Body

During the five years before people develop the first clinically recognized signs of multiple sclerosis (MS), they are up to four times more likely to be treated for nervous system disorders such as pain or sleep problems, and are 50 per cent more likely to visit a psychiatrist, according to new research from the University of British Columbia.

The study, the largest-ever effort to document symptoms of people before they know they have MS, could enable physicians to diagnose the disease - and thus start treating it - earlier, thus possibly slowing the damage it causes to the brain and spinal cord.

MS results from the body's immune system attacking myelin, the fatty material that insulates neurons and enables rapid transmission of electrical signals. When myelin is damaged, communication between the brain and other parts of the body is disrupted, leading to vision problems, muscle weakness, difficulty with balance and coordination, and cognitive impairments.

Because the symptoms are varied, often associated with other disorders, and can be transitory, diagnosing MS can be a challenge. Confirmation of the disease usually is done by magnetic resonance imaging (MRI), a test of nerve impulses, or an examination of spinal fluid.

Canada has one of the highest rate of MS in the world, for reasons that elude scientists.

The researchers, led by Helen Tremlett, a Professor in the Division of Neurology at UBC, examined health records of 14,000 people with multiple sclerosis from B.C., Saskatchewan, Manitoba and Nova Scotia between 1984 and 2014 and compared them to the health records of 67,000 people without the disease.

Tremlett and former postdoctoral fellow José Wijnands found that fibromyalgia, a condition involving widespread musculoskeletal pain, was more than three times as common in people who were later diagnosed with MS, and irritable bowel syndrome was almost twice as common.

Two other conditions with markedly higher rates among people to be diagnosed with MS: migraine headaches and any mood or anxiety disorder, which includes depression, anxiety and bipolar disorder.

The higher rates of those illnesses also corresponds with higher use of medications for musculoskeletal disorders, nervous system disorders, and disorders of the genito-urinary tract, along with antidepressants and antibiotics.

The study, published in Multiple Sclerosis Journal, provides definitive evidence that MS can be preceded by early symptoms - known as a prodrome - that aren't considered "classic" manifestations of the disease, like blurred vision or numbness or weakness in the limbs. As recently as 2000, medical textbooks asserted that MS did not have a prodrome.

"The existence of such 'warning signs' are well-accepted for Alzheimer's disease and Parkinson's disease, but there has been little investigation into a similar pattern for MS," said Tremlett, a Canada Research Chair in Neuroepidemiology and Multiple Sclerosis and member of the Djavad Mowafaghian Centre for Brain Health. "We now need to delve deeper into this phenomenon, perhaps using data-mining techniques. We want to see if there are discernible patterns related to sex, age, or the 'type' of MS they eventually develop."

TORONTO, July 13, 2018 - Death due to cardiovascular disease is on the rise in India, causing more than one quarter of all deaths in the country in 2015 and affecting rural populations and young adults the most, suggests a study published today in The Lancet Global Health.

This work is the first nationally representative study to measure cardiovascular mortality in India. Led by Dr. Prabhat Jha, director of the Centre for Global Health Research of St. Michael's Hospital in Toronto, Canada, it found that rates of dying from ischaemic heart disease - cardiac issues caused by a narrowing of the heart's arteries - in populations aged 30 to 69 increased rapidly in rural areas of India and surpassed those in urban areas between the year 2000 and 2015.

In contrast, the probability of dying from stroke decreased overall, but increased in India's northeastern states, where a third of premature stroke deaths occurred and only one sixth of the population lives. In these states, deaths due to stroke were about three times higher than the national average.

"The finding that cardiac disease rose nationally in India and that stroke rose in some states was surprising," said Dr. Jha, who is also a professor in the Dalla Lana School of Public Health at the University of Toronto. "This study also unearthed an important fact for prevention of death due to cardiovascular disease. Most deaths were among people with previously known cardiac disease, and at least half were not taking any regular medications."

Dr. Jha and his team also showed that younger adults, especially those born after 1970, have the highest rate of death due to heart problems caused by narrowing of the heart's arteries.

Cardiovascular disease, comprising mostly of ischaemic heart failure and stroke, is the leading cause of death worldwide. Until now, most of the evidence of cardiovascular mortality in India has come from small, local studies or from imprecise modeling exercises.

"This work equips us with more detailed information that we couldn't have predicted based on earlier studies," said Dr. Jha.

This research is part of the Million Death Study, one of the largest studies of premature deaths in the world. In India, most deaths occur at home and without medical attention. Hundreds of specially trained census staff in India knocked on doors to interview household members about deaths. Two physicians independently examined these "verbal autopsies" to establish the most likely cause of death.

"Making progress in fighting the leading cause of death in India is necessary for making progress at the global level," Dr. Jha said. "We demonstrated the unexpected patterns of heart attack and stroke deaths. Both conditions need research and action if the world is going to achieve the United Nations Sustainable Development Goal of reducing cardiovascular mortality by 2030."

CHAMPAIGN, Ill. -- A class of molecules formed when the body metabolizes omega-3 fatty acids could inhibit cancer's growth and spread, University of Illinois researchers report in a new study in mice. The molecules, called endocannabinoids, are made naturally by the body and have similar properties to cannabinoids found in marijuana - but without the psychotropic effects.

In mice with tumors of osteosarcoma - a bone cancer that is notoriously painful and difficult to treat - endocannabinoids slowed the growth of tumors and blood vessels, inhibited the cancer cells from migrating and caused cancer cell death. The results were published in the Journal of Medicinal Chemistry.

"We have a built-in endocannabinoid system which is anti-inflammatory and pain-reducing. Now we see it is also anti-cancer, stopping the cells from proliferating or migrating," said study leader Aditi Das, a professor of comparative biosciences and an affiliate of biochemistry at Illinois. "These molecules could address multiple problems: cancer, inflammation and pain."

In 2017, the Illinois team identified a new group of omega-3 fatty-acid metabolites called endocannabinoid epoxides, or EDP-EAs. They found that these molecules had anti-inflammatory properties and targeted the same receptor in the body that cannabis does.

Since cannabis has been shown to have some anti-cancer properties, in the new study the researchers investigated whether EDP-EAs also affect cancer cells. They found that in mice with osteosarcoma tumors that metastasized to their lungs, there was an 80 percent increase in naturally occurring EDP-EAs in cancerous lung tissues over the lungs of healthy mice.

"The dramatic increase indicated that these molecules were doing something to the cancer - but we didn't know if it was harmful or good," Das said. "We asked, are they trying to stop the cancer, or facilitating it? So we studied the individual properties and saw that they are working against the cancer in several ways."

The researchers found that in higher concentrations, EDP-EAs did kill cancer cells, but not as effectively as other chemotherapeutic drugs on the market. However, the compounds also combated the osteosarcoma in other ways: They slowed tumor growth by inhibiting new blood vessels from forming to supply the tumor with nutrients, they prevented interactions between the cells, and most significantly, they appeared to stop cancerous cells from migrating.

"The major cause of death from cancer is driven by the spread of tumor cells, which requires migration of cells," said study coauthor Timothy Fan, a professor of veterinary clinical medicine and veterinary oncology. "As such, therapies that have the potential to impede cell migration also could be useful for slowing down or inhibiting metastases."

The researchers isolated the most potent of the molecules and are working to develop derivatives that bind better to the cannabinoid receptor, which is plentiful on the surface on cancer cells.

"Dietary consumption of omega-3 fatty acids can lead to the formation of these substances in the body and may have some beneficial effects. However, if you have cancer, you want something concentrated and fast acting," Das said. "That's where the endocannabinoid epoxide derivatives come into play - you could make a concentrated dose of the exact compound that's most effective against the cancer. You could also mix this with other drugs such as chemotherapies."

Next, the researchers plan to perform preclinical studies in dogs, since dogs develop osteosarcoma spontaneously, similarly to humans. They also plan to study the effects of EDP-EAs derived from omega-3 fatty acids in other cancer types.

"Particular cancers that might be most interesting to study would be solid tumors or carcinomas, which tend to spread and cause pain within the skeleton. Some of the most common tumors that behave this way are breast, prostate, and lung carcinomas, and we can certainly explore these tumors in the future," said Fan, who is also a member of the Carle Illinois College of Medicine, the Cancer Center at Illinois and the Carl R. Woese Institute for Genomic Biology.

PORTLAND, Oregon - To help stem the nationwide opioid epidemic and related increases in HIV, hepatitis C and other infections, health care providers should routinely screen and treat patients for opioid abuse when they come to clinics and hospitals seeking other services.

That's one of five recommendations outlined in a paper published in the Annals of Internal Medicine. The paper supports a newly published document that outlines the proceedings of a March 12, 2018, workshop convened on the topic by the National Academies of Sciences, Engineering and Medicine.

"Treatment can save lives," said one of the paper's authors, Todd Korthuis, M.D., M.P.H. "The national opioid epidemic can turn around if we embrace opioid use disorder as a chronic medical condition that needs treatment instead of a moral issue or the result of poor willpower."

Korthuis, who is a professor of medicine (general internal medicine and geriatrics) and head of addiction medicine in the OHSU School of Medicine, also participated in the National Academies workshop and reviewed the resulting proceedings document. He co-wrote the paper with Sandra A. Springer, M.D., of the Yale School of Medicine and Carlos del Rio, M.D., of the Emory University School of Medicine, both of whom also participated in the workshop.

The workshop highlighted one of the many dire consequences of the opioid epidemic: more people are turning to injection drug use after their opioid prescriptions are cut off, which in turn has led to an increase in life-threatening infections of the skin, joint, blood, bone and more. These serious infections require expensive and lengthy hospital treatments, but most hospital staff don't regularly address the root cause: drug addiction.

OHSU is one of a few U.S. hospitals that already routinely screens and treats patients for opioid abuse when they come to OHSU for other services. Opioid use disorder treatment at OHSU is initiated through a novel service called Project IMPACT, or Improving Addiction Care Team, in which physicians, social workers, peer-recovery mentors and others meet with hospitalized patients who have drug use issues and begin addiction treatment during hospitalization. Honora Englander, M.D., an associate professor of medicine (hospital medicine) in the OHSU School of Medicine, presented Project IMPACT at the National Academies workshop.

Bottom Line: A study of two generations of women in England examined how common depression during pregnancy (prenatal depression) is in young mothers now compared with their mothers' generation. Depressed mood was measured using self-reported surveys in both generations and analysis of the data suggests depression in young pregnant women may be higher now than among their mothers' generation in the 1990s. Researchers acknowledge a number of plausible explanations for their findings requiring further study.

Authors: Rebecca M. Pearson, Ph.D., of the University of Bristol, United Kingdom, and coauthors

To Learn More: The full study is available on the For The Media website.

(doi:10.1001/jamanetworkopen.2018.0725)

Editor's Note: The article contains conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Prison employees experience PTSD on par with Iraq and Afghanistan war veterans, a new study from a Washington State University College of Nursing researcher found.

Working conditions in a prison can include regular exposure to violence and trauma, and threats of harm to the workers and their families. Previous studies have shown that prison workers have some of the highest rates of mental illness, sleep disorders and physical health issues of all U.S. workers. But the rate of PTSD among prison workers isn't well understood.

The new study, "Prison employment and post-traumatic stress disorder: Risk and protective factors," was conducted by lead investigator Lois James, Ph.D., assistant professor at the WSU College of Nursing, and co-investigator Natalie Todak, assistant professor at the University of Alabama at Birmingham.

It recently was published in the American Journal of Industrial Medicine and excerpted in Force Science News.

"Prison employees can face some of the toughest working conditions of U.S. workers," said James, "yet limited evidence exists on the specific risk and protective factors to inform targeted interventions."

Among the study's findings:

Prison employees work under an almost constant state of threat to their personal safety, and about a quarter of them routinely experience serious threats to themselves or their families.

Almost half have witnessed co-workers being seriously injured by inmates.

More than half have seen an inmate die or have encountered an inmate who recently died.

The vast majority have dealt with inmates who were recently beaten and/or sexually assaulted.

PTSD rates were higher among women, black employees, and employees with more than 10 years of experience. PTSD scores, using criteria from the Diagnostic and Statistical Manual of Mental Disorders, didn't differ based on where the employee worked, such as a minimum versus maximum security facility.

James and Todak note that the research included a small sample of 355 employees of one labor union at the Washington State Department of Corrections, and recommended further study of the issue.

Still, they said their findings suggest the corrections profession could benefit from specific training to promote resilience. They also said issues common to nearly every workplace also can protect prison employees from PTSD, such as having good relationships with supervisors and coworkers, and liking their work assignments.

Mailing colorectal cancer screening tests to patients insured by Medicaid increased screening rates for this population, report researchers at the University of North Carolina Comprehensive Cancer Center.

In collaboration with the Mecklenburg County Health Department in Charlotte, researchers with UNC Lineberger's Carolina Cancer Screening Initiative examined the impact of targeted outreach to more than 2,100 people insured by Medicaid who were not up-to-date with colorectal cancer screening. The project resulted in a nearly 9 percentage point percent increase in screening rates for patients who received a screening kit in the mail compared with patients who just received a reminder, and it demonstrated that their method could serve as a model to improve screening on a larger scale. The findings were published in the journal Cancer.

The American Cancer Society estimates that more than 97,000 people will be diagnosed with colorectal cancer in the United States this year, and it will result in approximately 50,600 deaths. It is third most common type of cancer in the United States, and the second leading cause of cancer death.

While colorectal cancer screening has proven effective in reducing cancer deaths, researchers report too few people are getting screened. Current guidelines from ACS recommend regular screening with either a high-sensitivity stool-based test or a structural (visual) exam for average-risk people aged 45 years and older, and that all positive results should be followed with colonoscopy. Despite these recommendation, studies have identified notable gaps in screening rates, including by race, geographic region and other socioeconomic factors. Among patients who are insured, people with Medicaid have the lowest rates of colorectal cancer testing.

"There has been a national push to increase colorectal cancer screening rates since colorectal cancer is a preventable disease, but screening rates are only about 63 percent, and low-income, and otherwise vulnerable populations, tend to be screened at even lower rates," said the study's first author UNC Lineberger's Alison Brenner, PhD, MPH, research assistant professor in the UNC School of Medicine Department of Internal Medicine.

For the project, researchers either mailed reminders about colorectal cancer screening and instructions on how to arrange one with the health department, or reminders plus a fecal immunochemical test, or FIT kit, which can detect blood in the stool - a symptom of colon cancer. The patient completes the test at home and returns it to a provider for analysis. Patients who have a positive FIT kit result will be scheduled for a colonoscopy.

The UNC Lineberger researchers worked with the Mecklenburg County Health Department staff, who coordinated the reminders and mailings and ran the test analyses. They also partnered with Medicaid care coordinators to provide patient navigation support to patients who had abnormal test results and required a colonoscopy.

Twenty-one percent of patients who received FIT kits in the mail completed the screening test, compared with 12 percent of patients who just received a reminder. Eighteen people who completed FIT tests had abnormal results, and 15 of those people were eligible for a colonoscopy. Of the 10 who completed the colonoscopy, one patient had an abnormal result.

"Preventive care amongst vulnerable populations rarely rises to the top of the mental queue of things that need to get done," Brenner said. "In North Carolina, many Medicaid recipients are on disability. Making something like colorectal cancer screening as simple and seamless as possible is really important. If it's right in front of someone, it's more likely to get done, even if there are simple barriers in place."

Brenner said the study shows the potential to harness resources like the county health department for health prevention services.

"This collaborative and pragmatic quality improvement effort demonstrates the feasibility, acceptability, and efficiency of using existing health services resources and infrastructure, including Medicaid-based navigation to colonoscopy to deliver timely cancer screening services to low income populations," said UNC Lineberger's Stephanie Wheeler, PhD, MPH, associate professor in the UNC Gillings School of Global Public Health and the study's senior author.

She said researchers plan to move forward to study whether they can implement their approach on a larger scale, and to understand all of the cost implications.

"This is looking at expanding the medical neighborhood - to harness community resources to target patients and in this case, insured patients, who are maybe not getting this from a primary health care organization, and how to increase screening rates in these types of vulnerable populations," Brenner said.

AUGUSTA, Ga. (July 13, 2018) -When it comes to diagnosing a condition in which the plasma cells that normally make antibodies to protect us instead become cancerous, it may be better to look at the urine as well as the serum of our blood for answers, pathologists say.

The condition is monoclonal gammopathy, in which immune cells called plasma cells start making just one immunoglobulin, or antibody, instead of their usual vast array. The result can be the cancer multiple myeloma.

"When you test the serum, we suggest you also test the urine whenever you suspect that somebody has a tumor of the plasma cells," says Dr. Gurmukh Singh, vice chair of clinical affairs for the Department of Pathology at the Medical College of Georgia at Augusta University.

The decades-old urine test is still used by pathologists and requested by physicians, but its use declined when the serum free light chain assay became available about a dozen years ago, Singh says, and some physicians may now think that the urine test is redundant. The different tests look in the serum or urine for signs of the abnormal antibody, and to see if the usual ratio is off for two types of a portion of the antibody, called light chains.

The new study, published in the Journal of Clinical Medicine Research, indicates that if the multiple myeloma is associated with the type called the lambda light chain, there is about a 25 percent chance the problem will not be detected by the serum test for free light chains, the investigators report from their retrospective review of tests on 175 patients.

"If you have a lambda chain-associated lesion and you don't do a urine study, just rely on the serum free light chain assay, about 1 out of 4 times, the assay will tell you that you don't have anything when you actually do," says Dr. Won Sok Lee, fourth-year pathology resident at MCG and AU Health and the study's coauthor.

Plasma cells are immune cells that live in our bone marrow and produce immunoglobulins, antibodies that attach to and attack invaders. When the plasma cells go bad, they instead start producing a single, dysfunctional immunoglobulin.

The Y-shaped immunoglobulins are comprised of pieces of protein called "heavy" and "light" chains and, as the name implies, the light chains are literally lighter. Light chains have two different types, kappa and lambda, which are distinctive in their amino acid sequence. We normally make about twice as many kappa light chains, but cancer can affect both light chains.

In multiple myeloma, the relevant light chain production goes up but kappa goes up a lot more, says Singh, the study's corresponding author and Walter L. Shepheard Chair in Clinical Pathology at MCG.

Sometimes their ratio stays normal even when an abnormal lambda immunoglobulin is showing up in the urine.

Conversely, nearly 40 percent of patients have an abnormal ratio without having monoclonal gammopathy, the investigators write.

These variabilities mean some patients, particularly those with the less-common lambda chain-associated lesions, could go undiagnosed, Lee says.

"You may go undiagnosed because the serum free light chain test either is not picking up those abnormal proteins or the lambda lesions don't make that many excess abnormal proteins," Singh notes.

Underdetection of the lambda light chains floating in the serum may account for the false negative ratio found in about 25 percent of patients who clearly had an abnormal antibody produced by a lambda lesion present in their urine, the investigators report.

Underproduction of lambda free light chains in these patients likely accounts for another 5 percent of false negatives, they write.

In fact, the kappa/lambda ratio showed excess kappa chains in about 90 percent of the patients who had an abnormal ratio without a tumor of the plasma cells, the investigators say.

With lambda chain-associated lesions, the ratio is not abnormal nearly as frequently. In fact, there is a high false negative rate for a lambda-dominant ratio in monoclonal gammopathies associated with lambda chains, they write, possibly due to the under-detection of lambda light chains in the serum.

Therein lies the problem with not looking for errant antibodies and light chain ratios in the urine, Lee says. Ratios can look normal in the serum, while the urine has monoclonal lambda chains.

"If it's in the urine, you are making abnormal free light chains," Lee says. Conversely, the ratio can look abnormal in the serum in people who don't have cancer.

Although more costly, the urine test is a better diagnostic tool in this case, because it enables the pathologist to give better information back to physicians and patients, Lee says. He notes that kappa lesions are more common.

The investigators found a systematic underdetection of serum free lambda light chains by the serum free light chain assay and an underdetection as well of the lambda dominant ratio.

Examination of serum free light chains is currently recommended for diagnosing and monitoring monoclonal gammopathies, although, the investigators write, there are differing opinions on its usefulness. If initial tests indicate a problem, a bone marrow biopsy is typically performed to confirm a diagnosis.

Excessive light chains produced normally are easily excreted in the urine because of their small size. With monoclonal gammopathy, some of the excess light chains can get trapped in the kidneys and damage kidney function.

They examined test results on 175 patients who had serum protein electrophoresis/serum protein immunofixation electrophoresis; urine protein electrophoresis/urine protein immunofixation electrophoresis; and serum free light chain assay from 2010-16.

Early symptoms of monoclonal gammopathy can be nonspecific, like feeling poorly, and if it becomes cancer, one of the first symptoms may be a fractured bone because the cancerous cells have started consuming bone, Singh says. Anemia, an increase in serum calcium and kidney failure are other symptoms.

Lebanon, NH - A new multi-institutional clinical trial compared outcomes of women with multiple ipsilateral breast cancer, or more than one site of disease in the same breast, who underwent breast-conserving surgery, with outcomes of those who converted to mastectomy. Out of 198 eligible women in the trial, 184 (92.9%) successfully completed breast-conserving surgery, 134 of those with a single operation. These findings have just been published online first in Annals of Surgical Oncology.

Advancements in breast cancer care allow for improved control over local disease in patients undergoing breast-conserving surgery. Other advancements such as more sensitive imaging techniques also now result in higher detection rates, which opens up new questions for both breast cancer patients and clinicians about how to best manage disease.

The question was approached in a new collaborative, multi-institutional study conducted by the Alliance for Clinical Trials in Oncology and led by Kari Rosenkranz, MD, a surgical oncologist and medical director of the Comprehensive Breast Program at Dartmouth's Norris Cotton Cancer Center and associate professor of surgery at Geisel School of Medicine at Dartmouth. "Our study is the first prospective study to assess the feasibility and safety of breast conservation in women with two or three malignant lesions in a single breast," says Rosenkranz. The endpoints measured include local recurrence at 5 years, as well as rates of surgical conversion to mastectomy or second surgeries due to positive margins (malignant tissue around the disease site remaining after surgery).

Based on retrospective studies from previous decades, mastectomy has been, and is still, the predominant surgical treatment option for women with multiple ipsilateral breast cancer. These studies, from an era prior to modern technology and multimodality breast cancer care, showed higher rates of local recurrence, ranging from 23-40%, for women in this category who underwent breast-conserving therapy.

This new study finds that for the majority of women enrolled in the trial, 92.9%, breast-conserving surgery is technically feasible. "Results show an acceptably low rate of conversion to mastectomy, and most women successfully achieving breast conservation with negative margins in a single operation," says Rosenkranz. "These data may inform conversations between patients and surgeons regarding management of multiple ipsilateral breast cancer."

Next steps include assessment of the primary study end point, which is local recurrence rates, as well as additional secondary endpoints including breast cosmetic improvement and appropriateness of radiation fields in this patient population.

Nearly a third of American adults have high blood pressure, also known as hypertension, putting them at higher risk for heart attacks, strokes, and death. A recent estimate from the Centers for Disease Control reports that high blood pressure--and the many conditions associated with it--contribute to over 400,000 deaths and cost the nation more than $40 billion each year.

Patients can avoid poor health effects by lowering blood pressure with medication and diet, but more than half of all Americans with hypertension don't have the condition under control. A few integrated healthcare systems, such as Kaiser Permanente Northern California, have achieved control rates as high as 90 percent in their patients, but this approach has been considered out of reach for the many low-income and minority patients who rely on less well-resourced safety-net settings for care.

Now, a new study led by UC San Francisco researchers, partnering with clinical leaders in the San Francisco Department of Public Health, shows that a simplified intervention can significantly improve rates of blood pressure control in the city's safety net clinics.

According to the new research, published June 12, 2018 in Circulation: Cardiovascular Quality and Outcomes, best practices established in well-resourced clinics can work in safety-net clinics that serve high-risk populations. Rather than being an afterthought, "this is the population to start with. This is where you'll get the biggest movement," said Valy Fontil, MD, MAS, the study's first author and assistant professor of medicine at UCSF.

If implemented across the country, the program could potentially improve blood pressure control in vulnerable populations and, eventually, address racial and socioeconomic disparities in hypertensive-related diseases. "Poor and minority communities are more likely to have high blood pressure, more likely to get high blood pressure early in life, and are less likely to have their blood pressure controlled," said senior author Kirsten Bibbins-Domingo, PhD, MD, MAS, the Lee Goldman MD endowed chair in medicine and professor and chair of the department of epidemiology and biostatistics. "We know what works, but we need to adapt our strategies to the communities that need them the most."

She and Fontil designed the study to investigate the commonly held view that safety-net clinics have what Fontil calls a "ceiling of achievement."

"People always think that clinics like Kaiser have a lot of money, a lot of resources, and healthy patients: advantages that safety-net clinics don't have, and so the clinics can't achieve the same quality of care. I don't usually believe that," said Fontil.

To test this idea, Fontil and his fellow researchers set about modifying a treatment program to suit the needs of the patients seen in the San Francisco Health Network (SFHN), 12 clinics run by the San Francisco Department of Public Health. "Let's learn what works over there," he said, "and see if we can adapt it here."

The first step was to develop an internal hypertension patient registry, in order to track blood pressure control. The tracking system was intended to benefit both the doctors monitoring their patients' health and the patients themselves, allowing appropriate outreach and reminders.

Next the team developed a treatment algorithm adapted for the SFHN. This algorithm encouraged the use of fixed-dose medications--two or more drugs in one pill--advantageous to their patients, who then require fewer trips to the pharmacy and don't have to manage as many individual pills. The researchers also adapted their algorithm to account for patients' potential social instability, which could make close monitoring required for some medications unrealistic; they took into account food insecurity and additional health conditions that could increase side effects from some of the recommended medications. In addition, the researchers took into account the financial burden imposed on patients whose insurance might not cover certain medications and made sure to only include medications covered by the most common insurers for these patients.

In addition to the algorithm, the blood pressure control program also included regular check-up visits to monitor blood pressure. Nurses and pharmacists were allowed to take standardized blood pressure measurements, allowing patients faster access to monitoring without requiring full doctor appointments. And with regular, trusted and standardized blood pressure measurements, doctors could be more proactive in adjusting medication dosages to fit their patients' needs when they did come in for appointments.

"We took some things out of the doctors' hands," explained Fontil, "so that they could concentrate on patient care."

The team tested the results of this program in one pilot clinic first. When preliminary outcomes looked positive, the team expanded the effort--dubbing the program "Bring it Down San Francisco"--to all 12 of the SFHN clinics. At the pilot site, the researchers saw blood pressure control rise from 68 percent to 74 percent, improving across all racial and ethnic groups surveyed over the course of 24 months; when the other clinics were added to the program, blood pressure control rates rose from 69 percent to 74 percent over 15 months.

"Cardiovascular disease is the most common cause of death in the world and it particularly plagues low income populations and ethnic minorities. That makes it a great case study for care for chronic diseases like diabetes and kidney disease, for example," said Fontil. Despite the disadvantages and difficulties faced by safety-net clinics, the data speak for themselves, said Fontil. "We didn't have a lot of funding for it, and it still worked."

Philadelphia, July 12, 2018-- A new study from a team of researchers at Children's Hospital of Philadelphia (CHOP) and the University of Pennsylvania School of Nursing (Penn Nursing) found that in the previous three months, about half of parents talked on a cell phone while driving when their children between the ages of 4 and 10 were in the car, while one in three read text messages and one in seven used social media.

The study also found a correlation between cell phone use while children were in the car and other risky driving behaviors, such as not wearing a seat belt and driving under the influence of alcohol whether or not children were present in the car.

The findings were published in the Journal of Pediatrics.

Crash fatalities and injuries caused by distracted driving constitute a public health crisis in the U.S., resulting in about one in four motor vehicle crashes. Previous research suggests that causes of distracted driving by parents and caregivers include talking on hand-held or hands-free cell phones or using phones to text, email, or access the Internet.

Researchers wanted to identify specific factors associated with cell phone-related distracted driving in parents and caregivers of children between the ages of 4 and 10.

"Technology has become increasingly intertwined with our daily lives," said lead author Catherine McDonald, PhD, RN, FAAN, a Senior Fellow with CHOP's Center for Injury Research and Prevention and an Assistant Professor of Nursing in the Family and Community Health Department at Penn Nursing. "The results from this research reinforce that risky driving behaviors rarely occur in isolation, and lay the groundwork for interventions and education specifically aimed at parents who drive with young children in their cars."

The study was conducted using an online sample of 760 adults from 47 U.S. states. The respondents had to be at least 18 years old, a parent or routine caregiver of a child between the ages of 4 and 10, and had driven their oldest child between those ages at least six times in the preceding three months.

In the preceding three months, 52.2 percent of parents had talked on a hands-free phone while driving with a young child in the car, while 47 percent had done so with a hand-held phone. The study also found that 33.7 percent of parents read text messages while 26.7 percent sent text messages while driving with children. Social media also contributed to distracted driving, with 13.7 percent of respondents reporting using social media while driving with children.

The study also looked at child restraint system (CRS) use for children in the same age group. The study found that 14.5 percent of parents did not consistently use their typical CRS when driving with their children. Drivers who did not consistently use their typical CRS were more likely to engage in cell phone use while driving.

Finally, the study looked at parent and caregiver risky behavior associated with driving, including not wearing a seat belt as a driver and driving under the influence of alcohol, whether or not their children were in the car. The researchers saw a direct correlation between a history of driving under the influence and increased likelihood of all types of cell phone use while driving with children in the car. All cell phone-related distracted driving behaviors other than talking on a hands-free phone increased if a person did not always wear their seat belt while driving with children.

"When clinicians are discussing child passenger safety with families, they can use the opportunity to ask and educate about parental driving behaviors such as seat belt use and cell phone use while driving," McDonald said. "This type of education is especially pivotal today, as in-vehicle technology is rapidly changing and there is increased - and seemingly constant - reliability on cell phones. However, it is also important to note that even parents who did not engage in risky behaviors, such as not wearing a seat belt as a driver or driving under the influence of alcohol, still used their cell phones while driving."

McDonald said that future studies are needed to understand if unsafe distracted driving behaviors by parents influences their children as they become young drivers in the future.

BOSTON - Previous studies have shown that when all members of the clinical care team feel comfortable speaking up, team performance improves. With intimate knowledge of patients' wishes, medical histories and clinical conditions, patients and their families are increasingly considered crucial members of the optimal patient-centered care team. However, to have an impact on patient safety, patients and families must feel comfortable voicing concerns about care to the medical team. Currently, little is known about patients' and their families' level of comfort with speaking up in real time in the ICU setting.

In a new study, a team led by clinician-researchers at Beth Israel Deaconess Medical Center (BIDMC) surveyed family members and patients with recent ICU experiences about their willingness to speak up about care concerns to medical providers. Their findings, published today in BMJ Quality and Safety, revealed that 50 to 70 percent of family member respondents with a loved one in the ICU at the time of the survey expressed hesitancy about voicing their concerns about common care situations with safety implications.

"Speaking up is a key component of safety culture, yet our study - the first to our knowledge to address this issue - revealed substantial challenges for patients and families speaking up during an ICU stay," said co-lead author Sigall K. Bell, the Director of Patient Safety and Discovery at OpenNotes, BIDMC and an Associate Professor of Medicine at Harvard Medical School. "In the ICU setting in particular, families - who are also among the most vigilant stakeholders - may hold key information clinicians may have overlooked, and may be the first to detect a change in clinical status. Our findings are important because true partnerships with patients and families may be limited if they don't feel supported to voice their concerns."

Using a questionnaire collaboratively designed by a multidisciplinary group including experts from the Patient and Family Advisory Council at BIDMC, BIDMC's Center for Healthcare Delivery Science, Department of Social Work and Department of Health Quality Care, and collaborators at Intermountain Medical Center at the University of Utah, Bell and colleagues surveyed 105 families of patients admitted to an urban academic hospital's ICUs from July 2014 to February 2015. The team also surveyed a panel of 1050 participants with recent ICU experience via the internet. (Given the demographic differences between the two groups, they were not compared statistically, but the findings showed consistent trends across both groups.)

The data revealed that while nearly two-thirds of current ICU patients and families reported feeling very comfortable discussing medications, only about one-third of respondents said they felt the same way about discussing hand hygiene or disagreements about aggressiveness of care desired by patients/families versus that proposed by clinicians. Only half of those surveyed reported feeling very comfortable asking for clarification about confusing or conflicting information or raising concerns about a possible error. Fear of being labeled a "troublemaker," not knowing whom to talk to, and the medical team's busyness were the most often cited reason for that hesitancy.

"We were surprised not knowing who to talk to about concerns -- a readily actionable issue -- was among the most highly cited barriers," said Bell. "Our results highlight the need to explicitly support patients and families to speak up in real time about perceived errors. Hesitancy to do so represents a real safety gap."

When Bell and colleagues looked at demographic characteristics affecting comfort with raising concerns, they saw that younger people, men and those without personal experience in health care were less likely speak up. The scientists noted that because the group surveyed at the urban academic hospital spoke only English and were disproportionately college educated and connected to the healthcare industry, their study likely underestimated the average patient and family member's hesitancy to speak up during an ICU admission.

The team's findings represent relatively low-cost opportunities to improve patient and family outcomes. Clear and systematic instructions about whom to contact with concerns are a critical first step. Culturally reframing speaking up more positively--from 'causing trouble' to being an 'engaged team member,' and ensuring that clinicians listen to patients and families when they do speak up may also help, the researchers suggest.

"The results highlight new areas for emphasis and improvement," said co-lead author Stephanie Dawn Roche, MPH, Quality Research Analyst at BIDMC's Center for Healthcare Delivery Science. "Empowering patients and families to speak up -- especially given their unique knowledge of the patient and the potential to prevent catastrophic outcomes such as serious medication errors -- has been identified as a critical next step in improving safety culture. BIDMC has been a longtime leader in patient engagement and we are excited about innovating ways to empower patients and families even more. We hope this research will open the door to new opportunities in patient-and-family-centered care and safety partnerships."

In areas of the country disproportionately affected by the opioid crisis, treatment programs are less likely to accept patients paying through insurance of any type or accept pregnant women, a new Vanderbilt study found.

While the opioid crisis has escalated across the U.S., there has been growing concern that treatment capacity has not kept pace. In 2016, more than 42,000 Americans died of an opioid-related overdose, more than any year on record. Opioid agonist therapies, like buprenorphine and methadone, have been shown to reduce risk of overdose death, and for pregnant women with opioid use disorder this benefit extends to the baby -- making it more likely the infant will be born at term and with higher birthweights.

Vanderbilt researchers focused on four Appalachian states -- Tennessee, Kentucky, North Carolina and West Virginia -- that have among the highest rates of opioid use in the country and are more affected by opioid overdose deaths. In their study published in the journal Substance Abuse, researchers found that only about 50 percent of opioid treatment providers took any insurance, and there was also a huge variance among the states in programs that accepted Medicaid.

While 83 percent of treatment programs in West Virginia accepted Medicaid insurance, only about 13 percent of programs in Tennessee accepted Medicaid. Additionally, the study found that while 91 percent of programs were accepting new patients, only 53 percent of outpatient buprenorphine would treat pregnant women.

"This work sheds further light on a critical public health problem facing pregnant women and their children and the importance of connecting pregnant women to the right resources," said senior author William Cooper, MD, MPH, vice chair the Department of Pediatrics and Cornelius Vanderbilt Professor of Pediatrics and Health Policy.

Researchers conducted a survey of opioid agonist therapy providers, opioid treatment programs that provide methadone and outpatient buprenorphine providers between April and May 2017, in the four predominately Appalachian states. The programs and providers were identified from a public listing provided by the Substance Abuse and Mental Health Administration.

"We know that opioid agonist therapies work but only a fraction of people that have opioid use disorder are actually getting them. With this study, we wanted to know if there were structural issues in terms of providers, or insurance type, or being pregnant itself, that may be a reason for that barrier," said Stephen W. Patrick, MD, MPH, MS, director of the Vanderbilt Center for Child Health Policy, assistant professor of Pediatrics and Health Policy in the Division of Neonatology at Monroe Carell Jr. Children's Hospital at Vanderbilt.

Surveyors asked the programs if they were accepting new patients or if they were accepting pregnant patients for treatment. Other questions centered on insurance requirements, including if programs accepted Medicaid, private insurance or self-pay.

The survey found that cash payments for treatment ranged from $20 to $175 for treatment intakes; $35 to $245 per week for outpatient buprenorphine treatment; and $49 to $160 per week for methadone treatment. Another finding of the study was that when pregnant women are accepted to opioid use disorder treatment programs they had shorter wait times than others with the disorder.

"We need to know why -- why is it that so many providers only take cash and why so few in some states take Medicaid. Then we need to craft policy solutions that increase the likelihood that people with opioid use disorder are able to get the evidence-based treatment that they need," Patrick said. "At the end of the day, the people that have opioid use disorder, particularly pregnant women, need the treatment that we know is evidence based. We know many aren't getting it and we are still seeing record highs of overdose deaths."

Glenview, IL, July 12, 2018 - Some patients with COPD demonstrate signs of accelerated aging. In a new study published in the journal CHEST® researchers report that measuring blood telomeres, a marker of aging of cells, can be used to predict future risk of the disease worsening or death. Further, they have determined that the drug azithromycin may help patients with short telomeres, an indicator of more rapid biological aging, stave off negative clinical outcomes.

"Previous studies have suggested that COPD may be a disease of accelerated aging for a variety of reasons including its close relation to senescence-related disorders, such as osteoporosis and dementia, and its exponential increase in prevalence beyond 50 years of age. One important biomarker of replicative senescence is telomere length. It is known that short telomeres are associated with common comorbidities of COPD, such as cardiovascular disease and cancer, but it was not known if there is a relationship between blood telomeres and patient-related outcomes in COPD," explained lead investigator Don D. Sin, MD, FCCP, of the Centre for Heart Lung Innovation, St. Paul's Hospital, and the Department of Medicine (Respiratory Division) of the University of British Columbia, Vancouver, BC, Canada.

Telomeres are specific repetitive DNA sequences found on the ends of chromosomes. Somewhat like aglets, the protective plastic tips found at the ends of shoelaces, they help to prevent harmful DNA events including abnormal genetic recombinations or deletions. Each time a cell replicates, the telomeres become progressively shorter until they cease to divide, a process known as cellular aging or senescence.

Researchers used data from the Macrolide Azithromycin for Prevention of Exacerbations of COPD (MACRO) study, which included participants from 17 sites across 12 academic health centers in the United States. This study included 576 patients with moderate-to-severe COPD, who had provided a blood sample for DNA analysis. Absolute telomere length was measured to determine the age of the cells in the blood samples. Previous research had found that telomere measurement in blood leukocytes (white blood cells) was associated with clinical findings in lung tissue. The researchers divided the group into individuals with shorter and longer telomere lengths, using the median value of absolute telomere length as the cutoff. Patients were followed for up to 3.5 years.

Researchers found that patients with short telomeres, indicating more rapidly aging blood cells, were 50 percent more likely to have exacerbations (new or increased respiratory symptoms) and nine times more likely to die than those with normal blood telomeres. Patients with short telomeres also experienced worse health status and poorer quality of life. Health status was measured using the St. George's Respiratory Questionnaire (SGRQ), which included assessment of daily activities, respiratory symptoms, and perceived psychological impact.

"The good news is that these differences were not observed when patients with short telomeres were treated with daily azithromycin therapy," reported Dr. Sin. "This suggests that this blood biomarker may help select those patients with COPD who will benefit most from azithromycin treatment. Peripheral leukocyte telomeres are readily accessible and easy to measure; thus, they may represent a clinically translatable biomarker for patient risk-stratification and identifying individuals at increased risk of poor patient-centered outcomes in COPD."

Boston, MA -- Cancer immunotherapies and targeted therapy have revolutionized how clinicians take care of patients with advanced skin cancer and have led to long lasting treatment responses for many of them. However, little is known about the survival impact of these therapies for a substantial group of patients. Melanoma patients with cancer that has spread to the brain have been excluded or underrepresented in clinical trials of immunotherapies due to concerns about whether such drugs can cross the blood-brain barrier or will interfere with other forms of treatment. A new study led by investigators at Brigham and Women's Hospital evaluates data from more than 1,500 cancer programs across the country to gather a large enough dataset to determine the effectiveness of checkpoint blockade immunotherapies. The study found that these therapies provided significant improvements in overall survival for patients with melanoma brain metastases. Their results are published this week in Cancer Immunology Research.

"Our findings build on the revolutionary success of checkpoint blockade immunotherapy clinical trials for advanced melanoma and demonstrate that their substantial survival benefits also extend to melanoma patients with brain metastases," said corresponding author J. Bryan Iorgulescu, MD, postdoctoral fellow in the Department of Pathology at Brigham and Women's Hospital/Harvard Medical School and Department of Medical Oncology at the Dana-Farber Cancer Institute.

Approximately 1 in 54 people will develop melanoma in their lifetime, most of whom will be diagnosed early and cured by having the tumor surgically removed. But for patients with advanced disease, the median overall survival rate is less than a year. Advanced melanoma tends to spread to the brain and is the third most common cause of metastatic brain cancer.

Recent FDA approval of checkpoint blockade immunotherapies and targeted therapies, such as BRAF inhibitors, have added new options for treating advanced melanoma. These novel therapeutics have produced exciting preliminary results in clinical trials of patients with advanced melanoma. However, many trials to date have excluded patients whose skin cancer has spread to the brain, making it unclear if these benefits would extend to this patient population.

In the current study, a research team that included investigators from the Brigham and Dana-Farber Cancer Institute compiled data from more than 2,753 patients from cancer hospitals across the country. Patients who received checkpoint blockade immunotherapy had an average survival of 12.4 months (compared to 5.2 months for those who did not receive immunotherapy), and had a four-year survival rate of 28.1 percent (compared to 11.1 percent for those who did not receive immunotherapy). For patients whose cancer had not spread beyond the brain (to the lungs and/or liver, for instance), these improvements were even more dramatic.

"Through the use of nationwide cancer data, for the first time we can evaluate the impacts on survival that these exciting new therapies have for patients with melanoma brain metastases," said senior author Timothy Smith, MD, PhD, MPH, Director of the Computational Neuroscience Outcomes Center at the Department of Neurosurgery at Brigham and Women's Hospital/Harvard Medical School. "This highlights the power of population data to help answer critical, but previously unanswerable, questions that we face every day in clinical practice."

"Historically, central nervous system metastases from melanoma as well as other solid tumor types have proven particularly challenging to treat, with most therapeutic approaches providing minimal clinical benefit for patients," said co-author David Reardon, MD, clinical director of the Center for Neuro-Oncology at Dana-Farber and professor of medicine at Harvard Medical School. "The results of our analyses indicate that immune checkpoint inhibitors can achieve a meaningful therapeutic benefit for metastatic melanoma, including spread to the central nervous system. At the same time, not all patients benefit, indicating that much research is still required to optimize the potential of anti-tumor immune responses for CNS metastatic disease."

The authors note that insurance status was an important barrier to receiving checkpoint blockade immunotherapy in melanoma brain metastasis patients. Uninsured patients were significantly less likely to receive the treatment than those who were insured privately or through Medicare - a situation suggesting that additional efforts are needed to ensure patient access to these critical therapies.