It May Be Time For Standard Breast Cancer Treatment To Change

Results from a clinical trial show that adding ribociclib, a targeted therapy drug, to the standard treatment plan for women with advanced hormone-receptor positive/HER2- breast cancer helps patients live longer and better quality lives. The researchers involved now believe the drug should be the first line of treatment for patients with this very common form of breast cancer.

Results from the Phase III clinical trial were presented at the 2019 European Society for Medical Oncology (ESMO) Congress 2019 last weekend. The trial involved 726 postmenopausal women with advanced hormone-receptor positive HER2-breast cancer who had not recieved endocrine therapy in the past, and aimed to see if the treatment could effectively increase lifespan.
Results showed that women who received the drug experienced significant improvement in survival. For example, there was a 28 percent reduction in risk of death in women who received ribociclib in combination with their standard therapy, when compared to those who were only treated with the standard hormone therapy.
The most commonly reported side effects experienced with this drug included low blood count, nausea and vomiting, fatigue, diarrhea and hair loss.

“Increasing overall survival is the hardest endpoint to move,” said lead researcher  Dr. Dennis Slamon, chair of hematology/oncology and director of Clinical/Translational Research at UCLA’s Jonsson Comprehensive Cancer Center. “We’re also seeing that the time of progression-free survival is the longest yet reported for any of the drugs in this class. And even when patients are off the drug, the effect seems to be long-lasting in terms of the benefit. It’s important because this means we are helping women live longer and have a better quality of life.”

Radiology service in a hospital in Haute-Savoie, France. A doctor interprets a mammogram. (Photo by: BSIP/Universal Images Group via Getty Images)

Universal Images Group via Getty Images

The majority of breast cancer is hormone receptive, meaning that the tumors will grow in response to estrogen. In the case of advanced hormone-receptor positive HER2-breast cancer, the cancer cells have too much of a growth-promoting protein. This causes the tumors to grow and in turn, spread the cancer throughout the body.
Hormone therapy is the standard treatment for most women with such forms of breast cancer. However, research into targeted therapy suggests that hormonal therapy alone may not be best to achieve the desired results in patients.
Targeted therapy, such as ribociclib, are sometimes used alongside hormone therapy to increase the chance of successful outcomes. Ribociclib is part of a class of CDK4/6 inhibitors. These work by blocking certain hormones in breast cancer cells, which in turn slow down the cancer’s growth and spread. Doctors often prescribe the standard treatment first and then add a targeted therapy later, based on how a patient is responding. However, Slamon argues that these results show there is no need to wait.
“We found there’s a significant difference when you use the combination of ribociclib with hormone therapy as the first line of therapy,” said Slamon. “There is absolutely no reason to wait to give women this treatment. This should be the new standard.”
The most recent study on ribociclib was sponsored by Novartis. The drug will next be involved in an international clinical trial titled NATALEE which will aim to test how effective ribociclib is in treatment women with early-stage breast cancer.
https://www.forbes.com/sites/danadovey/2019/10/03/it-may-be-time-for-standard-breast-cancer-treatment-to-change/#7c74e58d3aa7

Strong September healthcare hiring behind historically low jobless rate

Strong healthcare hiring helped push the overall unemployment rate to a historic low in September.

Healthcare added 38,800 jobs last month, making up nearly 30% of overall hiring and contributing to a lower, 3.5% unemployment rate. The U.S. unemployment rate hasn’t been this low since December 1969, according to preliminary data from the U.S. Bureau of Labor Statistics‘ September jobs report, released Friday.

September’s healthcare hiring was up slightly from August’s revised count of 37,200 jobs added, which was a significant revision from the preliminary estimate of 23,900 jobs added in August.

As usual, ambulatory hiring dominated the healthcare industry, making up about three-quarters of jobs added, or 28,700 new hires. Preliminary data indicated the ambulatory sector had made 12,100 new hires in August, which would have been down significantly from July. However, the actual number is likely much higher, given the agency’s revised total.

September was another strong month for hospitals, which added 8,100 jobs. That’s down from 8,800 new hires in August, according to the government’s preliminary data.

Within the ambulatory sector, physicians’ offices made 5,200 new hires in September, up 174% from August’s preliminary hiring total. Dentists’ offices made 900 new hires last month, down 44% from August’s preliminary count.

Home health added 5,700 new jobs in September, down 16% from August. September’s preliminary numbers show a strong upswing in offices of other health practitioners, which added 9,500 jobs last month. That’s after shedding 1,200 jobs in August, per the bureau’s preliminary estimate.

Hiring was weak in the nursing and residential care sector, adding just 2,000 jobs. Community care facilities for the elderly shed 300 jobs last month, and residential mental health facilities shed 100 jobs. Nursing care facilities added 1,100 jobs.

An analysis by Jefferies concluded healthcare employment remains “remarkably strong” and has grown month-over-month for 68 consecutive months, since February 2014.

“We believe the combination of strong demand growth from healthcare employers and shortages of many clinicians (nurses, physicians) creates a positive set-up for the healthcare temp staffing industry … for Q4 and into 2020,” the authors wrote.

Total non-farm payroll employment rose by 136,000 jobs last month, pushing the unemployment rate down 0.2 percentage point. The number of unemployed declined by 275,000 people last month to 5.8 million.

Employment in professional and business services grew by 34,000 jobs last month, and government employment grew by 22,000 jobs. Transportation and warehousing added 16,000 jobs in September, and retail trade shed 11,000 jobs.

https://www.modernhealthcare.com/healthcare-economics/strong-september-healthcare-hiring-behind-historically-low-unemployment-rate

Deep brain stimulation effective treatment for severest depression

A study published online on Friday, October 4, in the American Journal of Psychiatry found that deep brain stimulation (DBS) of an area in the brain called the subcallosal cingulate (SCC) provides a robust antidepressant effect that is sustained over a long period of time in patients with treatment-resistant depression—the most severely depressed patients who have not responded to other treatments.
The long-term data presented in this study, conducted at Emory University and led by Helen S. Mayberg, MD, now Professor of Neurology, Neurosurgery, Psychiatry, and Neuroscience, and Founding Director of the Nash Family Center for Advanced Circuit Therapeutics at the Icahn School of Medicine at Mount Sinai, validates earlier work conducted by the research team and lays the foundation for additional studies to refine and optimize DBS for these patients.
Deep brain stimulation, currently approved by the U.S. Food and Drug Administration to treat essential tremor, Parkinson’s disease, epilepsy, and obsessive-compulsive disorder, is a neurosurgical procedure involving the placement of a neurostimulator (sometimes referred to as a “brain pacemaker”), which sends high-frequency electrical impulses through implanted electrodes deep in the brain to specific brain areas responsible for the symptoms of each disorder.
Dr. Mayberg led the first trial of DBS of the subcallosal cingulate white matter, known as Brodmann Area 25, for treatment-resistant depression patients in 2005, demonstrating that it could have clinical benefit. Subsequent small open-label trials produced similarly favorable results, yet despite these encouraging open-label results, a multi-center, randomized trial was halted early due to a lack of statistically significant antidepressant response at the designated, six-month a priori time point.
“Despite the fact that larger trials were halted early, what my colleagues and I were seeing as we continued to follow patients from our initial trials was that over time, they were getting better and not only that, they were staying better. So we stayed the course,” says Dr. Mayberg. “Over eight years of observation, most of our study participants experienced an antidepressant response to the deep brain stimulation of Area 25 that was robust and sustained. Given that patients with treatment-resistant depression are highly susceptible to recurrent depressive episodes, the ability of DBS to support long-term maintenance of an antidepressant response and prevention of relapse is a treatment advance that can mean the difference between getting on with your life or always looking over your shoulder for your next debilitating depressive episode.”
Specifically, the study documents the long-term outcome data (4-8 years) for 28 patients who were enrolled in an open-label clinical trial of SCC DBS for treatment-resistant depression. Response and remission rates were maintained at or above 50 percent and 30 percent, respectively, through years 2-8 of the follow-up period. Three-quarters of all participants met the treatment response criterion for more than half of their participation in the study, with 21 percent of all participants demonstrating continuous response to treatment from the first year forward. Of 28 participants, 14 completed at least eight years of follow-up, 11 others completed at least four years, and three dropped out prior to eight years of participation. Data presented through this study support the long-term safety and sustained efficacy of SCC DBS for treatment-resistant depression.
“While clinical trials generally are structured to compare active and placebo treatments over the short term, our research results suggest that the most important strength of DBS in this hard-to-treat clinical population lies in its sustained effects over the long term,” says Andrea Crowell, MD, Assistant Professor of Psychiatry and Behavioral Health Sciences at Emory University School of Medicine. “For people suffering from inescapable depression, the possibility that DBS can lead to significant and sustained improvement in depressive symptoms over several years will be welcome news.”
All study participants met criteria for either major depressive disorder or bipolar disorder type 2 and were in a current depressive episode of at least 12 months duration with non-response to at least four antidepressant treatments, psychotherapy, and electroconvulsive therapy.
All study participants underwent SCC DBS surgery at Emory University School of Medicine with the same surgeon and received the same device. The first 17 participants were implanted between 2007-2009 in an open-label trial with a one-month, single-blind, stimulation-off, lead-in period. An additional 11 participants with major depressive disorder were implanted using tractography-guided anatomical targeting between 2011 and 2013. A total of 178 patient-years of data were collected and combined for analysis in this long-term follow-up study.
Participants were seen by a study psychiatrist weekly for 32 weeks, starting at least four weeks prior to surgery. Visits were then tapered to every six months for years 2-8 of the study. Currently, 23 patients continue in long-term follow-up.
“At the Center for Advanced Circuit Therapeutics at Mount Sinai, we are currently gearing up for the next phase of this research, now funded by the National Institutes of Health Brain Initiative. Our new study will recruit treatment-resistant depression patients, as before, but they will be implanted with a new research prototype DBS system (Summit RC+S) that allows simultaneous recordings of brain activity directly from the site of stimulation during active DBS therapy. Advanced imaging, behavioral, and physiological assessments will also be performed at regular intervals in the lab. These studies will provide an unprecedented opportunity to monitor the trajectory of recovery over days, weeks, and months at the neural level,” says Dr. Mayberg. “Building on preliminary findings from Emory, we anticipate that these brain signatures will provide important new insights into DBS mechanisms and, importantly, will help guide future decisions about DBS management that can further optimize clinical outcomes in our patients.”
https://medicalxpress.com/news/2019-10-long-term-dbs-effective-treatment-severe.html

A Dangerous Diagnosis: New Netflix Series May Do Harm

It was my first day on the complex care service during my clerkship. Not long after introducing myself to the team, I was assigned my first patient. She was in the hospital for the third time that summer with clots in her lungs. I nodded and took notes as she described how doctors had been unsuccessful in identifying a cause of her clots. Then she paused, laughed, and said, “They should put me on one of those medical mystery shows.” The intern pursed her lips and replied, “We’re doing all the same things here.”
Among the most recent of these “medical mystery shows” is Netflix’s Diagnosis, hosted by Lisa Sanders, MD, whose New York Times column with the same name was the inspiration for the award-winning TV series House—a show without which I may not be a medical student today. In each of its seven episodes, Diagnosis follows patients who had undergone an inconclusive or unsatisfactory workup, with respondents across the globe chiming in on each case. Despite the show’s numerous rave reviews, the documentary series runs the risk of negatively influencing the public’s view of the medical system.
At first blush, the show has an extremely effective way of depicting various diseases; as a third-year medical student, I only wish that my preclinical curriculum had more of those 3D models… Sanders is often able to describe complex biological processes in accessible language while combatting things like the misinformation and stigma surrounding functional neurological disorders. As a medical student watching the show, Diagnosis reminds me how important it is to explain and normalize medical conditions in a way that is effective for those who are not in the medical field.
Where Diagnosis becomes problematic, however, is in its portrayal of the inner workings of the medical system. The show claims to garner suggestions from a global audience to arrive at a more accurate diagnosis. By presenting itself as an opportunity for patients with chronic medical conditions to receive a new diagnosis that previous doctors did not suggest, Diagnosis implicitly conveys an image of medical practitioners as incompetent. And yet, according to my research, most cases ultimately arrive at a diagnosis that had been suggested by previous providers (Figure).

Furthermore, by operating under the premise that patients with previously undiagnosed conditions can receive a new diagnosis that might enable treatment, the show may also offer false hope to viewers with incurable medical conditions.
Diagnosis also focuses on a limited range of conditions. Human behavior, function, and consciousness are naturally interesting topics. However, the systems that underlie such conditions are also among the least understood and most limited in treatment options. Diagnosis episodes gravitate towards these less-understood conditions. In focusing on these, the program depicts an image that does not represent what the medical field is typically capable of and neglects the progress that has been made in treating conditions that were previously not understood, undiagnosable, or untreatable.
The major potential harm of Diagnosis is in instilling distrust in the healthcare system. Even as a medical student, I have already seen multiple cases in which a patient’s care was limited by skepticism toward or lack of trust in medicine and medical practitioners. By overlooking prior workups and focusing on cases that are difficult to characterize given the limits of medical knowledge, Diagnosis inherently supports misconceptions of healthcare providers as untrustworthy or potentially lacking in knowledge; this may have broader detrimental effects.
With rising distrust of the medical system, patients have become less likely to seek medical care, adhere to care plans or heed medical advice, and participate in health maintenance interventions such as vaccinations. Fortunately, the show has the opportunity to address these potential pitfalls in future seasons by doing the following:

• Dedicate more time to outlining the previous diagnostic workup, including what tests had been done in the past, why those tests were conducted, and how the results were interpreted. This way, the conclusions of those providers could be better justified, rather than portraying them as poor or inattentive diagnosticians.
• Involve consulting providers more in the show so that they can communicate their thought processes. Although the audience may not immediately understand the content of these discussions, witnessing the degree of knowledge and training involved in the traditional diagnostic process could instill a greater appreciation for and trust in medical providers.
• Incorporate a historical discussion on the diagnoses suggested by the public, including their discovery and characterization and how we now diagnose, define, and understand them in the modern day.
• Highlight conditions treated by a greater range of specialties. In doing so, the public could also learn about a wider variety of diseases and gain greater insight into more of the medical world.

Diagnosis appears to have established itself as a hit among viewers, but given the impact that the media can have on the public’s perception of medicine and the relationships that patients have with their own personal providers, the show may be harmful overall. With a greater emphasis on the diagnostic process and the mechanics of medicine, Diagnosis has an opportunity to simultaneously engage viewers in the medical process while also promoting a positive image of medicine that facilitates more productive conversation between patients and their providers.
Ramie Fathy is a third-year medical student and curriculum representative at the Perelman School of Medicine at the University of Pennsylvania. He is interested in the interaction between medicine, the media, and the public. The opinions expressed in this perspective are his own.
https://www.medscape.com/viewarticle/919202#vp_1

Pupils May Help Identify Alzheimer’s Decades Before Symptoms Appear

There’s an old saying that the eyes are the window to the soul. While that very well may be the case, a new study finds that they may also be a window to the mind and an accurate predictor of the onset of Alzheimer’s disease long before actual symptoms begin to appear.
Researchers from the University of California, San Diego, say that measuring how quickly and drastically a person’s pupil dilates while solving a problem or thinking critically may serve as an accurate, low-cost, and low-invasive way to screen for Alzheimer’s decades before any symptoms appear.
Alzheimer’s disease, a devastating condition that results in cognitive deterioration and memory loss, only reveals itself late in life. However, the condition actually begins taking root and damaging the brain many years before symptoms appear. With this in mind, early detection is key to slowing the disease’s progression. If the research team’s findings about pupil behavior are accurate and reliable, it would represent a major breakthrough in the early detection and treatment of Alzheimer’s among genetically at risk patients all over the world.
Up until now, the majority of researchers studying the early onset and progression of Alzheimer’s have focused on two areas: the build up of a certain type of protein plaques, amyloid-beta, in the brain, and the entanglement of another protein, called tau, in the brain. Both of these proteins have been shown to slowly damage and kill neurons, resulting in a slowly-but-surely progression into cognitive dysfunction, and ultimately Alzheimer’s.
For this study, the research team focused on pupil responses in the eye. Pupillary responses are controlled by a cluster of neurons in the brain stem called the locus coeruleus (LC). Besides just controlling pupil adjustments, the LC also helps regulate arousal and modulate cognitive function. Tau, one of the aforementioned proteins directly linked to cognitive decline, and Alzheimer’s earliest known biomarker, first develops within the LC.

Besides just changing pupil sizes in response to light and other stimulants, the LC also drives pupillary responses (changes in diameter) during cognitive tasks or critical thinking. Generally speaking, pupils get bigger the more difficult the task or question. So, researchers theorized that a buildup of tau in the LC may also influence pupil behavior during a cognitive task.
Furthermore, prior research has already suggested that adults with mild cognitive impairment, often an accurate indicator of Alzheimer’s development later on in life, exhibited greater pupil dilation and cognitive effort while performing a task compared to cognitively normal individuals. This was true even when both groups produced generally the same results in reference to the task.
For their experiment, the research team theorized that middle aged, cognitively normal individuals with a genetic predisposition for Alzheimer’s would also display greater, and faster, pupil dilation during a cognitive task. After performing an experiment with 1,119 men between the ages of 56-66, the researchers’ theory was confirmed: cognitively normal participants who showed no sign of Alzheimer’s besides a genetic susceptibility to the disease, were associated with greater pupil dilation and greater cognitive effort over all.
“Given the evidence linking pupillary responses, LC and tau and the association between pupillary response and AD polygenic risk scores (an aggregate accounting of factors to determine an individual’s inherited AD risk), these results are proof-of-concept that measuring pupillary response during cognitive tasks could be another screening tool to detect Alzheimer’s before symptom appear,” explains Dr. William S. Kremen, the study’s first author, in a release.
The study is published in the Neurobiology of Aging.
https://www.studyfinds.org/window-to-the-mind-pupils-may-help-identify-alzheimers-decades-before-symptoms-appear/

Generation Rx: Children Being Prescribed Off-Label Meds At Increasing Rates

American children are already being prescribed various types of medications at exceedingly high rates to begin with, but a new study conducted at Rutgers University finds that the frequency of off-label medication orders for children is on the rise as well.
“Off-label” refers to a medication being used to address a different condition than it was approved to treat by the FDA. An example of an off-label med prescription for a child would be a doctor recommending anti-depressant medication for ADHD symptoms.
The research team were alarmed by their findings, and believe this study illustrates a glaring need for improved oversight and regulation when it comes to ensuring that children are prescribed safe, and effective, medication.
Data collected between 2006-2015 by the CDC and Prevention’s National Ambulatory Medical Care Surveys was analyzed for the study. More specifically, researchers looked at information on doctor’s office visits all over the United States, and investigated the frequency, trends, and reasons why doctors prescribed off-label meds for individuals under the age of 18.
In many ways, this study is incredibly overdue — it is the first in a decade to look at trends among non-hospital doctors prescribing off-label medicine to children. Researchers focused specifically on systemic drugs, or drugs that work throughout the body but also carry a greater chance of toxicity.

According to researchers, many of the off-label drugs being prescribed to children by doctors all over the country haven’t even been properly tested among adolescent populations.

“Off-label medications – meaning medications used in a manner not specified in the FDA’s approved packaging label – are legal. We found that they are common and increasing in children rather than decreasing,” comments senior author Daniel Horton, assistant professor of pediatrics and a pediatric rheumatologist at Rutgers Robert Wood Johnson Medical School, in a release. “However, we don’t always understand how off-label medications will affect children, who don’t always respond to medications as adults do. They may not respond as desired to these drugs and could experience harmful effects.”
The research team studied an estimated two billion adolescent visits to a physician, and found that in about 19% of those visits the doctor ordered one or more off-label systemic drugs. Most of the time, these drugs were intended to treat a common problem, such as asthma or a respiratory infection. Among visits that resulted in at least one prescription, off-label drugs were ordered in 83% of newborn visits, 49% of infant visits, and about 40% of visits among other adolescent ages.
The study also noted that prescription of off-label meds has increased over time; among visits that resulted in at least one prescription, off-label rates increased from 42% in 2005 to 47% by 2015.
Interestingly, girls and children with chronic conditions seemed to be prescribed off-label meds more often than other patients. Furthermore, doctors practicing medicine in southern U.S. states exhibited higher instances of off-label drug orders than doctors from other areas of the country. Doctors focusing on a specific medical field, commonly referred to as specialists, also ordered off-label meds more often than general practitioners.
The most common off-label drugs prescribed by doctors included antihistamines for respiratory infections, anti-depressants for ADHD, and numerous types of antibiotics for respiratory infections.
“Despite the laws in this country and Europe that encourage and require research on medications for children, we found that physicians are increasingly ordering certain medications off-label for children,” Horton says. “Use of some off-label drugs is supported by high-quality evidence. For example, drugs approved to prevent vomiting caused by chemotherapy also work quite well in treating more common causes of vomiting in children, such as from viruses. We need this kind of evidence to determine the appropriateness of use of many other drugs currently used off-label to treat a wide range of conditions in children.”
The study is published in the scientific journal Pediatrics.
https://www.studyfinds.org/generation-rx-u-s-children-being-prescribed-off-label-meds-at-increasing-rates-study-finds/

Flu Season Alert: Hand Sanitizer Not Very Effective Against Virus Strain

Got four minutes? That’s how long researchers say it will take for a person to rub their hands together with sanitizer before Influenza-A is deactivated.

Flu season is fast approaching, which means millions will be using hand sanitizer more often in an effort to protect themselves from a flu infection. Most people, including medical professionals, believe that flu viruses are quickly neutralized after coming into contact with an ethanol-based sanitizer, but a new study finds that isn’t the case for at least one flu strain.
Researchers from Kyoto Profectural University of Medicine in Japan have discovered that the influenza A virus (IAV) remains active and infectious within infected wet mucus even after being exposed to an ethanol-based sanitizer — for two full minutes. According to their research, it took nearly four minutes of exposure to a sanitizer to completely deactivate the virus.
Needless to say, most people aren’t rubbing their hands together with sanitizer for four minutes.
The influenza A virus is able to survive so stubbornly thanks to the think consistency of sputum, a mixture of mucus and saliva commonly coughed up by flu patients, produced in infected individuals. The thick texture of the sputum impedes the ethanol in the sanitizer from reaching and neutralizing the influenza A virus.
So, imagine someone with the influenza A virus coughs on their hand and then shakes yours a few minutes later. You would have to rub your hands together with sanitizer for four minutes to deactivate the virus if even the slightest trace of wet, infected mucus were to make its way on to your hand.
“The physical properties of mucus protect the virus from inactivation,” says physician and molecular gastroenterologist Dr. Ryohei Hirose in a release by the American Society for Microbiology. “Until the mucus has completely dried, infectious IAV can remain on the hands and fingers, even after appropriate antiseptic hand rubbing.”
According to the study, a small splash of sanitizer quickly rubbed together for a few seconds just isn’t going to cut it against this particular flu virus. The research team say that doctors and other medical professionals should be especially careful; if they don’t properly deactivate the virus between seeing various patients they could quickly spread the flu to multiple people.

First, the study’s authors analyzed the physical properties of mucus, and just as they expected, they noted that ethanol had a much harder time moving through mucus than it does through saline. Next, sputum collected from IAV patients was dabbed on human fingers and analyzed. The researchers goal during this phase was to try and simulate a situation in which medical personnel transmit the virus as best they could.
After being exposed to an ethanol hand sanitizer for two minutes, the IAV virus was still active within the mucus on the fingertips. After four minutes, the virus was completely deactivated.
This study is especially noteworthy because it challenges previous research that had found ethanol to be effective against IAV. Dr. Hirose, however, believes he knows why his study came to such different conclusions: prior research had analyzed mucus that was already dry, while this study analyzed mucus that was still wet. In fact, when Dr. Hirose and his team repeated their experiment using dry mucus, the virus was completely deactivated by the sanitizer within 30 seconds.
It’s also worth noting that the fingertip test used for this study may not exactly mimic typical hand rubbing motions, which may be a bit more effective at spreading hand sanitizer throughout the hand.
Right now, both the Centers for Disease Control and Prevention and the World Health Organization officially recommend using sanitizer regularly for 15-30 seconds to ensure optimal hand hygiene. Unfortunately, that just isn’t enough rubbing to stop IAV, according to Dr. Hirose.
On the bright side, researchers did identify a hand-cleaning strategy that is even more effective than sanitizers. Washing hands together with antibiotic soap was shown to deactivate the IAV virus within 30 seconds, even when mucus was still wet.
The study is published in the scientific journal mSphere.
https://www.studyfinds.org/flu-season-alert-hand-sanitizer-not-very-effective-against-virus-strain/