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A new multi-national survey has revealed that asthma sufferers are missing nearly one-tenth of work hours due to their symptoms, which also results in a loss of productivity and affects their emotional wellbeing.

The World Health Organisation estimates that 235 million people around the world suffer from asthma. But little is known about the impact of asthma on symptomatic people's ability to work.

This new research, published in the Journal of Asthma and Allergy, surveyed over 1,500 symptomatic asthma patients across six countries and found that, on average three out of four workers could not work to their full potential.

Further, the survey indicated that asthma impacted the respondent's emotional well-being, including mental strain and embarrassment.A research team, led by Dr Kevin Gruffydd-Jones from Box Surgery, Wiltshire, UK, invited a random selection of participants from Brazil, Canada, Germany, Japan, Spain and the UK to participate in an online 'Work Productivity and Activity Impairment - Specific Health Problem' survey developed by Research Now ® (London, UK).

The survey quantified the impact of asthma on work time missed, loss of productivity while working and total work productivity loss for the seven days prior to the survey.

In addition, the questionnaire asked the open-ended question, "How does your asthma at work make you feel?" to judge the impact of a patient's asthma symptoms on their emotional well-being at work.

Respondents were selected to participate in the survey if they were over 18 years old, diagnosed with asthma by a healthcare professional, currently employed full- or part-time and a long-term user of a controller inhaler or preventative medication.

A total of 1,598 symptomatic patients completed the 5-minute survey between April and September 2015.The study results found that, on average, up to one-tenth (9.3%) of work hours were missed in a single week because of workers' asthma symptoms.

This averaged out to 5.4 work hours missed for both part- and full-time employees. Further, roughly three out of four (74%) workers reported being unable to work to their full potential because of their asthma, with 42% of workers experiencing a 'prominent' reduction in productivity.

Workers commonly reported feeling challenged by respiratory symptoms, as well as tiredness/weakness, mental strain and physical impairments.Overall, total work productivity dropped by one third (36%) due to asthma."But, what struck us most was the emotional response to asthma in the workplace," explains Dr Gruffydd-Jones.

"A significant number of patients felt guilt, shame and embarrassment when using inhalers at work."

Respondents also reported feeling inferior and disadvantaged compared to their non-symptomatic colleagues, and over two-thirds of respondents felt that asthma negatively impacted their work activities.

Despite capturing a one-week snapshot from a working year only, without comparison with asymptomatic patients or personnel with no asthma, this study highlights the global issue of asthma in the workplace, its impact on productivity and the personal challenges it causes workers.

The solution, Dr Gruffydd-Jones explains, requires a coordinated approach by clinicians, employers and occupational health teams.

"Clinicians must ask patients about the impact of asthma on their work and employers must encourage their workers to seek medical help and provide an 'asthma friendly' environment.

"This requires not only providing appropriate environmental controls but also a working environment that minimises embarrassment, such as allowing to staff to move out of the immediate work environment to use their inhalers."

Retinitis pigmentosa (RP) is a common hereditary eye disorder that leads to the gradual deterioration of rod cells causing reduced peripheral vision and night vision. Subsequent loss of cone photoreceptors cause the loss of high-resolution daylight and color vision.

Ophthalmology researchers at the University of Louisville have discovered the loss of vision in RP is the result of a disruption in the flow of nourishing glucose to the rods and cones. This disruption leads to the starvation of the photoreceptors.

In research published today in Cell Reports, the researchers, led by Douglas C. Dean, Ph.D., and Wei Wang, M.D., Ph.D., of the UofL Department of Ophthalmology and Visual Sciences, described metabolic changes that result in the reduced availability of glucose in the cells.

As research provides a better understanding of the progression of RP, this knowledge may lead to therapies that could slow or stop this process before the rods and cones are destroyed. In addition to the relevance for RP, the researchers discovered the failure in glucose metabolism in RP is similar to changes seen in lung cancer and may be useful in developing therapeutic targets for both diseases.

"Interestingly, these metabolic changes appear similar to those we also are investigating in other studies into lung cancer in the laboratory," Dean said. "Both lung cancer and neurons in the retina use glucose as a primary source for their metabolism. Attacking glucose utilization is a major strategy in fighting lung cancer. This unexpected connection in retinal and lung cancer metabolism has led us to link these seemingly unrelated systems to search for common drugs that target both lung cancer and retinal degeneration."

RP is an inherited disease in which the photoreceptor cells in the retina - rods and cones - deteriorate over time. Photoreceptors absorb and convert light into electrical signals, which are sent through the optic nerve to the brain. Rods, located in the outer regions of the retina, allow peripheral and low-light vision. Cones, located mostly in the central part of the retina, allow perception of color and visual detail.

In RP, rods deteriorate first, causing the peripheral and low light vision loss typically associated with the disease. In later stages, the cones also deteriorate. Without cone function, RP patients lose the high-resolution daylight vision necessary for reading, facial recognition and driving. As a result, this stage of RP vision loss is more debilitating than the loss of nighttime or peripheral vision. RP affects 1 in 4,000 people globally.

HOUSTON - (July 30, 2019) One of the most extensively studied genes in cancer, TP53 is well known for its role as a tumor suppressor. It senses cellular stress or damage, and in response stops cell division or initiates cell death, thereby preventing a damaged cell from reproducing. Mutation of this gene eliminates a key cellular fail-safe mechanism and is a step leading to cancer. Researchers at Baylor College of Medicine have conducted the most comprehensive study of TP53 mutations to better understand the processes leading to the inactivation of this important gene. Their findings, published in the journal Cell Reports, shed light on how the gene becomes mutated and how those mutations can help predict clinical outlook.

The team, led by Dr. Larry Donehower, professor of molecular virology and microbiology at Baylor College of Medicine, studied 10,225 patient samples from 32 different cancers, from The Cancer Genome Atlas, and compared them to another 80,000 mutations in a database collected over three decades by Dr. Thierry Soussi, professor of molecular biology at Sorbonne University. After analyzing this large data sample, they have a more thorough understanding of how the TP53 gene mutation impacts cancer.

The team found that across all cancer types studied, TP53 mutations were more frequent in patients with poorer survival rates. But they also identified a way to more accurately predict prognosis. Donehower said he identified four upregulated genes in mutant TP53 tumors, whose expression correlated to patient outcome.

"If you have a high expression of those four genes, you have a patient who's more likely to have a bad prognosis," Donehower, a member of the Dan L Duncan Cancer Center at Baylor, said. "Conversely, if that patient has a very low expression of those genes, he's probably going to survive longer and have a good prognosis. It will give you a better picture of how he'll fare than just knowing whether he's mutant for TP53 or not."

At the chromosomal level, the team found a noticeable pattern in TP53 gene loss.

"In some cancer genes, you'll see one copy of the two genes lost or mutated," Donehower said. "Over 91 percent of all cancers lose both TP53 genes, not just one."

This second gene loss occurred due to mutation, chromosomal deletion or gene duplication. According to Donehower, cases of gene duplication occurred at a much higher rate than previously thought.

The research also showed that TP53 mutation correlated strongly with genomic instability, indicative of the role of the normal protein in monitoring chromosome integrity. In most TP53 mutant tumors, other tumor suppressor genes were deleted, while oncogenes that allow cancer to develop were amplified.

While many studies have been conducted on TP53, this is the first to examine such a large number of tumors and cancer types using five different data collection methods. Donehower said the size of this study allowed his team to notice patterns and correlations that might not be evident in a smaller sample.

"Most studies on TP53 focus on one cancer type," Donehower said. "Looking at 32 different cancer types, you see that certain patterns hold up regardless of cancer type."

Study author and Director of Cancer Genomics in the Lester and Sue Smith Breast Center at Baylor College of Medicine Dr. David Wheeler said the results of this study may open the door to new approaches in treating cancer affected by loss of this gene.

"Since TP53 is one of the most important gatekeepers in cancer prevention, the better we understand this gene, the better able we will be to understand the basic biology of cancer. That will lead to better therapies," said Wheeler, a member of the Human Genome Sequencing Center and the Dan L Duncan Comprehensive Cancer Center at Baylor.

OAK BROOK, Ill. - Smoking reduces the chances of a successful procedure to treat blood vessel abnormalities in the lungs, according to a study published in the journal Radiology.

Pulmonary arteriovenous malformations (PAVMs) are abnormal connections between arteries and veins in the lungs. The abnormalities can become symptomatic and lead to potentially dangerous complications. PAVMs are strongly associated with an inherited disorder called Hereditary Hemorrhagic Telangiectasia (HHT).

"HHT is a disease that can manifest with patients having AVMs in their lungs," said study senior author Sanjay Misra, M.D., an interventional radiologist at the Mayo Clinic Department of Radiology in Rochester, Minn. "When these AVMs become symptomatic, we are asked to embolize them using coils."

In the embolization procedure, a catheter is threaded from a large blood vessel in the leg to the site of the PAVM. A small coil is then inserted to block the PAVM. The procedure is highly effective, but the PAVMs will persist in some patients.

For the new study, Dr. Misra and colleagues wanted to see how smoking might affect post-embolization PAVM persistence rates. They looked at 103 patients with HHT who underwent embolization for a total of 373 PAVMs. The patients were classified into smoking or non-smoking groups.

Smokers faced a higher rate of PAVM persistence following treatment than those who had never smoked. Patients reporting active tobacco use at the time of PAVM embolization had a five-year persistence rate of 26.3 percent compared with 13.5 percent in inactive smokers.

PAVMs persisted after treatment in more than a third of smokers with more than 20 pack-years, compared with only 12.2 percent of nonsmokers. Pack years is a measure of smoking intensity that accounts for how long and how much a person has smoked.

"Our five-year data showed that the cumulative incidence of persistence was 17.3 percent, or almost one in five patients," Dr. Misra said. "Smoking more than 20 pack years was associated with a fivefold increase in PAVM recurrence."

While the study did not assess the reason for the post-embolization persistence of PAVMs in smokers, previous research has linked smoking with inflammation and abnormalities in the formation of new blood vessels.

"Smoking creates an inflammatory response," Dr. Misra said. "More inflammation creates a greater likelihood of failure for smokers compared to those who never smoked."

The findings, if confirmed in larger studies, could be used to advise patients with HHT who might be considering embolization for PAVMs.

"Smoking cessation is very important if these patients want to help themselves and avoid further procedures," Dr. Misra said. "We should urge current smokers to stop smoking before treatment."

Bottom Line: This study (called a systematic review and meta-analysis) combined the results 31 randomized clinical trials with 12,464 adolescent participants to examine whether parent-based sexual health interventions were associated with three main outcomes: delayed sexual activity, improved condom use and parent-child sexual communication. The findings were generally modest but across the studies there was a significant association of parent-based interventions with improved condom use and parent-child sexual communication but no significant differences for delaying adolescents' sexual activity. The current study has several limitations, including variation in how outcomes were measured in the studies pooled for this analysis.

Author: Laura Widman, Ph.D., of North Carolina State University, Raleigh, and coauthors

(doi:10.1001/jamapediatrics.2019.2324)

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

What The Study Did: This randomized clinical trial with about 400 adults conducted in China investigated acupuncture as an added treatment to antianginal therapies in reducing the frequency of angina attacks in patients with chronic stable angina.

Authors: Fanrong Liang, M.D., of the Chengdu University of Traditional Chinese Medicine, Sichuan, China, is the corresponding author.

(doi:10.1001/jamainternmed.2019.2407)

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

Researchers at the University of Houston have found neuro biomarkers for Parkinson's disease that can help create the next generation of "smart" deep brain stimulators, able to respond to specific needs of Parkinson's disease patients. Those with the disease often undergo the high-frequency brain stimulation, a well-established therapy for the progressive nervous system disorder that affects movement, but the therapy has been imprecise.

Currently, stimulators can only be programmed clinically and are not adaptable to the fluctuating symptoms of the disease which can include tremors slowness or inability to walk. The biomarkers are key to improving the technology to make it responsive, or smart.

"We can now make the closed-loop stimulator adaptive to sense a patient's symptoms, so it can make the adjustments to the fluctuations in real time, and the patient no longer has to wait for weeks or months until the doctor can adjust the device," said Nuri Ince, associate professor of biomedical engineering. He and doctoral student Musa Ozturk, lead author of the paper, published their findings in Movement Disorders journal.

Nearly 10 million people worldwide are living with Parkinson's disease and approximately 60,000 Americans are diagnosed with the disease each year.

Redefining coupling

The team also reports a new understanding of the electrophysiology of Parkinson's disease after examining cross frequency coupling in the subthalamic nucleus of patients with Parkinson's disease both in the OFF state (before medication) and the ON state (after medication). Coupling, the interaction between the brain waves, has been reported in the past, but its significance and functional role have not been well understood.

The team reports that in the OFF state, the amplitude of high-frequency brain wave oscillations in the 200-300Hz range was coupled with the phase of low-beta (13-22Hz) in all patients. After transition to the ON state, three distinct coupling patterns were observed among subjects. Among these, patients showing ON coupling between high-beta (22-30Hz) and high-frequency oscillations in the 300-400Hz range had significantly greater improvement in bradykinesia, or slowness of movement, one of the cardinal manifestations of Parkinson's disease.

"Previous research showed coupling only existed in the basal ganglia of untreated patients and assumed to block the brain from functioning properly," said Ozturk. "We found that strong coupling also exists in treated patients, though at different frequencies, so in effect we have 'cleared coupling's name' and showed the frequencies involved in coupling impacts whether its effects are negative or positive."

Osaka, Japan - Optimal methods for predicting treatment efficacy in patients with esophageal cancer are seriously lacking. But now, researchers from Japan have found a useful alternative to existing methods for predicting patient outcomes.

In a study published this month in Annals of Surgery, researchers from Osaka University revealed that, compared with primary tumors, which are often used to assess treatment outcomes in many types of cancers, the response of lymph nodes to neoadjuvant chemotherapy (NACT) is more effective in predicting disease recurrence and patient survival in individuals with esophageal cancer.

Although imaging techniques such as computed tomography (CT) and endoscopy are often used to examine primary tumors in cancer patients, these techniques are not helpful when trying to measure primary tumors in the esophagus because of its shape. Thus, it is difficult for physicians to estimate recurrence and survival in patients with esophageal cancer. The research team attempted to address this issue by finding another indicator of patient outcome.

"The frequency of lymph node metastases are very high particularly in advanced esophageal cancer compared with other gastrointestinal cancers," say lead authors Shinya Urakawa and Tomoki Makino. "Consequently, we reasoned that the response of lymph nodes might be more useful than that of primary tumors for predicting chemotherapeutic efficacy and patient prognosis. Accordingly, we aimed to determine the clinical utility of lymph node responses to NACT for predicting long-term survival in patients with metastatic esophageal cancer."

To do this, the researchers used CT to measure metastatic lymph nodes before and after NACT in individuals with metastatic esophageal cancer. They evaluated the chemotherapeutic response by monitoring the respective sizes of primary tumors and all metastatic lymph nodes that met a specific set of criteria.

"CT scans conducted before and after NACT demonstrated a high discordance in the response between primary tumors and metastatic lymph nodes in patients with esophageal cancer," explains Yuichiro Doki.

In fact, the researchers found that every lymph node showed a different response, even those in the same patient. Thus, it might be helpful to consider all metastatic lymph nodes to obtain a precise assessment of the NACT response.

"The lymph node response facilitated precise predictions of patient prognosis," says Urakawa and Makino. In addition to facilitating outcome predictions, this finding could contribute to the optimization of treatment strategies, and eventually lead to improved survival in patients with metastatic esophageal cancer.

It's not the operating room that is risky for patients undergoing noncardiac surgery; it's the recovery period. According to a large international study, only 0.7% of deaths in these patients occurred in the operating room, whereas 29% of deaths occurred after discharge from hospital. The study, which included patients at 28 centres in 14 countries, was published in CMAJ (Canadian Medical Association Journal).

"Given that most deaths in adults undergoing noncardiac surgery occur not in the operating room, but afterwards, efforts to improve postsurgical care in hospital and at home has substantial potential to reduce mortality," says author Dr. P.J. Devereaux, McMaster University, Hamilton, Ontario.

The study, which included 40 004 adults aged 45 years or older in North and South America, Asia, Europe, Africa and Australia who underwent surgery between 2007 and 2013, found that 1.8% died within 30 days of noncardiac surgery. Major bleeding, injury to the heart muscle and severe infection (sepsis) accounted for a large portion of deaths (45%).

"Approximately 100 million adults aged 45 or older undergo noncardiac surgery worldwide every year, therefore an estimated 1.8 million people die of complications within 30 days," says Dr. Devereaux. "This means that death after surgery is a major global health burden."

The authors suggest that solutions focused on prevention, early identification and close management of bleeding, cardiac issues and infection may help to reduce these preventable deaths.

Data published are from the Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) study funded by more than 70 sources.

In a linked commentary, Dr. Barnaby Reeves, Bristol Medical School, University of Bristol, Bristol, United Kingdom, salutes the achievement of the study investigators but cautions policy-makers to be mindful of inherent biases in such studies when considering the observed relationships between complications and mortality.

"Association between complications and death within 30 days after noncardiac surgery" is published July 29, 2019.

Below please find summaries of new articles that will be published in the next issue of Annals of Internal Medicine. The summaries are not intended to substitute for the full articles as a source of information.

1. Candida auris is a new drug-resistant fungus emerging globally and in the U.S. Early detection is key to controlling spread of deadly drug-resistant fungus

Physicians should be aware of risk factors and screen patients suspected of infection or colonization

Abstract: http://annals.org/aim/article/doi/10.7326/M19-2205
URLs go live when the embargo lifts

Early identification of Candida auris, a potentially deadly fungus that causes bloodstream and intra-abdominal infections, is the key to controlling its spread. Its emergence has highlighted gaps in fungal identification capacity in the U.S. and around the world, and physicians should be on alert for risk factors. A commentary is published in Annals of Internal Medicine.

Candida auris is different from more familiar Candida species in several ways and its drug resistance is unprecedented among known human-pathogenic yeasts. Most Candida species are not believed to be transmitted in health care settings and do not require infection control measures when a patient develops an infection. However, unlike other Candida species, C auris is commonly transmitted between patients in health care settings, causing outbreaks that not only affect a single facility but also spread through networks of facilities. The ability of C auris to persist in and contaminate the health care environment and medical devices likely contributes to these outbreaks.

According to experts from the Centers for Disease Control and Prevention (CDC), previous hospitalization in a country with C auris transmission is a known risk factor for infection or colonization, as is receiving of health care in long-term acute care hospitals and nursing homes that take care of very sick patients who need long-term ventilators. Frequent hospitalizations and receiving of multiple courses of very-broad-spectrum antibiotics are also important risk factors. The authors suggest that being on high alert for these risk factors and screening appropriate patients is the key to controlling the spread of C auris.

Notes and media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Snigdha Vallabhaneni, MD, MPH, please contact media@cdc.gov.

2. Google Translate proves accurate for translating medical research into English

Abstract: http://annals.org/aim/article/doi/10.7326/M19-0891

URLs go live when the embargo lifts

Google Translate is a viable, accurate tool for translating non-English language trials for the purpose of conducting systematic reviews. Using this tool could help researchers maximize the number of trials available to include in scientific evidence reviews. Findings from a brief research report are published in Annals of Internal Medicine.

A critical marker of high-quality systematic reviews is the identification and inclusion of all relevant studies. Many systematic reviews have language restrictions, which can exclude important trials. A 2012 study assessing Google Translate recommended caution in using this service.

Researchers from around the world, let by a team from the Medical College of Wisconsin, searched PubMed for randomized controlled trials (RCTs) published in 9 languages (Chinese, French, German, Italian, Japanese, Korean, Romanian, Russian, and Spanish) over an 18 year period to determine how accurately Google Translate translated the data into English for the purpose of abstracting data for systematic reviews. Data from the original-language versions of the RCTs were abstracted by native-speaking physicians whose experience in conducting systematic reviews varied. In total, 6,370 variables from 45 articles were abstracted, with 91 percent overall agreement. Agreement for the 9 languages ranted from 85 percent to 97 percent. According to the researchers, these results suggest that Google Translate is a viable tool for translating articles published in languages other than English and that Google Translate is more accurate than previously reported.

Notes and media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Jeffrey L. Jackson, MD, MPH, please contact him directly at jjackson@mcw.edu.

3. SGLT-2 inhibitors not associated with increased risk for severe UTI

Abstract: http://annals.org/aim/article/doi/10.7326/M18-3136

Editorial: http://annals.org/aim/article/doi/10.7326/M18-1950

URLs go live when the embargo lifts

Patients taking sodium-glucose cotransporter-2 (SGLT-2) inhibitors do not seem to be at increased risk for severe urinary tract infections (UTIs) when compared to patients to patients taking other second-line antidiabetic therapies. Findings from a population-based cohort study are published in Annals of Internal Medicine.

Due to their mechanism of action, SGLT-2 inhibitors are thought to increase the risk for UTIs. In 2015, the U.S. Food and Drug Administration issued a warning about increased risk for serious UTIs with SGLT-2 inhibitor use, based on 19 cases of urosepsis and pyelonephritis reported to the Administration's Adverse Event Reporting System. Given the limitations of the data, it is not clear if this risk is present in clinical practice.

Researchers from Brigham and Women's Hospital studied two large, U.S.-based databases of commercial claims to assess whether patients initiating use of SGLT-2 inhibitors were at increased risk for severe UTI events compared with those initiating use of dipeptidyl peptidase-4 (DPP-4) inhibitors or glucagon-like peptide-1 receptor (GLP-1) agonists. Two cohorts were created and matched 1:1 on propensity score. UTI events among patients using SGLT-2 inhibitors were similar to those using other antidiabetic medications in both cohorts. According to the researchers, these findings suggest that other factors beyond risk for UTI should be considered in decisions about whether to prescribe SGLT-2 therapy for patients with diabetes in routine care settings.

The authors of an accompanying editorial from McGill University and Lady Davis Institute at the Jewish General Hospital say that these findings are reassuring, but should be considered with some caution. First, the study excluded high-risk patients and those with a history of UTI, key subgroups for which further evidence is needed. Second, some analyses of secondary outcomes (such as urosepsis) in some comparisons had more modest statistical power, suggesting further safety assessments may be needed to address these issues.

Notes and media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Chintan V. Dave, PharmD, PhD, please contact chintandave19@gmail.com. To reach the author of the accompanying editorial, Kristian Filion, PhD, please contact Tod Hoffman at tod.hoffman@ladydavis.ca.

4. Cardiac device implantation complications vary widely among hospitals

Abstract: http://annals.org/aim/article/doi/10.7326/M18-2810

Editorial: http://annals.org/aim/article/doi/10.7326/M19-1895

URLs go live when the embargo lifts

Quality of care may account for the wide variation in complication rates seen among hospitals following cardiovascular implantable electronic device (CIED) procedures. Findings from a cohort study are published in Annals of Internal Medicine.

CIEDs, including permanent pacemakers and implantable cardioverter-defibrillators, are among the most common and costly devices implanted in hospitals. While effective, these devices are associated with early device-related complications, such as infection, pneumothorax, and lead dislodgement. Whether or not these complications vary among institutions has not been confirmed.

Researchers from the University of Adelaide, South Australia, studied patient records at 174 hospitals in Australia and New Zealand to assess institutional variation in risk-standardized rates of CIED complications. The study included 81,304 patients who received a new CIED with 65,711 permanent pacemakers and 15,593 implantable cardioverter-defibrillators. The data showed that CIED complications are common (8.2 percent of patients with new CIEDs had a major device-related complication within 90 days) and complication rates varied 2-3 fold among hospitals, suggesting institutional variation in CIED care quality. Most of the complications were attributed to pacemakers which were implanted far more frequently. The authors suggest that concerted clinical and policy interventions may be needed to address CIED-related complications, especially for pacemakers.

The authors of an accompanying editorial from McMaster University say that this study adds to the understanding of the early complications associated with CIEDs and the institutional variability in the quality of CIED implantation.

Notes and media contacts: For an embargoed PDF please contact Lauren Evans at laevans@acponline.org. To speak with the lead author, Isuru Ranasinghe, MBChB, MMed, PhD please contact Crispin Savage at crispin.savage@adelaide.edu.au. To reach the lead editorialist, Jorge A. Wong, MD, MPH, please contact Jorge A. Wong, MD, MPH at Jorge.Wong@phri.ca.

BOSTON, July 29, 2019-- Measuring a menopausal woman's pulse wave at her wrist may help explain the increase in cardiovascular disease risk during menopause better than a standard blood pressure measurement, according to preliminary research presented at the American Heart Association's Basic Cardiovascular Sciences 2019 Scientific Sessions.

While research shows that age, gender and body mass index (BMI) play important roles in cardiovascular disease risk, it's not clear why the risk spikes when women are in menopause.

Researchers in this study used radial pulse waves, measuring the beat of the heart through the artery at the base of the wrist. Checking radial pulse waves is easy, non-invasive and can offer more data than just looking at systolic or diastolic blood pressures, the researchers said.

They studied 327 premenopausal and postmenopausal women with no history of heart disease, tracking the women's systolic and diastolic blood pressure measurements, as well as 12-second continuous radial pulse data.

"Through mathematical models, we converted the pressure wave of the radial pulse into frequency waves. Each frequency wave was assigned a corresponding harmonic amplitude classification from C1 to C5 which provides different information than pulse rate or blood pressure," said Chi-Wei Chang, Ph.D., the study lead author and director of research and development at the Mii-Ann Medical Research Center in Taipei, Taiwan.

"For example, a violin and clarinet can play the same note but sound different because of the harmonic components of these instruments' overtones," Chang said. "Two people can have a heart rate of 75 beats per minute, but their harmonic amplitudes can vary dramatically. Analyzing the differences between these harmonic components reveals more individualized information about a person's circulatory system."

The researchers found radial pulse wave information reflected changes during menopause that were not evident in systolic or diastolic blood pressure measurements. Specifically, the first and third harmonics -- C1 and C3 -- were impacted. C1 is related to heart attack and heart failure, according to Chang.

They also found:

BMI is the largest factor affecting a woman's blood pressure and risk for hypertension.

Age affects only systolic blood pressure.

Menopause does not change blood pressure but can increase one's cardiovascular disease risk, as seen in changes in harmonic components of the radial pulse.

Additionally, according to this study, the C1 and C3 harmonics in radial pulse waves may shed light on hormonal changes during menopause that indicate the progression of atherosclerosis, but more work is needed to know for sure, Chang said. This information can be useful in better understanding a woman's cardiovascular disease risk.

"Healthcare providers can measure a menopausal woman's radial pulse to see if the patient's C1 harmonic is affected. If it is, they can monitor a patient's situation more closely and take action to prevent cardiovascular disease from becoming more severe," Chang said.

One of the limitations of the study is this increase in the amplitude of the first and third harmonics of the radial pulse wave only suggests that menopause increases the risk of heart disease by exacerbating atherosclerosis. More research is needed to demonstrate how and why that occurs, Chang said.

The evolution of more severe infections is not necessarily driven by bacteria multiplying faster, new research shows.

Humans and animals can develop resistance to harmful bacteria (pathogens) over time or with antibiotics or vaccines, and it is usually assumed that pathogens respond by multiplying faster.

But the new study - led by the University of Exeter - shows pathogen virulence and replication rates can evolve separately.

The authors believe that, once resistance spreads in host species, virulence may be driven by other means such as by manipulating host immune systems.

The research examined the spread of bacteria called Mycoplasma gallisepticum among house finches - a rare example of a well-studied host-bacteria evolution where humans have not intervened with antibiotics or vaccines.

"We actually have a very poor understanding of how pathogens evolve in response to natural host resistance," said Dr Camille Bonneaud, of the Centre of Ecology and Conservation on Exeter's Penryn Campus in Cornwall.

"This is because there are very few systems in the wild that have been monitored in sufficient detail, without being subjected to human intervention.

"We typically assume that pathogens respond to host resistance (including to vaccines) by increasing their rate of replication, allowing them to transmit faster to other hosts before they are cleared by their current host.

"However, our study shows that pathogens can evolve to become more virulent without increasing their rate of replication.

"We hypothesise that the increase in virulence that we observed in this study was driven by an improved ability of the pathogen to manipulate the host immune system in order to generate the symptoms necessary for its transmission."

The authors say this could lead to new approaches for tackling pathogens.

For example, if trying to kill the pathogen inevitably leads to more virulent infections, it might be worth trying to slow down pathogen evolution by combining treatments that both eliminate the pathogen and prevent it manipulating host immune systems.

Some populations of house finches have been exposed to Mycoplasma gallisepticum for more than 20 years, while others have not - and have therefore not developed resistance.

In the study, carried out in Arizona and supported by Arizona State University and Auburn University, 57 finches from previously unexposed populations were exposed to the pathogen.

The findings show virulence has increased consistently over more than 150,000 bacterial generations since outbreak (1994 to 2015).

By contrast, while replication rates increased from outbreak to the initial spread of resistance (1994 to 2004), no further increases have occurred subsequently (2007 to 2015).

New research has found that antibiotic-resistant strains of Klebsiella pneumoniae, an opportunistic pathogen that can cause respiratory and bloodstream infections in humans, are spreading through hospitals in Europe. Certain strains of K. pneumoniae are resistant to the carbapenem antibiotics that represent the last line of defence in treating infections and are therefore regarded as extremely drug resistant (XDR).

During a Europe-wide survey of the Enterobacteriaceae family of bacteria, researchers at the Centre for Genomic Pathogen Surveillance, based at the Wellcome Sanger Institute, University of Freiburg and their partners, analysed the genomes of almost 2,000 K. pneumoniae samples taken from patients in 244 hospitals in 32 countries. The results, published today (29 July 2019) in Nature Microbiology, will inform public health efforts to control the spread of these infections in hospitals across Europe.

It is estimated that 341 deaths in Europe were caused by carbapenem-resistant K. pneumoniae in 2007; by 2015 the number of deaths had increased six-fold to 2,094*. The high number of deaths is down to the fact that once carbapenems are no longer effective against antibiotic-resistant bacteria, there are few other options left. Infants, the elderly and immuno-compromised individuals are particularly at risk.

The survey** is the largest of its kind and is the first step towards consistent surveillance of carbapenem-resistant bacteria in Europe. More than 2,000 samples of K. pneumoniae were collected from patients across the 244 hospitals and sent to the Wellcome Sanger Institute, where the genomes of 1,700 of them were sequenced.

Researchers identified a small number of genes that, when expressed, can cause resistance to carbapenem antibiotics. These genes produce enzymes called carbapenemases, which 'chew up' the antibiotics, rendering them useless.

Of concern to public health is the recent emergence of a small number of 'high-risk' clones carrying one or more carbapenemase genes, which have spread rapidly. It is thought that the heavy use of antibiotics in hospitals favours the spread of these highly-resistant bacteria, which outcompete other strains that are more easily treatable with antibiotics.

Dr Sophia David, first author of the study, based at the Centre for Genomic Pathogen Surveillance, said: "The 'One Health'*** approach to antibiotic resistance focuses on the spread of pathogens through humans, animals and the environment, including hospitals. But in the case of carbapenem-resistant Klebsiella pneumoniae, our findings imply hospitals are the key facilitator of transmission - over half of the samples carrying a carbapenemase gene were closely related to others collected from the same hospital, suggesting that the bacteria are spreading from person-to-person primarily within hospitals."

Antibiotic-resistant bacteria samples were also much more likely to be closely related to samples from a different hospital in the same country rather than across countries - suggesting that national healthcare systems as a whole play an important role in the spread of these antibiotic-resistant bacteria.

Despite the clear threat that carbapenem-resistant K. pneumoniae pose to patients, more effective infection control in hospitals, including consideration of how patients move between hospitals and hygiene interventions, will have an impact.

Professor Hajo Grundmann, co-lead author and Head of the Institute for Infection Prevention and Hospital Hygiene at the Medical Centre, University of Freiburg, said: "We are optimistic that with good hospital hygiene, which includes early identification and isolation of patients carrying these bacteria, we can not only delay the spread of these pathogens, but also successfully control them. This research emphasises the importance of infection control and ongoing genomic surveillance of antibiotic-resistant bacteria to ensure we detect new resistant strains early and act to combat the spread of antibiotic resistance."

The second survey of the Enterobacteriaceae bacteria family across hospitals in Europe is currently being planned. The data generated is made available through MicroReact****, a publicly-available, web-based tool developed by the Centre for Genomic Pathogen Surveillance. MicroReact will help researchers and healthcare systems to chart the spread of antibiotic resistance in pathogens like K. pneumoniae and monitor how they are evolving.

Professor David Aanensen, co-lead author and Director of the Centre for Genomic Pathogen Surveillance, said: "Genomic surveillance will be key to tackling the new breeds of antibiotic-resistant pathogen strains that this study has identified. Currently, new strains are evolving almost as fast as we can sequence them. The goal to establish a robust network of genome sequencing hubs will allow healthcare systems to much more quickly track the spread of these bacteria and how they're evolving."

Cancer researchers at the University of Virginia School of Medicine have identified a key to controlling the growth and progression of prostate cancer, the second most common cancer in men. The researchers have dubbed this key "HULLK," and they believe it could be used to target and stop the progression of a cancer that kills more than 30,000 American men every year.

"We have uncovered a novel non-coding RNA that may drive prostate cancer," said senior researcher Dan Gioeli, PhD, of UVA's Department of Microbiology, Immunology and Cancer Biology and the UVA Cancer Center. "This discovery could lead to new biomarkers of prostate cancer and more effective therapies for advanced prostate cancer."

HULLK and Prostate Cancer

HULLK is a form of RNA, which provides the blueprint, or code to, produce proteins. But HULLK is a "noncoding" RNA, which means that it isn't involved in coding a protein. Instead, noncoding RNAs play important roles in regulating biological processes inside our cells. To be more specific, it appears that HULLK controls the growth of prostate cancer cells.

The researchers found that there is more HULLK in tumor samples from patients with advanced prostate cancer. They also found that decreasing the level of HULLK in cultured prostate cancer cells slows tumor cell growth. "It is this data that illustrates the potential of HULLK to function as a biomarker and/or a therapeutic target," Gioeli said.

The production of HULLK is regulated by the male sex hormones known as androgens; these hormones stimulate its production. Cells that overproduce HULLK - those associated with the most aggressive cases of prostate cancer - were actually "hypersensitive" to androgen, the researchers found.

Early stage prostate cancer has long been treated with androgen deprivation therapy, where the level of androgen is therapeutically reduced. However, this type of therapy has many side effects that some men do not want to experience. Gioeli's discovery identifies HULLK as a potential target for developing new and better treatments that may avoid these side effects. In addition, the findings could allow researchers to develop blood or urine tests to determine how aggressive a patient's prostate cancer is prior to treatment. This could prove extremely useful for men who are weighing the pros and cons of their treatment options.

"There is still a lot of research to do on how HULLK functions in order realize the potential of this discovery in the clinic," Gioeli said. "We are excited to do that research and translate our basic science discovery into the clinic."

New Rochelle, NY, July 26, 2019--A new review of Pediatric Acute Respiratory Distress Syn-drome (PARDS) highlights the lack of data available for standard treatment approaches and adjunctive therapies, leading to significant variability in patient management. This compre-hensive review article, which also identifies a great need for studies to generate outcomes data in pediatric patients with ARDS, is published in Pediatric Allergy, Immunology, and Pulmonology, a peer-reviewed journal from Mary Ann Liebert, Inc., publishers. Click here to read the full-text open access article on the Pediatric Allergy, Immunology, and Pulmonology website.

In "The Current State of Pediatric Acute Respiratory Distress Syndrome" coauthors Kirsten E. Orloff, MD, David A. Turner, MD, FCCM, FCCP, and Kyle J. Rehder, MD, FCCM, FCCP, Duke Children's Hospital, Durham, NC, present the physiologic basis of PARDS and describe the unique pediatric definition of the disorder and what puts a child at risk. The au-thors provide a thorough discussion of the current best practice strategies, including lung protective strategies as well as adjunctive options for these critically ill children. In the sec-tion entitled "Next Steps," they call for more high-quality data to support the effectiveness of potential treatments, studies that focus on pediatric patients with severe PARDS, and out-comes data in pediatric survivors of ARDS that would assess its effects on lung function, quality of life, and neurocognitive functioning.

"Acute respiratory distress syndrome (ARDS) presents unique challenges in the pediatric age group and carries a mortality risk of approximately 24%. While this is both lower than the mortality risk for ARDS in adults and is decreasing over time in children, it continues to be a formidable problem. Accounting for up to 10% of all pediatric ICU admissions, PARDS confronts pediatric intensivists with the difficult task of identifying early signs of acute lung injury and selecting the best possible strategies for each individual child on a regular basis. This review provides a concise overview of best practice strategies to combat acute respiratory distress syndrome in children affected by this serious and potentially deadly condition," says Pediatric Allergy, Immunology, and Pulmonology Editor-in-Chief Mary Cataletto, MD, Professor of Clinical Pediatrics, Stony Brook University School of Medicine.