June 16, 2017
Women with breast cancer have long faced complicated choices about the best course of treatment. One particular concern has been the daily radiation therapy many women with breast cancer receive for six weeks after surgery. This form of therapy, also known as conventionally fractionated external beam radiation, has generally been recommended for most women undergoing breast conservation therapy. The goal has been to rid the body of any remaining cancerous cells that the surgeon’s tools could not remove. Radiation, however, can be time-consuming and expensive for the patient and society. It also carries a small risk for late complications, such as heart disease. New therapies have been tested that would shorten the length of radiotherapy from six weeks to three weeks, or deliver a single dose at the time of the lumpectomy procedure in the operating room. A shorter course of radiation means more convenience, perhaps, fewer side effects and fewer out-of-pocket expenses. And a single dose of radiation is much cheaper than whole breast radiation therapy delivered over multiple weeks, but is associated with a slightly higher risk of local recurrence. So which option should patients and physicians choose? In our recently published paper in the Journal of the National Cancer Institute, we came up with what we think is an answer. We showed through computer modeling that there is a better way for women – and one that can save our health care system nearly US$100 million every year. Problem and possible solutions For decades, breast cancer was considered such a formidable foe that doctors who treated it and women who had it wanted to use everything in their arsenal to fight it. That included the radical Halsted mastectomy, which often took out chest muscles along with the breast and left women disfigured. A woman’s chest a year after a double mastectomy. Flaxphotos/From www.shutterstock.com It also included lengthy radiation treatments, sometimes for as long as seven weeks (known as conventionally fractionated radiation), given every day Monday through Friday after surgery. This form of radiation comes at great cost to women and causes hardships for those who live far away from radiation clinics. In recent years, doctors studied new therapies for breast cancer. Halsted radical mastectomy has been replaced with a lumpectomy procedure that is usually performed on an outpatient basis. The radiation course has been shortened and is now delivered using sophisticated equipment, sparing unnecessary dose to the heart and lungs. The better equipment also began to allow researchers to look at ways to shorten treatment. Hypofractionated radiation, in which a portion of the breast is treated for a shorter time, was one result. Alternative therapies to conventional and hypofractionated radiation have also been recently introduced to deliver a single dose of radiation just to the tumor bed at the time of surgery. This is known is intraoperative radiotherapy, or IORT, meaning performed during the course of a surgical operation. Given the availability of choices with overlapping costs and outcomes, clinicians always face a dilemma: Which treatment is best for my patient? Likewise, patients can ask their clinicians, “What’s best for me?” And, if both treatments are equally effective, is there a difference in price that might guide decisions? Multiple randomized trials have shown that a 3- to 4-week course of whole breast radiation therapy is equivalent to a 6- to 8-week course. In fact, the National Comprehensive Cancer Network (NCCN) guidelines endorse the short hypofractionated course as the preferred approach. Despite all this, American doctors have not widely adopted the new strategy. The reasons for this are varied, including dissemination of new findings to private practitioners and financial incentives of treating with a longer course. Our current fee-for-service reimbursement structure pays more for the longer treatment, which may be a factor in the surprisingly slow adoption of the convenient hypofractionated whole breast radiotherapy approach. What might be adding more to this dilemma? Clinical trials have compared these treatment choices with one another. Several large randomized trials have compared a 6-week course to a 3- to 4-week course of whole breast treatment and found that the two treatment approaches are equivalent in terms of cancer control. In fact, one trial found that the shorter course of treatment yielded lower rates of acute toxic effects compared to the longer course. Several randomized trials have compared conventionally fractionated radiation therapy to a single fraction intraoperative treatment just to the tumor bed at the time of surgery. Although extremely convenient, IORT was slightly worse at controlling cancer recurrence. Yet, no single clinical trial has compared all three available options head-to-head. Another dilemma is that clinical trials usually follow patients for a period of five to 10 years, not a lifetime. That left an important question unanswered: How do we know which treatment is most beneficial over patient lifetime, and at what cost? Our study To solve this conundrum, we used computer modeling along with a cost-effectiveness analysis. In our study, our interdisciplinary team tried to identify the most optimal radiation therapy – that is, one that provides maximum value for money – for women diagnosed with early stage breast cancer. We simulated (created in computer) a hypothetical population of women diagnosed with early stage breast cancer. As per standard of care guidelines, women first get surgical treatment (lumpectomy). Now comes the uncertainty! These hypothetical women can get either conventional whole breast radiation, hypofractionated radiation or one-time intraoperative radiation. We obtained data from several clinical trials and databases to define treatment effectiveness and side effects, improvement or deterioration in quality of life, inconvenience (measures in term of travel time, lost wages, travel cost) and future consequences, including a possibility of cancer coming back or spreading to other organs. In our simulation, we then followed these hypothetical women over their lifetime to identify which treatment strategy is most valuable, or cost-effective. After extensive validation, we found that hypofractionated radiation is the most valuable treatment almost under all scenarios. It not only improves quality of life without compromising survival (adds four additional months of life with improved quality of health) but it also saves nearly $3,500 per patient. We also learned that IORT, or radiation treatment at the time of operation, may be appropriate for older women who live far from radiation facilities and would have to endure hardship when traveling for daily whole breast radiation for three to four weeks. Win-win for all! Our society saves health care dollars, and patients benefit most from treatment. Key takeaways Our analysis showed that conventionally fractionated radiation, in which women receive the radiation over six weeks, is not cost-effective under any scenario and should not be considered as a choice by physicians or patients. Our study is the first to evaluate this using the latest available data. A single dose of intraoperative radiation therapy, despite being much more convenient and less expensive, is associated with higher cancer recurrence rates. This difference in the risk of recurrence ends up costing the patient and society more than the hypofractionated treatment over a patient’s lifetime. Intraoperative radiation might be an option for older women who live in regions with poor access to health services. The shorter hypofractionated course is less expensive and improves quality of life substantially! With growing health care costs and an aging population, we are starting to focus more and more on identifying treatments that are less expensive and equally effective. We found that the use of the optimal strategy in this situation has the potential to improve health outcomes and save at least $100 million every year. This article was originally published on The Conversation. Read the original article.
June 16, 2017
Tourette syndrome is a mysterious medical curiosity that has puzzled doctors for more than a century. People who have it suffer from tics and other behavioral problems, such as obsessive compulsive traits and attention deficit disorder. In addition, they are cursed by a stereotype that they swear loudly and inappropriately. In reality, 10 percent actually experience these verbal outbursts, but many are stigmatized and isolated nonetheless. I have studied Tourette syndrome for years, and recently published a book about treatments and the common spectrum of behavioral disorders associated with it. Swearing isn’t even one of the more frequent ones. The fact is that over the last several years, many exciting and life-altering treatments have become available to Tourette patients and their families. We have reached a crossroads in this disease where it will become increasingly critical to reeducate the public and to make new therapies widely available. Twitches and tics French scientist Jean-Martin Charcot, the founder of modern clinical neurology, coined the eponym “Tourette syndrome” after his student, Georges Albert Gilles de la Tourette, who in 1885 described nine patients suffering from the tic “malady.” Jean-Martin Charcot, considered the founder of neurology. From wikimedia.com Researchers soon noticed that Tourette occurred among multiple family members across multiple generations. Over the generations, however, new knowledge came slowly. Critical gaps in our understanding of the syndrome remain, and half of all cases remain undiagnosed. Even the precise number of people affected has been hard to know. For example, the Centers for Disease Control and Prevention (CDC) estimates that one in 362 children, or 0.3 percent, has Tourette. The Tourette Association of America, on the other hand, estimates the disease is twice as common, with one in 166 kids (0.6 percent) affected. Some Tourette syndrome cases are mild, with symptoms such as nonbothersome eye blinking, or mild body twitching. In many cases, the motor tics will resolve in late adolescence or early adulthood. Many patients will even lead relatively normal lives. Lessons from the brain yield advances Knowledge of the syndrome has increased as scientists have learned more in general about the brain. The normal functions of the human brain seem to be dictated by rhythmic oscillations that continuously repeat over and over, much like a popular song on the radio. These oscillations change and modulate, and they act to control various human behaviors. If an oscillation “goes bad,” it can result in a disabling tic or other behavioral symptoms of Tourette syndrome. An important secret to the development of new therapies for Tourette is that we can alter these oscillations with rehabilitative therapies, cognitive behavioral intervention therapy (CBIT), medications such as tetrabenazine or even deep brain stimulation, which involves a small straw-like probe being inserted into the brain. Electricity can be delivered through this probe to disrupt the abnormal oscillations responsible for tics. Continued study also helping The genetics of Tourette remain opaque. Despite the fact that the disease tends to run in families, no one has discovered a single DNA abnormality linking all, or even most, cases. In the meantime, however, technology is offering new means of detection and treatment. Scientists have recorded tic signals from the human brain and even deployed the first smart devices to detect and suppress tics. Some investigators are studying newer generations of medicines that decrease the complications that can occur with old-fashioned drugs, such as Haloperidol, that have traditionally been used to treat Tourette. Scientists are also looking for way to suppress or modulate inappropriate brain signals, spurring development of new drugs with novel brain targets, such as cannabinoid receptors. Using marijuana to treat the symptoms of Tourette syndrome makes some scientific sense. Cannabinoids occur naturally in the body, and cannabinoid receptors are found throughout many brain regions. In fact, CB1 cannabinoid receptors are located in high concentrations in regions of the brain thought to be involved in Tourette syndrome. Living with Tourette syndrome While it may appear to the casual observer that someone with Tourette syndrome outgrows it in adolescence or early adulthood, in fact most do not. While the motor and vocal tics wane in most cases, the obsessive-compulsive and behavioral features may persist and even escalate. These behavioral features in Tourette syndrome, if left undiagnosed and untreated, will make it harder to live a normal life and will affect the person more than the noticeable motor and vocal tics. While new treatments may lie in the future, there are many things that patients and their families can do today. Many changes, often very simple, can be incorporated into patients’ lives. Comprehensive care teams from different disciplines play a key role. For example, a social worker can help to set up an individualized school education plan and connect families to resources that can transform difficult school situations into success stories. A rehabilitative therapist can now in many cases successfully address tics without the use of a single medication. Children and teens celebrate at the end of a week of camp at Twitch and Shout in Winder, Georgia in 2014. Building relationships with others who have Tourette syndrome is believed to be beneficial for young people. David Goldman/AP Our care team has taken care of close to 10,000 movement disorder patients at the University of Florida and tens of thousands more with our colleagues in the Southeast Regional Tourette Association of America Center of Excellence, which also includes neurologists, psychiatrists, rehabilitative specialists, social workers and scientists at the University of South Florida, Emory University, University of Alabama and the University of South Carolina. There are good reasons to try different treatments, even if none seems to work. Patients need to learn how to recognize when a plan or therapy isn’t working and how to speak with their doctors and care team about trying something else. The point is that left unchecked, brain vibrations can, in some Tourette cases, lead to neck-snapping tics which can cause injuries, even paralysis. Today even the most severe cases have a chance for treatment with deep brain stimulation. Though Tourette syndrome remains mysterious in the public eye, it is important that we teach families about the broad palette of options that provide tangible benefits for quality of life. That is definitely something worth shouting about. This article was originally published on The Conversation. Read the original article.
June 14, 2017
People who first became intoxicated as young teens have a greater risk of dying prematurely than those who first became drunk later in adolescence or not at all, according to a study led by University of Florida researchers. The findings appear online ahead of print in the journal Drug and Alcohol Dependence. “Although the causes remain uncertain and future studies are warranted, findings from this study suggest that early drunkenness is a strong predictor for premature mortality and can be used to identify high-risk populations for interventions,” said Hui Hu, Ph.D., the study’s lead author and a research assistant scientist in the department of epidemiology at the UF College of Public Health and Health Professions and the UF College of Medicine, both part of UF Health. Chronic alcohol misuse is associated with several health issues, including injuries, cardiovascular disease and cancer, as well as higher mortality rates. For the new study, researchers wanted to examine if becoming drunk at an early age might be associated with a higher risk of premature death later in life. Researchers used data collected from the National Institute of Mental Health Epidemiologic Catchment Area Survey, a large multisite study conducted in the early 1980s to understand the prevalence of adult mental health disorders. UF researchers linked those study participants to National Death Index records through 2007. Of the nearly 15,000 participants who answered questions about drinking in the original study, nearly 7,000 had died by the end of 2007. Eight percent of study participants reported first becoming intoxicated before the age of 15. Researchers found they were 23 percent more likely to die prematurely than those who reported first getting drunk at or after the age of 15, and 47 percent more likely to die prematurely than people who said they had never been drunk. While more research is needed to understand why people who get drunk for the first time in early adolescence may be at risk for dying prematurely, there are several possible contributing factors, Hu said. “People with early onset of drunkenness are more likely to develop alcohol use disorder, more likely to engage in other alcohol-related health behaviors such as smoking, fighting, unplanned and unprotected sex, and more likely to have low academic performance,” he said. The researchers were surprised to find early drunkenness was associated with premature mortality regardless of whether participants had alcohol use disorder at the time of the survey, suggesting there may be many factors at play. The UF researchers plan to explore the possible factors in future studies with the goal of informing interventions designed to decrease alcohol use among adolescents, Hu said. The Epidemiologic Catchment Area Survey is a unique study that is still providing researchers with valuable information 37 years after it was first conducted, said Linda B. Cottler, Ph.D., M.P.H., FACE, chair of the UF department of epidemiology, the senior author of the new study and coordinator of one of the five sites of the Epidemiologic Catchment Area Survey team in the 1980s. As new longitudinal studies are developed, it is important that researchers be thoughtful in the design of the questions, she said. “In epidemiology we design studies for life and questions that will stand the test of time,” said Cottler, PHHP’s associate dean for research and planning. In addition to Hu and Cottler, the study team included William W. Eaton, Ph.D., of The Johns Hopkins University, and James C. Anthony, Ph.D., of Michigan State University, who have both been involved in the Epidemiologic Catchment Area Survey since the beginning of the study, and Li-Tzy Wu, D.Sc., of Duke University Medical Center. The study was supported by funding from the National Institute on Drug Abuse.
June 6, 2017
Parents are often reminded to keep harmful substances out of their child’s reach. But what if a child’s experiences at home were as toxic to their health as household solvents and cleaners? On a basic level, toxins are poisonous substances that lead to disease. Although not stored in a bottle or on a shelf, stress in childhood meets the criteria. The phrase “toxic stress” describes the body’s reaction to negative experiences that are not only intense and chronic but also caused by the absence of safe, stable and nurturing adult relationships. Toxic stress “gets under our skin” to change the way we respond to our environment and can lead to disease and disability across the lifespan. My research at the University of Florida focuses on stressful experiences during childhood and how these experiences relate to a child’s health. We’re making progress in uncovering which health conditions are related to childhood stress and how we can prevent this stress. What stress does to the body When you are in a stressful situation, your brain prepares your body for one of three general responses: fight, flee or freeze. If you are attacked, for example, your body slows down processes that are not as important in that moment – like digestion – and speeds up processes that are important – like blood flow to muscles – so that you can either escape or defend yourself. When the crisis is over, your body goes back to its normal state. This ability to respond to and recover from stressful events is important for survival. When a child experiences toxic stress, however, that child loses the ability to respond and recover appropriately. If a child lives in a household that uses violence to solve problems, for example, then his or her brain might regularly prepare his or her bodies to fight or flee. This situation gives a body very little time to recover and reset. This repeated response to stress also changes the way a body reacts to future events. Some people who experience repeated stress become hyper-reactive, which might look like a quickness to react to situations and slowness to calm down. Others become hypo-reactive, which might look like a lack of awareness to situations that necessitate a response. Hypo-reactive individuals may fail to identify danger and become at risk for falling victim again. The effects of toxic stress are also seen “under the skin.” Experiencing repeated stress lowers our immune system and makes us more susceptible to illnesses, from the common cold to diabetes to asthma. Children with higher numbers of adverse childhood events are at higher risk of illness, ranging from the common cold to more serious diseases, such as asthma. Mastaco/Shutterstock Adverse childhood experiences, also called ACEs, can cause toxic stress. Most researchers focus on a dozen or so adverse experiences: physical abuse and neglect, emotional abuse and neglect, sexual abuse, caregiver separation or divorce, caregiver mental illness, caregiver substance use, caregiver incarceration and domestic violence. Click here to see your ACE score. In the first study of ACEs in the 1990s, researchers found that adults who reported experiencing three or more ACEs were more likely to have two of the top three causes of death of adults in the U.S.: heart disease and chronic obstructive pulmonary disease (e.g., emphysema or chronic bronchitis). Experiencing three or more ACEs was also associated with substance use, depression, liver disease, multiple sexual partners, sexually transmitted infections, unintended pregnancy, suicide attempt and even early death. Effects on the developing childhood brain Early childhood is a time for significant brain development. Given that brain development is affected by our environment, toxic stress during this time can be particularly problematic. In a recent study by my team, we examined adverse childhood experiences and health in a national survey of children aged 0-17 years. We included experiences like emotional abuse, financial struggles, caregiver divorce or separation, domestic violence, neighborhood violence and caregiver mental illness. We focused on how these experiences related to not just physical health (e.g., vision and hearing problems, asthma) but also mental health (depression, anxiety) and developmental outcomes like learning and intellectual disability in childhood. We found that experiencing three or more of these adverse experiences was associated with a two- to five-fold increase in the likelihood of having at least one condition in each of the three health categories above. Adverse experiences weren’t just associated with increased likelihood of having one condition. Experiencing multiple forms of adversity was also associated with increased likelihood of having at least one condition in two categories. Most alarming was that having three or more adverse experiences was associated with nearly a six-fold increase in the likelihood of having at least one physical, at least one mental and at least one developmental condition. These startling findings tell us two things about childhood adversity. First, negative health effects are seen before adulthood, and, second, they affect multiple domains of health and development simultaneously. This means that the effects of childhood adversity and toxic stress can be seen in the pediatrician’s clinic, the psychologist’s office and the teacher’s classroom. Kids with high numbers of adverse events often have problems at school. Lana Vardoome Poison control A critical component to toxic stress is that it occurs only in the absence of safe, stable and nurturing adult relationships. If children experience stress but also have a warm, loving adult to support them, then that child will be able to respond to and recover from even the most difficult of circumstances. Conversations around child safety need to extend beyond helmets and cleaning substances to include toxic stress and its causes. Parents need to be armed with strategies for creating safe, stable and nurturing relationships with their children. Building these relationships can reduce childhood adversity, toxic stress, and subsequent disease and disability. This article was originally published May 30, 2017 on The Conversation. Read the original article.
June 6, 2017
For decades, aspirin has been widely used to reduce the risk of cardiovascular problems. Now, a team led by a University of Florida Health researcher has found that aspirin may provide little or no benefit for certain patients who have plaque buildup in their arteries. Aspirin is effective in treating strokes and heart attacks by reducing blood clots. The researchers tracked the health histories of over 33,000 patients with atherosclerosis — narrowed, hardened arteries — and determined that aspirin is marginally beneficial for those who have had a previous heart attack, stroke or other blood-flow issues involving arteries. However, among atherosclerosis patients with no prior heart attack or stroke, aspirin had no apparent benefit. The findings were published May 18 in the journal Clinical Cardiology. Because the findings are observational, further study that includes clinical trials are needed before definitively declaring that aspirin has little or no effect on certain atherosclerosis patients, said Anthony Bavry, M.D., an associate professor in the UF College of Medicine’s department of medicine and a cardiologist at the Malcom Randall Veterans Affairs Medical Center in Gainesville. “Aspirin therapy is widely used and embraced by cardiologists and general practitioners around the world. This takes a bit of the luster off the use of aspirin,” Bavry said. Bavry said the findings do not undercut aspirin’s vital role in more immediate situations: If a heart attack or stroke is underway or suspected, patients should still take aspirin as a treatment measure. “The benefit of aspirin is still maintained in acute events like a heart attack or a stroke,” he said. Among more than 21,000 patients who had a previous heart attack or stroke, researchers found that the risk of subsequent cardiovascular death, heart attack or stroke was marginally lower among aspirin users. For those atherosclerosis patients who had not experienced a heart attack or stroke, aspirin appeared to have no effect. The risk of cardiovascular death, heart attack and stroke was 10.7 percent among aspirin users and 10.5 percent for non-users. Patients who enrolled in the nationwide study were at least 45 years old with coronary artery disease, cerebrovascular disease or peripheral vascular disease. Their medical data were collected between late 2003 and mid-2009. The researchers did identify one group that got some benefit from aspirin — people who had a coronary bypass or stent but no history of stroke, heart attack or arterial blood-flow condition. Those patients should clearly stay on an aspirin regimen, Bavry said. Bavry said discerning aspirin’s effectiveness for various patients is also important because the medicine can create complications, including gastrointestinal bleeding and, less frequently, bleeding in the brain. Because of insufficient data, the current study wasn’t able to address the extent of aspirin’s role in bleeding cases. “The cardiology community needs to appreciate that aspirin deserves ongoing study. There are many individuals who may not be deriving a benefit from aspirin. If we can identify those patients and spare them from aspirin, we’re doing a good thing,” he said. The current findings are the second time this year that Bavry and his collaborators have published research about the apparent ineffectiveness of aspirin therapy. In April, the group showed that the drug may not provide cardiovascular benefits for people with peripheral vascular disease, which causes narrowed arteries and reduced blood flow to the limbs. Bavry also cautioned patients with atherosclerosis or peripheral vascular disease not to quit aspirin therapy on their own. Instead, they should discuss the matter with their physician, he said. Scientists from France, England and Harvard Medical School collaborated on the research. Patient data were derived from The Reduction of Atherothrombosis for Continued Health registry, which was sponsored by the Waksman Foundation and pharmaceutical companies Sanofi and Bristol-Myers Squibb.
WEEKLY NEWS: June 8, 2017