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Barcelona--A combination of the EarlyCDT-Lung Test followed by CT imaging in Scottish patients at risk for lung cancer resulted in a significant decrease in late stage diagnosis of lung cancer and may decrease lung cancer specific mortality, according to research presented at IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (IASLC). The research was presented by Prof. Frank Sullivan, from the University of St Andrews, St Andrews/United Kingdom.

Scotland has one of the highest rates of lung cancer in the world - approximately 460 men and 340 women for every 100,000 Scottish citizens are diagnosed with lung cancer every year in the United Kingdom. Less than 9 percent of all lung cancer patients reach their five-year survival mark.

The EarlyCDT®-Lung Test is a novel autoantibody diagnostic test for the early detection of lung cancer that allows stratification of individuals according to their risk of developing lung cancer. The test identifies 41 percent of lung cancers with a high specificity of 90 percent, compared to CT scanning, which identifies 67 percent of lung cancers but with a low specificity of around 49 percent. Specificity refers to a test's ability to correctly identify those who are negative for a disease.

Sullivan and his team sought to determine whether using the EarlyCDT®-Lung Test, followed by X-ray and CT scanning, could identify those at high risk of lung cancer and reduce the incidence of patients with late-stage lung cancer or unclassified presentation (U) at diagnosis, compared to standard clinical practice.

To answer this question, Sullivan randomized 12,208 participants aged 50 to 75 who had a high risk of developing lung cancer over the next 24 months to either the study intervention or standard practice in the United Kingdom. Test positive patients were offered a chest X-ray followed by a non-contrast thoracic CT scan. If the initial CT scan revealed no evidence of lung cancer then subsequent CT scans were offered 6 monthly for 24 months. Individuals with abnormalities were followed up over the study period or referred for clinical care as appropriate. All individuals entering the study were followed up via trial monitoring software linked to Scottish Health Records including the Scottish Cancer Registry.

Sullivan's team discovered that 127 lung cancers were diagnosed in the study period (56 in the intervention group and 71 in the control arm) and 9.8 percent of the intervention group had a positive EarlyCDT-Lung test and 3.4 percent (n=18) of these were diagnosed with lung cancer in the study period.

"The study was not powered to detect a difference in mortality after two years, however there was a non-significant trend suggesting fewer deaths in the intervention arm compared to the control (87 vs 108 respectively). Similar results were noted relating to lung cancer-specific mortality (17 vs 24)," Sullivan reported.

Sullivan added that significantly fewer participants in the intervention group were diagnosed at a late-stage compared with the control group (33 vs 52).

"Our results show that the combination of the EarlyCDT-Lung followed by CT imaging in those with a positive blood test, results in a significant decrease in late stage diagnosis of lung cancer and may decrease all cause and lung cancer specific mortality. We shall continue follow up of all participants' lung cancer and mortality outcomes at 5 years using Scottish ISD (Information Services Division) data to study these effects further."

The rate of chronic hypertension among pregnant women has increased by more than 75 percent since 1970, with black women suffering from persistent high blood pressure at more than twice the rate of white women, according to a Rutgers study.

In the study, published in the journal Hypertension, researchers at Rutgers Robert Wood Johnson Medical School looked at the pregnancies of more than 151 million women in the United States between 1970-2010. Using data from the National Hospital Discharge Survey, which represents all pregnant women during that time, researchers found that while obesity and smoking are proven risk factors, they had no impact on the increase of hypertension throughout the country during the past four decades.

"Women are having children later - 4-5 years older, on average, now than in the 1970s and 1980s - and are experiencing higher rates of hypertension during pregnancy as a result," said Cande V. Ananth, lead author, and chief of the Division of Epidemiology and Biostatistics in the Department of Obstetrics, Gynecology and Reproductive Sciences.

Ananth said advanced maternal age was associated with the increase, with the rate of chronic hypertension increasing on average by 6% per year, 13 times what it was in 1970.

The study also discovered a substantial disparity between white and black expectant mothers. Researchers say this could be because black women have higher rates of preeclampsia, pregestational and gestational diabetes, preterm delivery and perinatal mortality.

Prior research has shown that compared with white women, black women have higher rates of obesity, are more likely to smoke and use drugs and are at greater social disadvantage, all of which may contribute to an increased risk of chronic hypertension.

Since the increasing age of pregnant women will probably not change, Ananth says the question now becomes how can the growing rates of hypertension be lessened to prevent possible adverse outcomes in pregnancy?

"Women need to better control their blood pressure before and during pregnancy. Smoking cessation, weight control, behavioral changes and effective anti-hypertensive therapy, - all modifiable factors - may lead to healthier lifestyle and will likely have a substantial beneficial effect on chronic hypertension and pregnancy outcomes," Ananth said.

The best outcome would be to control hypertension before becoming pregnant by reducing obesity, quitting smoking, adopting an overall healthier lifestyle before and during pregnancy, and treating high blood pressure effectively. For every 1-2 lbs. lost prior to pregnancy, blood pressure is reduced, Ananth said.

"Not only do these findings have implications for the health of the women and newborns during pregnancy, they have lasting implications on future risks of cardiovascular and stroke risks in women later in life. Being aware of your blood pressure before and during pregnancy, and taking steps to reduce it, is key to women's health during pregnancy," he said.

New research from The University of Toledo College of Medicine and Life Sciences strongly suggests postural orthostatic tachycardia syndrome, or POTS, is an autoimmune disorder and may help pave the way for a simple blood test that could help physicians diagnose the condition.

POTS is characterized by large increases in heart rate and sometimes decreases in blood pressure when standing up. That can cause lightheadedness, heart palpitations and even loss of consciousness. In addition to fainting, POTS patients also regularly suffer from a litany of additional symptoms, including fatigue, pain, gastrointestinal issues, bleeding disorders, anxiety and brain fog.

About 3 million Americans are believed to be affected, but because of its wide-ranging and seemingly unrelated symptoms, POTS is notoriously difficult to identify.

"The trouble with diagnosing POTS is that it's currently principally a clinical diagnosis. It's based on history, the absence of other illness as well as the finding of increase in heart rate when standing. There is no blood test right now to aid in the diagnosis. It can be an incredibly frustrating process for patients," said Dr. Blair Grubb, Distinguished University Professor of Medicine and Pediatrics in the UToledo College of Medicine and Life Sciences and director of electrophysiology services at The University of Toledo Medical Center.

In the largest study of POTS patients to date, published Sept. 9 in the Journal of the American Heart Association, Grubb and UToledo research collaborators found 89 percent of patients they examined had elevated levels of autoantibodies against the adrenergic alpha 1 receptor.

"People have suspected an autoimmune connection for years, and other small-scale studies have suggested it," said Grubb, one of the world's foremost experts in syncope and disorders of the autonomic nervous system. "We did a much larger cross-section of patients than has ever been done before, and found that almost all of them tested positive for autoimmune antibodies. That's a significant finding."

None of the 55 patients who participated in the study had another recognized autoimmune disorder. Fifty-two were female, with an average age of 30.

Researchers screened the patients' blood for autoantibodies against nine receptors. A handful of patients showed elevated levels against all nine. But it was the prevalence of adrenergic A1 subtype receptor autoantibodies that make their findings so intriguing.

"I think that we have identified a biomarker. We now might have the ability to diagnosis this, or at least have an inkling. Like other autoimmune disease, we can take a blood sample and detect if there are increased levels of autoantibodies present. According to our results, autoantibodies against this particular receptor should be present in about 90 percent of patients with POTS," said Dr. William Gunning, a professor of pathology in the UToledo College of Medicine and Life Sciences, and the paper's lead author.

Gunning and Grubb say much more research is needed. However, this study adds significantly to the evidence that POTS is an autoimmune disorder -- and it shows it may be possible to give physicians unfamiliar with the condition an easy way to test for it.

"What this does is prove the concept," Grubb said. "Other studies had used very expensive research tests. What we used are the same kind of testing methods that would be used by regular hospitals. We wanted to do something that would potentially be a test applicable to the general population, not just a research test."

While Gunning and Grubb caution they're still investigating the precise methods by which POTS is established, their study does raise the possibility that existing immune modulating medications could be a viable therapeutic method for some patients.

Johns Hopkins Medicine researchers report they have developed and validated a tablet-based app that offers a faster, easier and more accurate way for health care providers who don't have specialized training to assess the cognitive function of people with multiple sclerosis (MS). Multiple sclerosis is a chronic neurologic illness that affects the central nervous system, resulting in a variety of symptoms including motor issues, fatigue, visual disturbance, memory and concentration concerns, and mood changes.

MS is the most common form of disability in young adults other than traumatic injury. Diagnosis usually occurs between the ages of 20 and 50, and it is estimated that 1 million people in the United States are living with the disease. MS is most common among women -- three women are diagnosed for every one man.

In a study comparing the app, called iCAMS, to a standard, paper-based assessment tool, researchers say they found that the app produced highly accurate results while reducing test time from about 23 to 14 minutes. Study results are described in the July 2019 online issue of the International Journal of MS Care.

Meghan Beier, Ph.D., M.A., assistant professor of physical medicine and rehabilitation at the Johns Hopkins University School of Medicine and lead author of the study report, says that "results suggest that using the iCAMS app may make cognitive assessments of multiple sclerosis more convenient in a clinic setting, and therefore will be used more often to identify learning and memory problems."

According to Beier, up to 65% of people with MS experience cognitive problems. People with MS often require more time to perform mental tasks and face difficulty learning and retaining new information. Identifying cognitive issues earlier may help preserve and even improve function with targeted interventions such as cognitive rehabilitation, says Beier. Since cognitive decline can also be a result of aging, cardiovascular disease, depression and other conditions, specialized assessment tests have been developed to identify MS-related cognitive impairments. Certain exercises that improve learning ability, such as spaced learning and self-generated learning, may help MS-related cognitive difficulties. Therefore, it is important to identify these challenges.

Currently used paper testing tools are time consuming, or specially trained psychometrists must administer them. A study based in the United Kingdom involving the assessment and management of cognitive problems among people with MS shows that only 8% of MS specialists are using MS-validated cognition assessment tools.

In a bid to improve that record, Beier and her team adapted an internationally validated cognitive assessment tool for MS patients, called the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), to a digital tablet format. BICAMS, composed of three subtests, measures processing speed, or how fast the brain can take in and process environmental information such as recognizing a stoplight and sending a signal to the foot to push the brake; the ability to learn verbal information, such as remembering key aspects of the story a family member told; and the ability to learn visual information, such as creating a mental map of a hotel the person is visiting.

In the tablet-based app, researchers incorporated the BICAMS version of processing and visual learning tests, but for copyright reasons they used a comparable alternative subtest to assess verbal learning ability. iCAMS uses automatic prompts and written instructions to help medical assistants or other staff members guide patients through instructions to complete the assessment.

Study participants included 100 adults from the University of Washington Medicine Multiple Sclerosis Center who had a physician-confirmed MS diagnosis. Participants were between the ages of 18 and 79. The average age was 46, and 74% were female. The patients had MS for an average of 10 to 11 years, and 78% had relapsing-remitting MS, the most common form of the disorder. It is marked by symptoms that come and go, including vision loss, pain, fatigue, loss of motor coordination, cramping and dizziness.

Trained research assistants administered paper and iPad tests to participants. Half of the sessions were led by an administrator who provided the paper test, and the other half of the group received an iCAMS tablet test.

When researchers compared the test scores for each participant, the answers were the same 93% of the time, validating the accuracy of the app-based test, they say. Furthermore, the administration and scoring time for the app-based test was 40% shorter than the paper version.

The research team also asked test administrators to assess their experience giving the app-based test. Medical assistants overall found the experience positive, Beier says. "It was quick and very easy to learn how to administer," says Katie Rutter B.S., a medical assistant who participated in the study. "Participants enjoyed testing on an iPad and often told me how much fun it was."

Beier says that in addition to saving time and being easier to administer, a tablet-based test eliminates the need to store paper-based records and makes sharing information easier on electronic medical records. The app may also reduce the rate of errors in calculating and transferring scores.

"Our goal is to reduce barriers for patients to receive the testing that may benefit their treatment and health through the use of digital technology," adds Abbey Hughes, Ph.D., M.A., assistant professor of physical medicine and rehabilitation at the Johns Hopkins University School of Medicine and co-author of the study.

Researchers caution that the tests in the app are not identical to the paper version, although other studies have shown that the alternative test they used for verbal learning produced equivalent results to BICAMS.

They also note that because all three test components are based on copyrighted material, costs will likely be associated with downloading and/or using the app.

Ongoing efforts include the research team's plans for larger-scale testing of the app in more diverse patient populations, and altering the app to make it more user-friendly.

Women from villages in rural Indonesia are playing a key role in detecting and preventing the most common cause of death in Indonesia, cardiovascular disease, with the use of smart phones. Researchers have found that the intervention has resulted in an increase of 14.5% more appropriate use of preventive medicine than normal and a reduction in blood pressure of patients by 41%

The new health intervention, called SMARThealth, was developed by the George Institute in Australia along with researchers from The University of Manchester, and the University of Brawijaya, Indonesia.

SMARThealth works with volunteer health workers (known locally as kader); local women who have no college education but have experience of infant and maternal health. SMARTHealth provides the kader with training on blood sample collection, a smart phone to aid assessment and data collection, and health information specific to cardiovascular care. Data is then shared with qualified health professionals - resulting in a radical shift in the way healthcare is delivered and the potential for improved cardiovascular care.

Dr Tampubolon's early research in Indonesia demonstrated that nearly 70% of respondents with moderate to high cardiovascular risk lacked access to cardiovascular care. The George Institute's SMARThealth programme uses glucose and lipids from blood samples, to identify those at risk of cardiovascular issues and provide them with information that could help them manage their health.

Although the health workers can easily visit adults with cardiovascular risks, one of the challenges of the project was to ensure that people in villages respected the knowledge of the health workers. This is where the mobile app and its connection to a digital data cloud played a pivotal role. The data collected by relatively untrained health workers could now be accessed by cardiovascular doctors in Indonesian hospitals to initiate appointments, issue referrals and suggest treatments, such as necessary scans.

This information linked doctors to the health workers' visit, reinforcing the legitimacy and elevating the role of the village health worker. As the app and recommendations were devised by researchers and scientists, all involved felt confident in the information they were getting.

"To see village women producing scientific information that cardiovascular consultants can actually use, and seeing the health worker's eyes light up when they realise how useful this has been - that's been an exciting part of the project," said Dr Tampubolon.

Based on a study involving eight Indonesian villages and 6579 high-risk people in rural Indonesia, initial findings indicate a 14.5 % difference in the use of preventative medication, with 15.5% of individuals in the intervention villages reporting use of appropriate preventive medications compared with 1.0% in the control villages. The uptake of medication to lower blood pressure was 57% vs. 16%.

Barcelona--Adding immunotherapy in the form of durvalumab to chemotherapy improves overall survival in patients with extensive-stage small cell lung cancer, according to research presented today at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer (IASLC).

The research was presented by Dr. Luis Paz-Ares, from Hospital Universitario 12 de Octubre, H120-CNIO Lung Cancer Unit, Universidad Complutense and Ciberonc, in Madrid, Spain.

Extensive-stage small-cell lung cancer is defined as the stage during which the cancer has metastasized to other parts of the body, such as the liver or brain. Average survival time after diagnosis is 10 months.

In the CASPIAN trial, Paz-Ares and the multi-center, international research team, randomized 537 previously untreated patients with extensive-stage lung cancer to receive either durvalumab plus 4 courses of etoposide-platinum (EP) chemotherapy, durvalumab plus tremelimumab plus EP for 4 cycles or up to 6 cycles of EP alone. Data presented at the WLCC concerned to the durvalumab arm as compared to the control treatment.

Paz-Ares and his team found that patients in the immunotherapy arm of the trial achieved a median overall survival of 13 months compared to 10.3 months for the etoposide-platinum control group. And, 33.9 percent of the patients who received durvalumab were alive at 18 months as compared to just 24.7 in the control arm of the trial.

"The addition of durvalumab to EP as first-line treatment for extensive-stage non-small cell lung cancer significantly improved overall survival (27% reduction in risk of death) versus a robust control arm that permitted up to 6 cycles of etoposide. Of note, this chemo-immunotherapy regimen offers flexibility in platinum choice (carboplatin or cisplatin), reflecting current clinical practice for this challenging disease," he said.

Scientists have found that antidepressants and other psychiatric drugs can change the quantity and composition of gut bacteria in rats. These results raise questions about the specificity of psychoactive drug action, and if confirmed in humans whether psychiatrists might need to consider the effects on the body before prescribing. The research team is currently carrying out a large-scale human observational study which aims to answer the questions posed by these findings. This work is presented at the ECNP Conference in Copenhagen following part-publication in a peer-review journal (see Notes for Editors).

Scientists are increasingly finding that the microbiome - the bacterial content of the digestive system - has effects on other functions in the body, and vice versa. A group of Irish-based scientists has given 7 groups of rats (8 animals in each group) normal or slightly elevated levels of individual psychopharmaceuticals, including Lithium, valproate, and the antidepressants fluoxetine (Prozac) and escitalopram. After 4 weeks of treatment, the scientists examined the gut bacteria - the microbiome - to see what the effects the drugs had (see abstract for experimental details).

They found that some drugs consistently increased the number of certain bacteria in the gut. For example, lithium and valproate (both used for bipolar disorder) increased the numbers of Clostridium and other bacteria. In contrast, the (SSRI) antidepressants escitalopram and fluoxetine significantly inhibited growth of bacterial isolated strains such as E.coli.

Describing the work, lead researcher, Ms Sofia Cussotto (University College, Cork) said:

"We found that certain drugs, including the mood stabiliser lithium and the antidepressant fluoxetine, influenced the composition and richness of the gut microbiota. Although some psychotropic drugs have been previously investigated in in vitro settings, this is the first evidence in an animal model.

There are several implications of this work. First of all, some studies have shown that depressed or schizophrenic patients can have altered microbiota composition, therefore psychotropic drugs might work on intestinal microbes as part of their mechanisms of action. Of course, this has to be proved. Given that antidepressants, for example work on some people but not others, making an allowance for microbiome may change an individual's response to antidepressants. On the other hand, microbiome-targeting effects might be responsible for the side effects associated with these medications. All these hypotheses have to be tested in preclinical models and in humans, and this is our next step".

Commenting, Professor Serguei Fetissov from Rouen University, France said:

"These early data are intriguing, and worthy of further investigation. At the moment it would be premature to ascribe a direct role of gut bacteria in the action of antidepressant drugs until this work can be reproduced in humans, which is what the authors now hope to do. The composition of gut microbiota is very sensitive to the metabolic processes of the body and can change naturally, through drug-induced metabolic shifts in the brain and other organs. Some of the changes reported here, for example increased Christensenella, can be indeed beneficial, but overall significance of drug-induced changes of bacterial composition on the metabolic and mental health needs further research.

Barcelona-- Tumor mutational burden was not significantly associated with efficacy of pembrolizumab plus chemotherapy or placebo plus chemotherapy as first-line therapy for metastatic nonsquamous non-small cell lung cancer, according to research reported today by Dr. M. Garassino from the Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Dr. Garassino presented this new data today at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer.

Tumor mutational burden is a measurement of mutations carried by tumor cells and is a predictive biomarker being studied to evaluate its association with response to immunotherapy. TMB, in concert with PD-L1 expression, has been demonstrated to be a useful biomarker across some cancer types.

To test this notion, Dr. Garassino and her colleagues randomized 616 patients 2:1 to pembrolizumab plus chemotherapy or placebo plus chemotherapy. TMB was determined by whole-exome sequencing of tumor and matched normal DNA. The clinical utility of TMB on outcomes was assessed using prespecified TMB cut points of 175 and 150 Mut/.

Of the 616 patients enrolled, 293 (48.3%) had evaluable TMB data: 207 for pembrolizumab plus chemotherapy, 86 for placebo plus chemotherapy. Baseline characteristics and outcomes were generally similar in the TMB-evaluable and total populations. TMB as a continuous variable was not significantly associated with overall survival, progression-free survival or objective response rate for pembrolizumab plus chemotherapy or placebo plus chemotherapy. Pembrolizumab plus chemotherapy improved overall survival, progression-free survival and objective response rate.

"Tumor mutational burden was not significantly associated with efficacy of pembrolizumab plus chemotherapy or placebo plus chemotherapy as first-line therapy for metastatic nonsquamous NSCLC," said Dr. Garassino. "Pembrolizumab plus chemotherapy had a similar OS benefit in the TMB-high and low subgroups."

Barcelona--Lung cancer screening efforts have accelerated in the last decade, with researchers showing that low dose CT screening is effective in reducing lung cancer mortality. Now, researchers in Milan report that using a blood test, accompanied by low dose CT screening, is safe and effective. The results were shared today at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer.

The National Lung Screening Trial (NLST) showed that lung cancer screening by three annual rounds of low-dose computed tomography (LDCT) reduced lung cancer mortality. The Multicentric Italian Lung Detection (MILD) provided additional evidence that extended intervention beyond five years, with annual or biennial rounds, enhanced the benefit of low-dose CT screening.

Ugo Pastorino, MD, of the Istituto Nazionale dei Tumori Foundation and the lead researcher on the MILD trial, reports on results from a new trial, the bioMILD trial, which tested the additional value of blood microRNA assay at the time of LDCT on a large number of volunteers, with the aim of targeting next LDCT intervals on the basis of individual risk profile.

The bioMILD trial prospectively enrolled 4,119 volunteers at Istituto Nazionale Tumori of Milan with the median age of 60 years, median pack-years 42, current smokers 79% and females 39%. At the end of March 2019, a total of 11,012 LDCTs and 9,156 miRNA tests were performed, with an overall compliance at the 3-year LDCT of 93% and a median follow-up 4.2 years.

Pastorino had previously reported that that microRNA expression profiles in tumors and, for the first time, also in normal lung tissue, are indicative of aggressive lung cancer development and that specific microRNA signatures can be identified in plasma samples of patients up to two years before spiral-CT detection of the disease.

The BioMILD trial offered a lung cancer screening program combining LDCT and blood microRNA assay to heavy smokers (current or former ?10 years) aged 50-75 years. At baseline, LDCT and miRNA were tested independently with blind evaluation. According to LDCT and miRNA profile, different screening intervals were chosen for the following repeats, and participants with double negative LDCT and miRNA were sent to a 3-year interval.

Preliminary analysis showed a significantly higher lung cancer incidence and overall mortality in subjects with positive LDCT and/or miRNA at baseline. No detrimental effects on stage I lung cancer proportion, resection rates, or interval cancer incidence were observed in the group of subjects sent to 3-year LDCT repeat. Sensitivity and specificity analyses of LDCT and miRNA at baseline and subsequent screening rounds will be presented.

"BioMild showed that the combination of microRNA assay and LDCT is a valuable and safe tool to assess individual risk profile and reduce unnecessary LDCT repeats in lung cancer screening," said Dr. Pastorino.

Barcelona--The relationship between gene alterations and response to anti-PD-L1 with and without anti-CTLA-4 are not well characterized. Dr. N. Rizvi from Columbia University Medical Center in New York today presented an update from the Phase III MYSTIC study that showed poorer outcomes across treatment arms in patients with metastatic non-small cell lung cancer and mutations in STK11 or KEAP1 genes compared with those without the corresponding mutations. In patients receiving durvalumab with tremelimumab, ARID1Am was associated with survival benefits compared with ARID1Awt.

Rizvi presented his data today at the IASLC 2019 Word Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer.

The MYSTIC trial is a randomized, open-label, multi-center, global Phase III trial of durvalumab monotherapy or durvalumab in combination with tremelimumab versus chemotherapy in the 1st-line treatment of patients with epidermal growth factor receptor and anaplastic lymphoma kinase wild-type, locally-advanced or metastatic non-small cell lung cancer. The trial was conducted at 203 sites in 17 countries. Previously, according to research published in the American Association of Cancer Research, blood tumor mutational burden, at various thresholds from greater to or equal to 12 mut/Mb to ?20 mut/Mb, has been associated with improved overall survival with first-line durvalumab with or without tremelimumab versus chemotherapy.

In the current exploratory analysis, researchers obtained circulating tumor DNA from baseline plasma specimens from 1003 patients which was then profiled using the GuardantOMNI platform. Survival outcomes were analyzed in those with (designation with m) and without (wt) non-synonymous somatic mutations.

In the mutation-evaluable population (n=943), STK11 mutation, KEAP1 mutation, and ARID1A mutation frequencies were 16 percent, 18 percent and 12 percent, respectively (19 percent, 20 percent, and 11 percent [nonsquamous]; 7 percent, 13 percent, and 15 percent [squamous]).

Across treatment arms, patients with STK11m or KEAP1m had a shorter median overall survival than patients with STK11wt or KEAP1wt metastatic NSCLC. In the durvalumab + tremelimumab arm, patients with ARID1A mutations had a longer median overall survival rate than patients with ARID1A without mNSCLC.

NEW ORLEANS, Sept. 7, 2019 -- Native Hawaiians who participated in a blood-pressure-lowering program incorporating their cultural dance of hula lowered their blood pressure more than those who received standard education on diet and exercise, according to preliminary research presented at the American Heart Association's Hypertension 2019 Scientific Sessions.

"Despite medical treatment of hypertension, many Native Hawaiians have difficulty controlling their high blood pressure, which increases their risk for coronary heart disease and stroke," said Keawe'aimoku Kaholokula, Ph.D., lead author of the study and professor and chair of the department of Native Hawaiian health at the University of Hawaii at Manoa in Honolulu. "The rates of heart disease and stroke are four times higher among Native Hawaiians than in non-Hispanic whites, and they also get these diseases 10 years younger than whites and Asians in Hawaii."

In previous research, Kaholokula and his colleagues found that typical lifestyle programs aimed at lowering blood pressure are less attractive to Native Hawaiians, who find the activity components boring or expensive and the dietary goals unrealistic and difficult to sustain over time.

"We found that Native Hawaiians want group-based and culturally relevant lifestyle interventions that resonate with their cultural values and perspectives," Kaholokula said. "We created an intervention based on hula, the traditional dance of Native Hawaiians, which can be performed at different levels of intensity by men and women of all ages and is practiced as a form of cultural and creative expression."

The researchers recruited more than 250 Native Hawaiians (average age 58 years, 80% female) who, although under medical treatment for high blood pressure, still had a systolic (top number) blood pressure of 140mmHg or higher or had a systolic blood pressure of 130mmHg or higher and also had type 2 diabetes.

After three one-hour sessions of hypertension education that included information on diet, exercise and the use of medications, participants were randomly assigned to a control group that received no further additional intervention or to the hula intervention. Hula participants attended one-hour group hula classes twice a week for three months, followed by one monthly lesson for three additional months with self-directed practice, as well as group activities to reinforce hypertension education and healthy behaviors. All participants continued their usual medical treatment during the study.

After adjusting for the participants' weight and blood pressure at the start of the study, at six months, researchers found that, compared with people in the control group, those who did hula were:

More likely to have lowered their blood pressure to under 130/80 mmHg, the current target for blood pressure treatment for patients without diabetes;

More likely to have lowered their systolic (top number) blood pressure more than 10 mmHg, an amount that significantly reduces the risk of heart attack, stroke and heart failure; and

Able to sustain their improvements in blood pressure at one-year follow-up, which was six months after the study's hula classes ended.

"The participants said the hula was fun and helped meet their spiritual and cultural needs," Kaholokula said. "More than 80% stayed with the program for six months and 77% were still at it 12 months in, which reflects high interest in a culturally grounded program like this."

"These results reinforce the idea that for most people, the best physical activity for your health is one that makes you breathe a little faster and gets your heart beating a little faster," said David Goff, M.D., Ph.D., Director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health which funded the study. "Whether that's dancing, biking, swimming, surfing, or hiking, the key is to move more and more often. Being active with friends and family can help sustain the healthy fun over time."

"While the physical benefits of dancing hula are clear, other positive impacts include creating family-like social support and increasing self-confidence and acceptance of others," said Mapuana de Silva, a cultural expert on hula and a consultant to the study. "This all comes from the essential cultural value of aloha which is fundamental to hula."

Although the study was conducted in Native Hawaiians, results may apply to other groups.

"Other similar cultural activities, especially those that include physical activity that meets national guidelines, and social and cultural activities that engage and empower people to make behavioral changes, could be used in a similar fashion in other indigenous groups such as American Indians, Alaska Natives, First Nation People in Canada, Maori in New Zealand, Aboriginals of Australia and many others," Kaholokula said.

"This study is a great example of how interventions can be more effective when tailored for cultural relevance to participants," said the American Heart Association's Chief Medical Officer for Prevention Eduardo Sanchez, M.D., M.P.H. "Not only are people achieving health-promoting levels of physical activity, they are also having fun, engaging in a valued cultural practice, and connecting with their community in the group classes -- all important for well-being. This is an approach that can easily be applied to other groups and dancing styles, such as ballroom dancing, line dancing or salsa dancing. It supports the American Heart Association's philosophy to meet people where they are to help them live longer, healthier lives."

NEW ORLEANS, Sept. 7, 2019 -- A measurement of central blood pressure in people with difficult-to-treat high blood pressure could help reduce risk of heart disease better than traditional arm cuff readings for some patients, according to preliminary research presented at the American Heart Association's Hypertension 2019 Scientific Sessions.

Central blood pressure, also called blood pressure amplification, is measured at the aorta, the artery closest to the heart. Researchers found this measurement can more accurately reflect heart disease risk in people with treatment-resistant high blood pressure based on findings from their study.

"We found that higher differences in blood pressure between the arm and the aorta are associated with increased incidence of heart disease in the general population," said Badhma Valaiyapathi, M.B.B.S., M.P.H., lead study author and a postdoctoral fellow in vascular biology at the hypertension clinic at the University of Alabama at Birmingham. "We looked specifically at people whose high blood pressure is resistant to treatment, meaning patients' arm blood pressure readings remain out of control despite the patient being on high blood pressure medications."

The researchers studied adult patients with high blood pressure including some with difficult-to-treat high blood pressure. Blood pressure and pulse pressure were measured using the traditional arm cuff as well as with pulse wave analysis, to measure central blood pressure when the heart is pumping. Based on the measurements, patients were categorized into three groups: controlled nonresistant blood pressure; controlled resistant blood pressure; and uncontrolled resistant blood pressure. Blood pressure amplification was calculated as the difference between the two measures.

The highest blood pressure amplification was found in patients with uncontrolled resistant high blood pressure. The lowest blood pressure amplification was noted among patients who were in the controlled non-resistant category, explaining why risk severity tends to be highest among some adults who have uncontrolled high blood pressure and are resistant to certain medications, according to Valaiyapathi.

"The findings imply that amplification of blood pressure and pulse pressure remains high in patients with resistant hypertension regardless of blood pressure control," he said. "This means their arteries are stiffer than patients with controlled blood pressure, and they're having problems in their vessels that are leading to heart disease even though they are on medications and even though their blood pressure is under control."

Valaiyapathi suggested doctors should tailor blood pressure treatment for treatment-resistant high blood pressure patients by taking into consideration central blood pressure, amplification and reinforcing the importance of lifestyle modifications to patients -- not only medications -- to reduce heart disease risk.

Among the limitations of the study are its small size and that it was done in the southern U.S., so the results might not be reproducible in the general U.S. population.

NEW ORLEANS, Sept. 7, 2019 -- Adults who received more intensive treatment to lower their blood pressure were less likely to experience drastic blood pressure drops, which can cause dizziness and increase risk of falling, according to preliminary research presented at the American Heart Association's Hypertension 2019 Scientific Sessions.

The study of more than 2,800 adults, average age 63 with a recent stroke, found that a lower systolic blood pressure goal was associated with a lower risk of sudden drops in blood pressure when changing position from sitting to standing -- a condition known as orthostatic hypotension (OH). Systolic blood pressure is the top number in a blood pressure reading and a marker of the force of blood flow against the arteries when the heart contracts.

Optimal blood pressure helps reduce the risk for heart attacks and strokes, however, aggressive blood pressure treatment in older adults has long been thought to contribute to falls. Falling is a well-known risk factor for fractures, prolonged hospitalization and even death in older individuals. One in four older adults experience a fall each year, according to the National Council on Aging.

"Falls can be devastating in this older population," said lead study author Stephen Juraschek, M.D., Ph.D., an assistant professor of medicine at Harvard Medical School and an internal medicine physician at Beth Israel Deaconess Medical Center in Boston, Mass. "As a result, there is substantial concern about anything that might increase their fall risk. However, our study provides strong evidence that intense blood pressure treatment does not induce orthostatic hypotension or its symptoms."

Previous studies have yielded inconclusive evidence, the researchers said. In this study, Juraschek and team set out to determine how lower systolic blood pressure affects symptoms of OH.

The researchers monitored response to blood pressure medication in two groups of patients. Half of the participants were treated more aggressively, aiming to reduce blood pressure to levels below 130/80 mmHg. The other half received less intensive therapy allowing them to maintain a slightly higher blood pressure of between 130-149/80-90 mmHg or more.

Researchers monitored blood pressure levels and symptoms during 36,342 visits, for an average of 15 visits per participant. During each visit, a participant's blood pressure was measured three times while seated and one time after two minutes of standing up to capture any changes and symptoms of OH.

Participants who received more intensive therapy and achieved lower systolic blood pressure (130 mm/Hg or under) had better overall blood pressure control and had fewer OH episodes.

Researchers have found that focusing powerful non-invasive magnet stimulation on a specific brain area can improve the symptoms of Obsessive Compulsive Disorder (OCD). This opens the way to treat the large minority of sufferers who do not respond to conventional treatment. The work is presented at the ECNP Conference in Copenhagen*.

OCD is broadly defined as recurrent thoughts or urges, or excessive repetitive behaviours which an individual feels driven to perform. Around 12 adults in every thousand suffer from OCD in any given year, although 2.3% of adults will suffer at some point in their life. It is generally treated through exposure and response prevention (ERP) therapy (which exposes the patient to the content of his obsessions\urges without performing the compulsions) and medication, such as SSRIs (Selective Serotonin Reuptake Inhibitors e.g. fluoxetine (Prozac/Sarafem) or Sertraline (Paxil) or Serotonin Reuptake Inhibitors e.g. clomipramine (Anafranil), however between a third and a half of patients don't respond well to treatment

Deep Transcranial Magnetic Stimulation (dTMS) is a type of brain stimulation technique where pulsed magnetic fields are generated by a coil placed on the scalp. This field activates the neuronal circuits at the target brain area, resulting in symptom improvement. It is clinically used for treatment of some difficult cases of depression.

Dr Lior Carmi (along with Prof. Joseph Zohar and Prof. Abraham Zangen), from the Chaim Sheba Medical Center in Israel, led an international group of scientists in a multi-centre randomised controlled trial (RCT) spread over 11 centres. 99 patients with Obsessive Compulsive Disorder were assigned to either be treated with dTMS, or to receive pretend treatment (sham treatment). All the patients in the trial had previously failed to respond to antidepressant treatment.

Dr Carmi said "An interesting point about this trial is that we deliberately provoked the patients for about 5 minutes before each dTMS session. We did this by tailoring a provocation for each patient according to their own specific OCD obsessions. For example, if someone had obsessions about getting contaminated, we exposed him to a situation in which these obsessions where aroused, for instance, touching a bathroom's door handle or the trash can. Another example would be if someone had obsessions regarding not closing the water tap at home, we deliberately aroused the doubt about that. All these exposures were designed for each individual patient. During the first meeting with the patient we learned his symptoms and created a list of which exposures to use during the study. The idea is to deliver the treatment when the brain circuitry is aroused and not while the patient is thinking about the shopping he needs to do after the session will be over".

The sessions consisted of 6 weeks of daily dTMS (20Hz) treatment focused on specific areas of the brain related to OCD**. This is the first time these areas have been targeted for this disorder. The degree of response was measured using the generally-accepted Yale-Brown Obsessive Compulsive Scale (YBOCS) questionnaire. After 6 weeks, 38% of those being treated responded to the treatment. They showed an average reduction of more than 30% in symptom severity, as opposed to 11% of patients receiving the sham treatment.

A month after treatment finished the response rate was 45.2% in the active group versus 17.8% in the sham group. Around a third of both the treated group and the untreated group complained of headaches, but only 2 dropped out over the trial due to pain.

Lior Carmi said, "Researchers have tested TMS for OCD in the past, but this is the first time we have stimulated this region of the brain and done so while we tailored exposures to each patient. In addition, we have done so using a standardised protocol in a multi-centre randomised trial (at 11 cites in U.S, Canada and Israel). This means that we have achieved these positive results although the variety of patients and variety of clinicians who rated the response. Where the existing treatment works for OCD, it can work well; our method is primarily aimed at those who do not respond to conventional treatment".

Commenting, Professor Jose M Menchon (Bellvitge University Hospital, University of Barcelona, Barcelona, Spain) said:

"This is a very exciting study because it shows positive results in OCD using deep transcranial magnetic stimulation. Until now, the clinical trials with TMS in OCD had been carried out with non-deep TMS, which may have limitations in its effect because the magnetic field can only reach the cortical surface. However, deep TMS allows reaching and modulating deeper brain regions that can be more critically involved in OCD. Deep TMS may become a useful therapeutic strategy if these positive results are confirmed in further studies".

(Salt Lake City) - Doctors have identified a previously unrecognized characteristic of the vaping-related respiratory illness that has been emerging in clusters across the U.S. in recent months. Within the lungs of these patients are large immune cells containing numerous oily droplets, called lipid-laden macrophages.

The finding may allow doctors to definitively diagnose the nascent syndrome more quickly and provide the right treatment sooner. It could also provide clues into the causes of the new and mysterious condition. Investigators at University of Utah Health reported the findings in a letter published in the New England Journal of Medicine on Sept. 6.

"While it is too soon to be sure, these lipid-laden macrophages may turn out to be useful to confirm or rule out this disease," said the study's senior author Scott Aberegg, M.D., a critical care pulmonologist at U of U Health. "They may also be helpful in understanding what is causing this illness," Aberegg added.

Watch a video of physicians and patients talking about their experiences with the vaping illness here.

Lung scans from patients with vaping illness look like a serious viral or bacterial pneumonia, but those tests come back negative. Instead, diagnosis has been based on exclusion of known causes of similar respiratory illnesses combined with knowing the patient has a history of vaping.

U of U Health investigators identified the lipid-laden macrophages in six out of six cases seen at University of Utah Hospital in Salt Lake City by the time of submitting the results for publication. The cells were found in samples after performing a procedure called bronchoalveolar lavage where fluid is squirted into a small section of the lungs and then collected for examination. Macrophages are a type of cell from the immune system that gather at sites of infection and perform the role of cleaning up debris. Staining them with a dye called Oil-red-O highlighted the oily droplets littered throughout these cells.

"These cells are very distinctive, and we don't often see them. That made everybody start to think carefully about why they were there. Are they scavenging debris in the lungs that was introduced through vaping?" Aberegg said.

Doctors at the U had the test performed on the first vaping patient treated at U of U Health in July 2019, after the referring doctor had suggested the patient could have lipoid pneumonia. The condition is diagnosed by screening for lipid-laden macrophages. After finding the marker in this patient, doctors performed the same test in subsequent patients suspected to have the vaping illness, and all were positive. Since submitting their findings for publication, the number of vaping illness cases with lipid-laden macrophages has risen to ten of ten patients examined, with new cases arriving weekly.

The question remains as to whether the vaping respiratory illness is a type of lipoid pneumonia. Despite similarities, there are also differences. Unlike the vaping illness, classic lipoid pneumonia is typically seen in older individuals, typically caused by accidentally breathing in oil-based laxatives. Classic lipoid pneumonia also presents differently on x-rays of the lungs. Additional testing will need to be done to determine whether the vaping illness can be categorized as a new kind of lipoid pneumonia.

"We need to determine if these cells are specific for the illness or whether they are also seen in vaping patients who are not ill and don't have symptoms. If they are only seen in patients who get sick, we can begin to make some connections between what we're seeing in the lipid laden macrophages and whatever components of the vaping oils may be causing this syndrome" Aberegg said.