE over a 2-year period has substantial incremental value for identifying those at elevated risk for developing dementia," the authors write. "This simple test may help distinguish older adults who need further cognitive examination from those in whom a watchful waiting policy is justified."
It's okay when you're not okay: Study re-evaluates resilience in adults
The graph shows some possible response patterns in adults following adversity. The top line (hashed) shows the response that has been reported as the most common. This flat line indicates that living through an adverse event causes minimal or no disruption to psychological functioning. When the data are analyzed with growth mixture models that are set up using appropriate assumptions, the most common response pattern after adversity is shown by the bottom line. The most common response to adversity is a decrease in psychological functioning followed by a return to normal or near-normal after a period of time. Credit: Rob Ewing, Arizona State University Department of PsychologyAdversity is part of life: Loved ones die. Soldiers deploy to war. Patients receive terminal diagnoses. Research on how adults deal with adversity has been dominated by studies claiming the most common response is uninterrupted and stable psychological functioning. In other words, this research suggests that most adults are essentially unfazed by major life events such as spousal loss or divorce. These provocative findings have also received widespread attention in the popular press and media.
18 aug 2018--The idea that most adults are minimally affected by adversity worries Frank Infurna and Suniya Luthar, of the Arizona State University Department of Psychology, because it disagrees with other research on how adults respond to adversity and could negatively affect people living through adversity. Infurna and Luthar closely examined the research studies and found problems with how studies were designed and how the data were analyzed. The researchers summarize the problems and re-evaluate adult resilience research in a Clinical Psychology Review, which is in press and now available online.
A dip and recovery
Infurna and Luthar are an ideal team to tackle the discrepancy between studies on adult responses to adversity that contradict 80 years of research in child development. Infurna, an associate professor of psychology, is an expert on using complex statistical models to study health and well-being in adulthood and old age. Luthar, a Foundation Professor of Psychology, is an international expert on resilience in children, with 30 years of experience and highly influential publications on the concept of resilience and how best to study it.
"As experts, the onus is on us to be careful about how research is conducted and communicated," Luthar said. "There has been a message percolating in the popular press that most people are unaffected by major life events like bereavement or a deployment, but that is not the whole picture."
The project started over two years ago, when Infurna downloaded publicly-available data for re-analysis. The data had been analyzed using "growth mixture modeling—a statistical model that can classify how different people in a population respond to adversity. After classifying the study participants into groups based on their response to adversity, the model outputs the response patterns for each group.
Infurna and Luthar noticed the results depended on how the model was set up in the software used for statistical analysis. Setting up a model for data analysis requires a researcher to define some assumptions, or educated guesses about aspects of the model like how the data are organized or how much error was included in the experimental measurements. The assumptions identified as problematic by Infurna and Luthar were that the variations in the data were the same for the entire participant group and that the psychological functioning of all participants changed at the same rate. These assumptions also corresponded to the default settings in several software programs commonly used for statistical analysis. When the default software settings were used to run the growth mixture model, the most common response pattern was a flat line, which indicated stable and largely uninterrupted psychological functioning after adversity.
When the growth mixture models were set up with more appropriate assumptions, the researchers found the most common response pattern was a temporary decrease followed by an increase. Such a response pattern indicates a decline in psychological functioning followed by a return to normal, which agrees with 80 years of resilience research in children. This response pattern also agrees with the conventional wisdom that in general, most people struggle to some degree after a major life event and recover after a period of time.
"The idea that 'it is okay to not be okay' following adversity is important," Infurna said. "Sometimes it can take months or years to recover after a traumatic or upsetting event because resilience depends on the person and the resources they have available to them, their past experiences and the type of adverse event."
Life is multidimensional and so is resilience
How adults respond to adversity has typically been measured with longitudinal assessments, or surveys that are repeated over a time interval like once a year. Many research studies have tracked just one psychological outcome, such as life satisfaction, positive or negative emotions or general physical health.
"How do you define doing well?" Luthar asked. "An individual's response to adversity is multidimensional, so that success in one area can coexist with considerable trouble in others. Just because a person is effectively meeting deadlines at work does not mean she is not struggling at home, perhaps crying herself to sleep or estranged from her partner."
Infurna and Luthar recently examined how resilience depended on measures such as life satisfaction, negative or positive emotions, general health or physical health. When just one measure was considered, the percentage of people classified as resilient was high, ranging from 19-66%, but when all measures were considered, only 8% of the adult participants were resilient.
Child development researchers have solved the problem of defining resilience by qualifying different types. For example, children who have lived through adversity and are functioning well in school are described as having "academic resilience." Researchers are also careful not to generalize a child's performance in school to how they might be functioning in other aspects of their lives.
The way forward for adult resilience research and its applications
In the Clinical Psychology Review paper, the main goal of Infurna and Luthar was to prevent the misinterpretation of what a common response to adversity looks like: it is typically some decline followed by an increase back towards normal.
Infurna and Luthar made several recommendations to improve adult resilience research in the future, in addition to changing the assumptions used with growth mixture modeling. They also encourage researchers to assess more than one measure of psychological functioning and to administer longitudinal surveys at more frequent time intervals.
"It is very important for the public and for policy-makers to know what a normal or common response to adversity is," Luthar said. "This knowledge can help people avoid self-blame when they are hurting or have a set-back in the aftermath of a major loss or other traumatic event. And it can help clinicians and policy-makers continue to provide support resources that are often critical in helping adults overcome major life adversities."
More information: Frank J. Infurna et al, Re-evaluating the notion that resilience is commonplace: A review and distillation of directions for future research, practice, and policy, Clinical Psychology Review (2018). DOI: 10.1016/j.cpr.2018.07.003
Provided by Arizona State University
Friday, August 17, 2018
Moderate carbohydrate intake may be best for longevity
Credit: CC0 Public DomainEating carbohydrates in moderation seems to be optimal for health and longevity, suggests new research published in The Lancet Public Health journal. The observational study of more than 15,400 people from the Atherosclerosis Risk in Communities Study (ARIC) in the USA found that diets both low (< 40% energy) and high (>70% energy) in carbohydrates were linked with an increase in mortality, while moderate consumers of carbohydrates (50-55% of energy) had the lowest risk of mortality.
17 aug 2018--The primary findings, confirmed in a meta-analysis of studies on carbohydrate intake including more than 432,000 people from over 20 countries, also suggest that not all low-carbohydrate diets appear equal—eating more animal-based proteins and fats from foods like beef, lamb, pork, chicken and cheese instead of carbohydrate was associated with a greater risk of mortality. Alternatively, eating more plant-based proteins and fats from foods such as vegetables, legumes, and nuts was linked to lower mortality.
"We need to look really carefully at what are the healthy compounds in diets that provide protection", says Dr. Sara Seidelmann, Clinical and Research Fellow in Cardiovascular Medicine from Brigham and Women's Hospital, Boston, USA who led the research.
"Low-carb diets that replace carbohydrates with protein or fat are gaining widespread popularity as a health and weight loss strategy. However, our data suggests that animal-based low carbohydrate diets, which are prevalent in North America and Europe, might be associated with shorter overall life span and should be discouraged. Instead, if one chooses to follow a low carbohydrate diet, then exchanging carbohydrates for more plant-based fats and proteins might actually promote healthy ageing in the long term."
Previous randomised trials have shown low carbohydrate diets are beneficial for short-term weight loss and improve cardiometabolic risk. However, the long-term impact of carbohydrate restriction on mortality is controversial with prospective research so far producing conflicting results. What's more, earlier studies have not addressed the source or quality of proteins and fats consumed in low-carb diets.
To address this uncertainty, researchers began by studying 15,428 adults aged 45-64 years from diverse socioeconomic backgrounds from four US communities (Forsyth County, NC; Jackson, MS; Minneapolis, MN; and Washington County, MD) enrolled in the ARIC cohort between 1987 and 1989. All participants reported consuming 600-4200 kcal per day for men and 500-3600 kcal per day for women, and participants with extreme (high or low) caloric intake were excluded from the analysis.
At the start of the study and again 6 years later, participants completed a dietary questionnaire on the types of food and beverages they consumed, what portion size and how often, which the researchers used to estimate the cumulative average of calories they derived from carbohydrates, fats, and protein.
The researchers assessed the association between overall carbohydrate intake (categorised by quantiles) and all cause-mortality after adjusting for age, sex, race, total energy intake, education, exercise, income level, smoking, and diabetes. During a median follow-up of 25 years, 6283 people died.
Results showed a U-shape association between overall carbohydrate intake and life expectancy, with low (less than 40% of calories from carbohydrates) and high (more than 70%) intake of carbohydrates associated with a higher risk of mortality compared with moderate intake (50-55% of calories).
The researchers estimated that from age 50, the average life expectancy was an additional 33 years for those with moderate carbohydrate intake—4 years longer than those with very low carbohydrate consumption (29 years), and 1 year longer compared to those with high carbohydrate consumption (32 years). However, the authors highlight that since diets were only measured at the start of the trial and 6 years later, dietary patterns could change over 25 years, which might make the reported effect of carbohydrate consumption on lifespan less certain.
In the next step of the study, the authors performed a meta-analysis of data from eight prospective cohorts (including ARIC) involving data from 432,179 people in North American, European, and Asian countries. This revealed similar trends, with participants whose overall diets were high and low in carbohydrates having a shorter life expectancy than those with moderate consumption.
As Seidelmann explains, "A midrange of carbohydrate intake might be considered moderate in North America and Europe where average consumption is about 50% but low in other regions, such as Asia, where the average diet consists of over 60% carbohydrates."
In further analyses examining whether the source of proteins and fats favoured in low-carbohydrate diets—plant-based or animal-based—was associated with length of life, researchers found that replacing carbohydrates with protein and fat from animal sources was associated with a higher risk of mortality than moderate carbohydrate intake. In contrast, replacing carbohydrates with plant-based foods was linked to a lower risk of mortality.
"These findings bring together several strands that have been controversial. Too much and too little carbohydrate can be harmful but what counts most is the type of fat, protein, and carbohydrate," says Walter Willett, Professor of Epidemiology and Nutrition at Harvard T. H. Chan School of Public Health and co-author of the study.
The findings show observational associations rather than cause and effect. Considering evidence from other studies, the authors speculate that Western-type diets that heavily restrict carbohydrates often result in lower intake of vegetables, fruit, and grains and lead to greater consumption of animal proteins and fats—some of which have been implicated in stimulating inflammatory pathways, biological ageing, and oxidative stress—and could be a contributing factor to the increased risk of mortality. Whilst high carbohydrate diets (common in Asian and less economically advantaged nations) tend to be high in refined carbohydrates such as white rice, may also contribute to a chronically high glycaemic load and worse metabolic outcomes.
"This work provides the most comprehensive study of carbohydrate intake that has been done to date, and helps us better understand the relationship between the specific components of diet and long term health", says Dr. Scott Solomon, The Edward D Frohlich Distinguished Chair at Brigham and Women's Hospital and Professor of Medicine at Harvard Medical School, and senior author on the paper. "While a randomized trial has not been performed to compare the longer term effects of different types of low carbohydrate diets, these data suggest that shifting towards a more plant-based consumption is likely to help attenuate major morbid disease."
The authors note some limitations including that dietary patterns were based on self-reported data, which might not accurately represent participants' food consumption; and that their conclusions about animal-based sources of fat and protein might have less generalisability to Asian populations which tend to have diets high in carbohydrates, but often consume fish rather than meat. Finally, given the relatively small number of individuals following plant-based low-carb diets, further research is needed.
Writing in a linked Comment, Dr. Andrew Mente and Dr. Salim Yusuf from McMaster University, Hamilton, Canada say, "Such differences in risk associated with extreme differences in intake of a nutrient are plausible, but observational studies cannot completely exclude residual confounders when the apparent differences are so modest. Based on first principles, a U-shaped association is logical between most essential nutrients versus health outcomes. Essential nutrients should be consumed above a minimal level to avoid deficiency and below a maximal level to avoid toxicity. This approach maintains physiological processes and health (ie, a so-called sweet spot). Although carbohydrates are technically not an essential nutrient (unlike protein and fats), a certain amount is probably required to meet short-term energy demands during physical activity and to maintain fat and protein intakes within their respective sweet spots. On the basis of these principles, moderate intake of carbohydrate (eg, roughly 50% of energy) is likely to be more appropriate for the general population than are very low or very high intakes."
USPSTF: insufficient evidence to screen for atrial fibrillation
There is insufficient evidence to support screening for atrial fibrillation (AF) with electrocardiography (ECG) in older, asymptomatic patients, according to a U.S. Preventive Services Task Force (USPSTF) final recommendation published in the Aug. 7 issue of the Journal of the American Medical Association.
16 aug 2018--Susan J. Curry, Ph.D., from the University of Iowa in Iowa City, and USPSTF colleagues reviewed the evidence on the benefits and harms of screening for AF with ECG in adults 65 years and older. They also assessed the effectiveness of screening with ECG for detecting previously undiagnosed AF compared with usual care, as well as the benefits and harms of anticoagulant or antiplatelet therapy for the treatment of screen-detected AF in older adults.
The Task Force found that most older adults with previously undiagnosed AF have a stroke risk above the threshold for anticoagulant therapy and would be eligible for treatment, which is effective for stroke prevention in symptomatic adults. However, there was inadequate evidence to determine whether screening with ECG and subsequent treatment in asymptomatic adults is more effective than usual care. The harms of diagnostic follow-up and treatment resulting from abnormal ECG results are well established and include misdiagnosis and invasive testing.
"Clinicians should use their medical judgement on whether to screen for AF in people 65 years and older with no signs or symptoms," Task Force member Michael Barry, M.D., said in a statement.
People with dementia and financial abuse – the warning signs and how to avoid it
Credit: ShutterstockWhen most of us go online to our internet banking account and set up a direct debit to pay a bill, we probably do it swiftly without much thought. But in reality it's not that easy. In fact, there are a lot of complex processes involved in how we manage our finances, which older people, especially those with dementia, often struggle to deal with.
14 aug 2018--Dementia affects an estimated 850,000 in the UK, with numbers expected to rise to over a million in the next few years. Each year, dementia care is costing £26.3 billion in the UK alone. Most of this involves care in nursing homes and supporting people with dementia with their daily activities.
If we look at the whole raft of daily activities a person does, such as preparing a hot drink or a meal, or doing the laundry, financial management is one of the earliest tasks to deteriorate in dementia. These processes are complex, which is why people with dementia often struggle to count change, use a cash machine, pay bills or manage tax records sometimes even before their diagnosis.
Daily activities as a whole are often underpinned by a complex network of cognition. This can include different types of memory for past and future events, so the need to remember to do a task at 8pm tonight for example, involves problem solving skills, and attention. But there are other factors that can hinder someone when performing a task, such as motor problems or their environment.
Warning signs
In a recent analysis of a large data set collected from 34 clinical centres across the US, my colleagues and I looked at what kinds of behaviour are a warning sign for problems with paying bills and managing taxes in people with dementia.
When we obtained the data set, we only looked at people with dementia living in the community, who also had a family caregiver, and a diagnosis of the three dementia subtypes: Alzheimer's disease, behavioural-variant fronto-temporal dementia, and Lewy body dementia. We then performed an analysis using statistical models to help identify the degree to which certain factors – such as language or motor skills – can predict a particular outcome. In this case, paying bills was the outcome for one model, and managing taxes was the outcome for the second model.
We found that between 11% and 14% of the ability to manage those financial tasks is predicted by executive functioning, or problem solving skills, language, and motor problems. So this means, if a person has problems solving difficult tasks, problems with language, they fall frequently and are moving slowly, and are also more likely to also struggle with financial tasks. Slowness and falls are particularly prominent in people with Lewy body dementia, which is different to Alzheimer's disease, the most common form of dementia.
Get prepared
This knowledge can help people with dementia. Older people, including people with dementia, can often be subject to financial exploitation. This can be through online or telephone scamming, or knocking on someone's door trying to sell something. And when people with dementia struggle using internet or telephone banking, they may be more prone to telling strangers their bank details.
One way to support people in managing their finances may be to provide training to improve their cognition. It's important to bear in mind that dementia is neurodegenerative. So while we can help people maintain certain skills for longer, there will come a point where full support for finance tasks is needed. This could involve arranging a lasting power of attorney and naming a person that is trusted to look after financial decisions.
Another way may be to adapt the homes of people with dementia to avoid falls and allow them to move around more freely. In our analysis, we found that falls were linked to poor finance management, meaning that noticing your loved one fall more frequently than usual could be a warning sign that they may also struggle managing their finances. If we can drag out the need for full support for as long as possible, we can help someone stay in their own home for longer. And that is exactly where people feel the happiest.
Other, larger financial questions loom for people with dementia, such as inheritance and dealing with payments for formal care – both at home and in future in a nursing home. These are big financial concerns, which should be discussed once a diagnosis is made, but ideally done before. That way the person is better able to judge what they think should be done with their money, and is less likely to be financially exploited than in the later stages of the condition. The Alzheimer's Society has also produced some good further guidelines on how to deal with financial abuse in dementia.
While it may be the last thing someone wants to think about who has just received a diagnosis, the best way to avoid financial abuse is to put things in place right away. If that isn't motivation enough, staying independent in all sorts of activities improves well-being. And that is our ultimate goal, whether we have dementia or not.
Doctors nudged by overdose letter prescribe fewer opioids
Nudging clinicians toward better opioid prescribing. Credit: USC Schaeffer Center for Health Policy & EconomicsIn a novel experiment, doctors got a letter from the medical examiner's office telling them of their patient's fatal overdose. The response: They started prescribing fewer opioids. Other doctors, whose patients also overdosed, didn't get letters. Their opioid prescribing didn't change. More than 400 "Dear Doctor" letters, sent last year in San Diego County, were part of a study that, researchers say, put a human face on the U.S. opioid crisis for many doctors.
12 aug 2018--"It's a powerful thing to learn," said University of Southern California public policy researcher Jason Doctor, lead author of the paper published Thursday in the journal Science.
Researchers used a state database to find 861 doctors, dentists and others who had prescribed opioids and other risky medications to 170 people who died of an overdose involving prescription medicines. Most states have similar databases to track prescribing of dangerous drugs, where doctors can check patients' previous prescriptions.
Most of the deaths involved opioid painkillers, many taken in combination with anti-anxiety drugs. On average, each person who died had filled prescriptions for dangerous drugs from five to six prescribers in the year before they died.
Half the prescribers received letters that began: "This is a courtesy communication to inform you that your patient (name, date of birth) died on (date). Prescription drug overdose was either the primary cause of death or contributed to the death."
The letters offered guidance for safer prescribing. The tone was supportive: "Learning of your patient's death can be difficult. We hope that you will take this as an opportunity" to prevent future deaths.
Then the researchers watched what happened over three months.
Letter recipients reduced their average daily opioid prescribing—measured in a standard way, morphine milligram equivalents—by nearly 10 percent compared to prescribers who didn't get letters. Opioid prescribing in the no-letter group didn't change.
Recipients put fewer new patients on opioids than those who didn't get letters. They wrote fewer prescriptions for high-dose opioids.
The strategy is original, helpful and could be duplicated elsewhere, said pain medicine expert Dr. David Clark of Stanford University, who wasn't involved in the study. He was surprised the letter's effect wasn't larger.
"It may have been easy for physicians to feel it was somebody else prescribing who got the patient in trouble," Clark said, adding that changing even one patient's care takes time, requiring "very difficult conversations."
Opioid prescribing has been declining in the U.S. for several years in response to pressure from health systems, insurers and regulators.
Yet deaths keep rising. Nearly 48,000 Americans died of opioid overdoses last year, according to preliminary numbers released last month, a 12 percent increase from a year before.
Now illegal fentanyl, another opioid, is the top killer, surpassing pain pills and heroin. Lead author Doctor said reducing the number of prescribed opioids will, over time, close off a gateway to illicit drugs by shrinking the pool of dependent people.
The study didn't analyze whether the deaths were caused by inappropriate prescribing or whether the prescribing changes resulted in patients doing better or worse.
That's a flaw in an otherwise careful study, said addiction researcher Dr. Stefan Kertesz of University of Alabama at Birmingham, who has raised red flags about policies that cause doctors to take patients off opioids too fast and without a plan for treating addiction.
Patients can fall into despair or contemplate suicide if they are involuntarily tapered off opioids without support, he said.
"What actually happens to patients should be our concern, rather than just making a number go down," Kertesz said.
Study co-author Dr. Roneet Lev, chief of emergency medicine at Scripps Mercy Hospital in San Diego, discovered her own name in the data.
Lev prescribed 15 opioid pain pills to an ER patient with a broken eye socket, without knowing the patient got 300 painkillers from another doctor a day earlier. Lev didn't get a "Dear Doctor" letter because the patient's death fell outside the timeline of the study, July 2015-June 2016.
Still, she felt the impact and believes she could have done better. Said Lev: "It was an opportunity to look at all the records on that patient and say, 'Wow, I'm really worried about you.'"
Dietary carbohydrates could lead to osteoarthritis, new study finds
Credit: CC0 Public DomainDo your knees ache? According to new findings from the Oklahoma Medical Research Foundation, your diet could be a culprit. In a study led by OMRF scientist Tim Griffin, Ph.D., researchers found that the carbohydrate composition of diets increased the risk of osteoarthritis in laboratory mice—even when the animals didn't differ in weight.
11 aug 2018--"We know increased body fat elevates risk, but we haven't appreciated as much how diet itself affects the disease risk," said Griffin. "These findings give us new clues that there can be significant dietary effects linked to increased OA risk even in the absence of obesity."
Osteoarthritis, or OA, is the most common form of arthritis and the most widespread form of disability in the country, affecting nearly 27 million people in the U.S. It occurs when the cartilage that cushions bones in the joints breaks down and wears away, causing the bones to rub against one another.
Several factors can increase risk, including high-impact physical jobs, previous joint injuries, age and genetics, but carrying extra body weight is among the most proven contributors.
"Obesity is the one of the most significant factors for developing disease in the knee joint," said Griffin. "However, therapeutic strategies to prevent or treat obesity-associated OA are limited because of the uncertainly about the root cause of the disease."
To study how, exactly, obesity contributes to osteoarthritis, Griffin and his lab placed groups of mice on different high-fat diets. However, over time, they observed that the carbohydrate makeup of the rodents' low-fat control diet was alone sufficient to alter their chances of developing OA.
The primary culprits: fiber and sugar.
In particular, Griffin's team found that changing the amount of sucrose—table sugar—and fiber in the diet altered OA pathology in the rodents. The high-sucrose diet increased signs of joint inflammation, while the high-fiber diet caused changes in cartilage genes and cellular stress-response pathways.
While the study involved mice, Griffin said the findings could ultimately have human implications.
"It's important to understand how our diet affects the health of our joints," he said. "We were surprised to see so many OA-related differences between the two high-carb diets even though body weight and body fat were the same."
Griffin next plans to investigate how different types of dietary fiber and other components of our diets can contribute to OA, and also look at the role the body's microbiome and gut bacteria play in the disease.
More information: Elise L. Donovan et al, Independent effects of dietary fat and sucrose content on chondrocyte metabolism and osteoarthritis pathology in mice, Disease Models & Mechanisms (2018). DOI: 10.1242/dmm.034827
Provided by Oklahoma Medical Research Foundation
Thursday, August 09, 2018
Most antipsychotics prescribed in nursing homes initiated there
Antipsychotic therapy prescribed to nursing home residents is mostly initiated in nursing homes rather than hospitals or outpatient settings, according to a study published in the June issue of the Journal of the American Geriatrics Society.
09 aug 2018--Yan Zhang, from the University of Iowa in Iowa City, and colleagues used a linked dataset of Chronic Condition Data Warehouse Medicare claims and Long-Term Care Minimum Data Set (MDS) 3.0 to determine care settings of antipsychotic initiations among 7,496 fee-for-service Medicare beneficiaries who had nursing home stays between Jan. 1, 2011, and Dec. 31, 2014.
The researchers found that 64 percent of study participants had new antipsychotic use initiated in nursing homes, 18.6 percent had initiation in hospitals, and 17.5 percent had initiation in outpatient settings. Antipsychotics were often prescribed early in nursing home stays, with 40.4 percent of the entire sample receiving antipsychotic therapy within the first seven days of nursing home admission. Just over half of antipsychotic initiations (58 percent) were potentially appropriate based on indications captured in MDS records.
"Most residents initiated antipsychotic therapy in nursing homes, confirming that nursing home providers are [an] appropriate primary target of interventions to reduce antipsychotic initiation in their residents," the authors write. "Many antipsychotics were continued from other settings, indicating a need to evaluate the necessity of continued antipsychotic treatment after such transitions of care."
In microscopic images of muscle tissue from normal fruit flies (left), fluorescent tags reveal uniform levels of the structural protein actin (blue) and almost no poly-UB, a protein aggregate that is broken apart and recycled by healthy cells. In muscle tissue from flies lacking HSP gene activity (right), actin levels are reduced and cells contain a toxic buildup of poly-UB. Credit: James McNew/Rice UniversityJames McNew's and Michael Stern's biochemical hunt for the root cause of a rare, paralyzing genetic disorder is a 10-year quest that's taken an unexpected turn toward everyday killers such as Alzheimer's disease, cancer and aging.
05 aug 2018--The National Institutes of Health has awarded the Rice University scientists a five-year R01 grant to investigate a biochemical domino effect that begins with a critical regulatory protein called TOR and ends with cells dying of oxidative stress. TOR regulates cell growth and survival and only recently became a focus for Stern and McNew, professors of biochemistry and cell biology in Rice's Department of BioSciences and co-investigators on the $1.9 million grant from the NIH's National Institute of Neurological Disorders and Stroke.
"It's known that TOR controls starvation in virtually every animal, including humans," McNew said. "Decreased TOR activity has even been found to increase the life span of yeast, worms and fruit flies, and some studies have found that TOR-inhibiting drugs increase the life span of mice. Increased TOR activity is also involved in cancer and has been implicated in Alzheimer's, Parkinson's and other neurodegenerative diseases, including one called hereditary spastic paraplegia (HSP) that we have studied for many years."
HSP, a rare disorder that affects about 20,000 people in the U.S., is marked by numbness and weakness in the legs and feet due to progressive deterioration of the longest cells in the body—the neurons that connect the spine to the lower legs.
In 2016 Stern, McNew and colleagues used hundreds of experiments on dozens of mutant strains of fruit flies to show how an HSP gene produced defective synapses at the junctions between nerve and muscle cells. In follow-up work last year, McNew, Stern and postdoctoral researcher Shiyu Xu conducted more experiments to see exactly how these synapse defects caused neurons to malfunction and die.
"Shiyu wasn't able to find any evidence of neurodegeneration, but he did find evidence of muscle degeneration," Stern said. "That was a surprise, and we didn't know what to make of it at first. Even though nerve damage is a known cause of muscle atrophy, conventional wisdom is that the nerve cells die first."
Intrigued, the group conducted experiments to see what was happening at the molecular level. Tests suggested elevated TOR activity in the degenerating muscle cells. TOR is short for "target of rapamycin"; when TOR was discovered in the early 1990s, researchers only knew it was the target of a natural compound called rapamycin, an immunosuppressant that had been widely prescribed for decades to transplant recipients.
"We were convinced it was TOR after Shiyu showed he could slow down the muscle degeneration by giving the flies rapamycin," Stern said.
At a healthy synapse (top), neuron-muscle communication (thick green arrow) prevents TOR activation in muscle, permitting repair of cellular structures and muscle survival. Synapse defects (bottom) from HSP mutations and other neuronal disorders disrupt this communication (thin green arrow), which activates TOR protein in the muscle, allowing junk proteins to build up and cause muscle degeneration and ultimately death. Credit: James McNew/Rice UniversityTOR is an important master regulator of growth and nutrient-sensing. When fully activated, TOR promotes growth so aggressively that cells forgo daily chores such as repairing structural damage and recycling partially functional organelles. In times of extreme stress or starvation, TOR is fully deactivated so the cell can enter a survival mode and conserve scarce resources.
"TOR isn't an on-off switch as much as a knob for dialing growth up or down," McNew said. "It's not that high TOR is bad and low TOR is good. Each is needed under certain conditions, and TOR's function—which is essential in all higher-order life, from yeast to humans—is to modulate growth to match the conditions it's detecting."
Stern said, "What appears to be happening in the muscle cells that aren't receiving neuronal signals is that the knob gets switched onto high and stays there. TOR locks the cells into this aggressive, pro-growth mode and they stop cleaning up all of the reactive oxygen species, or free radicals, which gradually build up and cause such high levels of stress that the cell dies."
Stern said this hypothesis jibes with observations from numerous other studies that have found high TOR levels and high levels of oxidative stress in the brain cells of patients with Alzheimer's as well as the atrophied muscles of patients who are paralyzed or bedridden.
"In muscle atrophy studies in mice, where the motor neuron is cut, they've found that TOR is activated," he said. "This might be mechanistically similar to our case or to what's been seen in Alzheimer's because people have also found activation of the stress pathway that's induced by reactive oxygen species."
Stern said previous studies also have identified some of the molecular players involved in the degeneration domino effect—including two proteins known as the JNK kinase and the FOXO transcription factor—but he and McNew are the first to connect the dots between TOR and the stress-pathway proteins.
"We also see FOXO activation in our degeneration model, but we know—or at least we think we know—what is activating FOXO," Stern said. "We hypothesize that TOR causes a buildup of reactive oxygen species that in turn activates a molecule called JNK, which activates FOXO."
McNew said focusing on the damage from overactive TOR means that any clues he and Stern find could potentially apply to any disease or condition in which TOR activation is implicated.
"The things that cause TOR to get turned on in a neuron are probably very different than those that turn it on in a liver cell or a white blood cell," he said. "We're focused on the downstream part because once you get TOR turned on, we think it does a handful of things we understand and can directly test. And those are likely to be uniform across different cell types and different conditions. That means anything we find could inform not only HSP pathology but also cancer and neurodegenerative diseases like Alzheimer's and Parkinson's."
Provided by Rice University
Friday, August 03, 2018
World experts target guidance on managing dementia symptoms
Credit: CC0 Public DomainNew research which brings together the views of the world's leading experts has concluded that non-drug approaches should be prioritised in treating agitation in people with Alzheimer's disease.
03 aug 2018--The research, published in International Psychogeriatrics and led by the University of Michigan, the University of Exeter and John Hopkins University, provided more specific guidance on the management of behavioural and psychological symptoms in people with Alzheimer's disease.
It gives the most specific and targeted treatment for psychosis and agitation. Both symptoms are common in dementia and have a significant impact on individuals, families and carers.
The International Delphi Consensus paper incorporates views of a panel of experts from across the globe, who have both clinical and research expertise. Undertaken as an International Psychogeriatric Association taskforce, it brought together the latest evidence on how best to treat symptoms such as psychosis and agitation, to help get the best treatment for the 40 million people with dementia worldwide.
By ranking available treatments in order of the quality of evidence, the paper provides guidance on the order in which clinicians should prioritize treatments.
For treating agitation in people with dementia, the first four highly ranked treatments were all non-pharmacological approaches. Assessment and management or underlying causes, educating caregivers, adapting environment, person-centred care and a tailored activity programme all ranked more highly than any of the pharmacological treatments. The highest ranked pharmacological treatment was the antidepressant citalopram, which came in at number six.
Of note, of the currently used atypical antipsychotic drugs only risperidone reached consensus as a recommended treatment, at number 7 in the list.
Helen C. Kales, MD, director of the program for positive aging at the University of Michigan and research investigator at the VA Center for Clinical Management Research noted: "This research advocates a significant shift from current practice, recommending that non-pharmacological treatments are a first-line approach for agitation in dementia. Aside from risperidone at number 7 in the list, none of the other atypical antipsychotic drugs were recommended. This is a very welcome change, given the known harms associated with these treatments."
For the treatment of psychosis in people with dementia, including symptoms such as hallucinations and delusions, the panel advocated a thorough assessment and management of underlying causes as the first approach. The atypical antipsychotic risperidone came second, as the only pharmacological treatment with any supporting evidence that it works. This highlights a particular gap in the treatment of psychosis in people with dementia, which is a distressing and disabling symptom, and emphasizes tis as a priority area for further research.
Overall, the DICE (describe, investigate, create and evaluate) therapy approach, which involves identifying triggers, and using music were both found to be effective in managing symptoms without prescribing drugs.
Clive Ballard, Professor of Age-Related Diseases at the University of Exeter Medical School, said: "Symptoms such as psychosis and agitation can be particularly distressing and challenging for people with dementia, their carers and their families. Many commonly prescribed medications can cause harm, in some cases significantly increasing risk of stroke or death. We now know that non-drug approaches are the best starting points and can prove effective. This research provides more specific and targeted guidance to support clinicians to give the best possible treatment options."
Provided by University of Exeter
Wednesday, August 01, 2018
Drugs for heart failure are still under-prescribed, years after initial study
Credit: CC0 Public DomainA UCLA-led study found that many people with heart failure do not receive the medications recommended for them under guidelines set by the American College of Cardiology, American Heart Association and Heart Failure Society of America.
01 aug 2018--The research also found that doctors frequently prescribe medications at doses lower than those recommended by the guidelines, especially for older people, those with kidney disease, those with worsening symptoms or those who were recently hospitalized for heart failure. Further study is needed to determine why people in those four groups specifically were prescribed lower-than-recommended doses.
The study, which looked at the three categories of heart failure medications, found that between 27 percent and 67 percent of patients were not prescribed the recommended drugs. And when patients did receive the medications, they were generally at a lower-than-recommended dose. Less than 25 percent of patients simultaneously received all three medication types, and only 1 percent received the target doses of all three medication types.
About 5.7 million people in the United States have heart failure, according to a 2016 report by the American Heart Association. Heart failure is associated with a lower quality of life and frequent hospitalizations, and it contributes to more than 300,000 deaths each year in the U.S. In half of people with heart failure, the disease is caused by a weak heart muscle that prevents the heart from ejecting a normal amount of blood with each heartbeat, a condition called reduced ejection fraction.
Several medications have been proven in large clinical trials to help people with heart failure and reduced ejection fraction live longer and feel better. Research conducted between 2007 and 2009 showed that many patients were not receiving the recommended doses of these medications. The new study sought to determine if there have been improvements in prescribing practice as well as which patients are most likely to receive less medication than recommended.
The study included 3,518 patients from 150 primary care and cardiology practices who were enrolled in the Change the Management of Patients with Heart Failure registry, or CHAMP-HF, a study of adult outpatients who were diagnosed with heart failure with reduced ejection fraction.
The results suggest that use and dosing of heart failure medications has not improved over the past decade. The report says new strategies are needed to more effectively achieve and maintain recommended doses of heart failure medications and that there is a substantial opportunity to improve dosing of heart failure medications, which would improve the care and outcomes for people with heart failure.
The study appears in the July 24 issue of the Journal of the American College of Cardiology.
More information: Stephen J. Greene et al, Medical Therapy for Heart Failure With Reduced Ejection Fraction, Journal of the American College of Cardiology (2018). DOI: 10.1016/j.jacc.2018.04.070
