Body

In a nationwide study, researchers used magnetic resonance imaging (MRI) to scan the brains of hundreds of participants in the National Institutes of Health's Systolic Blood Pressure Intervention Trial (SPRINT) and found that intensively controlling a person's blood pressure was more effective at slowing the accumulation of white matter lesions than standard treatment of high blood pressure. The results complement a previous study published by the same research group which showed that intensive treatment significantly lowered the chances that participants developed mild cognitive impairment.

"These initial results support a growing body of evidence suggesting that controlling blood pressure may not only reduce the risk of stroke and heart disease but also of age-related cognitive loss," said Walter J. Koroshetz, M.D., director of the NIH's National Institute of Neurological Disorders and Stroke (NINDS). "I strongly urge people to know your blood pressure and discuss with your doctors how to optimize control. It may be a key to your future brain health."

Brain white matter is made up of billions of thin nerve fibers, called axons, that connect the neurons with each other. The fibers are covered by myelin, a white fatty coating that protects axons from injury and speeds the flow of electrical signals. White matter lesions, which appear bright white on MRI scans, represent an increase in water content and reflect a variety of changes deep inside the brain, including the thinning of myelin, increased glial cell reactions to injury, leaky brain blood vessels, or multiple strokes. These changes are associated with high blood pressure, or "hypertension".

As described on the NIH's Mind Your Risks website, several studies have suggested that people who have hypertension have a greater chance of accumulating white matter lesions and also of experiencing cognitive disorders and dementia later in life.

These observations were tested in a "gold standard" randomized clinical trial, called SPRINT Memory and Cognition in Decreased Hypertension (MIND), which examined whether controlling blood pressure levels could prevent or slow white matter lesion progression and aging brain disorders. The results were published on Aug. 13, 2019 in the Journal of the American Medical Association.

"These findings on white matter lesions - primarily in the aggressive control of blood pressure - are encouraging as we continue to advance the science of understanding and addressing the complexities of brain diseases such as Alzheimer's and related dementias," said Richard J. Hodes, M.D., director of the NIH's National Institute on Aging (NIA).

Launched in 2010, the NIH-supported SPRINT effort initially enabled scientists to compare the effects of standard versus intensive blood pressure control on cardiovascular health and mortality. More than 9,300 adults who were at least 50 years old and had a high risk for cardiovascular disease received either standard treatment, which lowered systolic blood pressure, the first of two numbers measured during an exam, to less than 140 mm Hg (

The NIA and NINDS supported sub-study, SPRINT MIND, enabled scientists from 27 clinical sites to examine the effects these treatments had on the brain by measuring cognitive function and acquiring MRI scans on a subset of SPRINT participants. The researchers compared brain scans of 449 participants that were taken at enrollment and four years later. During this time, the average increase in total volume of white matter lesions on scans of the intensive treatment group was 0.92 cm3, which was less than the 1.45 cm3 seen on scans from the standard treatment participants.

"Intensive treatment significantly reduced white matter lesion accumulation in people who had a higher chance of experiencing this kind of damage because they had high blood pressure," said Clinton B. Wright, M.S., M.D., director of the Division of Clinical Research at NINDS, and an author of the study.

The SPRINT MIND researchers also reported slightly more loss of brain volume in the intensive treated group than those in the standard treatment. The effect was seen predominantly in males. However, the authors noted this loss was generally very small and of unclear clinical significance.

"SPRINT MIND has produced promising initial results in the battle against the nation's growing problem with aging brain disorders. Both the brain scans and the cognitive tests reinforce the potential benefits that intensive blood pressure management may have on the brain," said Lenore J. Launer, Ph.D., a senior investigator in the NIA Laboratory of Epidemiology and Population Sciences and co-author of the paper. "We hope that these findings will become the foundation for future studies on how to protect the brain throughout a person's life."

In the future, SPRINT MIND researchers plan to look at how controlling blood pressure may affect the accumulation of white matter lesions in critical regions of the brain affected by aging brain disorders and what factors may make some people more responsive to treatment.

With the help of new technology, the researchers of the University of Turku in Finland have gained more detailed information on the diversity of the human lymphatic system than before. The research results can help to understand the human defence mechanisms on the molecular level even better than before. Several cancers, such as breast cancer and head and neck cancers, spread primarily via the lymphatic system.

The transfer of white blood cells between the lymphatic vessels, lymphoid organs, and blood circulation is the backbone of the human defence mechanism.

"The lymphatic system transports pathogens from the inflamed area, such as flesh wound, to sentinel lymph nodes, in which lymphocytes become activated and trained to destroy the intruders. Ready for action, the lymphocytes then leave the lymph nodes and proceed purposefully via blood circulation to the wound to wipe out the pathogens," explains Academician of Science, Professor of Immunology Sirpa Jalkanen from the University of Turku.

However, lymphocyte activation requires time, and that is why briskly functioning neutrophils are needed in the frontline of defence to destroy the pathogens and to prevent the inflammation from spreading without the training phase.

"For decades, the lymphatic vasculature has been thought to be only a passive set of channels in which cells and fluids flow from the peripheral parts of the body and return to blood circulation with the pumping force powered by heartbeat and the valves preventing the reflux of lymph," says Jalkanen.

Led by Jalkanen, the research group analysed the lymphatic vasculature of the human lymph nodes with the help of single-cell sequencing and found six different groups of lymphatic vessels that are situated at strategic spots in the lymph nodes and express molecules typical of each group. Single-cell sequencing is a revolutionary technique used to investigate cell diversity.

The researchers focused particularly on the trafficking and adhesion molecules used by neutrophils that have previously been completely unknown. They were able to show that neutrophils are situated as gatekeepers at the mouths of the vessels exiting the lymph nodes. This is needed in case of inflammations in order to prevent the pathogens from spreading elsewhere in the body.

"Our research results open up new perspectives to understanding the defence mechanism on the molecular level. For drug development, the results also offer potential new target molecules to regulate immune defence and prevent the spread of cancer, as several cancers, such as breast cancers and head and neck cancers, spread primarily via the lymphatic system," says Postdoctoral Researcher Akira Takeda, who is the first author of the research publication.

Regular exercise is healthy and reduces the risk of cardiovascular disease. Nevertheless, it appears that prolonged and/or intensive exercise can lead to an increase in cardiac biomarkers in the blood, such as the regulatory protein troponin. Troponin is a protein that is present in every heart muscle cell. In the event of damage to the heart, these proteins leak into the blood vessels. An increased troponin concentration in the blood is therefore used to diagnose a heart attack, among other purposes. But the implications of increased troponin levels after exercise had not been systematically investigated until now.

Research involving participants in a long-distance walking event

To investigate the relevance of this increased troponin concentration after exercise, physiologists of the Radboud University Medical Center (Nijmegen, the Netherlands) and John Moores University (Liverpool, United Kingdom) took blood samples from 725 walkers before and after a bout of prolonged walking exercise and determined the troponin concentration. Subsequently, the research team contacted the walkers annually to determine their cardiovascular health and survival status.

Higher risk

"After ten years of research we can finally answer this important question," says researcher Thijs Eijsvogels. "Of the participants who had a high troponin concentration after walking, 27% developed severe cardiovascular disease or died during follow-up, while this was the case for only 7% in the group of participants with a low troponin concentration after walking. This study shows for the first time that an exercise-related increase in troponin is clinically relevant."

Stress test for the heart

PhD student Vincent Aengevaeren emphasizes that these findings are not necessarily bad news for people who exercise regularly: "You can consider exercise as a stress test for the heart, and walkers with a high troponin concentration may be suffering from sub-clinical cardiovascular disease that has not yet been diagnosed. Therefore, our findings may contribute to early identification of susceptible individuals in the future, so that appropriate treatment can be started." Eijsvogels also warns against misinterpreting the results: "It is simply not the case that exercise is harmful to your heart. People who exercise regularly live 3 to 6 years longer than those who do not, so getting enough exercise remains important for everyone."

PHILADELPHIA -A new large population-based study from the Sidney Kimmel Cancer Center - Jefferson Health shows that novel oral androgen signaling inhibitor therapies are associated with an increased risk of death in patients with pre-existing cardiovascular conditions. The research was published in the journal European Urology.

"Data from published clinical trials revealed a small but significant increase in the incidence of cardiovascular toxicity in patients treated with androgen deprivation therapy," says corresponding author Grace Lu-Yao, PhD, MPH, professor and vice chair of medical oncology at Thomas Jefferson University and associate director of population science at the Sidney Kimmel Cancer Center - Jefferson Health. "However, little was known about the short-term mortality in men with cardiovascular risk factors treated with these novel oral androgen signaling inhibitor therapies, especially among patients who did not qualify for clinical trials."

"This study fills that major knowledge gap: what are the clinical outcomes of men with advanced prostate cancer and pre-existing cardiovascular conditions treated with these novel oral androgen inhibitor therapies?" says Dr. Lu-Yao. "The outcomes of this study provide new relevant data to facilitate patient-physician discussions about the risks and benefits of treatment for men with advanced prostate cancer."

Men with advanced prostate cancer that progressed on androgen deprivation therapy (ADT) are typically treated with novel androgen signaling inhibitor therapies such as abiraterone acetate and enzalutamide. Many of the pivotal studies which led to the approval of these therapies excluded men with multiple cardiovascular co-morbidities. As a result, the risk in these patients is poorly understood.

In order to explore this question, Dr. Lu-Yao and colleagues conducted a large-scale population-based study. The team examined data from 3,876 patients with advanced prostate cancer collected in the Surveillance, Epidemiology, and End Results (SEER) database, which covers about 30% of the US population. Sixty-seven percent of the men treated with abiraterone acetate or enzalutamide had at least one pre-existing cardiovascular condition (such as congestive heart failure, acute myocardial infarction, stroke, atrial fibrillation and ischemic heart disease) in addition to prostate cancer. The results showed a higher 6-mortality after starting androgen-inhibition therapy in patients who had pre-existing cardiovascular conditions.

To explore that result in finer detail, the study examined the outcomes by chemotherapy use, since patients whose cancers no longer respond to chemotherapy tend to have more advanced disease and shorter life expectancy than those who have not been on chemotherapy. They found that compared to patients receiving the same therapy for prostate cancer without pre-existing cardiovascular conditions, those with at least three heart conditions had a 43% increase in the relative risk of 6-month mortality (if they had chemotherapy before using the oral androgen signaling inhibitor therapy) and a 56% increase in the relative risk of 6-month mortality among patients without documented chemotherapy use. In essence, having three or more pre-existing cardiovascular conditions was associated with roughly a 50% increase in mortality.

In addition, the researchers examined changes in hospitalization rates following the use of the two oral androgen inhibitors. Among the no-chemotherapy group, abiraterone acetate is associated with an increase in post-treatment hospitalization but the same pattern was not observed in enzalutamide patients. Among patients with at least three pre-existing cardiovascular conditions and no history of chemotherapy, enzalutamide is associated with a 41% lower post-treatment hospitalization rate compared to abiraterone acetate.

The researchers found that abiraterone acetate is associated with increased hospitalizations in patients taking various classes of medications. "In addition to blocking androgen synthesis, abiraterone acetate may interact with many drugs and lead to higher risk of toxicity from a wide range of other medications," says Dr. Lu-Yao. "Further studies are warranted to understand the potential mechanisms underlying the observations."

"The findings bring home the importance in having multidisciplinary teams weigh-in on treatment decisions for cancer patients," says co-author Wm. Kevin Kelly, DO, professor of medical oncology and director of solid tumor oncology at the Sidney Kimmel Cancer Center - Jefferson Health.

In response to the study's findings, Drs. Lu-Yao and Kelly are working with cardiologists to monitor the risk of adverse CVD events and develop alternative treatment strategies.

Baltimore, MD., August. 13 -- The vaginal microbiome is believed to protect women against Chlamydia trachomatis, the etiological agent of the most prevalent sexually transmitted infections (STIs) in developed countries. New research by the University of Maryland School of Medicine (UMSOM) shows how the microbiome can either protect or make a woman more susceptible to these serious infections.
The research is important amid a rising number of cases of chlamydia worldwide. In the U.S. alone, 1.7 million cases of chlamydia were reported in 2017, a 22% increase since 2013, according to data from the Centers for Diseases Control and Prevention (CDC).

"Chlamydia is a major growing health issue in the U.S., and more work is needed to understand why some women are apparently naturally protected while other are not," commented Jacques Ravel, PhD, Professor of Microbiology and Immunology, Associate Director and Senior Scientist at the Institute for Genome Sciences (IGS) at UMSOM. Dr. Ravel is also a Principal Investigator for this research.

"Our novel research aims to decipher the mechanistic and functional underpinnings of communication between the host and the cervicovaginal microbiome to better understand resistance and susceptibility to this infection."

An Important Mechanism in Vaginal Microbiome

While Lactobacillus-dominated microbiota in a woman's vagina has long been suspected to provide a protective barrier against STIs like chlamydia, investigators at IGS and the University of Maryland School of Dentistry (UMSOD) are reporting for the first time a mechanism enabling specific types of cervicovaginal microbiome to predispose cells in the vagina and cervix to resist chlamydial infection.

"We will now be able to leverage these microbiomes to identify women at risk of infections, but more importantly to develop improved strategies to restore an optimal protection when it is lacking. Unlike our genes, the vaginal microbiome can be modulated to increase protection against chlamydia, but also against other sexually transmitted infections, including HIV," said Dr. Ravel of the research, which was published today in mBio, "Cervicovaginal Microbiota-Host Interaction Modulates Chlamydia trachomatis Infection."

The investigators have shown previously that five major types of vaginal microbiome exist, four of which are dominated by a different species of Lactobacillus, while the fifth has very low numbers of Lactobacillus bacteria and is associated with an increased risk of adverse outcomes including STIs, such as HIV, and even premature births.

The current research showed that Lactobacillus iners, a bacterium actually commonly found in the vagina did not optimally protect human cells against chlamydial infection, while products of Lactobacillus crispatus, another Lactobacillus species frequently found in the vagina, did.

Previously published research has hinted at L. iners being a risk factor for STI; however, the mechanism by which these bacteria were specifically suboptimal at protecting women against STI has remained elusive. Like other Lactobacillus, L. iners produces lactic acid, but only the L isoform. The researchers found that D-lactic acid, not L-lactic acid, down-regulates cell cycling through epigenetic modifications thus blocking C. trachomatis entry into the cell, one of the pathogen key infectious process, among other processes.

Thus, a rather unexpected result of this study is that the vaginal microbiome does not affect the pathogen per se, but drives susceptibility or resistance to infection, by modifying the cells that line up the cervicovaginal epithelium. The researchers further demonstrated that exposure to optimal vaginal microbiota provided long term protection, which has major implication on how a woman is protected. These mechanisms are now being exploited to develop strategies to optimize protection against C. trachomatis infections but also other STIs.

Patrik Bavoil, PhD, Professor & Chair, Department of Microbial Pathogenesis, University of Maryland School of Dentistry, a well-known expert in C. trachomatis biology and pathogenesis, is a Co-Principal Investigator with Dr. Ravel on the NIH funding that supported this study. The investigators also collaborated with Larry Forney, PhD at the University of Idaho.

"Chlamydia is reputed to be a most difficult microorganism to study. By hiding inside cells, the pathogen routinely avoids antimicrobial host defenses. By causing mostly asymptomatic infection, it often escapes detection by both the infected host and the physician alike," said Dr. Bavoil. "What we have done in this study through several years of hard work by dedicated researchers is to provide, for the first time, a huge, new stepping stone on which future translational research to exploit the microbiome in the fight against chlamydial infection and disease, can be based."

Consuming flavonoid-rich items such as apples and tea protects against cancer and heart disease, particularly for smokers and heavy drinkers, according to new research from Edith Cowan University (ECU).

Researchers from ECU's School of Medical and Health Sciences analysed data from the Danish Diet, Cancer and Health cohort that assessed the diets of 53,048 Danes over 23 years.

They found that people who habitually consumed moderate to high amounts of foods rich in flavonoids, compounds found in plant-based foods and drinks, were less likely to die from cancer or heart disease.

No quick fix for poor habits

Lead researcher Dr Nicola Bondonno said while the study found a lower risk of death in those who ate flavonoid-rich foods, the protective effect appeared to be strongest for those at high risk of chronic diseases due to cigarette smoking and those who drank more than two standard alcoholic drinks a day.

"These findings are important as they highlight the potential to prevent cancer and heart disease by encouraging the consumption of flavonoid-rich foods, particularly in people at high risk of these chronic diseases," she said.

"But it's also important to note that flavonoid consumption does not counteract all of the increased risk of death caused by smoking and high alcohol consumption. By far the best thing to do for your health is to quit smoking and cut down on alcohol.

"We know these kind of lifestyle changes can be very challenging, so encouraging flavonoid consumption might be a novel way to alleviate the increased risk, while also encouraging people to quit smoking and reduce their alcohol intake."

How much is enough?

Participants consuming about 500mg of total flavonoids each day had the lowest risk of a cancer or heart disease-related death.

"It's important to consume a variety of different flavonoid compounds found in different plant based food and drink. This is easily achievable through the diet: one cup of tea, one apple, one orange, 100g of blueberries, and 100g of broccoli would provide a wide range of flavonoid compounds and over 500mg of total flavonoids".

Dr Bondonno said while the research had established an association between flavonoid consumption and lower risk of death, the exact nature of the protective effect was unclear but likely to be multifaceted.

"Alcohol consumption and smoking both increase inflammation and damage blood vessels, which can increase the risk of a range of diseases," she said.

"Flavonoids have been shown to be anti-inflammatory and improve blood vessel function, which may explain why they are associated with a lower risk of death from heart disease and cancer.".

Dr Bondonno said the next step for the research was to look more closely at which types of heart disease cancers were most protected by flavonoids.

LEAWOOD, Kansas--Early findings from two major federally funded initiatives aimed at accelerating the development and dissemination of health care innovation in the United States were published today as a special supplement to the Annals of Family Medicine. The collective body of work, funded by the Centers for Medicare and Medicaid Services, will help inform how the United States will support medical practice transformation and community health improvement efforts in the years ahead.

In 2015, CMS launched the Transforming Clinical Practice Initiative to help transform the US health care system to one that rewards value over volume. The four-year, nearly $700 million initiative linked more than 140,000 clinicians in all specialties through networks designed to coach, mentor and assist practices in developing the core competencies required to successfully participate in value-based payment arrangements. TCPI also facilitated connections with national and regional professional associations and public-private partnerships to ensure the sustainability of transformation efforts through the active engagement of specialty societies.

The Agency for Health Care Research and Quality's EvidenceNOW initiative received $112 million in grant funding to help primary care practices across the country more rapidly improve the heart health of Americans. Specifically, aligned with the US Department of Health and Human Services Million Hearts® initiative, EvidenceNOW aimed to reduce the research-to-practice delay in implementing best practices to deliver the ABCS of cardiovascular disease prevention: aspirin in high-risk individuals, blood pressure control, cholesterol management, and smoking cessation.

The special report by Kaufman et al in this supplement reminds us of the important history behind EvidenceNOW and TCPI. Section 5405 of the Patient Protection and Affordable Care Act authorized the Primary Care Extension Program, which was modeled after the US Department of Agriculture's Cooperative Extension Program. That USDA program revolutionized farming in the United States over the last century by testing and speeding dissemination of innovation and best practices. Its application to health care was pilot-tested by the Regional Extension Centers under the Health Information Technology for Economic and Clinical Health Act of 2009. The success of that pilot program inspired the design of EvidenceNOW and further supported the decision by CMS to invest in the TCPI demonstration project.

This supplement to the Annals of Family Medicine combines early findings from multiple examples of health extension and practice transformation support. The supplement consists of seven original research articles, one research brief, three special reports, three one-page innovations in primary care, and two commentaries from nationally recognized experts in primary care research and practice transformation.

Original research findings include:

Primary care transformation requires continuing efforts to monitor and address clinician and staff burnout.
Practice changes that reduce clinician burnout may not decrease--and may potentially worsen--burnout among staff.

A Longitudinal Study of Trends in Burnout During Primary Care Transformation
By Kevin Grumbach, et al, San Francisco, California

http://www.annfammed.org/content/17/Suppl_1/S9

Small independent primary care practices perceived facilitation to be an important resource for connecting their practice to the external health care environment.
Connecting to the external health care environment helps small independent practices build their quality improvement capacity through teaching, hands-on support and EHR-driven solutions.

Clinician Perspectives on the Benefits of Practice Facilitation for Small Primary Care Practice
By Erin Rogers, DrPH, et al, New York, New York

http://www.annfammed.org/content/17/Suppl_1/S17

The Primary Care Redesign team-based model promotes simultaneous improvements in quality, access and clinician experience while maintaining staffing costs.
The model increased the ratio of medical assistants and expanded their role in patient care. Clinicians experienced a reduction in burnout without increasing staffing costs.

Practice Transformation Under the University of Colorado's Primary Care Redesign Model
By Peter Chabot Smith, MD, et al, Aurora, Colorado

http://www.annfammed.org/content/17/Suppl_1/S24

Technical assistance to help practices expand access to urgent care can be provided remotely and at scale at low per-practice cost.
Through the provision of timely, easily accessed ambulatory care, optometrists were able to improve patient experience, reduce emergency department use and lower costs.

Transformation Support Provided Remotely to a National Cohort of Optometry Practices
By Ronald Adler, MD, et al, Worcester, Massachusetts

http://www.annfammed.org/content/17/Suppl_1/S33

A practice's ability to reach improved clinical quality measurement performance may be enhanced by adding both educational outreach visits and shared learning to practice facilitation.
Smaller practices can improve their performance on cardiovascular disease risk factors with external support. However, these practices many lack the capacity to participate in these additional supports.

A Randomized Trial of External Practice Support to Improve Cardiovascular Risk Factors in Primary Care
By Michael Parchman, MD, MPH, et al, Seattle, Washington

http://www.annfammed.org/content/17/Suppl_1/S40

The methods by which cognitive clinical functions are assigned among team members is challenging and requires facilitation.
The distribution of macrocognitive functions across team members in the patient-centered medical home model is a skill that can be taught, but it cannot be learned from meetings, seminars or lists of best practices. Practice facilitation is essential.

Differences In Team Mental Models Associated With Medical Home Transformation Success
By Lee Green, MD, MPH, et al, Edmonton, Alberta

http://www.annfammed.org/content/17/Suppl_1/S50

Telemedicine is a feasible intervention in multiple primary care settings.
The TIP model (Telemedicine IMPACT - Interprofessional Model of Practice for Aging and Complex Treatments) Plus allows patients to have an active role in their health management, supported by their health care team. This model effectively addresses the needs of the most complex patients and their primary care physicians.

Connecting People With Multimorbidity to Interprofessional Teams Using Telemedicine
By Jocelyn Charles, MD, MScCH, et al, Toronto, Ontario

http://www.annfammed.org/content/17/Suppl_1/S57

EDITORIALS

Facilitating Practice Transformation in Frontline Health Care
By Robert Phillips, Jr, MD, MSPH, et al, Lexington, Kentucky

The articles published in this supplement tell a story of practices needing relationships and real support in achieving meaningful improvement, if not fundamental transformation. The researchers offer insight for helping practices make use of technology to strengthen relationships with patients and to offer complex patients expanded services. They bring to the fore the complexity and spectrum of practice culture and the need to meet them where they are in order to help the difficult process of change.

http://www.annfammed.org/content/17/Suppl_1/S24

Contribution of the Transforming Clinical Practice Initiative in Advancing the Movement to Value-Based Care
By Meena Abraham, DrPH, MPH and Paul McGann, MD, Baltimore, Maryland

This editorial provides context about the ongoing TCPI test model to help readers understand the broader effort addressed by the quality improvement articles in this supplement. To put patients first, CMS is working in concert with partners in the private, public, and nonprofit sectors to transform the nation's health care system to one that rewards value over volume, more closely aligning payment with the quality of care. One way to do this is through alternative payment models, payment approaches developed in partnership with the clinician community that provide added incentives for delivering high-quality, cost-efficient care. To ease the transition for practices, CMS launched TCPI to prepare them for success in achieving outcomes to demonstrate APM success and improvements critical to practice success. The TCPI service delivery (nonpayment) model ends in September 2019, and the continuation of practice transformation and commitment to value-based care rests with the professional associations and clinical practice that took part in the initiative. Although continued efforts will be necessary to move toward a value-based system in the future, the TCPI Practice Transformation Networks and Support and Alignment Networks have identified best practices for preparing both primary care and specialty care clinicians for participation in APMs. Practices that graduated from TCPI are well positioned to participate in APMs, including in the new models announced by the CMS Innovation Center.

http://www.annfammed.org/content/17/Suppl_1/S67

SPECIAL REPORTS

The Role of Health Extension in Practice Transformation and Community Health Improvement: Lessons From 5 Case Studies
By Arthur Kaufman, MD, et al, Albuquerque, New Mexico

http://www.annfammed.org/content/17/Suppl_1/S67

Practice Transformation Analytics Dashboard for Clinician Engagement
By Niharika Khanna, MD, MBBS, DGO, et al, Baltimore Maryland

http://www.annfammed.org/content/17/Suppl_1/S73

Supporting Physicians & Practice Teams in Efforts to Address the Opioid Epidemic
By Lisa M. Letourneau,MD, MPH, et al, Augusta, Maine

http://www.annfammed.org/content/17/Suppl_1/S77

RESEARCH BRIEF

Clinicians' Overestimation of Their Geographic Service Area
By Robert Rock, MD, et al, Bronx, New York

http://www.annfammed.org/content/17/Suppl_1/S63

INNOVATIONS IN PRIMARY CARE

Brief one-page articles that describe novel innovations from health care's front lines.

Improved Outcomes Associated With Interprofessional Collaborative Practice
By Thomas P. Guck, PhD, et al, Omaha, Nebraska

http://www.annfammed.org/content/17/Suppl_1/S82

Coaching Small Primary Care Practices to Utilize Patient Portals
By Lauren Gritzer; MPH, et al, Baltimore, Maryland

http://www.annfammed.org/content/17/Suppl_1/S83

An Empanelment Toolkit for the Safety-Net Clinic Setting
By Stella Gukasyan, EdM, and Mike Wong, MPH, San Diego, California

http://www.annfammed.org/content/17/Suppl_1/S84

Rift Valley fever virus is a global health concern that is caused by infected mosquitos and the handling of infected animal carcasses.

Every 10 to 15 years, the viral disease has led to outbreaks in Africa. In the late 1990s, it spread across five African countries and infected 90,000 people, killing 500 of them. That's not even counting the waves of livestock deaths reported by farmers and veterinarians.

What would happen if Rift Valley fever virus ever hit the United States?

With multiple routes of entry into the U.S. and the most likely path of introduction being an infected traveler from overseas, the consequences for humans and livestock would be significant, according to research by a team at Colorado State University.

The researchers investigated mosquito communities near livestock feedlots in Northern Colorado to determine the potential for mosquitoes to transmit the virus. They found that Culex tarsalis mosquitoes, which were abundant in feedlots and at nearby sites, could serve as a vector or means of transmitting Rift Valley fever virus between livestock and humans in Colorado.

The study was published earlier this year in Transboundary and Emerging Diseases.

Rebekah Kading, assistant professor in CSU's Department of Microbiology, Immunology and Pathology, said that previous research analyzing possible transmission of the virus was conducted only in laboratory settings.

This new CSU research and fieldwork adds ecological context to the lab data, in terms of determining which mosquito species actually feed on humans and livestock. This is important to uncover clues as to how Rift Valley fever virus might circulate in the real world. Combining this information from laboratory and field studies also will help determine which mosquitoes would be a priority to control to prevent a possible outbreak.

Public Enemy No. 1

Culex tarsalis mosquitoes are the main vector transmitting West Nile virus in Colorado, and they are known to easily transmit other viruses in the lab.

"It's one of the most medically important species in Colorado and in the United States," Kading said.

Daniel Hartman, the study's lead author and a CSU doctoral student studying microbiology, described Culex tarsalis mosquitoes as Public Enemy No. 1.

"Lab studies show these mosquitoes have very high transmission rates," he said. "We've now found that this mosquito is in and near feedlots. It will bite a cow and, presumably, it would bite another cow. That's the complete transmission cycle for a virus."

Assistant Professor Rebekah Kading has been studying Rift Valley fever virus for a number of years. Nicholas Bergren, a postdoctoral fellow in Kading's Lab, is looking at vertical transmission, the transfer of a virus from the female mosquito to her offspring. Photo: John Eisele/CSU Photography

The research team studied mosquitoes at four Northern Colorado locations, pairing livestock feedlots and sites without livestock less than 1.5 miles away. Mosquitoes were collected over several months in summer 2016. Researchers subsequently analyzed their blood meals to learn more about their diet.

Kading, who joined the CSU faculty in 2016, first became interested in the virus seven years ago, when she was working at the Centers for Disease Control and Prevention's Division of Vector-Borne Diseases in Fort Collins.

She has traveled to the Zika forest of Uganda to study the role of bats in disease transmission and conducted research on malaria in Zambia as part of her doctoral dissertation.

Tracking behavior, virus transmission between mosquitoes, offspring

Hartman said he and the team are now taking a closer look at the behavior of the mosquitoes, to try to get a better sense of how different species of mosquitoes could contribute to transmitting Rift Valley fever if it was introduced in the U.S.

"We also know that deer are highly susceptible to this virus, so we can look at the magnitude of transmissions," he said.

Kading said the CSU team will continue to fill in gaps in the data related to this virus.

"With some of the mosquito species from our field study, we learned more about blood meals from deer and cattle," she said. "But there is little or no vector competence data available for them. Now, in the lab, we want to 'challenge' those mosquitoes, to see if they're capable of transmitting Rift Valley fever virus."

In addition to this lab research, Kading's team is looking at vertical transmission, the transfer of a virus from the mother mosquito to her offspring.

Nicholas Bergren, a co-author on the paper and a postdoctoral fellow in Kading's Lab, explained how the transmission works. "The eggs get infected, so the female passes the virus on to offspring mosquitoes, which then continue to transmit the virus," he said.

Researchers have documented this type of vertical transmission with bunyaviruses including La Crosse encephalitis.

Eating extra servings typically shows up on the scale later, but how this happens has not been clear. A new study published today in the Journal of Clinical Investigation by a multi-institutional team led by researchers at Baylor College of Medicine reveals a previously unknown gut-brain connection that helps explain how those extra servings lead to weight gain.

Mice consuming a high-fat diet show increased levels of gastric inhibitory polypeptide (GIP), a hormone produced in the gut that is involved in managing the body's energy balance. The study reports that the excess GIP travels through the blood to the brain where it inhibits the action of leptin, the satiety hormone; consequently, the animals continue eating and gain weight. Blocking the interaction of GIP with the brain restores leptin's ability to inhibit appetite and results in weight loss in mice.

"We have uncovered a new piece of the complex puzzle of how the body manages energy balance and affects weight," said corresponding author Dr. Makoto Fukuda, assistant professor of pediatrics at Baylor and the USDA/ARS Children's Nutrition Research Center at Baylor and Texas Children's Hospital.

Researchers know that leptin, a hormone produced by fat cells, is important in the control of body weight both in humans and mice. Leptin works by triggering in the brain the sensation of feeling full when we have eaten enough, and we stop eating. However, in obesity resulting from consuming a high-fat diet or overeating, the body stops responding to leptin signals - it does not feel full, and eating continues, leading to weight gain.

"We didn't know how a high-fat diet or overeating leads to leptin resistance," Fukuda said. "My colleagues and I started looking for what causes leptin resistance in the brain when we eat fatty foods. Using cultured brain slices in petri dishes we screened blood circulating factors for their ability to stop leptin actions. After several years of efforts, we discovered a connection between the gut hormone GIP and leptin."

GIP is one of the incretin hormones produced in the gut in response to eating and known for their ability to influence the body's energy management. To determine whether GIP was involved in leptin resistance, Fukuda and his colleagues first confirmed that the GIP receptor, the molecule on cells that binds to GIP and mediates its effects, is expressed in the brain.

Then the researchers evaluated the effect blocking the GIP receptor would have on obesity by infusing directly into the brain a monoclonal antibody developed by Dr. Peter Ravn at AstraZeneca that effectively prevents the GIP-GIP receptor interaction. This significantly reduced the body weight of high-fat-diet-fed obese mice.

"The animals ate less and also reduced their fat mass and blood glucose levels," Fukuda said. "In contrast, normal chow-fed lean mice treated with the monoclonal antibody that blocks GIP-GIP receptor interaction neither reduced their food intake nor lost body weight or fat mass, indicating that the effects are specific to diet-induced obesity."

Further experiments showed that if the animals were genetically engineered to be leptin deficient, then the treatment with the specific monoclonal antibody did not reduce appetite and weight in obese mice, indicating that GIP in the brain acts through leptin signaling. In addition, the researchers identified intracellular mechanisms involved in GIP-mediated modulation of leptin activity.

"In summary, when eating a balanced diet, GIP levels do not increase and leptin works as expected, triggering in the brain the feeling of being full when the animal has eaten enough and the mice stop eating," Fukuda said. "But, when the animals eat a high-fat diet and become obese, the levels of blood GIP increase. GIP flows into the hypothalamus where it inhibits leptin's action. Consequently, the animals do not feel full, overeat and gain weight. Blocking the interaction of GIP with the hypothalamus of obese mice restores leptin's ability to inhibit appetite and reduces body weight."

These data indicate that GIP and its receptor in the hypothalamus, a brain area that regulates appetite, are necessary and sufficient to elicit leptin resistance. This is a previously unrecognized role of GIP on obesity that plays directly into the brain.

Although more research is needed, the researchers speculate that these findings might one day be translated into weight loss strategies that restore the brain's ability to respond to leptin by inhibiting the anti-leptin effect of GIP.

Given the recent remarkable advancements in genetics, it's easy to assume that 21st century scientists have at their disposal a clear, quick way to run a genomic sequence scan and find out which genes among thousands can be expressed and which cannot. Gene expression is the process by which information encoded within genes leads to key products, such as proteins.

Surprisingly, that hasn't been possible until now. Biologists at the University of California San Diego have developed the first system for determining gene expression based on machine learning. Given the lack of such a method, the new process is considered a type of genetic Rosetta Stone for biologists.

"This paper represents the first method to distinguish genes that can be expressed from those that cannot," said Steve Briggs, a Division of Biological Sciences professor and senior author of the paper. "This is the basis for all of biology. Whether it's drug discovery or plant breeding or evolution, this touches the basic studies of biology."

The method, developed by graduate student Ryan Sartor, Briggs and their colleagues, is described August 12, 2019 in the Proceedings of the National Academy of Sciences.

Biologists have previously classified gene expression through experimental observations and scientific literature references. But the genomics field lacked a formalized process for revealing this information, called the "expressible gene set," or EGS, which comprises all protein-coding genes with the potential to be expressed.

"In biology, there is no method to do this," said Briggs. "In the past we've just had empirical approaches to making catalogs--we haven't had scientific criteria that classifies the genes based on their molecular features."

The new method leverages machine learning, the use of algorithms and other processes to analyze data, and is based on an example set of nearly 30,000 maize plant genes containing specific, detailed molecular features. An advanced algorithm was trained on the data and "learned" to classify gene expression at 99.4 percent accuracy.

The key to the advancement is bringing together chromatin biology, which contributes to regulating the DNA packaging within cells, with molecular features that are known to determine gene expression. Combining these with mathematical machine learning, the new method of determining the species-wide set of transcribed genes, or "expressome," then creates an atlas of expressible genes. The method may also be useful in understanding evolutionary mechanisms that silence certain genes.

Briggs is now applying the method to sorghum, an important grain for food and fodder, but says it can be useful beyond plant species. Ultimately, he says the new method is like a word decoder.

"The genome sequence is like a book," said Briggs. "The words are the genes. Until now, we couldn't tell which DNA sequences were real words and which merely resembled words. By removing non-words we now have a much more accurate reading of the book."

WASHINGTON (August 12, 2019) -- Resistance to two critical antibiotic types, one a "drug of last resort" when all others fail against some "superbugs," are widely distributed in Southeast Asia, raising the risk of untreatable infections, say a team of investigators led by Georgetown University Medical Center.

The study, published in the International Journal of Antimicrobial Agents, is a comprehensive analysis of resistance to two critical classes of drugs, carbapenems and polymyxins, in eleven nations of Southeast Asia.

The World Health Organization (WHO) has urgently called for global surveillance of antibiotic resistance, and, along with U.S. Centers for Disease Control and Prevention (CDC), identified resistance to these drugs as critical threats. To help better understand the risk in Southeast Asia, the researchers searched widely, extracting and analyzing available international scientific and clinical data. They evaluated resistance to these drugs among E. coli and Klebsiella, two common bacteria that can cause severe infections in humans, particularly in health care settings.

"The picture the data paints is of a serious emerging public health threat. We document that resistance to each drug is geographically widespread in the region, including many areas where the distribution of strains resistant to each type of antibiotic overlaps," says the study's senior investigator, infectious disease specialist Jesse Goodman, MD, MPH, a professor of medicine and director of Georgetown's Center on Medical Product Access, Safety and Stewardship (COMPASS).

The investigators' findings included that resistance to carbapenems, often at significant levels, and resistance to polymyxins, were each widespread and geographically overlapped in 8 countries. Both bacteria also carry and can spread "mobile genetic elements" which can contain genes responsible for conferring resistance that may be transmitted to other bacteria, facilitating the rapid spread of resistance.

Carbapenems have, until recently, been the "go to" treatment for E. coli and Klesiella resistant to more commonly used drugs. However, carbapenem resistant strains have spread around the world. The only available "drugs of last resort" to treat many carbapenem resistant infections have been polymyxins, including colistin. Unfortunately, Goodman says, "in the last few years we have seen the shocking global emergence of colistin resistance, particularly in Asia, in part likely related to use of these drugs in food animal production."

"Although combined carbapenem and colistin resistance is fortunately still rare, the coexistence of mobile resistance genes for both drugs in the same areas, such as we describe, raises the risk of organisms acquiring both, causing essentially untreatable infections."

As the study notes, "These findings highlight the urgent need for sufficiently resourced robust antimicrobial resistance surveillance."

Goodman adds, "we need to enhance infection prevention, treatment and control practices, and related research and development globally, and ensure we use our remaining precious antibiotics wisely. This challenge is global in reach, scope and solutions."

A researcher from the University of Houston has found that adults who take prescription opioids for severe pain are more likely to have increased anxiety, depression and substance abuse issues if they also use marijuana.

"Given the fact that cannabis potentially has analgesic properties, some people are turning to it to potentially manage their pain," Andrew Rogers, said in describing the work published in the Journal of Addiction Medicine. Rogers focuses on the intersection of chronic pain and opioid use, and identifying the underlying psychological mechanisms, such as anxiety sensitivity, emotion regulation, pain-related anxiety, of these relationships. Rogers is a doctoral student in clinical psychology who works in the UH Anxiety and Health Research Laboratory and its Substance Use Treatment Clinic.

Under the guidance of advisor Michael Zvolensky, Hugh Roy and Lillie Cranz Cullen Distinguished University Professor of psychology and director of the lab and clinic, Rogers surveyed 450 adults throughout the United States who had experienced moderate to severe pain for more than three months. The study revealed not only elevated anxiety and depression symptoms, but also tobacco, alcohol, cocaine and sedative use among those who added the cannabis, compared with those who used opioids alone. No increased pain reduction was reported.

Importantly, said Rogers, while the co-use of substances generally is associated with poorer outcomes than single substance use, little work has examined the impact of mixing opioids and cannabis.

Opioid misuse constitutes a significant public health problem and is associated with a host of negative outcomes. Despite efforts to curb this increasing epidemic, opioids remain the most widely prescribed class of medications. Prescription opioids are often used to treat chronic pain, despite the risks, and chronic pain remains an important factor in understanding this epidemic.

Cannabis is another substance that has recently garnered attention in the chronic pain literature, as increasing numbers of people use it to manage chronic pain.

"There's been a lot of buzz that maybe cannabis is the new or safer alternative to opioid, so that's something we wanted to investigate," said Rogers, who said the idea for the study evolved from a conversation with Zvolensky. Rogers was studying opioid use and pain management when they began discussing the role of cannabis in managing pain.

"The findings highlight a vulnerable population of polysubstance users with chronic pain and indicates the need for more comprehensive assessment and treatment of chronic pain," said Rogers.

In Australia, more than 10,000 patients a year acquire a serious bacterial infection called Clostridioides difficile, often while in hospital, resulting in the death of up to 300 people per year. The Centers for Disease Control in the United States (US) call C. difficile a major health threat causing half a million infections and 15,000 deaths every year in the US (around 40 deaths per day). The bacterium thrives in the large intestine when the gut environment has been disrupted by antibiotics.

Researchers from the Monash Biomedicine Discovery Institute (BDI) have discovered an antibiotic that could prevent the life-threatening diarrhoea caused by C. difficile. The treatment strategy could also potentially counter diseases caused by other similar spore-producing bacteria, including the lethal anthrax, a key bioterrorism tool.

The research, led by Professor Dena Lyras, was published in Nature Microbiology on Tuesday 13 August.

According to Professor Lyras the increased use of antibiotics has exacerbated the rise in C. difficile infections.

"Infection with C. difficile arises because of the use of antibiotics," Professor Lyras said.

"The increasing use of antibiotics has perpetuated the problem," she said.

The bacterium produces spores that lie dormant, allowing it to survive in environments where actively growing bacteria would normally perish. The spores can infect and re-infect patients causing disease that can last months.

The interdisciplinary team of researchers serendipitously discovered that a particular class of antibiotic, called cephamycins, can prevent C. difficile spore formation. The researchers were using a liquid commonly used to grow C. difficile in the laboratory and were puzzled that while the bacterium was able to grow, it was not able to produce spores. They found that there was a cephamycin in the media that prevented the formation of spores.

"To confirm this, we used assays to examine spore numbers and found that cultures containing cephamycins had a big reduction in spore numbers," lead author Dr Yogitha Srikhanta said.

Treatment using cephamycins could significantly advance drug development to control other important spore-forming bacteria, the study found.

"We looked at other pathogens including Bacillus cereus - a major contaminant in the food industry which causes food poisoning and spoilage, and showed that cephamycins can also reduce its spore production," Dr Srikhanta said.

Cephamycins could potentially help control the bioterrorism agent anthrax, a disease caused by inhaling the airborne spores of Bacillus anthracis.

"We believe this anti-sporulation treatment strategy could be used with current treatments because it specifically targets a particular pathway that has not been targeted before," Dr Srikhanta said.

"What we've shown in our paper is that when we co-treat mice with the current best standard of care together with our treatment we can prevent recurrent C. difficile disease - that's a big development because recurrent disease accounts for approximately one third of C. difficile treatment costs worldwide," said Dr Sheena McGowan, co-senior author with Professor Lyras.

The treatment could potentially be developed to counter lethal outbreaks of C. difficile such as those that occurred in Canada, the United Kingdom, the US and parts of Europe in the early 2000s.

"C. difficile is not really on peoples' radar the way golden staph is but it's a problem in every single hospital around the world," said Professor Lyras, a world-leading infectious disease researcher and Monash BDI Deputy Director.

Dr McGowan said the fact that cephamycins were already approved as drugs and on the market made the path to clinical trials and outcomes easier.

"Our preliminary study provides an entirely new route to treatment and controlling C. difficile infection. We can see there's going to be a clinical use for the combination treatment we're pursuing," she said.

In the two years since the Korey Stringer Institute (KSI) first assessed all 50 states and the District of Columbia on key health and safety policies for high school athletes, 31 states have adopted new policies -- 16 this year alone.

With more than 7.8 million high school students participating in sanctioned sports each year, the need for comprehensive safety policies and training is critical. Adopting evidence-based safety measures significantly reduces risks, says Douglas Casa, professor of kinesiology and the CEO of KSI at the University of Connecticut.

Now in its third iteration, the annual state-by-state review takes into account the extent to which they met a series of evidence-based best practice guidelines. It is believed to be the only comprehensive assessment of high school sports and safety policies, rating states on implementing important safety guidelines intended to protect student athletes from heat stroke, sudden cardiac arrest, and other potentially life-threatening conditions that may be prevented.

After the original study was released, in 2017, safety advocates and KSI launched a national health and safety campaign, working with state officials and representatives to create new policies and practices to protect student athletes. Now in its third year, the review reflects a wave of improvements since it was introduced.

"We are excited to see so many positive health and safety policy changes for high school athletes across the nation," says Casa. "Many key advocates in states have made strides to push the envelope and make sports safer for those kids - and we are so grateful for their efforts."

New Jersey now leads the nation in safety for student athletes as determined by the adoption of the most health and safety policies. Following New Jersey are Massachusetts, North Carolina, Kentucky, and Georgia, in that order. Three of those states -- North Carolina, Kentucky, and Massachusetts -- have had the best high school sport safety programs in the country since the study was first launched.

Massachusetts is among the many states this year that newly required the use of wet-bulb globe temperature for monitoring the environment during heat waves. That technology offers a comprehensive measure to aid in determining the environmental stress placed on an athlete. Schools in Massachusetts are now required to measure the environment and to make modifications to their activity based on the readings.

"The student athletes deserve these standards and I am happy to see them in place," says John Jardine, Massachusetts Interscholastic Athletic Association (MIAA) sports medicine advisory committee member. "It is exciting that the MIAA has made these strides to implement environmental monitoring policies."

Georgia's policy changes include the requirement of CPR/AED training for all coaches, emergency action plan standards and the mantra "cool first, transport second" for exertional heat stroke treatment. Bud Cooper, a member of the sports medicine advisory committee for the Georgia High School Association says, the association "has been proactive in providing guidance and comprehensive policies that ensure student-athletes are provided the safest environment for participation."

Additional states that adopted important new safety policies over the past year include Utah, Oregon, West Virginia and Colorado. Among those:

Oregon, Colorado and West Virginia now require athletic trainers to be licensed to practice in the state.

New Jersey and Massachusetts both improved their environmental monitoring policies and require their member schools to use wet bulb globe temperature as a measurement of environmental stress placed on athletes.

Utah improved its safety measures by requiring cold water immersion and coaching education in sudden death.

KSI is a national sports safety research and advocacy organization named after a former Minnesota Vikings offensive lineman who died from exertional heat stroke in 2001. The mission of the KSI is to provide research, education, advocacy and consultation to maximize performance, optimize safety and prevent sudden death for the athlete, warfighter and laborer.

Casa notes, "we still have much work to do to get all states to comply with the 2013 best practices recommendations to prevent sudden death in secondary school athletics."

Among women who are kidney transplant recipients, Hispanic women have a higher likelihood of pregnancy than white women, according to new research from the University of Cincinnati (UC). The study, published in the PLOS ONE journal, demonstrates the importance of understanding the factors responsible for these disparities in pregnancy rates.

"Child-bearing is an integral part of a woman's life," says Silvi Shah, MD, assistant professor in the Division of Nephrology, Kidney CARE Program in the Division of Internal Medicine at the UC College of Medicine and lead author of the study. "Although kidney transplant improves reproductive function in women with end-stage kidney disease (ESKD), pregnancy in patients with a kidney transplant is challenging due to risk of adverse maternal and fetal outcomes. Since pregnancy is not uncommon in kidney transplant recipients, it further becomes important to examine the racial differences and factors associated with pregnancy in this high-risk population."

The study evaluated 7,966 women of childbearing age who received a kidney transplant between Jan. 1, 2005 and Dec. 31, 2011, using the United States Renal Data System. The study finds a pregnancy rate of 13.8 per-thousand person years (PTPY) overall, and Hispanic women were 56% more likely than white women to become pregnant.

Overall, 293 pregnancies were identified with a mean age of the study population at the time of transplant of just under 34 years. The rate of pregnancy was highest in Hispanic women (21.4 PTPY) followed by blacks (8.7 PTPY) and whites (7.8 PTPY). The overall rates of pregnancy were higher during the second and third year following the kidney transplant than the first year after the transplant. The study also showed that among transplant recipients, pregnancy was more likely in women with ESKD due to cystic disease or glomerulonephritis (an inflammation in the kidneys) as compared to women with ESKD due to diabetes. The type of donor, duration of dialysis and type of immunosuppression at transplant did not impact the likelihood of pregnancy.

Shah says the study is unique in that it evaluates a comprehensive racial group of patients in the first three years post-transplant to better understand the incidence of pregnancy and factors associated with it among kidney transplant patients. The study further took into account patients with complete Medicare coverage, thus avoiding the potential shortfalls of registries dependent on voluntary reporting or patient recall. The research shows for the first time that pregnancy rates in women with kidney transplants remained constant and did not show a decline, and, in fact, were higher than those shown in prior reports over the previous 10 years.

"This is telling us that there are additional factors, which could be cultural or biological, contributing to these racial differences," Shah says. "While socioeconomic factors and health literacy could play an important role, the real reasons remain unknown. It is imperative to advocate for the inclusion of all races in all studies, and tailor therapies to specific biological states."